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Abstract Background Microalgae have emerged as sustainable alternatives to fossil fuels and high-value petrochemicals. Despite the commercial potential of microalgae, their low biomass productivity is a significant limiting factor for large-scale production. In the photoautotrophic cultivation of microalgae, achievable cell density levels depend on the light transmittance of the production system, which can significantly decrease the photosynthetic rate and biomass production. In contrast, the mixotrophic cultivation of microalgae using heterotrophic carbon sources enables high-density cultivation, which significantly enhances biomass productivity. The identification of optimal production conditions is crucial for improving biomass productivity; however, it is typically time- and resource-consuming. To overcome this problem, high-throughput screening (HTS) system presents a practical approach to maximize biomass and lipid production and enhance the industrial applicability of microalgae. Results In this study, we proposed a two-step HTS assay that allows effective screening of heterotrophic conditions compatible with new microalgal isolates. To confirm the effectiveness of the HTS assay, three microalgal isolates with distinctive morphological and genetic traits were selected. Suitable cultivation conditions, including various heterotrophic carbon sources, substrate concentrations, and temperatures, were investigated using a two-step HTS assay. The optimized conditions were validated at the flask scale, which confirmed a significant enhancement in the biomass and lipid productivity of each isolate. Moreover, the two-step HTS assay notably enhanced economic and temporal efficiency compared to conventional flask-based optimization. Conclusions These results suggest that our two-step HTS assay is an efficient strategy for investigating and optimizing microalgal culture conditions to maximize biomass and lipid productivity. This approach has the potential to enhance the industrial applicability of microalgae and facilitate the seamless transition from laboratory to field applications.

Abstract Hepatocellular carcinoma (HCC) presents a major health issue worldwide. This study introduces the HepScope gene set, developed through a hybrid approach that utilizes single-cell RNA sequencing (scRNA-seq), spatial transcriptomics (stRNA-seq), bulk RNA-seq, and proteomics data, along with the adaptation of Convolutional Neural Network (CNN) techniques. Comprising 113 genes significantly upregulated in malignant hepatocytes, HepScope gene set includes 77 genes unique to this set compared to other HCC-related gene sets. Unlike existing solutions, HepScope gene set demonstrated superior discriminatory power in distinguishing malignant from non-malignant hepatocytes, as validated by Seurat's module score, outperforming five other gene sets across multiple datasets. A 1D-CNN model, specifically adapted for the HepScope gene set, achieved superior accuracy (0.71), AUROC (0.82), and F1 score (0.85) compared to models trained on other gene sets, underscoring its enhanced predictive precision and robustness. Rigorous cross-validation and benchmarking against alternative models confirmed HepScope’s consistent performance. Additionally, we evaluated the prognostic capability of the HepScope gene set across two independent cohorts, demonstrating that the HepScope-based risk score is a strong independent predictor of overall and disease-free survival, making it a valuable tool for patient prognosis. Collectively, our findings position HepScope as a promising gene set for both diagnostic and prognostic applications in HCC, highlighting its potential in precision medicine for HCC and offering insights into personalized therapy development.

Abstract Background Microalgae are potential sustainable resources for the production of value-added chemicals that can be used as biofuels, pharmaceuticals, and nutritional supplements. Arachidonic acid (ARA), a omega-6 fatty acid, plays a crucial role in infant development and immune response, and can be used in cosmetics and pharmaceuticals. Demand for industrial-scale ARA production is continuously increasing because of its broad applicability. To address this demand, there has been a significant shift towards microorganism-based ARA production. To accelerate large-scale ARA production, it is crucial to select suitable strains and establish optimal culture conditions. Results Here, we isolated a novel microalga Lobosphaera incisa CFRC-1, a valuable strain that holds promise as a feedstock for ARA production. Optimal cultivation conditions were investigated using a high-throughput screening method to enhance ARA production in this novel strain. Out of 71 candidates, four organic carbon substrates were identified that could be utilized by L. incisa CFRC-1. Through flask-scale verification, fructose was confirmed as the optimal organic carbon substrate for promoting microalgal growth, total lipid accumulation, and ARA production. Subsequently, we investigated appropriate substrate concentration and cultivation temperature, confirming that the optimal conditions were 30 g L− 1 of fructose and 27 ℃ of temperature. Under these optimized conditions, biomass and ARA production reached 13.05 ± 0.40 g L− 1 and 97.98 ± 7.33 mg L− 1, respectively, representing 9.6-fold and 5.3-fold increases compared to the conditions before optimization conditions. These results achieved the highest biomass and ARA production in flask-scale cultivation, indicating that our approach effectively improved both production titer and productivity. Conclusions This study presents a novel microalgae and optimized conditions for enhancing biomass and ARA production, suggesting that this approach is a practical way to accelerate the production of valuable microalgae-based chemicals. These findings provide a basis for large-scale production of ARA-utilizing microalgae for industrial applications.

