An RNA-hydrolyzing recombinant minibody prevents both influenza A virus and coronavirus in co-infection models.

With the lifting of COVID-19 non-pharmaceutical interventions, the resurgence of common viral respiratory infections was recorded in several countries worldwide. It facilitates viral co-infection, further burdens the already over-stretched healthcare systems. Racing to find co-infection-associated efficacy therapeutic agents need to be rapidly established. However, it has encountered numerous challenges that necessitate careful investigation. Here, we introduce a potential recombinant minibody-associated treatment, 3D8 single chain variable fragment (scFv), which has been developed as a broad-spectrum antiviral drug that acts via its nucleic acid catalytic and cell penetration abilities. In this research, we demonstrated that 3D8 scFv exerted antiviral activity simultaneously against both influenza A viruses (IAVs) and coronaviruses in three established co-infection models comprising two types of coronaviruses [beta coronavirus-human coronavirus OC43 (hCoV-OC43) and alpha coronavirus-porcine epidemic diarrhea virus (PEDV)] in Vero E6 cells, two IAVs [A/Puerto Rico/8/1934 H1N1 (H1N1/PR8) and A/X-31 (H3N2/X-31)] in MDCK cells, and a combination of coronavirus and IAV (hCoV-OC43 and adapted-H1N1) in Vero E6 cells by a statistically significant reduction in viral gene expression, proteins level, and approximately around 85%, 65%, and 80% of the progeny of 'hCoV-OC43-PEDV', 'H1N1/PR8-H3N2/X-31', and 'hCoV-OC43-adapted-H1N1', respectively, were decimated in the presence of 3D8 scFv. Taken together, we propose that 3D8 scFv is a promising broad-spectrum drug for treatment against RNA viruses in co-infection.

Revisit and explore the ethylene-independent mechanism of sex expression in cucumber (Cucumis sativus).

KEY MESSAGE: This review provides a thorough and comprehensive perspective on the topic of cucumber sexual expression. Specifically, insights into sex expression mediated by pathways other than ethylene are highlighted. Cucumber (Cucumis sativus L.) is a common and important commercial crop that is cultivated and consumed worldwide. Additionally, this species is commonly used as a model for investigating plant sex expression. Cucumbers exhibit a variety of floral arrangements, comprising male, female, and hermaphroditic (bisexual) flowers. Generally, cucumber plants that produce female flowers are typically preferred due to their significant impact on the overall output. Various environmental conditions, such as temperature, light quality, and photoperiod, have been also shown to influence the sex expression in this species. Multiple lines of evidence indicate that ethylene and its biosynthesis genes are crucial in regulating cucumber sex expression. Gibberellins, another well-known phytohormone, can similarly influence cucumber sex expression via an ethylene-independent route. Further studies employing the next-generation sequencing technology also visualized a deeper slice of the molecular mechanism such as the role of the cell cycle program in the cucumber sex expression. This review aims to provide an overview of the sex expression of cucumber including its underlying molecular mechanism and regulatory aspects based on recent investigations.

Determining the factors impacting the quality of life among the general population in coastal communities in central Vietnam.

People living in coastal areas are frequently affected by natural disasters, such as floods and storms. This study aimed to assess the quality of life (QoL) of people living in disadvantaged coastal communes (subdivision of Vietnam) and identify their associated factors by using the World Health Organization's quality of life instrument (WHOQOL-BREF). To achieve this, a cross-sectional descriptive study was conducted on 595 individuals aged 18 years and above living in the coastal communes in Thua Thien Hue province, Vietnam, from October 2022 to February 2023. The results showed that the mean overall QoL (mean ± SD) was 61.1 ± 10.8. Among the four domains of QoL, the physical health (57.2 ± 12.3) domain had a lower score than the psychological health (61.9 ± 13.0), social relations (63.4 ± 13.4), and environment (61.9 ± 13.3) domains. The QoL score of the domains for participants affected by flooding was significantly lower than that of those not affected, except for social relations. Multivariable logistic regression showed that subjects with not good QoL had the educational background with no formal education (Odds ratio (OR) = 2.63, 95% CI 1.19-5.83), fairly poor/poor households (OR = 2.75, 95% CI 1.48-5.12), suffered Musculoskeletal diseases (OR = 1.61, 95% CI 1.02-2.56), unsatisfaction with health status (OR = 5.27, 95% CI 2.44-11.37), family conflicts (OR = 4.51, 95%CI 2.10-9.69), and low levels of social support (OR = 2.62; 95% CI 1.14-6.02). The analysis also revealed that workers (OR = 0.17, 95% CI 0.04-0.66) had a better QoL than farmer-fisherman. QoL in disadvantaged coastal communes was low, with the lowest scores in the physical health domain. Based on the socioeconomic factors associated with not good QoL identified here, it is recommended that local authorities take more appropriate and practical measures to increase support, including measures for all aspects of physical health, psychological health, social relations, and the living environment, especially for people affected by floods.

