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Protein aggregation, a consequence of misfolding and impaired proteostasis, can lead to cellular malfunctions such as various proteinopathies. The mechanisms protecting proteins from aggregation in complex cellular environments have long been investigated, often from a protein-centric viewpoint. However, our study provides insights into a crucial, yet overlooked actor: RNA. We found that depleting RNAs from Escherichia coli lysates induces global protein aggregation. Our quantitative mass spectrometry analysis identified over 900 statistically significant proteins from the Escherichia coli proteome whose solubility depends on RNAs. Proteome-wide characterization showed that the RNA dependency is particularly enriched among acidic proteins, intrinsically disordered proteins, and structural hub proteins. Moreover, we observed distinct differences in RNA-binding mode and Gene Ontology categories between RNA-dependent acidic and basic proteins. Notably, the solubility of key molecular chaperones [Trigger factor, DnaJ, and GroES] is largely dependent on RNAs, suggesting a yet-to-be-explored hierarchical relationship between RNA-based chaperone (termed as chaperna) and protein-based chaperones, both of which constitute the whole chaperone network. These findings provide new insights into the RNA-centric role in maintaining healthy proteome solubility in vivo, where proteins associate with a variety of RNAs, either stably or transiently.

Abstract Non-small cell lung cancer (NSCLC) is histologically classified into lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LSCC). However, some tumors are histologically ambiguous and other pathophysiological features or microenvironmental factors may be more prominent. Here we report integrative multiomics analyses using data for 229 patients from a Korean NSCLC cohort and 462 patients from previous multiomics studies. Histological examination reveals five molecular subtypes, one of which is a NSCLC subtype with PI3K-Akt pathway upregulation, showing a high proportion of metastasis and poor survival outcomes regardless of any specific NSCLC histology. Proliferative subtypes are present in LUAD and LSCC, which show strong associations with whole genome doubling (WGD) events. Comprehensive characterization of the immune microenvironment reveals various immune cell compositions and neoantigen loads across molecular subtypes, which predicting different prognoses. Immunological subtypes exhibit a hot tumor-enriched state and a higher efficacy of adjuvant therapy.

NORM is used as a raw material in various industries worldwide. According to the IAEA, radiological effects may occur in the environment due to raw materials and by-products generated from NORM industries. The objective of this study was to assess radiological environmental impact of the phosphate processing industry to identify the radiological effects on the general public. The resident farmer scenario was chosen as the exposure scenario due to the living characteristics of the public around the facility and the conservatism of the assessment. The RESRAD-OFFSITE code was used to evaluate the radiation dose to the public. The maximum radiation dose to the public was 6.13 × 10−3 mSv/y. Main exposure pathways were aquatic food ingestion, radon inhalation, and meat ingestion. The uranium series accounted for about 99 % of the total radiation dose, while the thorium series and K-40 nuclides accounted for less than 1 %. These study results can be used for management of radiological impact to the public around domestic NORM industries.

To obtain site-specific values of the Derived Concentration Guideline Levels (DCGLs) for decommissioning of KRR-1&2, the soil density and distribution coefficient values for Cs-137, a major contaminant radionuclide, were determined. The soil density was evaluated according to the test method established by the Korean Agency for Technology and Standards of the Ministry of Trade, Industry, and Energy (KATS). The distribution coefficient was evaluated using a batch test. The validity of using the evaluated soil density and distribution coefficient as site-specific values was assessed through radiation dose assessment reflecting these values. Average soil density value obtained was 1.738 g/cm3, which was within the typical range of normal soil density, 1.0–1.8 g/cm3. The average distribution coefficient value was 7,754 mL/g. Applying the maximum, average, and minimum values of the evaluated soil density and distribution coefficient showed similar radiation dose results, thus suggesting that it is reasonable to use the average values of each parameter as site-specific values. Findings of this study can help determine DCGLs that reflect the characteristics of the research reactor site.

