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Vascular calcification and vascular ageing are “silent” diseases but are highly prevalent in patients with end stage renal failure and type 2 diabetes, as well as in the ageing population. Melatonin (MT) has been shown to induce cardiovascular protection effects. However, the role of MT on vascular calcification and ageing has not been well-identified. In this study, the aortic transcriptional landscape revealed clues for MT related cell-to-cell communication between endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) in vascular calcification and vascular ageing. Furthermore, we elucidated that it was exosomes that participate in the information transportation from ECs to VSMCs. The exosomes secreted from melatonin-treated ECs (MT-ECs-Exos) inhibited calcification and senescence of VSMCs. Mechanistically, miR-302d-5p was highly enriched in MT-ECs-Exos, while depletion of miR-302d-5p blocked the ability of MT-ECs-Exos to suppress VSMC calcification and senescence. Notably, Wnt3 was a bona fide target of miR-302d-5p and modulated VSMC calcification and senescence. Furthermore, we found that maturation of endothelial derived exosomal miR-302d-5p was promoted by WTAP in an N6-methyladenosine (m6A)-dependent manner. Interestingly, MT alleviated vascular calcification and ageing in 5/6-nephrectomy (5/6 NTP) mice, a chronic kidney disease (CKD) induced vascular calcification and vascular ageing mouse model. MT-ECs-Exos was absorbed by VSMCs in vivo and effectively prevented vascular calcification and ageing in 5/6 NTP mice. ECs-derived miR-302d-5p mediated MT induced anti-calcification and anti-ageing effects in 5/6 NTP mice. Our study suggests that MT-ECs-Exos alleviate vascular calcification and ageing through the miR-302d-5p/Wnt3 signaling pathway, dependent on m6A methylation.

This study investigated the optimization of hatch spacing to enhance both the build rate and the density of parts produced by laser powder bed fusion of commercially pure titanium. Employing a multi-layer single track experiment, we derived the average width of melt pools, which adjusted hatch spacing to preserve the density of a part, and we proposed a modified build rate having a quadratic function of scanning speed. Nine process conditions were evaluated with a fixed laser power, while varying hatch spacing and scanning speed, to identify optimal conditions that yield a high density and maximize the build rate. The optimal process condition was a laser power of 310 W, scanning speed of 1943 mm/s, and hatch spacing of 106.7 μm. We confirmed that our process condition derived by a modified build equation could achieve higher build rate with a high density over 99.0% than prior studies. It is expected that this approach can be applied for industries requiring a high productivity of LPBF.

Although previous studies have examined the relationship between obesity and genetics in response to the growing obesity epidemic, research on the relationship between obesity and long-term changes in body mass index (BMI) is limited. To investigate this relationship, data from 1030 cases in the Anseong and Ansan cohorts were collected from the Korean Genome and Epidemiology Study conducted by the Korea National Institute of Health between 2000 and 2014. Cases lacking participants’ BMI data throughout the study were excluded, resulting in a final sample size of 3074. An increase or decrease in BMI was analyzed using PLINK, STRING, and DAVID, with significant differences observed in the AEN, ANKS1B, CSF1, EEF2K, FRAS1, GRIK4, PDGFC, THTPA, and TREH genes. These genes were observed to cluster with pathways related to type 2 diabetes, cardiovascular disease, metabolic processes, and endocytosis-related genes. These results suggest that several genes are involved in BMI changes and that several pathways are associated with obesity risk. Moreover, some genetic variants appear to influence BMI changes in Korean adults.

Abstract Alzheimer’s disease (AD) is a brain network disorder where pathological proteins accumulate through networks and drive cognitive decline. Yet, the role of network connectivity in facilitating this accumulation remains unclear. Using in-vivo multimodal imaging, we show that the distribution of tau and reactive microglia in humans follows spatial patterns of connectivity variation, the so-called gradients of brain organization. Notably, less distinct connectivity patterns (“gradient contraction”) are associated with cognitive decline in regions with greater tau, suggesting an interaction between reduced network differentiation and tau on cognition. Furthermore, by modeling tau in subject-specific gradient space, we demonstrate that tau accumulation in the frontoparietal and temporo-occipital cortices is associated with greater baseline tau within their functionally and structurally connected hubs, respectively. Our work unveils a role for both functional and structural brain organization in pathology accumulation in AD, and supports subject-specific gradient space as a promising tool to map disease progression.

