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Fungi produce diverse secondary metabolites with agricultural and medical potential. Xylaria grammica EL000614 synthesizes grammicin, an isomer of patulin, which shows nematicidal activity against root-knot nematodes with low cytotoxicity. However, the genetic basis of grammicin biosynthesis remains unclear. Here, we characterized two genes, xgpatK and xgpatL , encoding a 6-methylsalicylic acid synthase XgPatK and a Zn(II)2Cys6 transcription factor XgPatL, respectively, within a putative grammicin biosynthetic cluster. Comparative genomic analysis identified 11 cluster genes in X. grammica that are also conserved in patulin-producing fungi, including Aspergillus clavatus and Penicillium expansum . Deletion of xgpatK or xgpatL abolished grammicin production, while complementation restored it, confirming their essential roles. Furthermore, constitutive overexpression of xgpatL increased grammicin production three-fold compared with the wild-type. These findings provide the first genetic and functional evidence of grammicin biosynthesis in X. grammica and demonstrate the regulatory role of XgPatL. Our study advances the understanding of fungal secondary metabolism and highlights grammicin as a potential agent for sustainable biological control of plant-parasitic nematodes.

Procedural sedation is often performed by non-anesthesiologists in various settings and can lead to respiratory depression. A tool that enables early detection of respiratory compromise could not only enhance patient safety during procedural sedation, but also reduce the risk of medical liability. In this study, we aimed to develop a machine learning model that integrates detailed body composition data from patients undergoing liposuction to enhance the prediction of respiratory depression during procedural sedation. Features from bioelectrical impedance analysis, 3D body scanning, and manual measurements were extracted and used to train machine learning models. SHAP analysis, an explainable AI approach, was conducted to visually interpret feature importance. The XGBoost model, particularly when incorporating 3D body scanning data, demonstrated superior predictive performance, achieving an AUROC of 0.856 and a sensitivity of 0.805. The main predictors identified were upper abdominal volume, BMI, and age, highlighting the importance of the acquisition of detailed body composition data for assessing respiratory risks during sedation. The developed model effectively predicts the risk of respiratory depression in patients undergoing liposuction, offering a potential for personalized sedation protocols.

The multifunctional carbon catabolite repression negative on TATA-box-less complex (CCR4-NOT) is a multi-subunit complex present in all eukaryotes, including fungi. This complex plays an essential role in gene expression; however, a functional study of the CCR4-NOT complex in the rice blast fungus Magnaporthe oryzae has not been conducted. Seven genes encoding the putative CCR4-NOT complex were identified in the M. oryzae genome. Among these, a homologous gene, MoNOT3, was overexpressed during appressorium development in a previous study. Deletion of MoNOT3 in M. oryzae resulted in a significant reduction in hyphal growth, conidiation, abnormal septation in conidia, conidial germination, and appressorium formation compared to the wild-type. Transcriptional analyses suggest that the MoNOT3 gene affects conidiation and conidial morphology by regulating COS1 and COM1 in M. oryzae. Furthermore, Δmonot3 exhibited a lack of pathogenicity, both with and without wounding, which is attributable to deficiencies in the development of invasive growth in planta. This result was also observed in onion epidermal cells, which are non-host plants. In addition, the MoNOT3 gene was involved in cell wall stress responses and heat shock. Taken together, these observations suggest that the MoNOT3 gene is required for fungal infection-related cell development and stress responses in M. oryzae.