Fire blight is a bacterial disease caused by Erwinia amylovora. In Korea, fire blight was first reported in 2015 in an orchard. If the infection is confirmed, all trees in the orchard must be removed and the orchard must remain closed for 3 years. Since 2020, if the number of trees infected with fire blight is less than 5% of the total trees in the orchard, only the infected tree and adjacent trees are removed in Korea. Three years after removal, the trees can be replanted after confirming that the orchard soil is free from E. amylovora. In this study, a protocol was established for detecting E. amylovora in soil via selective enrichment, using tryptic soy broth with 0.05% bile salts and 50 μg/ml cycloheximide, and real-time polymerase chain reaction. This protocol resulted in a 1,000-times improved detection limit for E. amylovora in soil samples compared to that in unenriched samples. Soil monitoring was performed for orchards where fire blight–infected trees had been removed 3–27 months prior; the selected orchards were monitored every 3 months. Monitoring confirmed that E. amylovora was not present in the soil at any site in any of the orchards. A new detection protocol facilitates the monitoring of E. amylovora in soil and could help permit the replanting of trees in orchards. Also monitoring results provide evidence that trees can be planted earlier.

Erwinia amylovora is a plant pathogen that causes fire blight on apples and pears. Bacteriophages, which are viruses that selectively infect specific species of bacteria and are harmless to animal cells, have been considered as biological control agents for the prevention of bacterial pathogens. In this study, we aimed to use bacteriophages that infect E. amylovora as biocontrol agents against fire blight. We isolated bacteriophages Fifi044 and Fifi318 infecting E. amylovora, and characterized their morphology, plaque form, and genetic diversity to use as cocktails for disease control. The stabilities of the two phages were investigated at various temperatures and pH values and under sunlight, and long-term storage experiment was conducted for a year. To evaluate whether the two phages were suitable for use in cocktail form, growth curves of E. amylovora were prepared after treating the bacterial cells with single phages and a phage cocktail. In addition, a disease control test was conducted using immature apples and in vitro cultured apple plantlets to determine the biocontrol effects of the phage cocktail. The two phages were morphologically and genetically different, and highly stable up to 50°C and pH value from 4 to 10. The phages showed synergistic effect when used as a cocktail in the inhibition of host bacterial growth and the disease control. This study demonstrated that the potential of the phage cocktail as a biocontrol agent for commercial use.

Abstract Tumor necrosis factor superfamily (TNFSF) resistance contributes to the development and progression of tumors and resistance to various cancer therapies. Tumor-intrinsic alterations involved in the adaptation to the TNFSF response remain largely unknown. Here, we demonstrate that protein kinase C substrate 80K-H (PRKCSH) abundance in lung cancers boosts oncogenic IGF1R activation, leading to TNFSF resistance. PRKCSH abundance is correlated with IGF1R upregulation in lung cancer tissues. Specifically, PRKCSH interacts with IGF1R and extends its half-life. The PRKCSH-IGF1R axis in tumor cells impairs caspase-8 activation, increases Mcl-1 expression, and inhibits caspase-9, leading to an imbalance between cell death and survival. PRKCSH deficiency augmented the antitumor effects of natural killer (NK) cells, representative TNFSF effector cells, in a tumor xenograft IL-2Rg-deficient NOD/SCID (NIG) mouse model. Our data suggest that PRKCSH plays a critical role in TNFSF resistance and may be a potential target to improve the efficacy of NK cell-based cancer therapy.

We introduce a novel dual redox mediator synthesized by covalently linking ferrocene dicarboxylic acid (FcDA) and thionine (TH) onto a pre-treated glassy carbon electrode. This unique structure significantly enhances the electro-oxidation of dopamine (DA) and the reduction of hydrogen peroxide (H2O2), offering a sensitive detection method for both analytes. The electrode exhibits exceptional sensitivity, selectivity, and stability, demonstrating potential for practical applications in biosensing. It facilitates rapid electron transfer between the analyte and the electrode surface, detecting H2O2 concentrations ranging from 1.5 to 60 µM with a limit of detection (LoD) of 0.49 µM and DA concentrations from 0.3 to 230 µM with an LoD of 0.07 µM. The electrode’s performance was validated through real-sample analyses, yielding satisfactory results.