This study aims to report the complete chloroplast genome of Solidago altissima L., a globally recognized invasive plant. The complete genome length of S. altissima is 152,961 bp; S. altissima has a typical quadripartite structure (including a large single copy of 84,829 bp, a small single copy of 18,084 bp, and two inverted repeat regions of 25,024 bp), which is commonly found in angiosperms. The genome contains 129 genes, consisting of 85 coding sequences, 36 tRNA genes, and 8 rRNA genes. To understand the phylogenetic relationship between S. altissima and its related species, maximum likelihood analysis was performed. The results revealed that S. altissima is closely related to Symphyotrichum subulatum. The findings of the present study could provide fundamental data for the future phylogenetic and evolutionary studies, while also research on species invasion and resolving complexity of S. altissima.

AbstractWe sequenced and published the chloroplast genome of Commelina caroliniana Walter, which was previously misidentified as C. diffusa owing to their morphological similarities until 1989. The genome of C. caroliniana is 160,857 bp long [large single copy region: 88,064 bp; a small single copy region: 18,549 bp; two inverted repeat regions: 27,122 bp] and has a GC content of 35.7%. The genome comprises 133 genes, including 87 coding sequences (CDSs), 38 tRNAs, and eight rRNAs. The phylogenetic relationship between C. caroliniana and related species was analyzed using the maximum likelihood method based on the 79 CDSs of the chloroplast genome. Phylogenetic analysis revealed that C. caroliniana is closely related to C. communis. Our findings will contribute to studies on species identification and phylogenetic and evolutionary research. These results enhance our understanding of the Commelina genus.

This study investigates the effects of low energy density laser rescanning of Additive Manufacturing (AM) called Laser-Powder Bed Fusion (L-PBF) on the microstructure, residual stresses, and mechanical characteristics of CoCrMo alloy specimens. Specimens were fabricated under four conditions, i.e., secondary laser scanning with energy density 5 %, 10 %, and 20 %, compared to the first laser irradiation energy densities (AB, 19.41 J/mm3). To confirm the effect of the second laser irradiation, the phase change was analyzed using X-ray diffraction (XRD), and the shape and distribution of the face-centered cubic (FCC) and hexagonal closed packing (HCP) phases were confirmed through electron backscatter diffraction (EBSD) analysis. In particular, the correlation between microstructural stability and residual stress reduction was analyzed, and the effects of microstructural changes on mechanical properties were studied. Through this study, it was confirmed that the appropriate laser conditions during the L-PBF process can act as a heat source, resulting in a heat treatment effect.

Digital Twin (DT) technology has evolved to contextualize real-time interactions between the physical and digital worlds. It has gained increasing attention in various research areas and industries, including the manufacturing, aerospace, and automotive industries, while facing challenges in processing and analyzing large datasets. To address these challenges, this paper proposes an edge computing-based DT (E-DT) framework and elaborates on its functional and informational aspects. The functional aspect is represented using ISO 23247 as the reference architecture, while the informational aspect is elaborated by introducing a data fusion model. Then, an E-DT for Wire+Arc Additive Manufacturing (WAAM) is developed, its performance is evaluated, and the benefits of edge computing in enhancing real-time processing and decision-making are verified. In addition, a typical non-edge computing-based DT for WAAM is implemented according to ISO 23237 for comparison. The results show that the proposed E-DT for WAAM achieved reduction in latency through faster data processing, smaller data upload volume, and more consistent data upload speed.

Abstract Allergens from domestic cats (Felis catus) cause allergy-related health problems worldwide. Fel d 1 is a major allergen that causes severe allergic reactions in humans, including rhinitis, conjunctivitis, and life-threatening asthma. Therefore, patients with cat allergies anticipate hypoallergenic cats. We successfully generated Fel d 1 chain 2 (CH2) genome-edited cats using the CRISPR-Cas9 system in this study. T7 endonuclease 1 assay and Sanger sequencing were used to confirm the mutation in CH2 genome-edited cats. Fel d 1 level in CH2 genome-edited cats were assessed by enzyme-linked immunosorbent assay (ELISA). Remarkably, ELISA showed that the level of Fel d 1 in the CH2 homozygous genome-edited cat (Name: Alsik) was extremely low compared with that in wild type domestic cats and could be hypoallergenic cats. Additionally, we successfully cloned the CH2 homozygous genome-edited cat using cytoplasm injection clone technology. The cloned CH2 homozygous genome-edited cat was verified using microsatellite analysis. Creating hypoallergenic cats using the CRISPR-Cas9 system is a significant step forward because these cats can safely approach allergic patients.