Transreplication Preference of the Tomato Leaf Curl Joydebpur Virus for a Noncognate Betasatellite through Iteron Resemblance on Nicotiana bethamiana.

Pepper plants (Capsicum annuum) with severe leaf curl symptoms were collected in 2013 from Bangalore, Karnataka, India. The detection results showed a co-infection between the tomato leaf curl Joydebpur virus (ToLCJoV) and tomato leaf curl Bangladesh betasatellite (ToLCBDB) through the sequencing analysis of PCR amplicons. To pinpoint the molecular mechanism of this uncommon combination, infectious clones of ToLCJoV and two different betasatellites-ToLCBDB and tomato leaf curl Joydebpur betasatellite (ToLCJoB)-were constructed and tested for their infectivity in Nicotiana benthamiana. Together, we conducted various combined agroinoculation studies to compare the interaction of ToLCJoV with non-cognate and cognate betasatellites. The natural non-cognate interaction between ToLCJoV and ToLCBDB showed severe symptoms compared to the mild symptoms of a cognate combination (ToLCJoV × ToLCJoB) in infected plants. A sequence comparison among betasatellites and their helper virus wasperformed and the iteron resemblances in ToLCBDB as well as ToLCJoB clones were processed. Mutant betasatellites that comprised iteron modifications revealed that changes in iteron sequences could disturb the transreplication process between betasatellites and their helper virus. Our study might provide an important consideration for determining the efficiency of transreplication activity between betasatellites and their helper virus.

Asymptomatic congenital ductus arteriosus aneurysm in a newborn: Case by approach.

A ductus arteriosus aneurysm is a rare congenital lesion with a localized saccular or tubular dilation of the ductus arteriosus. This lesion usually appears in all ages. Some case reports suggest the most common age of diagnosis is less than 2 months. We reported a case of an asymptomatic ductus arteriosus aneurysm in neonates. Echocardiography at 2 days of age revealed a tubular dilation of the ductus arteriosus connected to the pulmonary artery. Computed tomography angiogram showed a ductus arteriosus aneurysm with thrombus at the pulmonary end. It resolved spontaneously in the six months of life without serious complications.

Psychological impacts of COVID-19 on Vietnamese health workers over the prolonged restricted COVID-19 responses: a cross-sectional study.