Abstract Autism spectrum disorder (ASD) is a neurodevelopmental disorder associated with impaired social behavior and communication, repetitive behaviors, and restricted interests. In addition to genetic factors, environmental factors such as prenatal drug exposure contribute to the development of ASD. However, how those prenatal factors induce behavioral deficits in the adult stage is not clear. To elucidate ASD pathogenesis at the molecular level, we performed a high-resolution mass spectrometry-based quantitative proteomic analysis on the prefrontal cortex (PFC) of mice exposed to valproic acid (VPA) in utero, a widely used animal model of ASD. Differentially expressed proteins (DEPs) in VPA-exposed mice showed significant overlap with ASD risk genes, including differentially expressed genes from the postmortem cortex of ASD patients. Functional annotations of the DEPs revealed significant enrichment in the Wnt/β-catenin signaling pathway, which is dysregulated by the upregulation of Rnf146 in VPA-exposed mice. Consistently, overexpressing Rnf146 in the PFC impaired social behaviors and altered the Wnt signaling pathway in adult mice. Furthermore, Rnf146-overexpressing PFC neurons showed increased excitatory synaptic transmission, which may underlie impaired social behavior. These results demonstrate that Rnf146 is critical for social behavior and that dysregulation of Rnf146 underlies social deficits in VPA-exposed mice.

The objective of this study was the establishment of clearance method that can ensure radiological safety and reasonably minimize radioactive waste when demolishing contaminated buildings at KRR-1&2. By reviewing Korean and international laws related to decommissioning, the method for clearance of contaminated buildings presented in this study is to first decontaminate the building and then conduct a radiological safety assessment, such as measuring residual radioactivity, to determine whether the radiation dose criteria for clearance are satisfied. The measurement results meet the radiation dose criteria, the contaminated buildings are regarded as clearance and can be converted into the general buildings. The demolition of the cleared buildings is carried out using conventional demolition methods. The waste generated during the demolition is classified as general construction waste and is disposed of according to relevant laws. The proposed method significantly optimized the number of samples analyzed and reduced the time and cost associated with the decommissioning. The established method will be applied to the ongoing decommissioning of contaminated buildings at KRR-1&2, and its application will be verified by regulatory bodies. The study suggests that this method could be used for the decommissioning of contaminated buildings at other Korean nuclear facilities in the future.© 2017 Elsevier Inc. All rights reserved.

Abstract Non-alcoholic fatty liver disease (NAFLD) is an increasingly prevalent immuno-metabolic disease that can progress to hepatic cirrhosis and cancer. NAFLD pathogenesis is extremely complex and is characterized by oxidative stress, impaired mitochondrial function and lipid metabolism, and cellular inflammation. Thus, in-depth research on its underlying mechanisms and subsequent investigation into a potential drug target that has overarching effects on these features will help in the discovery of effective treatments for NAFLD. Our study examines the role of endogenous paraoxonase-2 (PON2), a membrane protein with reported antioxidant activity, in an in vitro cell model of NAFLD. We found that the hepatic loss of PON2 activity aggravated steatosis and oxidative stress under lipotoxic conditions, and our transcriptome analysis revealed that the loss of PON2 disrupts the activation of numerous functional pathways closely related to NAFLD pathogenesis, including mitochondrial respiratory capacity, lipid metabolism, and hepatic fibrosis and inflammation. We found that PON2 promoted the activation of the autophagy pathway, specifically the mitophagy cargo sequestration, which could potentially aid PON2 in alleviating oxidative stress, mitochondrial dysfunction, lipid accumulation, and inflammation. These results provide a mechanistic foundation for the prospect of PON2 as a drug target, leading to the development of novel therapeutics for NAFLD.

Abstract Background Despite the applications of Bacillus subtilis group species in various sectors, limited information is available regarding their phages. Here, 61 B. subtilis group species-infecting phages (BSPs) were studied for their taxonomic classification considering the genome-size, genomic diversity, and the host, followed by the identification of orthologs taxonomic signature genes. Results BSPs have widely ranging genome sizes that can be bunched into groups to demonstrate correlations to family and subfamily classifications. Comparative analysis re-confirmed the existing, BSPs-containing 14 genera and 21 species and displayed inter-genera similarities within existing subfamilies. Importantly, it also revealed the need for the creation of new taxonomic classifications, including 28 species, nine genera, and two subfamilies (New subfamily1 and New subfamily2) to accommodate inter-genera relatedness. Following pangenome analysis, no ortholog shared by all BSPs was identified, while orthologs, namely, the tail fibers/spike proteins and poly-gamma-glutamate hydrolase, that are shared by more than two-thirds of the BSPs were identified. More importantly, major capsid protein (MCP) type I, MCP type II, MCP type III and peptidoglycan binding proteins that are distinctive orthologs for Herelleviridae, Salasmaviridae, New subfamily1, and New subfamily2, respectively, were identified and analyzed which could serve as signatures to distinguish BSP members of the respective taxon. Conclusions In this study, we show the genomic diversity and propose a comprehensive classification of 61 BSPs, including the proposition for the creation of two new subfamilies, followed by the identification of orthologs taxonomic signature genes, potentially contributing to phage taxonomy.

