Analysis of N6-Methyladenosine Modification of HBV RNA by Methylated RNA Immunoprecipitation.

Of all the chemical modifications of RNAs, the N6-methyladenosine (m6A) modification is the most prevalent and well-characterized RNA modification that is functionally implicated in a wide range of biological processes. The m6A modification occurs in hepatitis B virus (HBV) RNAs and this modification regulates the HBV life cycle in several ways. Thus, understanding the mechanisms underlying m6A modification of HBV RNAs is crucial in understanding HBV infectious process and associated pathogenesis. Here, we describe the currently utilized method in the detection and characterization of m6A-methylated RNAs during viral infection.

Effectiveness of sensory integration therapy in children, focusing on Korean children: A systematic review and meta-analysis.

BACKGROUND: Sensory integration intervention is highly related to the child's effective interaction with the environment and the child's development. Currently, various sensory integration interventions are being applied, but research methodological problems are arising due to unsystematic protocols. This study aims to present the optimal intervention protocol by presenting scientific standards for sensory integration intervention through meta-analysis. AIM: To prove the effectiveness of sensory integration therapy, examine the latest trend of sensory integration studies in Korea, and provide clinical evidence for sensory integration therapies. METHODS: The database of Korean search engines, including RISS, KISS, and DBpia, was used to search for related literature published from 2001 to October 2020. The keywords, "Children", "Sensory integration", "Integrated sensory", "Sensory-motor", and "Sensory stimulation" were used in this search. Then, a meta-analysis was conducted on 24 selected studiesRISS, KISS, and DBpia, was used to search for related literature published from 2001 to October 2020. The keywords, "Children", "Sensory integration", "Integrated sensory", "Sensory-motor", and "Sensory stimulation" were used in this search. Then, a meta-analysis was conducted on 24 selected studies. RESULTS: Sensory integration intervention has been proven effective in children with cerebral palsy, autism spectrum disorder, attention deficit/hyperactivity disorder, developmental disorder, and intellectual disability in relation to the diagnosis of children. Regarding sensory integration therapies, 1:1 individual treatment with a therapist or a therapy session lasting for 40 min was most effective. In terms of dependent variables, sensory integration therapy effectively promoted social skills, adaptive behavior, sensory processing, and gross motor and fine motor skills. CONCLUSION: The results of this study may be used as therapeutic evidence for sensory integration intervention in the clinical field of occupational therapy for children, and can help to present standards for sensory integration intervention protocols.

Development of a Parturition Detection System for Korean Native Black Goats.

Korean Native Black Goats deliver mainly during the cold season. However, in winter, there is a high risk of stunted growth and mortality for their newborns. Therefore, we conducted this study to develop a KNBG parturition detection system that detects and provides managers with early notification of the signs of parturition. The KNBG parturition detection system consists of triaxial accelerometers, gateways, a server, and parturition detection alarm terminals. Then, two different data, the labor and non-labor data, were acquired and a Decision Tree algorithm was used to classify them. After classifying the labor and non-labor states, the sum of the labor status data was multiplied by the activity count value to enhance the classification accuracy. Finally, the Labor Pain Index (LPI) was derived. Based on the LPI, the optimal processing time window was determined to be 10 min, and the threshold value for labor classification was determined to be 14 240.92. The parturition detection rate was 82.4%, with 14 out of 17 parturitions successfully detected, and the average parturition detection time was 90.6 min before the actual parturition time of the first kid. The KNBG parturition detection system is expected to reduce the risk of stunted growth and mortality due to hypothermia in KNBG kids by detecting parturition 90.6 min before the parturition of the first kid, with a success rate of 82.4%, enabling parturition nursing.

Characterization of SsHog1 and Shk1 Using Efficient Gene Knockout Systems through Repeated Protoplasting and CRISPR/Cas9 Ribonucleoprotein Approaches in Sclerotinia sclerotiorum.