AbstractEuphorbia prostrata Aiton 1789, an annual herb, is native to tropical and subtropical Americas and was introduced into many parts of the Old-World including Korea. We determined the genomic characteristics of the complete chloroplast genome of E. prostrata with a de novo assembly strategy. The complete chloroplast genome was 162,858 bp long, and harbored 86 protein coding, 37 tRNA and 8 rRNA. The genome showed the typical quadripartite structure consisting of a large single copy (LSC) (90,580 bp), a small single copy (SSC) (18,570 bp) and a pair of inverted repeats (IRs) (26,854 bp). The phylogenetic tree inferred from chloroplast genomes of 25 taxa, which belong to Euphorbiaceae indicated that the Euphorbia is a monophyletic group and E. prostrata is closely related with E. humifusa, E. thymifolia and E. hirta, forming a well-supported clade. Our findings can be valuable for understanding the phylogenetic relationships and the evolution in Euphorbiaceae and will provide basic information for future studies on E. prostrata from genomic perspective.

We determined the complete chloroplast genome sequence of Epilobium parviflorum Schreb. The genome is 161,284 bp in length [including a large single copy (LSC): 89,063 bp; a small single copy (SSC): 17,323 bp; and two inverted repeat (IR) regions: 27,499 bp] with 38.1% GC content and contains 84 coding genes (CDS), 37 transfer RNA genes, and 8 rRNA genes. Among them, infA was annotated as a pseudogene. The maximum-likelihood analysis based on CDS sequences of chloroplast genomes was conducted for investigating the phylogenetic relationship among Epilobium and related species. The results showed a close relationship between E. parviflorum and E. hirsutum L. Our study added new genetic information of E. parviflorum and helped to understand the relationship with related species and evolutionary history in Onagraceae.

The current status of Lepidium ruderale L. is uncertain in Korea. This alien species was previously reported as a new record of the Korean flora and placed under L. ruderale. Although some taxonomists have suggested that it belongs to another Lepidium taxon, no conclusions have been reached. Therefore, in this study, the holotype and protologue of L. ruderale were obtained and carefully examined. The description of this species is as follows: basal leaves are 1–3 pinnate; cauline leaf blades are linear to lanceolate and entire and ciliate; petals are absent or rudimentary; flowers have two stamens; and fruits are winged at the apex, have an apical notch, and are glabrous. These features distinguish it from other Lepidium species. Examination of numerous specimens and analysis of multiple characteristics demonstrated that the voucher specimens of L. ruderale belong to L. pinnatifidum Ledeb. Therefore, L. ruderale is not distributed in Korea.

Bacterial leaf blight in carrot is one of the most important diseases in the worldwide. In the past decade, its introduction into Korea is causing great concern due to the potential damage to carrot crops domestically. This bacterial disease is caused by Xanthomonas hortorum pv. carotae (Xhc). This study aimed to isolate and identify bacterial strains from the soil of carrot farms in Jeju Island. The bacterial isolates showing characteristics similar with those of Xhc were selected when cultured on artificial media. Through DNA sequencing and analysis based on NCBI data, some of the selected bacterial strains were identified as Xhc. Furthermore, the bacterial strains caused the typical symptom of bacterial leaf blight after inoculation on carrot leaves. The results of this study showed the potential establishment of Xhc in the soil of Jeju Island and it may be valuable data for establish a strategy preventing the domestic spread of carrot bacterial leaf blight in the future.

Bacterial blight of carrot caused by Xanthomonas hortorum pv. carotae (Xhc) is one of the serious diseases of carrot, of which control measures has not been still established in the domestic farm. In this study, in order to select effective sterilizer for bacterial blight of carrots, three antibiotics such as streptomycin, oxolinic acid, kasugamycin, two copper compounds like copper hydroxide and copper sulfate basic and three rhizobacteria Burkholderia gladioli MRL408-3, Pseudomonas fluorescens TRH415-2 and Bacillus cereus KRY505-3 were selected to investigate their direct antibacterial effects using artificial media, aiming to identify effective pesticides against Xhc. Among them, treated medium with antibiotics such as streptomycin, oxolinic acid, and the antagonistic rhizobacteria MRL408-3 were formed inhibition zone. The agrochemicals and the rhizobacteria MRL408-3, which showed antibacterial effects on carrot leaves, pre-treated on the carrot leaves and then inoculated with Xhc. High control effects were shown on the carrot leaves pre-treated with both streptomycin and oxolinic acid. Scanning electron microscopy images of the carrot leaf surfaces showed that the population of bacteria decreased significantly on leaves pre-treated with streptomycin and oxolinic acid. From these results, it can be inferred that antibiotics like streptomycin and oxolinic acid exhibit superior control effects compared to other agents. This study provides valuable insights towards establishing an effective control system for bacterial blight of carrot.