OBJECTIVE: We assessed the psychological impact posed by COVID-19 and its associated factors on the healthcare workforce nationwide during the peak of Vietnam's fourth outbreak. DESIGN: A cross-sectional study. SETTING: Our study was conducted in 61 provinces of Vietnam. METHODS: A total of 2814 healthcare professionals in 61/63 provinces of Vietnam. An online questionnaire using Patient Health Questionnaire-9 (PHQ-9), Perceived Stress Scale-4 (PSS-4) and Generalised Anxiety Disorder-7 (GAD-7) scales was distributed randomly to a subgroup of 503 respondents. PRIMARY AND SECONDARY OUTCOME MEASURES: To determine the impact of COVID-19 on the psychological of health workers, we conducted analyses to test a primary hypothesis related to participants based on three main scales including PHQ-9, PSS-4 and GAD-7 scales. RESULTS: Nearly half (49.7%) of healthcare workers experienced mild depression symptoms, 34.0% underwent moderate anxiety symptoms and 49.3% reported high-stress levels. Respondents who had a monthly income below 5 million VND (~US$212) and had more than 3 days of duty per week had a higher score on the anxiety scales. Compared with medical doctors, nurses/midwives had lower PHQ-9 (Coef=-2.53; 95% CI=-3.71 to -1.36) and GAD-7 scores (Coef=-2.36; 95% CI=-3.56 L to -1.16). Increased workload and work time was the harmful factor that increase the PHQ-9, GAD-7 or PSS-4 scores. More than half (53.9%) of respondents stated no demand for mental healthcare services. CONCLUSIONS: Health workers who gained less financial rewards are reported to have higher levels of mental distress than others, implying the need for a raise in basic salary as well as compensation and encouragement schemes. To tackle hesitancy in seeking mental help, integrating online mental health therapy with e-health consultations via social media can be strategically implemented to augment service delivery, and simultaneously enhance the standard of mental health services.

Mechanisms Linking Physical Activity with Psychiatric Symptoms Across the Lifespan: A Systematic Review.

BACKGROUND: Physical activity has been suggested as a protective factor against psychiatric symptoms. While numerous studies have focused on the magnitude of physical activity's effect on psychiatric symptoms, few have examined the potential mechanisms. OBJECTIVE: The current review aimed to synthesize scientific evidence of the mechanisms through which physical activity might reduce psychiatric symptoms across the lifespan. METHODS: We included articles that were published before March 2022 from five electronic databases (MEDLINE, Web of Science, PsycINFO, Embase, and Cochrane). A qualitative synthesis of studies was conducted. The risk of bias assessment was performed using The Joanna Briggs Institute Critical Appraisal Tool for Systematic Reviews. Studies were included if they explored the possible mechanisms through which physical activity influences psychiatric symptoms (i.e., internalizing and externalizing symptoms) across the lifespan. RESULTS: A total of 22 articles were included (three randomized controlled trials, four non-randomized controlled trials, three prospective longitudinal studies, and 12 cross-sectional studies). Overall, most of the studies focused on children, adolescents, and young adults. Our findings showed that self-esteem, self-concept, and self-efficacy were the only consistent paths through which physical activity influences psychiatric symptoms (specifically depressive and anxiety symptoms) across the lifespan. There were insufficient studies to determine the role of neurobiological mechanisms. CONCLUSIONS: Overall, future physical activity interventions with the purpose of improving mental health should consider these mechanisms (self-esteem, self-concept, self-efficacy) to develop more effective interventions. CLINICAL TRIAL REGISTRATION: The protocol of this study was registered in the PROSPERO database (registration number CRD42021239440) and published in April 2022.

Genome assembly of the Korean intertidal mud-creeper Batillaria attramentaria.

Batillaridae is a common gastropod family that occurs abundantly in the shallow coastal zone of the intertidal mudflats of the northwest Pacific Ocean, Australasia, and North America. In this family, Batillaria attramentaria is known for its biological invasion and colonization in estuarine and intertidal zones. It can endure and adapt the harsh intertidal conditions such as frequent temperature alteration, salinity, and air exposure. Therefore, we sequenced and assembled this Korean batillariid genome to get insight into its intertidal adaptive features. Approximately 53 Gb of DNA sequences were generated, and 863 scaffolds were assembled into a draft genome of 0.715 Gb with 97.1% BUSCO completeness value. A total of 40,596 genes were predicted. We estimated that B. attramentaria and Conus consors diverged about 230 million years ago (MYA) based on the phylogenetic analysis of closely related gastropod species. This genome study sets the footstep for genomics studies among native and introduced Batillaria populations and the Batillaridae family members.

Predicting amyloid-beta pathology in the general population.