Sclerotinia sclerotiorum is the causal agent of sclerotinia stem rot in over 400 plant species. In a previous study, the group III histidine kinase gene of S. sclerotiorum (Shk1) revealed its involvement in iprodione and fludioxonil sensitivity and osmotic stress. To further investigate the fungicide sensitivity associated with the high-osmolarity glycerol (HOG) pathway, we functionally characterized SsHog1, which is the downstream kinase of Shk1. To generate knockout mutants, split marker transformation combined with a newly developed repeated protoplasting method and CRISPR/Cas9 ribonucleoprotein (RNP) delivery approach were used. The pure SsHog1 and Shk1 knockout mutants showed reduced sensitivity to fungicides and increased sensitivity to osmotic stress. In addition, the SsHog1 knockout mutants demonstrated reduced virulence compared to Shk1 knockout mutants and wild-type. Our results indicate that the repeated protoplasting method and RNP approach can generate genetically pure homokaryotic mutants and SsHog1 is involved in osmotic adaptation, fungicide sensitivity, and virulence in S. sclerotiorum.

The Significance of N6-Methyladenosine RNA Methylation in Regulating the Hepatitis B Virus Life Cycle.

N6-methyladenosine (m6A) RNA methylation has recently emerged as a significant co-transcriptional modification involved in regulating various RNA functions. It plays a vital function in numerous biological processes. Enzymes referred to as m6A methyltransferases, such as the methyltransferaselike (METTL) 3-METTL14-Wilms tumor 1 (WT1)-associated protein (WTAP) complex, are responsible for adding m6A modifications, while m6A demethylases, including fat mass and obesity-associated protein (FTO) and alkB homolog 5 (ALKBH5), can remove m6A methylation. The functions of m6A-methylated RNA are regulated through the recognition and interaction of m6A reader proteins. Recent research has shown that m6A methylation takes place at multiple sites within hepatitis B virus (HBV) RNAs, and the location of these modifications can differentially impact the HBV infection. The addition of m6A modifications to HBV RNA can influence its stability and translation, thereby affecting viral replication and pathogenesis. Furthermore, HBV infection can also alter the m6A modification pattern of host RNA, indicating the virus's ability to manipulate host cellular processes, including m6A modification. This manipulation aids in establishing chronic infection, promoting liver disease, and contributing to pathogenesis. A comprehensive understanding of the functional roles of m6A modification during HBV infection is crucial for developing innovative approaches to combat HBV-mediated liver disease. In this review, we explore the functions of m6A modification in HBV replication and its impact on the development of liver disease.

Monitoring of Benzimidazole Resistance in Botrytis cinerea Isolates from Strawberry in Korea and Development of Detection Method for Benzimidazole Resistance.

Botrytis cinerea is a major fungal plant pathogen that causes gray mold disease in strawberries, leading to a decrease in strawberry yield. While benzimidazole is widely used as a fungicide for controlling this disease, the increasing prevalence of resistant populations to this fungicide undermines its effectiveness. To investigate benzimidazole resistant B. cinerea in South Korea, 78 strains were isolated from strawberries grown in 78 different farms in 2022, and their EC50 values for benzimidazole were examined. As a result, 64 strains exhibited resistance to benzimidazole, and experimental tests using detached strawberry leaves and the plants in a greenhouse confirmed the reduced efficacy of benzimidazole to control these strains. The benzimidazole resistant strains identified in this study possessed two types of mutations, E198A or E198V, in the TUB2 gene. To detect these mutations, TaqMan probes were designed, enabling rapid identification of benzimidazole resistant B. cinerea in strawberry and tomato farms. This study utilizes TaqMan real-time polymerase chain reaction analysis to swiftly identify benzimidazole resistant B. cinerea, thereby offering the possibility of effective disease management by identifying optimum locations and time of application.

Analysis of the effectiveness of cognitive rehabilitation for patients with chronic mental illness: A meta-analysis.