Background: Ageing alters the ECM, leading to mitochondrial dysfunction and oxidative stress, which triggers an inflammatory response that exacerbates with age. Age-related changes impact satellite cells, affecting muscle regeneration, and the balance of proteins. Furthermore, ageing causes a decline in NAD+ levels, and alterations in fat metabolism that impact our health. These various metabolic issues become intricately intertwined with ageing, leading to a variety of individual-level diseases and profoundly affecting individuals' healthspan. Therefore, we hypothesize that vutiglabridin capable of alleviating these metabolic abnormalities will be able to ameliorate many of the problems associated with ageing. Method: The efficacy of vutiglabridin, which alleviates metabolic issues by enhancing mitochondrial function, was assessed in aged mice treated with vutiglabridin and compared to untreated elderly mice. On young mice, vutiglabridin-treated aged mice, and non-treated aged mice, the Senescence-associated beta-galactosidase staining and q-PCR for ageing marker genes were carried out. Bulk RNA-seq was carried out on GA muscle, eWAT, and liver from each group of mice to compare differences in gene expression in various gene pathways. Blood from each group of mice was used to compare and analyze the ageing lipid profile. Results: SA-β-gal staining of eWAT, liver, kidney, and spleen of ageing mice showed that vutiglabridin had anti-ageing effects compared to the control group, and q-PCR of ageing marker genes including Cdkn1a and Cdkn2a in each tissue showed that vutiglabridin reduced the ageing process. In aged mice treated with vutiglabridin, GA muscle showed improved homeostasis compared to controls, eWAT showed restored insulin sensitivity and prevented FALC-induced inflammation, and liver showed reduced inflammation levels due to prevented TLO formation, improved mitochondrial complex I assembly, resulting in reduced ROS formation. Furthermore, blood lipid analysis revealed that ageing-related lipid profile was relieved in ageing mice treated with vutiglabridin versus the control group. Conclusion: Vutiglabridin slows metabolic ageing mechanisms such as decreased insulin sensitivity, increased inflammation, and altered NAD+ metabolism in adipose tissue in mice experiments, while also retaining muscle homeostasis, which is deteriorated with age. It also improves the lipid profile in the blood and restores mitochondrial function in the liver to reduce ROS generation.

Eicosanoids play important roles in inflammation, allergy, fever, and immune responses. In the eicosanoid pathway, cyclooxygenase (COX) catalyzes the conversion of arachidonic acid to prostaglandins and is a crucial target of nonsteroidal anti-inflammatory drugs (NSAIDs). Thus, toxicological studies on the eicosanoid pathway are important for drug discovery and the evaluation of adverse health outcomes due to environmental contaminants. However, experimental models are limited owing to concerns regarding ethical standards. Thus, new alternative models for evaluating toxic effects on the eicosanoid pathway must be developed. To this end, we adopted an invertebrate species, Daphnia magna, as an alternative model. D. magna was exposed to ibuprofen, a major NSAID, for 6 and 24 h. Transcription of eicosanoid-related genes (pla2, cox, pgd synthase, pgd2r2, ltb4dh, and lox) was analyzed by qPCR, eicosanoids (arachidonic acid, prostaglandin F2, dihydroxy prostaglandin F2, and 5-hydroxyeicosatetraenoate) were quantified by multiple reaction monitoring, and enzyme-linked immunosorbent assay was used to determine protein levels of arachidonic acid and prostaglandin E2 (PGE2). After 6 h of exposure, transcription of the pla2 and cox genes was downregulated. In addition, the whole-body level of arachidonic acid, an upstream of COX pathway, increased by over 1.5-fold. The levels of PGE2, a downstream of COX pathway, decreased after 24 h of exposure. According to our results, it is expected that the eicosanoid pathway might be conserved in D. magna, at least partially. This indicates the plausibility of D. magna as an alternative model for the screening of new drugs or chemical toxicity.