Lichens are symbiotic organisms that produce various unique chemicals that can be used for pharmaceutical purposes. With the aim of screening new anti-cancer agents that inhibit cancer cell motility, we tested the inhibitory activity of seven lichen species collected from the Romanian Carpathian Mountains against migration and invasion of human lung cancer cells and further investigated the molecular mechanisms underlying their anti-metastatic activity. Among them, Alectoria samentosa, Flavocetraria nivalis, Alectoria ochroleuca, and Usnea florida showed significant inhibitory activity against motility of human lung cancer cells. HPLC results showed that usnic acid is the main compound in these lichens, and (+)-usnic acid showed similar inhibitory activity that crude extract have. Mechanistically, β-catenin-mediated TOPFLASH activity and KITENIN-mediated AP-1 activity were decreased by (+)-usnic acid treatment in a dose-dependent manner. The quantitative real-time PCR data showed that (+)-usnic acid decreased the mRNA level of CD44, Cyclin D1 and c-myc, which are the downstream target genes of both β-catenin/LEF and c-jun/AP-1. Also, Rac1 and RhoA activities were decreased by treatment with (+)-usnic acid. Interestingly, higher inhibitory activity for cell invasion was observed when cells were treated with (+)-usnic acid and cetuximab. These results implied that (+)-usnic acid might have potential activity in inhibition of cancer cell metastasis, and (+)-usnic acid could be used for anti-cancer therapy with a distinct mechanisms of action.

Lichens are symbiotic organisms which produce distinct secondary metabolic products. In the present study, we tested the cytotoxic activity of 17 lichen species against several human cancer cells and further investigated the molecular mechanisms underlying their anti-cancer activity. We found that among 17 lichens species, F. cucullata exhibited the most potent cytotoxicity in several human cancer cells. High performance liquid chromatography analysis revealed that the acetone extract of F. cucullata contains usnic acid, salazinic acid, Squamatic acid, Baeomycesic acid, d-protolichesterinic acid, and lichesterinic acid as subcomponents. MTT assay showed that cancer cell lines were more vulnerable to the cytotoxic effects of the extract than non-cancer cell lines. Furthermore, among the identified subcomponents, usnic acid treatment had a similar cytotoxic effect on cancer cell lines but with lower potency than the extract. At a lethal dose, treatment with the extract or with usnic acid greatly increased the apoptotic cell population and specifically activated the apoptotic signaling pathway; however, using sub-lethal doses, extract and usnic acid treatment decreased cancer cell motility and inhibited in vitro and in vivo tumorigenic potentials. In these cells, we observed significantly reduced levels of epithelial-mesenchymal transition (EMT) markers and phosphor-Akt, while phosphor-c-Jun and phosphor-ERK1/2 levels were only marginally affected. Overall, the anti-cancer activity of the extract is more potent than that of usnic acid alone. Taken together, F. cucullata and its subcomponent, usnic acid together with additional component, exert anti-cancer effects on human cancer cells through the induction of apoptosis and the inhibition of EMT.

Brown leaf spot disease caused by Alternaria spp. is among the most common diseases of potato crops. Typical brown spot symptoms were observed in commercial potato-cultivation areas of northern Korea from June to August 2020–2021. In total, 68 isolates were collected, and based on sequence analysis of the internal transcribed spacer (ITS) region, the collected isolates were identified as Alternaria spp. (80.9%). Phylogenetic analysis revealed that a majority of these isolates clustered within a clade that included A. alternata. Additionally, the ITS region and rpb2 yielded the most informative sequences for the identification of A. alternata. Pathogenicity tests confirmed that the collected pathogens elicited symptoms identical to those observed in the field. In pathogenicity tests performed on seven commercial cultivars, the pathogens exhibited strong virulence in both wound and non-wound inoculations. Among the cultivars tested, Arirang-1ho, Arirang-2ho, and Golden Ball were resistant to the pathogens. Furthermore, among the fungicides tested in vitro, mancozeb and difenoconazole were found to be effective for inhibiting mycelial growth. In summary, our findings suggest that A. alternata plays a critical role in leaf disease in potato-growing regions and emphasise the necessity of continuous monitoring and management to protect against this disease in Korea.