BACKGROUND: People suffering from chronic mental illness are sensitive to stressful stimuli, lack coping skills, and have low self-esteem due to problems such as social situations. They also experience depression, isolation, fear, and frustration. Due to cognitive dysfunction, people suffering from chronic mental illness have inadequate cognitive processes that lead to distorted thinking. AIM: To confirm the effectiveness of cognitive rehabilitation therapy in improving cognitive function and alleviating behavioral and psychological symptoms in patients with chronic mental illness, and to identify the cognitive function that had the main effect. METHODS: The quality of the studies was evaluated using the Assessment of Multiple Systematic Reviews criteria, and data published from 2011 to December 2022 were searched using PubMed, Cochrane, RISS, KISS, and DBpia. The keywords used in the search were "mental illness," "cognitive rehabilitation," "cognition," and "mental." A meta-analysis was conducted on the 12 selected papers. RESULTS: The level of evidence for the 12 documents was that of a randomized experimental study. Intervention types in cognitive rehabilitation can be divided into cognitive behavior, cognitive training, cognitive rehabilitation, and computerized cognitive programs. Most of the studies were on schizophrenia, and the measurement areas were cognitive functions (e.g., concentration, memory, and executive function) as well as depression, sociability, and quality of life. As a result of the meta-analysis of each variable, the effect size for cognitive rehabilitation treatment was in the following order: Sociability, memory, concentration, executive function, quality of life, and depression. Particularly, sociability and memory exhibited significant effects. CONCLUSION: Cognitive rehabilitation aids cognitive function and sociability in patients with chronic mental illness and can be used as evidence for cognitive rehabilitation in mental health and occupational therapy.

Meta-analysis on the effectiveness of parent education for children with disabilities.

BACKGROUND: Parents of children with disabilities often have difficulty understanding their child's behavior and are unable to do it appropriately because they do not know what to do. The more we properly understand children with disabilities, the more positive the importance of parent education becomes in various aspects. AIM: To demonstrate the effectiveness of parent education for children with disabilities in various aspects and present it as evidence that can be used clinically. METHODS: For a meta-analysis on the effectiveness of parent education for children with disabilities, literature was collected from 2002 to 2022 using PubMed, Embase, Web of Science, Directory of Open Access Journals, and Europe PMC. Search terms were "disabled children," "disabled children," "parent education," "parent training," and "parent coaching." The final searched literature included a total of 11 articles. To calculate the effect size, the mean, standard deviation, and sample size of the experimental and control groups were analyzed, and a meta-analysis was performed using RevMan version 5.4.1. To analyze statistical heterogeneity, a chi-square test was performed to evaluate the significance of Q statistics to indicate statistical heterogeneity. RESULTS: The final literature totaled 11 articles, and a total of 4 items were analyzed. There were 5 studies on parental depression, the heterogeneity was 98%, and the effect size for parental depression was 0.35 [confidence interval (CI: 0.30-0.40)], indicating a small but statistically significant effect size. There were 4 studies on parenting attitude, the heterogeneity was 100%, the effect size on parenting attitude was 0.41 (CI: 0.37-0.46), which was a medium effect size, and the P value showed a statistically significant score. Additionally, face-to-face parent education was found to have a larger effect size than non-face-to-face education. Regarding parent education methods, face-to-face parent education had a medium effect size [0.57 (CI: 0.52-0.61]), while non-face-to-face parent education had a small effect size [0.23 (CI: 0.18-0.28]). CONCLUSION: Parental education has shown high effectiveness in child development, and it has proven to be even more effective when face-to-face parenting education is conducted. Accordingly, more effective and objective data was presented. Based on this study, it is believed that parent education research applying various diagnostic groups should continue to be conducted.

Proximate Content Monitoring of Black Soldier Fly Larval (Hermetia illucens) Dry Matter for Feed Material using Short-Wave Infrared Hyperspectral Imaging.