This study investigated the correlation between the microstructure and the mechanical properties of pure Ti specimens manufactured via selective laser melting (SLM) using the stress relief heat-treatment process. Similar heat treatments were performed at a rate of 10 °C/min with a dwell time of 2 h to reach post-treatment temperatures ranging from of 490–890 °C in intervals of 100 °C. Phase change analysis using X-ray diffraction was conducted to verify the effects of the post-treatment process, while electron backscatter diffraction analysis was conducted to study the effects of microstructural changes induced by the post-treatment process on the mechanical properties of pure Ti specimens. In addition, a comprehensive analysis was performed to analyze residual stress following the stress relief heat treatment. The findings of this study establish a clear relationship between the mechanical properties and microstructural changes in SLM-manufactured pure Ti after heat treatment across a broad temperature range. Furthermore, the study confirms that heat treatment effectively relieves the residual stress in SLM Ti specimens.

Abstract Alzheimer’s disease (AD) is the most common dementia. It is known that women with one ApoE4 allele display greater risk and earlier onset of AD compared with men. In mice, we previously showed that follicle–stimulating hormone (FSH), a gonadotropin that rises in post–menopausal females, activates its receptor FSHR in the hippocampus, to drive AD–like pathology and cognitive impairment. Here we show in mice that ApoE4 and FSH jointly trigger AD-like pathogenesis by activating C/EBPβ/δ-secretase signaling. ApoE4 and FSH additively activate C/EBPβ/δ-secretase pathway that mediates APP and Tau proteolytic fragmentation, stimulating Aβ and neurofibrillary tangles. Ovariectomy-provoked AD-like pathologies and cognitive defects in female ApoE4-TR mice are ameliorated by anti-FSH antibody treatment. FSH administration facilitates AD-like pathologies in both young male and female ApoE4-TR mice. Furthermore, FSH stimulates AD-like pathologies and cognitive defects in ApoE4-TR mice, but not ApoE3-TR mice. Our findings suggest that in mice, augmented FSH in females with ApoE4 but not ApoE3 genotype increases vulnerability to AD-like process by activating C/EBPβ/δ-secretase signalling.

Abstract Vascular calcification often occurs in patients with chronic renal failure (CRF), which significantly increases the incidence of cardiovascular events in CRF patients. Our previous studies identified the crosstalk between the endothelial cells (ECs) and vascular smooth muscle cells (VSMCs), and the paracrine effect of VSMCs, which regulate the calcification of VSMCs. Herein, we aim to investigate the effects of exosomes secreted by high phosphorus (HPi) -induced adventitial fibroblasts (AFs) on the calcification of VSMCs and the underlying mechanism, which will further elucidate the important role of AFs in high phosphorus vascular wall microenvironment. The conditioned medium of HPi-induced AFs promotes the calcification of VSMCs, which is partially abrogated by GW4869, a blocker of exosomes biogenesis or release. Exosomes secreted by high phosphorus-induced AFs (AFsHPi-Exos) show similar effects on VSMCs. miR-21-5p is enriched in AFsHPi-Exos, and miR-21-5p enhances osteoblast-like differentiation of VSMCs by downregulating cysteine-rich motor neuron 1 (Crim1) expression. AFsHPi-Exos and exosomes secreted by AFs with overexpression of miR-21-5p (AFsmiR21M-Exos) significantly accelerate vascular calcification in CRF mice. In general, AFsHPi-Exos promote the calcification of VSMCs and vascular calcification by delivering miR-21-5p to VSMCs and subsequently inhibiting the expression of Crim1. Combined with our previous studies, the present experiment supports the theory of vascular wall microenvironment. Graphical Abstract

Abstract Magnesium‐ion batteries (MIBs) have promising applications because of their high theoretical capacity and the natural abundance of magnesium Mg. However, the kinetic performance and cyclic stability of cathode materials are limited by the strong interactions between Mg ions and the crystal lattice. Here, we demonstrate the unique Mg2+‐ion storage mechanism of a hierarchical accordion‐like vanadium oxide/carbon heterointerface (V2O3@C), where the V2O3 crystalline structure is reconstructed into a MgV3O7∙H2O phase through an anodic hydration reaction upon first cycle, for the improved kinetic and cyclic performances. As verified by in situ/ex situ spectroscopic and electrochemical analyses, the fast charge transfer kinetics of the V2O3@C cathode were due to the crystal‐reconstruction and chemically coupled heterointerface. The V2O3@C demonstrated an ultrahigh rate capacity of 130.4 mAh g−1 at 50 000 mA g−1 and 1000 cycles, achieving a Coulombic efficiency of 99.6%. The high capacity of 381.0 mA h g−1 can be attributed to the reversible Mg2+‐ion intercalation mechanism observed in the MgV3O7∙H2O phase using a 0.3 M Mg(TFSI)2/ACN(H2O) electrolyte. Additionally, within the voltage range of 2.25 V versus Mg/Mg2+, the V2O3@C exhibited a capacity of 245.1 mAh g−1 when evaluated with magnesium metal in a 0.3 M Mg(TFSI)2 + 0.25 M MgCl2/DME electrolyte. These research findings have important implications for understanding the relationship between the Mg‐ion storage mechanism and reconstructed crystal phase of vanadium oxides as well as the heterointerface reconstruction for the rational design of MIB cathode materials.