INTRODUCTION: Reliable models to predict amyloid beta (Aß) positivity in the general aging population are lacking but could become cost-efficient tools to identify individuals at risk of developing Alzheimer's disease. METHODS: We developed Aß prediction models in the clinical Anti-Amyloid Treatment in Asymptomatic Alzheimer's (A4) Study (n = 4,119) including a broad range of easily ascertainable predictors (demographics, cognition and daily functioning, health and lifestyle factors). Importantly, we determined the generalizability of our models in the population-based Rotterdam Study (n = 500). RESULTS: The best performing model in the A4 Study (area under the curve [AUC] = 0.73 [0.69-0.76]), including age, apolipoprotein E (APOE) ε4 genotype, family history of dementia, and subjective and objective measures of cognition, walking duration and sleep behavior, was validated in the independent Rotterdam Study with higher accuracy (AUC = 0.85 [0.81-0.89]). Yet, the improvement relative to a model including only age and APOE ε4 was marginal. DISCUSSION: Aß prediction models including inexpensive and non-invasive measures were successfully applied to a general population-derived sample more representative of typical older non-demented adults.

Construction of an Agroinfectious Clone of a Korean Isolate of Sweet Potato Symptomless Virus 1 and Comparison of Its Infectivity According to Agrobacterium tumefaciens Strains in Nicotiana benthamiana.

Sweet potato symptomless virus 1 (SPSMV-1) is a single-stranded circular DNA virus, belonging to the genus Mastrevirus (family Geminiviridae) that was first identified on sweet potato plants in South Korea in 2012. Although SPSMV-1 does not induce distinct symptoms in sweet potato plants, its co-infection with different sweet potato viruses is highly prevalent, and thus threatens sweet potato production in South Korea. In this study, the complete genome sequence of a Korean isolate of SPSMV-1 was obtained by Sanger sequencing of polymerase chain reaction (PCR) amplicons from sweet potato plants collected in the field (Suwon). An infectious clone of SPSMV-1 (1.1-mer) was constructed, cloned into the plant expression vector pCAMBIA1303, and agro-inoculated into Nicotiana benthamiana using three Agrobacterium tumefaciens strains (GV3101, LBA4404, and EHA105). Although no visual differences were observed between the mock and infected groups, SPSMV-1 accumulation was detected in the roots, stems, and newly produced leaves through PCR. The A. tumefaciens strain LBA4404 was the most effective at transferring the SPSMV-1 genome to N. benthamiana. We confirmed the viral replication in N. benthamiana samples through strand-specific amplification using virion-sense- and complementary-sense-specific primer sets.

A reverse pattern in work motivation among Vietnamese health care workers during the prolonged COVID-19 outbreak of 2021: Determinants and implications.

Background: The workload burden of the COVID-19 pandemic on health systems requires not only financial support but also long-term and contextualized policies. We assessed the work motivation and its determinants among health workers at Vietnamese hospitals and facilities during the prolonged COVID-19 outbreaks in 2021. Methods: A cross-sectional study was conducted among 2814 health care professionals across all three regions of Vietnam from October to November 2021. An online questionnaire, including the Work Motivation Scale, distributed by the snowball method to a subgroup of 939 respondents, investigated changes in working characteristics due to COVID-19, work motivation, and occupational intention. Results: Only 37.2% of respondents committed to their current job and about 40% reported a decrease in their job satisfaction. The Work Motivation Scale scored the lowest in "financial motivation" and the highest in "perception of work value". Participants who were in the north region, of younger age, unmarried, and who had a low level of adaptability to external work pressure, shorter experience, and less job satisfaction tended to be less motivated and committed to their current job. Conclusions: Intrinsic motivation has increased in importance during the pandemic. Therefore, policymakers should develop interventions that raise intrinsic, psychological motivation instead of only focusing on salary raises. Issues about intrinsic motivations of health care workers such as low adaptability to stress and professionalism in routine work should be prioritized during the pandemic preparedness and control.

Facile preparation of porphyrin@g-C3N4/Ag nanocomposite for improved photocatalytic degradation of organic dyes in aqueous solution.