Edible insects are gaining popularity as a potential future food source because of their high protein content and efficient use of space. Black soldier fly larvae (BSFL) are noteworthy because they can be used as feed for various animals including reptiles, dogs, fish, chickens, and pigs. However, if the edible insect industry is to advance, we should use automation to reduce labor and increase production. Consequently, there is a growing demand for sensing technologies that can automate the evaluation of insect quality. This study used short-wave infrared (SWIR) hyperspectral imaging to predict the proximate composition of dried BSFL, including moisture, crude protein, crude fat, crude fiber, and crude ash content. The larvae were dried at various temperatures and times, and images were captured using an SWIR camera. A partial least-squares regression (PLSR) model was developed to predict the proximate content. The SWIR-based hyperspectral camera accurately predicted the proximate composition of BSFL from the best preprocessing model; moisture, crude protein, crude fat, crude fiber, and crude ash content were predicted with high accuracy, with R2 values of 0.89 or more, and root mean square error of prediction values were within 2%. Among preprocessing methods, mean normalization and max normalization methods were effective in proximate prediction models. Therefore, SWIR-based hyperspectral cameras can be used to create automated quality management systems for BSFL.

Rapid Detection of Single- and Co-Contaminant Aflatoxins and Fumonisins in Ground Maize Using Hyperspectral Imaging Techniques.

Aflatoxins and fumonisins, commonly found in maize and maize-derived products, frequently co-occur and can cause dangerous illness in humans and animals if ingested in large amounts. Efforts are being made to develop suitable analytical methods for screening that can rapidly detect mycotoxins in order to prevent illness through early detection. A method for classifying contaminated maize by applying hyperspectral imaging techniques including reflectance in the visible and near-infrared (VNIR) and short-wave infrared (SWIR) regions, and fluorescence was investigated. Machine learning classification models in combination with different preprocessing methods were applied to screen ground maize samples for naturally occurring aflatoxin and fumonisin as single contaminants and as co-contaminants. Partial least squares-discriminant analysis (PLS-DA) and support vector machine (SVM) with the radial basis function (RBF) kernel were employed as classification models using cut-off values of each mycotoxin. The classification performance of the SVM was better than that of PLS-DA, and the highest classification accuracies for fluorescence, VNIR, and SWIR were 89.1%, 71.7%, and 95.7%, respectively. SWIR imaging with the SVM model resulted in higher classification accuracies compared to the fluorescence and VNIR models, suggesting that as an alternative to conventional wet chemical methods, the hyperspectral SWIR imaging detection model may be the more effective and efficient analytical tool for mycotoxin analysis compared to fluorescence or VNIR imaging models. These methods represent a food safety screening tool capable of rapidly detecting mycotoxins in maize or other food ingredients consumed by animals or humans.

Durability and Performance Analysis of Polymer Electrolyte Membranes for Hydrogen Fuel Cells by a Coupled Chemo-mechanical Constitutive Model and Experimental Validation.

In this paper, a chemo-mechanically coupled behavior of Nafion 212 is investigated through predictive multiphysics modeling and experimental validation. Fuel cell performance and durability are critically determined by the mechanical and chemical degradation of a perfluorosulfonic acid (PFSA) membrane. However, how the degree of chemical decomposition affects the material constitutive behavior has not been clearly defined. To estimate the degradation level quantitatively, fluoride release is measured. The PFSA membrane in tensile testing shows nonlinear behavior, which is modeled by J2 plasticity-based material modeling. The material parameters, which contain hardening parameters and Young's modulus, are characterized in terms of fluoride release levels by inverse analysis. In the sequel, membrane modeling is performed to investigate the life prediction due to humidity cycling. A continuum-based pinhole growth model is adopted in response to mechanical stress. As a result, validation is conducted in comparison with the accelerated stress test (AST) by correlating the size of the pinhole with the gas crossover generated in the membrane. This work provides a dataset of degraded membranes for performance and suggests the quantitative understanding and prediction of fuel cell durability with computational simulation.

Development of a Mercury Bromide Birefringence Measurement System Based on Brewster's Angle.