Abstract Recently, membrane‐modified mammalian exosomes have been considered strong candidates for targeted drug delivery carriers because of their biocompatibility, biodistribution, and low immune response. However, the widespread utilization of exosomes still requires overcoming several challenging issues, including low stability, high production cost, and low mass productivity. Therefore, artificial extracellular vesicles (EVs) derived from cell membranes or liposomes containing various lipids have been suggested. However, only a few meet the demands of cost‐effective mass production and durability of EVs. Therefore, this study investigates the feasibility of replacing mammalian cell exosomes and liposomes with plant‐derived extracellular vesicles (pEVs) as targeted drug delivery carriers. They are characterized by nontoxicity, high stability, and high yield. Adding a functionalizable lipid moiety with a maleimide group at the membrane of grapefruit‐derived pEVs imparts targeting ability. The targeting function can be easily enhanced by attaching an aptamer using click chemistry. Indeed, treatment of brain cells with pEV‐aptamers (hCMEC/D3 and U87MG) confirms that aptamer functionalization of pEV enhanced selective cellular uptake. Functionalization of the pEV membrane using aptamer is expected to be effective in providing low‐cost and mass‐producible targeted drug delivery carriers with similar efficacy as mammalian exosomes or liposomes.

Docosahexaenoic acid (DHA), a representative omega-3 (ω-3) polyunsaturated fatty acids, undergoes metabolism to produce biologically active electrophilic species. 17-Oxo-DHA is one such reactive metabolite generated from DHA by cyclooxygenase-2 and dehydrogenase in activated macrophages. The present study was aimed to investigate the effects of 17-oxo-DHA on ultraviolet B (UVB)-induced oxidative stress, inflammation, and carcinogenesis in mouse skin. UVB-induced epidermal cell death was ameliorated by topically applied 17-oxo-DHA. Topical application of 17-oxo-DHA onto hairless mouse skin inhibited UVB-induced phosphorylation of the proinflammatory transcription factor, STAT3 on tyrosine 705 (Tyr705). The 17-oxo-DHA treatment also reduced the levels of oxidative stress markers, 4-hydroxynonenal-modified protein, malondialdehyde, and 8-oxo-2′-deoxyguanosine. The protective effects of 17-oxo-DHA against oxidative damage in UVB-irradiated mouse skin were associated with activation of Nrf2. 17-Oxo-DHA enhanced the engulfment of apoptotic JB6 cells by macrophages, which was related to the increased expression of the scavenger receptor CD36. The 17-oxo-DHA-mediated potentiation of efferocytic activity of macrophages was attenuated by the pharmacologic inhibition or knockout of Nrf2. The pretreatment with 17-oxo-DHA reduced the UVB-induced skin carcinogenesis and tumor angiogenesis. It was also confirmed that 17-oxo-DHA treatment significantly inhibited the phosphorylation of the Tyr705 residue of STAT3 and decreased the expression of its target proteins in cutaneous papilloma. In conclusion, 17-oxo-DHA protects against UVB-induced oxidative cell death, dermatitis, and carcinogenesis. These effects were associated with inhibition of STAT3-mediated proinflammatory signaling and also activation of Nrf2 with subsequent upregulation of antioxidant and anti-inflammatory gene expression.

Abstinence from prolonged psychostimulant use prompts stimulant withdrawal syndrome. Molecular adaptations within the dorsal striatum have been considered the main hallmark of stimulant abstinence. Here we explored striatal miRNA–target interaction and its impact on circulating miRNA marker as well as behavioral dysfunctions in methamphetamine (MA) abstinence. We conducted miRNA sequencing and profiling in the nonhuman primate model of MA abstinence, followed by miRNA qPCR, LC–MS/MS proteomics, immunoassays, and behavior tests in mice. In nonhuman primates, MA abstinence triggered a lasting upregulation of miR-137 in the dorsal striatum but a simultaneous downregulation of circulating miR-137. In mice, aberrant increase in striatal miR-137-dependent inhibition of SYNCRIP essentially mediated the MA abstinence-induced reduction of circulating miR-137. Pathway modeling through experimental deduction illustrated that the MA abstinence-mediated downregulation of circulating miR-137 was caused by reduction of SYNCRIP-dependent miRNA sorting into the exosomes in the dorsal striatum. Furthermore, diminished SYNCRIP in the dorsal striatum was necessary for MA abstinence-induced behavioral bias towards egocentric spatial learning. Taken together, our data revealed circulating miR-137 as a potential blood-based marker that could reflect MA abstinence-dependent changes in striatal miR-137/SYNCRIP axis, and striatal SYNCRIP as a potential therapeutic target for striatum-associated cognitive dysfunction by MA withdrawal syndrome.