In the quest of improving the photocatalytic efficiency of photocatalysts, the combination of two and more semiconductors recently has garnered significant attention among scientists in the field. The doping of conductive metals is also an effective pathway to improve photocatalytic performance by avoiding electron/hole pair recombination and enhancing photon energy absorption. This work presented a design and fabrication of porphyrin@g-C3N4/Ag nanocomposite using acid-base neutralization-induced self-assembly approach from monomeric porphyrin and g-C3N4/Ag material. g-C3N4/Ag material was synthesized by a green reductant of Cleistocalyx operculatus leaf extract. Electron scanning microscopy (SEM), X-ray diffraction (XRD), FT-IR spectroscopy, and UV-vis spectrometer were utilized to analyse the properties of the prepared materials. The prepared porphyrin@g-C3N4/Ag nanocomposite showed well integration of porphyrin nanostructures on the g-C3N4/Ag's surface, in which porphyrin nanofiber was of the diameter in nanoscales and the length of several micrometers, and Ag NPs had an average particle size of less than 20 nm. The photocatalytic behavior of the resultant nanocomposite was tested for the degradation of Rhodamine B dye, which exhibited a remarkable RhB photodegrading percentage. The possible mechanism for photocatalysis of the porphyrin@g-C3N4/Ag nanocomposite toward Rhodamine B dye was also proposed and discussed.

Higher-dose venetoclax with measurable residual disease-guided azacitidine discontinuation in newly diagnosed acute myeloid leukemia.

Venetoclax+azacitidine is the standard of care for newly-diagnosed patients with acute myeloid leukemia (AML) for whom intensive chemotherapy is inappropriate. Efforts to optimize this regimen are necessary. We designed a clinical trial to investigate two hypotheses: i) higher doses of venetoclax are tolerable and more effective, and ii) azacitidine can be discontinued after deep remissions. Forty-two newly diagnosed AML patients were enrolled in the investigator-initiated High Dose Discontinuation Azacitidine+Venetoclax (HiDDAV) Study (clinicaltrials gov. Identifier: NCT03466294). Patients received one to three "induction" cycles of venetoclax 600 mg daily with azacitidine. Responders received MRD-positive or MRDnegative "maintenance" arms: azacitidine with 400 mg venetoclax or 400 mg venetoclax alone, respectively. The toxicity profile of HiDDAV was similar to 400 mg venetoclax. The overall response rate was 66.7%; the duration of response (DOR), event-free survival (EFS) and overall survival were 12.9, 7.8 and 9.8 months, respectively. The MRD negativity rate was 64.3% by flow cytometry and 25.0% when also measured by droplet digital polymerase chain recation. MRD-negative patients by flow cytometry had improved DOR and EFS; more stringent measures of MRD negativity were not associated with improved OS, DOR or EFS. Using MRD to guide azacitidine discontinuation did not lead to improved DOR, EFS or OS compared to patients who discontinued azacitidine without MRD guidance. Within the context of this study design, venetoclax doses >400 mg with azacitidine were well tolerated but not associated with discernible clinical improvement, and MRD may not assist in recommendations to discontinue azacitidine. Other strategies to optimize, and for some patients, de-intensify, venetoclax+azacitidine regimens are needed.

An Effective Integrated Machine Learning Framework for Identifying Severity of Tomato Yellow Leaf Curl Virus and Their Experimental Validation.

Tomato yellow leaf curl virus (TYLCV) dispersed across different countries, specifically to subtropical regions, associated with more severe symptoms. Since TYLCV was first isolated in 1931, it has been a menace to tomato industrial production worldwide over the past century. Three groups were newly isolated from TYLCV-resistant tomatoes in 2022; however, their functions are unknown. The development of machine learning (ML)-based models using characterized sequences and evaluating blind predictions is one of the major challenges in interdisciplinary research. The purpose of this study was to develop an integrated computational framework for the accurate identification of symptoms (mild or severe) based on TYLCV sequences (isolated in Korea). For the development of the framework, we first extracted 11 different feature encodings and hybrid features from the training data and then explored 8 different classifiers and developed their respective prediction models by using randomized 10-fold cross-validation. Subsequently, we carried out a systematic evaluation of these 96 developed models and selected the top 90 models, whose predicted class labels were combined and considered as reduced features. On the basis of these features, a multilayer perceptron was applied and developed the final prediction model (IML-TYLCVs). We conducted blind prediction on 3 groups using IML-TYLCVs, and the results indicated that 2 groups were severe and 1 group was mild. Furthermore, we confirmed the prediction with virus-challenging experiments of tomato plant phenotypes using infectious clones from 3 groups. Plant virologists and plant breeding professionals can access the user-friendly online IML-TYLCVs web server at https://balalab-skku.org/IML-TYLCVs, which can guide them in developing new protection strategies for newly emerging viruses.