Mercury bromide (Hg2Br2) has been used to develop acousto-optic tunable filters (AOTFs) because it has several advantages, including a high refractive index, a broad optical bandwidth, and a relatively high figure of merit. Therefore, the measurement of its birefringence is a highly important factor for ensuring AOTF quality. However, for single crystals, it is difficult (at the millimeter scale) to quantify the birefringence using an ellipsometer, as this equipment is only designed to conduct measurements on thin films. In this study, a simple birefringence measurement system for Hg2Br2 was developed based on Brewster's angle at the millimeter scale. The planar distributions of the Hg2Br2 crystal along the (100), (010), and (001) planes were used in the experiments. The developed measurement system can measure the reflected light intensity of the Hg2Br2 crystal depending on the incidence angles (rotations at 0.01125° steps) and can calculate the ordinary and extraordinary refractive indices and birefringence. The calculated birefringence of the Hg2Br2 crystal was 0.8548; this value exhibits an error of 0.64% compared with a value of 0.86 reported in the literature. The developed measurement system demonstrates the ability to be used to evaluate the quality of birefringent single crystals.

New Approaches to Produce Large-Area Single Crystal Thin Films.

Wafer-scale growth of single crystal thin films of metals, semiconductors, and insulators is crucial for manufacturing high-performance electronic and optical devices, but still challenging from both scientific and industrial perspectives. Recently, unconventional advanced synthetic approaches have been attempted and have made remarkable progress in diversifying the species of producible single crystal thin films. This review introduces several new synthetic approaches to produce large-area single crystal thin films of various materials according to the concepts and principles.

Is altitude a determinant of the health benefits of nature exposure? A systematic review and meta-analysis.

Introduction: Nature exposure is a widely accepted option for promoting public health owing to the recent surge of scientific evidence. However, the actual settings to facilitate this initiative is yet to be extensively reviewed. In this systematic review, we have aimed to provide an up-to-date summary of interventional studies investigating the psycho-physiological effects of forests and urban forests, including details on their physical settings, and investigate an effect-modifying role of altitude and summarize data on the magnitude and shape of the association. Methods: A keyword search using five electronic academic databases (PubMed, Embase, PsycINFO, Web of Science, and Scopus) was conducted to identify relevant articles published in English from the inception year to the end of February 2022. The methodological quality was evaluated using the ROBINS-I or ROB2 tool, depending on the study design. Meta-regression and random effects model were jointly used to examine the relationship between altitude and health outcomes. Results: We included 27 eligible studies and 31 cases extracted from 19 studies were used for the meta-analysis. In the meta-regression, we observed a non-linear association between altitude and psycho-physiological effects. Altitude had a positive quadratic association with anxiety (p < 0.000, adjusted R 2 = 96.79%), depression (p < 0.000, adjusted R 2 = 98.78%), and fatigue (p < 0.000, adjusted R 2 = 64.74%) alleviating effects. Conversely, altitude demonstrated a negative non-linear association with the blood pressure-lowering effect (p = 0.009, adjusted R 2 = 32.83%). Additionally, the thermal index (THI) and illuminance (lx) levels were significantly associated with effect sizes of psychological restoration. Discussion: This review provides moderate-certainty evidence for an effect-modifying role of altitude. The meta-regression results suggested the optimal and minimal altitude ranges for psychological restoration and physiological relaxation, respectively. Despite some limitations, the study findings provide a significant basis for utilizing altitude, which is easily accessible and simple, to promote the health benefits of nature-based initiatives. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022310894, identifier: CRD42022310894.

CNT-Reinforced Self-Healable Epoxy Dynamic Networks Based on Disulfide Bond Exchange.

The design and utilization of polymers with healing capability have drawn increasing attention owing to their enhanced chain mobility and opportunity to heal minor cracks in composites. Rehealable thermoset polymers promise reduction in the maintenance cost and thus prolonged lifetime, reshaping, and recyclability. Introducing reversible covalent bonds is the mainstay strategy to achieve such plasticity in crosslinked polymers. Herein, we report a dynamic epoxy, which includes associative covalent adaptive networks (CANs) based on disulfide exchange bonds. Epoxy resin is chosen to study rehealing, as it is one of the most critical thermosetting polymers for various industries from aerospace to soft robotics. This study enlightens us about not only the consequences of CANs in the epoxy but also various factors such as soft segments and carbon nanotubes (CNTs). Epoxy dynamic networks are investigated in an attempt to explore the synergistic effect of the soft-segmented resins and CNTs on the healing and reshaping characteristics of epoxy networks along with varying stiffness. This research discusses epoxy dynamic networks in three main aspects: crosslink density, CAN density, and CNTs. Introducing soft segments into the epoxy network enhances the healing efficiency due to the increased chain mobility. A higher CAN density accelerates network rearrangement, improving the healing efficiency. It should also be noted that even with a low weight fraction of nanotubes, CNT-reinforced samples restored their initial strength more than neat samples after healing. The tensile strength of dynamic networks is at least 50 MPa, which is significant for their utility in primary or secondary structural components.