Citrus melanose, caused by Diaporthe citri, has been one of the serious diseases, and chemical fungicides were used for protection in many citrus orchards of Jeju Island. Establishing a disinfectant resistance management system and reducing pesticide usage would be important for contributing to safe agricultural production. In this study, monitoring of chemical resistance was performed with 40 representative D. citri isolates from many citrus orchards in Jeju Island. Four different fungicides, kresoxim-methyl, benomyl, fluazinam, and prochloraz manganese, with seven different concentrations were tested in vitro by growing the mycelium of the fungal isolates on the artificial medium potato dextrose agar. Among the 40 fungal isolates, 12 isolates were investigated as resistant to kresoxim-methyl which could not inhibit the mycelium growth to more than 50%. Especially isolate NEL21-2 was also resistant against benomyl, whose hyphae grew well even on the highest chemical concentration. However, any chemical resistance of fungal isolates was found against neither fluazinam nor prochloraz manganese. On the other hand, in vivo bio-testing of some resistant isolates was performed against both kresoxim-methyl and benomyl on young citrus leaves. Typical melanose symptoms developed on the citrus leaves pre-treated with both agrochemicals after inoculation with the resistant isolates. However, no or less symptoms were observed when the susceptible isolates were inoculated. Based on these results, it was suggested that some resistant isolates of D. citri occurred against both systemic fungicides, which may be valuable to build a strategy for protecting citrus disease.

Citrus melanoses caused by Diaporthe citri, has been one of the serious diseases in many citrus orchards of Jeju Island. To protect melanose in citrus farms, a fast and exact diagnosis method is necessary. In this study, diseased leaves and dieback twigs were collected from a total of 49 farms within March to April in 2022. A total of 465 fungal isolates were obtained from a total of 358 isolated plant samples. Among these fungal isolates, 40 representatives of D. citri isolates which were isolated from 22 twigs and 18 leaves on 23 farms were found based on cultural characteristics on potato dextrose agar and conidial morphology. Additionally, the molecular assay was carried out and compared with those by morphological diagnosis. All isolates were identified as D. citri by analyzing the sequences at the internal transcribed spacer (ITS) rDNA region using primers of ITS1/ITS4 or at β-tubulin using primer Btdcitri-F/R. Therefore, based on the present study, where the results of morphological identification of conidial type were consistent with DNA sequence analysis of certain gene, choosing a suitable method for a fast diagnosis of citrus melanose was suggested.

Introduction: Cerebral small vessel disease (SVD) is a common co-pathology in elderly and individuals with dementia. Neuroimaging markers of SVD include white matter hyperintensities (WMH) and MRI-visible perivascular spaces (PVS). However, the mechanisms underlying changes in these markers over time, whether ischemic or beta-amyloid (Aβ)-related, remain elusive. Here, we evaluated the effects of microstructural injury in the normal-appearing white matter and Aβ in the cerebral cortex on the progression of WMH and PVS over three years. Methods: Data was obtained from two independent cohorts: (i) TRIAD, comprising cognitively normal, MCI, and AD dementia participants (baseline: N=199, follow-up year 1 and 2: N=102 and 62); and (ii) MITNEC-C6, comprising “real-world” patients with mixed dementia and moderate-to- severe WMH burden (baseline: N=52, 2 years follow-up: N=25). We quantified global WMH and PVS volumes from FLAIR and T1w MRI. At baseline, we examined associations between these volumes and diffusion MRI-derived free water. Longitudinally, we employed linear [mixed-effect] models to investigate the relation of WMH or PVS volume changes over time with baseline free water, using cortical Aβ-PET, age, sex, and APOE-ε4 as covariates. Results: In TRIAD and MITNEC-C6 respectively, mean ages were 72±6 and 77±8 y, 60% and 42% were female, and 41% and 48% were Aβ-positive. At baseline, higher free water in normal- appearing white matter was associated with higher WMH volume (β_TRIAD=+0.34±0.06, P_TRIAD