A time-calibrated mitogenomic phylogeny suggests that Korean Hyalessa fuscata is a bridge between Chinese and Japanese H.maculaticollis.

The cicada species, Hyalessa fuscata and H. maculaticollis(Hemiptera: Cicadidae), share numerous morphological characters, and their status as distinct species remains controversial. We reconstructed a phylogeny based on two new mitogenomes of H. fuscata from Korea and H. maculaticollis from Japan, in combination with GenBank sequences of H. maculaticollis from China and Japan, and other closely related cicada species. Maximum likelihood and Bayesian inference phylogenies showed that H. fuscata from Korea is more closely related to H. maculaticollis from China than either is to H. maculaticollis from Japan. The time-calibrated Bayesian evolutionary analysis by sampling trees (BEAST) phylogeny indicated that the mainland and insular forms diverged approximately 1.7-2.6 million years ago. This coincides with the formation of the East China Sea land bridge between East Asia and the Japanese archipelago, which would provide a dispersal corridor for Hyalessa from the mainland via the Korean peninsula southeastward to Japan. East Asian H. fuscata is a geographic variant that may be considered synonymous with H. maculaticollis.

Synchronization of breeding and its impact on genetic parameters and evaluation of female fertility traits.

Achieving an acceptable level of fertility in herds is difficult for many dairy producers because identifying cows in estrus has become challenging owing to poor estrus expression, increased herd size, and lack of time and skilled labor for estrus detection. As a result, synchronization of estrus is often used to manage reproduction. The aims of this study were (1) to identify artificial inseminations (AI) that were performed following synchronization and (2) to assess the effect of synchronization on genetic parameters and evaluation of fertility traits. This study used breeding data collected between 1995 and 2021 from over 4,600 Australian dairy herds that had at least 30 matings per year. Because breeding methods were not reported, the recording pattern of breeding dates showing a large proportion of the total AI being recorded on a single date of the year served as an indicator of synchronization. First, the proportion of AI recorded on each day of the year was calculated for each herd-year. Subsequently, synchronization was defined when a herd with, for instance, only 30 matings in a year, had at least 0.20 or more AI on the same day. As the number of breedings in a herd-year increased, the threshold for classifying AI was continuously reduced from 0.20 to as low as 0.03 under the assumption that mating of many cows on a single date becomes increasingly difficult without synchronization. From the current data, we deduced that 0.11 of all AI were possibly performed following synchronization (i.e., timed AI, TAI). The proportion of AI classified as TAI increased over time and with herd size. Although the deviation from equal numbers of mating on 7 d of the week was not used for classifying AI, 0.44 of AI being categorized as TAI were performed on just 2 d of the week. When data classified as TAI were used for estimating genetic parameters and breeding values, the interval between calving and first service (CFS) was found to be the most affected trait. The phenotypic and additive genetic variance and heritability, as well as variability and reliability of estimated breeding values of bulls and cows for CFS were lower for TAI than for AI performed following detected estrus (i.e., estrus-detected AI, EAI). For calving interval, first service nonreturn rate (FNRR), and successful calving rate to first service, genetic correlations between the same trait measured in TAI and EAI were close to 1, in contrast to 0.55 for CFS. The lower genetic variances and heritabilities for FNRR and calving interval in TAI than in EAI suggests that synchronization reduces the genetic variability of fertility. In conclusion, TAI makes CFS an ineffective measure of fertility. One approach to minimize this effect on genetic evaluations is to identify TAI (using the method described for example) and then set the CFS of these cows as missing records when running multitrait genetic evaluations of fertility traits that include CFS. In the long term, the most practical and accurate way to reduce the effect of synchronization on genetic evaluations is to record TAI along with mating data.