Epoxy-Based Catalyst-Free Self-Healing Elastomers at Room Temperature Employing Aromatic Disulfide and Hydrogen Bonds.

In this paper, catalyst-free room-temperature healing epoxy vitrimer-like materials (S-vitrimer) are introduced. The S-vitrimer can be healed at room temperature without any external stimuli such as solvent, pressure, heat, and catalyst through an aromatic disulfide exchange reaction and a hydrogen bond because the glass transition temperature of the S-vitrimer is lower than room temperature. Self-healing materials are attracting widespread attention nowadays with their potential to increase the durability of the materials. However, there is still elevating need for research, considering the limitations of various self-healing methods. To the best of our knowledge, epoxy-based catalyst-free room-temperature healing materials have not been investigated until now, yet they are promising to make self-healing easier. Moreover, the S-vitrimer showed higher healing efficiency when healed for a longer time and at a higher temperature. Especially when healed at room temperature for 96 h, the S-vitrimer presented an 80% healing efficiency. The S-vitrimer also showed an 80% healing efficiency when healed at 60 °C for 48 h. To investigate the factors affecting self-healing behavior, three control experiments were carried out. Control experiments showed that the S-vitrimer is healed mainly due to a disulfide exchange reaction, but hydrogen bonds also contribute to self-healing behavior. Also, it was found that tightly packed segments can hinder self-healing through control experiments.

Near-infrared hyperspectral imaging for online measurement of the viability detection of naturally aged watermelon seeds.

The viability status of seeds before sowing is important to farmers as it allows them to make yield predictions. Monitoring the seed quality in a rapid and nondestructive manner may create a perfect solution, especially for industrial sorting applications. However, current offline laboratory-based strategies employed for the monitoring of seed viability are time-consuming and thus cannot satisfy industrial needs where there is a substantial number of seeds to be analyzed. In this study, we describe a prototype online near-infrared (NIR) hyperspectral imaging system that can be used for the rapid detection of seed viability. A wavelength range of 900-1700 nm was employed to obtain spectral images of three different varieties of naturally aged watermelon seed samples. The partial least square discriminant analysis (PLS-DA) model was employed for real-time viability prediction for seed samples moving through a conveyor unit at a speed of 49 mm/sec. A suction unit was further incorporated to develop the online system and it was programmatically controlled to separate the detected viable seeds from nonviable ones. For an external validation sample set showed classification accuracy levels of 91.8%, 80.7%, and 77.8% in relation to viability for the three varieties of watermelon seed with healthy seedling growth. The regression coefficients of the classification model distinguished some chemical differences in viable and nonviable seed which was verified by the chromatographic analysis after the detection of the proposed online system. The results demonstrated that the developed online system with the viability prediction model has the potential to be used in the seed industry for the quality monitoring of seeds.

Field Application of a Vis/NIR Hyperspectral Imaging System for Nondestructive Evaluation of Physicochemical Properties in 'Madoka' Peaches.