Heterojunction structures using 2D materials are promising building blocks for electronic and optoelectronic devices. The limitations of conventional silicon photodetectors and energy devices are able to be overcome by exploiting quantum tunneling and adjusting charge balance in 2D p–n and n–n junctions. Enhanced photoresponsivity in 2D heterojunction devices can be obtained with WSe2 and BP as p‐type semiconductors and MoS2 and WS2 as n‐type semiconductors. In this study, the relationship between photocurrent and the charge balance of electrons and holes in van der Waals heterojunctions is investigated. To observe this phenomenon, a p‐WSe2/n‐WS2/n‐MoS2 heterojunction device with both p–n and n–n junctions is fabricated. The device can modulate the charge carrier balance between heterojunction layers to generate photocurrent upon illumination by selectively applying electrostatic doping to a specific layer. Using photocurrent mapping, the operating transition zones for the device is demonstrated, allowing to accurately identify the locations where photocurrent generates. Finally, the origins of flicker and shot noise at the different semiconductor interfaces are analyzed to understand their effect on the photoresponsivity and detectivity of unit active area (2.5 µm2, λ = 405 nm) in the p‐WSe2/n‐WS2/n‐MoS2 heterojunction device. By selectively applying electrostatic doping to a specific channel layer, a p‐WSe2/n‐WS2/n‐MoS2 heterojunction device with both p–n and n–n junctions can modulate the charge carrier balance between heterojunction layers to generate photocurrent upon illumination. The relationship between photocurrent and the charge balance of electrons and holes in van der Waals heterojunctions is investigated.

VE is a powerful technique for analyzing a design with a focus on functionality, reducing costs, and increasing value. However, in order to proceed with the design of VE, the theoretical basis for the VE target selection process, which must be preceded in the preparation stage, is lacking, and as a result, it is difficult to verify the most effective target selection. Thus, a theoretical basis is needed. In this study, we intend to quantify the “Worth” value of the “Cost to Worth” technique and present an objective model of the target selection method using the derived value index (VI). For this purpose, cost worth (Worth C) was calculated based on the performance data of 1008 cases for 15 building types provided by the Domestic Public Procurement Service and the share of 83 detailed processes in seven fields. Then, a survey was conducted targeting the ordering companies, and the final worth (Worth F) was calculated by multiplying the derived customer value (Worth V) weight for each detailed work type. We calculated the value index (VI) by comparing “Cost” and “Worth F” for each detailed construction type of the VE project and developed a model to select construction types that exceed the VI standard value derived using the standard error of the population. Both cost experts and non-cost experts can use the developed model to specify the VE target selection criteria in order to easily select the key target, objectively sort the values that serve as the basis for calculating the value index, and make it possible to more easily select the VE target selection criteria based on theoretical evidence. Also, the model can be used to obtain effective detailed design VE results.

Four new compounds, phomalichenones A–D (1–4), and seven known compounds (5–11) were isolated from the cultures of an endolichenic fungus Phoma sp. EL002650. Their structures were determined by the analysis of their spectroscopic data (NMR and MS). Compounds 1 and 6 inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. In addition, compound 1 diminished the protein expression levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and decreased the mRNA expression levels of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin(IL)-1β, and IL-6.

Lichens produce various unique chemicals that can be used for pharmaceutical purposes. To screen for novel lichen secondary metabolites showing inhibitory activity against lung cancer cell motility, we tested acetone extracts of 13 lichen samples collected in Chile. Physciosporin, isolated from Pseudocyphellaria coriacea (Hook f. & Taylor) D.J. Galloway & P. James, was identified as an effective compound and showed significant inhibitory activity in migration and invasion assays against human lung cancer cells. Physciosporin treatment reduced both protein and mRNA levels of N-cadherin with concomitant decreases in the levels of epithelial-mesenchymal transition markers such as snail and twist. Physciosporin also suppressed KITENIN (KAI1 C-terminal interacting tetraspanin)-mediated AP-1 activity in both the absence and presence of epidermal growth factor stimulation. Quantitative real-time PCR analysis showed that the expression of the metastasis suppressor gene, KAI1, was increased while that of the metastasis enhancer gene, KITENIN, was dramatically decreased by physciosporin. Particularly, the activity of 3'-untranslated region of KITENIN was decreased by physciosporin. Moreover, Cdc42 and Rac1 activities were decreased by physciosporin. These results demonstrated that the lichen secondary metabolite, physciosporin, inhibits lung cancer cell motility through novel mechanisms of action.