Abstract Background This study aimed to produce Odontoglossum ringspot virus (ORSV)-free Cymbidium orchid ‘New True’ plants from ORSV-infected mother plants by culturing their meristems and successively repeating subcultures of protocorm-like bodies (PLBs) derived from the meristems. Results Initially, ORSV was confirmed as the causative agent of viral symptoms in orchid leaves via reverse transcription-polymerase chain reaction (RT-PCR) analysis. Meristems from infected plants were cultured to generate PLBs, which in sequence were repeatedly subcultured up to four times. RT-PCR and quantitative RT-PCR analyses revealed that while ORSV was undetectable in shoots derived from the first subculture, complete elimination of the virus required at least a second subculture. Genetic analysis using inter-simple sequence repeat markers indicated no somaclonal variation between regenerated plants and the mother plant, suggesting that genetic consistency was maintained. Conclusion Overall, our findings demonstrate that subculturing PLBs for a second time is ideal for producing genetically stable, ORSV-free Cymbidium orchids, thus offering a practical means of generating genetically stable, virus-free plants and enhancing plant health and quality in the orchid industry.

Abstract T cell immunoglobulin and mucin-containing molecule 3 (TIM-3) exhibits unique, cell type- and context-dependent characteristics and functions. Here, we report that TIM-3 on myeloid cells plays essential roles in modulating lung inflammation. We found that myeloid cell-specific TIM-3 knock-in (FSF-TIM3/LysM-Cre+) mice have lower body weight and shorter lifespan than WT mice. Intriguingly, the lungs of FSF-TIM3/LysM-Cre+ mice display excessive inflammation and features of disease-associated pathology. We further revealed that galectin-3 levels are notably elevated in TIM-3-overexpressing lung-derived myeloid cells. Furthermore, both TIM-3 blockade and GB1107, a galectin-3 inhibitor, ameliorated lung inflammation in FSF-TIM3/LysM-Cre+/− mice. Using an LPS-induced lung inflammation model with myeloid cell-specific TIM-3 knock-out mice, we demonstrated the association of TIM-3 with both lung inflammation and galectin-3. Collectively, our findings suggest that myeloid TIM-3 is an important regulator in the lungs and that modulation of TIM-3 and galectin-3 could offer therapeutic benefits for inflammation-associated lung diseases.

Abstract Hepatocellular carcinoma (HCC) is known to be lethal disease. However, its prognosis remains poor, primarily because the precise oncogenic mechanisms underlying HCC progression remain elusive, thus hampering effective treatment. Here, we aimed to identify the potential oncogenes in HCC and elucidate the underlying mechanisms of their action. To identify potential candidate genes, an integrative analysis of eight publicly available genomic datasets was performed, and the functional implications of the identified genes were assessed in vitro and in vivo. Sortilin 1 (SORT1) was identified as a potential candidate oncogene in HCC, and its overexpression in HCC cells was confirmed by analyzing spatial transcriptomic and single-cell data. Silencing SORT1 in Huh-7 and Hep3B cells significantly reduced HCC progression in vitro and in vivo. Functional analyses of oncogenic pathways revealed that SORT1 expression regulated the Notch signaling pathway activation and CD133 expression. Furthermore, analysis of epigenetic regulation of the candidate gene and its clinical implications using The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA LIHC) and our HCC cohort (AJOU_HCC cohort) data demonstrated an inverse correlation between the methylation status of the SORT1 promoter region, specifically at the cg16988986 site, and SORT1 mRNA expression, indicating the epigenetic regulation of SORT1 in HCC. In addition, the distinct methylation status of cg16988986 was significantly associated with patient survival. In conclusion, SORT1 plays a pivotal role in HCC by activating the Notch signaling pathway and increasing CD133 expression. These findings suggest SORT1 as a promising therapeutic target for HCC.