Abstract The selective autophagy of damaged mitochondria is called mitophagy. Mitochondrial dysfunction, mitophagy, and apoptosis have been suggested to be interrelated in various human lung carcinomas. Leucine zipper EF-hand-containing transmembrane protein-1 (LETM1) was cloned in an attempt to identify candidate genes for Wolf–Hirschhorn syndrome. LETM1 plays a role in mitochondrial morphology, ion homeostasis, and cell viability. LETM1 has also been shown to be overexpressed in different human cancer tissues, including lung cancer. In the current study, we have provided clear evidence that LETM1 acts as an anchoring protein for the mitochondria-associated ER membrane (MAM). Fragmented mitochondria have been found in lung cancer cells with LETM1 overexpression. In addition, a reduction of mitochondrial membrane potential and significant accumulation of microtubule-associated protein 1 A/1B-light chain 3 punctate, which localizes with Red-Mito, was found in LETM1-overexpressed cells, suggesting that mitophagy is upregulated in these cells. Interestingly, glucose-regulated protein 78 kDa (GRP78; an ER chaperon protein) and glucose-regulated protein 75 kDa (GRP75) were posited to interact with LETM1 in the immunoprecipitated LETM1 of H460 cells. This interaction was enhanced in cells treated with carbonyl cyanide m-chlorophenylhydrazone, a chemical mitophagy inducer. Treatment of cells with honokiol (a GRP78 inhibitor) blocked LETM1-mediated mitophagy, and CRISPR/Cas9-mediated GRP75 knockout inhibited LETM1-induced autophagy. Thus, GRP78 interacts with LETM1. Taken together, these observations support the notion that the complex formation of LETM1/GRP75/GRP78 might be an important step in MAM formation and mitophagy, thus regulating mitochondrial quality control in lung cancer.

Dose monitoring in CT patients requires accurate dose estimation but most of the CT dose calculation tools are based on Caucasian computational phantoms. We established a library of organ dose conversion coefficients for Korean adults by using four Korean adult male and two female voxel phantoms combined with Monte Carlo simulation techniques. We calculated organ dose conversion coefficients for head, chest, abdomen and pelvis, and chest-abdomen-pelvis scans, and compared the results with the existing data calculated from Caucasian phantoms. We derived representative organ doses for Korean adults using Korean CT dose surveys combined with the dose conversion coefficients. The organ dose conversion coefficients from the Korean adult phantoms were slightly greater than those of the ICRP reference phantoms: up to 13% for the brain doses in head scans and up to 10% for the dose to the small intestine wall in abdominal scans. We derived Korean representative doses to major organs in head, chest, and AP scans using mean CTDIvol values extracted from the Korean nationwide surveys conducted in 2008 and 2017. The Korean-specific organ dose conversion coefficients should be useful to readily estimate organ absorbed doses for Korean adult male and female patients undergoing CT scans.

The objective of this study was to derive derived concentration guideline levels (DCGLs) reflecting the site-specific characteristics of KRR-1&2. A total of 7 nuclides (H-3, C-14, Co-60, Sr-90, Cs-137, Eu-152, and Eu-154) were selected for DCGLs derivation. Radiation dose at the sites was evaluated with RESRAD-ONSITE program. The dose contribution due to direct external exposure was the highest during the entire evaluation period. Ingestion had the second effect. The DCGLs of Co-60 was derived to be 0.051 Bq/g, and DCGLs of Cs-137 was 0.193 Bq/g. The DCGLs of H-3 showed the highest value of 129 Bq/g. The ratio of DCGLs derived by applying site-specific values and default values ranged from 0.27 to 19.6. For six nuclides excluding H-3, KRR-1&2 sites and the overseas NPP sites showed similar DCGLs. H-3 showed large differences in DCGLs from this study and overseas NPPs. The large difference resulted from input parameter values applied to the sites. In conclusion, it is critical to apply site-specific parameter values reflecting the site characteristics to derive DCGLs for decommissioned site clearance. The result of this study can be used as a reference for nuclide selection and DCGLs derivation reflecting the site characteristics when decommissioning nuclear facilities, including nuclear power plants in Korea.