Extensive research has been performed on the in-field nondestructive evaluation (NDE) of the physicochemical properties of 'Madoka' peaches, such as chromaticity (a*), soluble solids content (SSC), firmness, and titratable acidity (TA) content. To accomplish this, a snapshot-based hyperspectral imaging (HSI) approach for filed application was conducted in the visible and near-infrared (Vis/NIR) region. The hyperspectral images of 'Madoka' samples were captured and combined with commercial HSI analysis software, and then the physicochemical properties of the 'Madoka' samples were predicted. To verify the performance of the field-based HSI application, a lab-based HSI application was also conducted, and their coefficient of determination values (R2) were compared. Finally, pixel-based chemical images were produced to interpret the dynamic changes of the physicochemical properties in 'Madoka' peach. Consequently, the a* values and SSC content shows statistically significant R2 values (0.84). On the other hand, the firmness and TA content shows relatively lower accuracy (R2 = 0.6 to 0.7). Then, the resultant chemical images of the a* values and SSC content were created and could represent their different levels using grey scale gradation. This indicates that the HSI system with integrated HSI software used in this work has promising potential as an in-field NDE for analyzing the physicochemical properties in 'Madoka' peaches.

N6-Methyladenine Modification of Hepatitis Delta Virus Regulates Its Virion Assembly by Recruiting YTHDF1.

Hepatitis delta virus (HDV) is a defective satellite virus that uses hepatitis B virus (HBV) envelope proteins to form its virions and infect hepatocytes via the HBV receptors. Concomitant HDV/HBV infection continues to be a major health problem, with at least 25 million people chronically infected worldwide. N6-methyladenine (m6A) modification of cellular and viral RNAs is the most prevalent internal modification that occurs cotranscriptionally, and this modification regulates various biological processes. We have previously described a wider range of functional roles of m6A methylation of HBV RNAs, including its imminent regulatory role in the encapsidation of pregenomic RNA. In this study, we present evidence that m6A methylation also plays an important role in the HDV life cycle. Using the methylated RNA immunoprecipitation (MeRIP) assay, we identified that the intracellular HDV genome and antigenome are m6A methylated in HDV- and HBV-coinfected primary human hepatocytes and HepG2 cell expressing sodium taurocholate cotransporting polypeptide (NTCP), while the extracellular HDV genome is not m6A methylated. We observed that HDV genome and delta antigen levels are significantly decreased in the absence of METTL3/14, while the extracellular HDV genome levels are increased by depletion of METTL3/14. Importantly, YTHDF1, an m6A reader protein, interacts with the m6A-methylated HDV genome and inhibits the interaction between the HDV genome and antigens. Thus, m6A of the HDV genome negatively regulates virion production by inhibiting the interaction of the HDV genome with delta antigens through the recruitment of YTHDF1. This is the first study that provides insight into the functional roles of m6A in the HDV life cycle. IMPORTANCE The functional roles of N6-methyladenine (m6A) modifications in the HBV life cycle have been recently highlighted. Here, we investigated the functional role of m6A modification in the HDV life cycle. HDV is a subviral agent of HBV, as it uses HBV envelope proteins to form its virions. We found that m6A methylation also occurs in the intracellular HDV genome and antigenome but not in the extracellular HDV genome. The m6A modification of the HDV genome recruits m6A reader protein (YTHDF1) onto the viral genome. The association of YTHDF1 with the HDV genome abrogates the interaction of delta antigens with the HDV genome and inhibits virion assembly. This study describes the unique effects of m6A on regulation of the HDV life cycle.

What Activities in Forests Are Beneficial for Human Health? A Systematic Review.

Over the past decade, clinical trials of forest-based interventions have increased, leading to their recognition as preventive medicine. However, little is known about the differences in health effects according to the activity characteristics of interventions. This study aimed to understand the types of activities and their associated health effects to identify differences in health effects between activities. PubMed, PsycINFO, Web of Science, and Scopus databases were searched, and methodological quality was assessed using Cochrane ROB2. A total of 32 randomized controlled trials (RCTs) met the eligibility criteria. Health outcomes were collected from 6264 participants aged 6-98 years, and the sample size was 12-585. The Interventions were walking (n = 21), staying (n = 7), exercise (n = 4), indirect exposure (n = 4), and the activity time was between 10 and 240 min. Overall, walking showed consistent positive health effects, and there were differences in effects on anxiety and depression, cognitive function, stress hormone, and inflammation according to the activity. However, most of the included studies had a high risk of bias, and interventions were limited to specific activities, durations, and frequencies. Although a few limitations remain, the findings in this study are of great significance in providing the basis for the design of forest-based interventions.