Emergence of Asian endemic begomoviruses as a pandemic threat.

Plant viruses are responsible for the most devastating and commercially significant plant diseases, especially in tropical and subtropical regions. The genus begomovirus is the largest one in the family Geminiviridae, with a single-stranded DNA genome, either monopartite or bipartite. Begomoviruses are transmitted by insect vectors, such as Bemisia tabaci. Begomoviruses are the major causative agents of diseases in agriculture globally. Because of their diversity and mode of evolution, they are thought to be geographic specific. The emerging begomoviruses are of serious concern due to their increasing host range and geographical expansion. Several begomoviruses of Asiatic origin have been reported in Europe, causing massive economic losses; insect-borne transmission of viruses is a critical factor in virus outbreaks in new geographical regions. This review highlights crucial information regarding Asia's four emerging and highly destructive begomoviruses. We also provided information regarding several less common but still potentially important pathogens of different crops. This information will aid possible direction of future studies in adopting preventive measures to combat these emerging viruses.

Conformational change of organic cofactor PLP is essential for catalysis in PLP-dependent enzymes.

Pyridoxal 5'-phosphate (PLP)-dependent enzymes are ubiquitous, catalyzing various biochemical reactions of approximately 4% of all classified enzymatic activities. They transform amines and amino acids into important metabolites or signaling molecules and are important drug targets in many diseases. In the crystal structures of PLP-dependent enzymes, organic cofactor PLP showed diverse conformations depending on the catalytic step. The conformational change of PLP is essential in the catalytic mechanism. In the study, we review the sophisticated catalytic mechanism of PLP, especially in transaldimination reactions. Most drugs targeting PLP-dependent enzymes make a covalent bond to PLP with the transaldimination reaction. A detailed understanding of organic cofactor PLP will help develop a new drug against PLP-dependent enzymes. [BMB Reports 2022; 55(9): 439-446].

MicroRNA-Based Diagnosis and Therapy.

MicroRNAs (miRNAs) are a group of endogenous non-coding RNAs that regulate gene expression. Alteration in miRNA expression results in changes in the profile of genes involving a range of biological processes, contributing to numerous human disorders. With high stability in human fluids, miRNAs in the circulation are considered as promising biomarkers for diagnosis, as well as prognosis of disease. In addition, the translation of miRNA-based therapy from a research setting to clinical application has huge potential. The aim of the current review is to: (i) discuss how miRNAs traffic intracellularly and extracellularly; (ii) emphasize the role of circulating miRNAs as attractive potential biomarkers for diagnosis and prognosis; (iii) describe how circulating microRNA can be measured, emphasizing technical problems that may influence their relative levels; (iv) highlight some of the circulating miRNA panels available for clinical use; (v) discuss how miRNAs could be utilized as novel therapeutics, and finally (v) update those miRNA-based therapeutics clinical trials that could potentially lead to a breakthrough in the treatment of different human pathologies.

BayesR3 enables fast MCMC blocked processing for largescale multi-trait genomic prediction and QTN mapping analysis.

Bayesian methods, such as BayesR, for predicting the genetic value or risk of individuals from their genotypes, such as Single Nucleotide Polymorphisms (SNP), are often implemented using a Markov Chain Monte Carlo (MCMC) process. However, the generation of Markov chains is computationally slow. We introduce a form of blocked Gibbs sampling for estimating SNP effects from Markov chains that greatly reduces computational time by sampling each SNP effect iteratively n-times from conditional block posteriors. Subsequent iteration over all blocks m-times produces chains of length m × n. We use this strategy to solve large-scale genomic prediction and fine-mapping problems using the Bayesian MCMC mixed-effects genetic model, BayesR3. We validate the method using simulated data, followed by analysis of empirical dairy cattle data using high dimension milk mid infra-red spectra data as an example of "omics" data and show its use to increase the precision of mapping variants affecting milk, fat, and protein yields relative to a univariate analysis of milk, fat, and protein.