Although pig-to-non-human primate (NHP) corneal xenotransplantation has shown long-term graft survival, xenogeneic antigen-related immune responses are still stronger than allogeneic antigen-associated responses. Therefore, there is an unmet need to investigate major rejection pathways in corneal xenotransplantation, even with immunosuppression. This study aimed to identify biomarkers in aqueous humor for predicting rejection and to investigate rejection-related pathways in grafts from NHPs transplanted with porcine corneas following the administration of steroids combined with tacrolimus/rituximab. NHPs who had received corneas from wild-type (WT) or α-1,3-galactosyltransferase gene-knockout (GTKO) pigs were divided into groups with or without rejection according to clinical examinations. Liquid chromatography-mass spectrometry (LC-MS) was used to analyze the proteomes of corneal tissues or aqueous humor. The biological functions of differentially expressed proteins (DEPs) were assessed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) for pathways and protein–protein interaction network analysis. Among the 66 DEPs in aqueous humor, complement proteins (C3, C5, and C9) and cholesterol metabolic proteins (APOA1 and APOA2) were related to xenogeneic rejection as biomarkers, and alternative pathways of the complement system seemed to be important in xenogeneic graft rejection. Among the 416 DEPs of the cornea, NF-κB1 and proteosomes (PSMD7, PSMA5, and PSMD3) seemed to be related to xenogeneic graft rejection. Additionally, oxidative phosphorylation and leukocyte activation-related pathways are involved in rejection. Overall, our proteomic approach highlights the important role of NF-κB1, proteosomes, oxidative phosphorylation, and leukocyte activation-related inflammation in the cornea and the relevance of complement pathways of the aqueous humor as a predictive biomarker of xenogeneic rejection.

In the original publication [...]

The accumulation of protein-bound uremic toxins (PBUT) is associated with increased cardiovascular outcomes in patients on dialysis. However, the efficacy of PBUT removal for a medium-cutoff (MCO) membrane has not been clarified. This study was designed to assess the efficacy of PBUT clearance according to dialysis modalities. In this prospective and cross-over study, we enrolled 22 patients who received maintenance hemodiafiltration (HDF) thrice weekly from three dialysis centers. The dialysis removal of uremic toxins, including urea, beta 2-microglobulin (B2MG), lambda free light chain (λ-FLC), indoxyl sulfate (IS), and p-cresyl sulfate (pCS), was measured in the 22 patients on high-flux HD (HF-HD), post-dilution online HDF (post-OL-HDF), and MCO-HD over 3 weeks. The average convection volume in post-OL-HDF was 21.4 ± 1.8 L per session. The reduction rate (RR) of B2MG was higher in post-OL-HDF than in MCO-HD and HF-HD. The RR of λ-FLC was the highest in MCO-HD, followed by post-OL-HDF and HF-HD. The dialysate albumin was highest in MCO-HD, followed by post-OL-HDF and HF-HD. Post-dialysis plasma levels of IS and pCS were not statistically different across dialysis modalities. The total solute removal and dialytic clearance of IS and pCS were not significantly different. The clearance of IS and pCS did not differ between the HF-HD, post-OL-HDF, and MCO-HD groups.

Bacillus subtilis is an important bacterial species due to its various industrial, medicinal, and agricultural applications. Prophages are known to play vital roles in host properties. Nevertheless, studies on the prophages and temperate phages of B. subtilis are relatively limited. In the present study, an in silico analysis was carried out in sequenced B. subtilis strains to investigate their prevalence, diversity, insertion sites, and potential roles. In addition, the potential for UV induction and prevalence was investigated. The in silico prophage analysis of 164 genomes of B. subtilis strains revealed that 75.00% of them contained intact prophages that exist as integrated and/or plasmid forms. Comparative genomics revealed the rich diversity of the prophages distributed in 13 main clusters and four distinct singletons. The analysis of the putative prophage proteins indicated the involvement of prophages in encoding the proteins linked to the immunity, bacteriocin production, sporulation, arsenate, and arsenite resistance of the host, enhancing its adaptability to diverse environments. An induction study in 91 B. subtilis collections demonstrated that UV-light treatment was instrumental in producing infective phages in 18.68% of them, showing a wide range of host specificity. The high prevalence and inducibility potential of the prophages observed in this study implies that prophages may play vital roles in the B. subtilis host.