Abstract The arginyl-transferase ATE1 is a tRNA-dependent enzyme that covalently attaches an arginine molecule to a protein substrate. Conserved from yeast to humans, ATE1 deficiency in mice correlates with defects in cardiovascular development and angiogenesis and results in embryonic lethality, while conditional knockouts exhibit reproductive, developmental, and neurological deficiencies. Despite the recent revelation of the tRNA binding mechanism and the catalytic cycle of yeast ATE1, the structure-function relationship of ATE1 in higher organisms is not well understood. In this study, we present the three-dimensional structure of human ATE1 in an apo-state and in complex with its tRNA cofactor and a peptide substrate. In contrast to its yeast counterpart, human ATE1 forms a symmetric homodimer, which dissociates upon binding of a substrate. Furthermore, human ATE1 includes a unique and extended loop that wraps around tRNAArg, creating extensive contacts with the T-arm of the tRNA cofactor. Substituting key residues identified in the substrate binding site of ATE1 abolishes enzymatic activity and results in the accumulation of ATE1 substrates in cells.

Background/Aims Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality worldwide. Despite identification of several biomarkers for HCC diagnosis, challenges such as low sensitivity and intratumoral heterogeneity have impeded early detection, highlighting the need for etiology-specific blood biomarkers. Methods We generated whole-transcriptome sequencing (WTS) and targeted proteome data from buffy coat and plasma samples from HCC patients. By integrating etiological information on viral infection, we investigated the etiology-specific gene expression landscape at the blood level. Validation of differentially expressed genes (DEGs) was performed using publicly available RNA-seq datasets and qRT‒PCR with AUC analyses. Results Differential expression analyses with multiomics data revealed distinct gene expression profiles between HBV-associated HCC and nonviral HCC, indicating the presence of etiology-specific blood biomarkers. The identified DEGs were validated across multiple independent datasets, underscoring their utility as biomarkers. Additionally, single-cell RNA-seq analysis of HCC confirmed differences in DEG expression across distinct immune cell types. Conclusions Our buffy coat WTS data and plasma proteome data may serve as reliable sources for identifying etiology-specific blood biomarkers of HCC and might contribute to discovery of therapeutic targets for HCC across different etiologies.

Abstract N 6-adenosine methylation (m6A) is critical for controlling cancer cell growth and tumorigenesis. However, the function and detailed mechanism of how m6A methyltransferases modulate m6A levels on specific targets remain unknown. In the current study, we identified significantly elevated levels of RBM15, an m6A writer, in basal-like breast cancer (BC) patients compared to nonbasal-like BC patients and linked this increase to worse clinical outcomes. Gene expression profiling revealed correlations between RBM15 and serine and glycine metabolic genes, including PHGDH, PSAT1, PSPH, and SHMT2. RBM15 influences m6A levels and, specifically, the m6A levels of serine and glycine metabolic genes via direct binding to target RNA. The effects of RBM15 on cell growth were largely dependent on serine and glycine metabolism. Thus, RBM15 coordinates cancer cell growth through altered serine and glycine metabolism, suggesting that RBM15 is a new therapeutic target in BC.

Previous studies examining the flora in the Korean Demilitarized Zone and its surroundings focused only on specific locations or ways to utilize these areas. We investigated vascular plant distribution in this area across the entire Korean Peninsula. Species richness, endemism, and alien species richness were examined for 54,948 occurrence records. Biodiversity and protection status were assessed, and a self-organizing map algorithm was used to divide the flora distribution into an Eastern region (including the Central region) and a Western region. Environmental factors of each distribution type were analyzed. The whole study area had 1,790 taxa of 655 genera and 151 families. The flora of the Central region was similar to that of the Eastern region, which had the richest biodiversity, whereas the Western region contained various invasive alien plants. Most areas with high biodiversity were classified as protected by international agreements. In the self-organizing map, the Eastern and Central regions exhibited large distribution of endemic and northern lineage plants, and the Western region showed high abundances of invasive alien plants. The considerable biodiversity of this area is threatened due to continuous housing development and military operations. Therefore, policies to ensure sustainable conservation of plant biodiversity “hotspots” are required.

Pancreatic cancer is among the most lethal cancers with limited treatment options. Traditional herbal medicines have been explored as potential adjunct therapies for enhancing the effectiveness of standard chemotherapies. In this study, we investigated the safety and efficacy of Rhus verniciflua Stokes (RVS) in combination with first-line chemotherapy for unresectable locally advanced and metastatic pancreatic cancer in a prospective setting. This prospective observational pilot study enrolled patients with confirmed inoperable stage III or IV pancreatic cancer undergoing or scheduled to receive 5-fluorouracil-based or gemcitabine-based first-line chemotherapy with RVS treatment and were followed up for up to 20 months. The primary endpoint was the safety profile of RVS, which was assessed through adverse events. The secondary endpoints included overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Cox regression analysis identified possible prognostic factors for PFS and OS. Of the enrolled 25 patients, 18 completed the follow-up. The median RVS treatment duration was 6.14 months (range 2.23–8.01 months) and the median RVS daily dose was 3.8 capsules/day (range 2.1–5.7 capsules/day). RVS showed a favorable safety profile, with only one case of non-severe pruritus possibly related to RVS treatment. No hepatotoxicity and nephrotoxicity related to RVS was reported. The ORR and DCR were 5.6% and 72.2%, respectively. The median PFS and OS were 7.24 months (95% CI: 3.15–12.9) and 13.9 months (95% CI: 1.14–27.72), respectively. Cox regression analysis showed that baseline CA19-9 level was an independent prognostic factor for OS, and the daily dose of RVS was an independent prognostic factor for PFS and OS. In conclusion, RVS can be administered safely to patients with unresectable locally advanced metastatic pancreatic cancer who are undergoing first-line chemotherapy, and the daily dose was an independent prognostic factor for cancer survival. Further randomized controlled studies are warranted to confirm the exact benefits of RVS treatment.Clinical trial registrationhttps://cris.nih.go.kr, identifier KCT0007496.

Protein therapeutics are emerging as essential technologies due to their functional and chemical properties. However, their application is currently limited to delivery by oral and injection methods—the former being inefficient and the latter invasive and potentially tissue damaging. Researchers are, therefore, exploring noninvasive delivery systems for proteins through the skin, including transdermal and topical delivery. The large molecular size of proteins presents a key challenge for skin penetration, hindering their ability to penetrate the dense skin lamellar structure. This review focuses on using nanoparticles as carriers to increase protein stability and enhance skin penetration. The use of noninvasive or minimally invasive enhancers for controlling and improving penetration depth is also examined. Furthermore, the physical properties of nanoparticles that affect delivery are evaluated, aiming to propose ways to advance transdermal and topical delivery methods in the future.

Abstract This study delves into the development of a novel 10 by 10 sensor array featuring 100 pressure sensor pixels, achieving remarkable sensitivity up to 888.79 kPa−1, through the innovative design of sensor structure. The critical challenge of strain sensitivity inherent is addressed in stretchable piezoresistive pressure sensors, a domain that has seen significant interest due to their potential for practical applications. This approach involves synthesizing and electrospinning polybutadiene‐urethane (PBU), a reversible cross‐linking polymer, subsequently coated with MXene nanosheets to create a conductive fabric. This fabrication technique strategically enhances sensor sensitivity by minimizing initial current values and incorporating semi‐cylindrical electrodes with Ag nanowires (AgNWs) selectively coated for optimal conductivity. The application of a pre‐strain method to electrode construction ensures strain immunity, preserving the sensor's electrical properties under expansion. The sensor array demonstrated remarkable sensitivity by consistently detecting even subtle airflow from an air gun in a wind sensing test, while a novel deep learning methodology significantly enhanced the long‐term sensing accuracy of polymer‐based stretchable mechanical sensors, marking a major advancement in sensor technology. This research presents a significant step forward in enhancing the reliability and performance of stretchable piezoresistive pressure sensors, offering a comprehensive solution to their current limitations.