Conversion of albumin into a BODIPY-like photosensitizer by a flick reaction, tumor accumulation and photodynamic therapy.

The accumulation of photosensitizers (PSs) in lesion sites but not in other organs is an important challenge for efficient image guiding in photodynamic therapy. Cancer cells are known to express a significant number of albumin-binding proteins that take up albumin as a nutrient source. Here, we converted albumin to a novel BODIPY-like PS by generating a tetrahedral boron environment via a flick reaction. The formed albumin PS has almost the same 3-dimensional structural feature as free albumin because binding occurs at Sudlow Site 1, which is located in the interior space of albumin. An i.v. injection experiment in tumor-bearing mice demonstrated that the human serum albumin PS effectively accumulated in cancer tissue and, more surprisingly, albumin PS accumulated much more in the cancer tissue than in the liver and kidneys. The albumin PS was effective at killing tumor cells through the generation of reactive oxygen species under light irradiation. The crystal structure of the albumin PS was fully elucidated by X-ray crystallography; thus, further tuning of the structure will lead to novel physicochemical properties of the albumin PS, suggesting its potential in biological and clinical applications.

UV photochemistry of the L-cystine disulfide bridge in aqueous solution investigated by femtosecond X-ray absorption spectroscopy.

The photolysis of disulfide bonds is implicated in denaturation of proteins exposed to ultraviolet light. Despite this biological relevance in stabilizing the structure of many proteins, the mechanisms of disulfide photolysis are still contested after decades of research. Herein, we report new insight into the photochemistry of L-cystine in aqueous solution by femtosecond X-ray absorption spectroscopy at the sulfur K-edge. We observe homolytic bond cleavage upon ultraviolet irradiation and the formation of thiyl radicals as the single primary photoproduct. Ultrafast thiyl decay due to geminate recombination proceeds at a quantum yield of >80 % within 20 ps. These dynamics coincide with the emergence of a secondary product, attributed to the generation of perthiyl radicals. From these findings, we suggest a mechanism of perthiyl radical generation from a vibrationally excited parent molecule that asymmetrically fragments along a carbon-sulfur bond. Our results point toward a dynamic photostability of the disulfide bridge in condensed-phase.

Leuconostoc koreense sp. nov., isolated from kimchi, a fermented vegetable.

The novel strain CBA3628T was isolated from kimchi, a Korean fermented vegetable. CBA3628T is a cocci-shaped, Gram-stain-positive, catalase- and oxidase-negative and facultatively anaerobic bacterium. The results of phylogenetic analysis based on 16S rRNA gene sequencing indicated that CBA3628T represented a member of the genus Leuconostoc of the family Leuconostocaceae. CBA3628T has a circular chromosomal genome and three plasmids of 1 864 558 bp (37% DNA G+C content), containing 1,887 genes, 1,762 predicted protein-coding genes, 4 complete rRNA loci and 70 tRNA genes. The cells were non-haemolytic, non-motile and non-spore forming. The optimal growth of CBA3628T occurred at 30 °C, pH 6.0 and with 0-2% (w/v) NaCl. The major polar lipids of CBA3628T were diphosphatidylglycerol and phosphatidylglycerol. The major fatty acids (>10%) of CBA3628T were C16  :  0, C20  :  0 and C19 : 0 cyclo ω8c. CBA3628T contained A3α-type peptidoglycans. CBA3628T was most closely related to Leuconostoc mesenteroides subsp. mesenteroides ATCC 8293T, L. mesenteroides subsp. dextranicum DSM 20484T and L. suionicum DSM 20241T with 99.52% 16S rRNA gene sequence similarity. However, the average nucleotide identities of 91.9%, 91.7% and 91.1% and the digital DNA-DNA hybridisation values of 45.6%, 45.4% and 45.4% indicated that the novel isolate represented a distinct species. Phylogenetic analyses of both the 16S rRNA gene and genome sequences revealed that CBA3628T formed a distinct phylogenetic lineage within the genus Leuconostoc and was most closely related to Leuconostoc litchii MB7T. The ANI and dDDH values between CBA3628T and L. litchii MB7T were 84.9 and 22.8%, respectively. Functional genes belonging to COG categories E, J and K were enriched in the genome of CBA3628T (>7.9%). On the basis of its physiological, chemotaxonomic, phylogenetic and genomic properties, strain CBA3628T represents a novel species from the genus Leuconostoc, for which we propose the name Leuconostoc koreense sp. nov., with the type strain CBA3628T (= KACC 23049T = DSM 116836T).

The therapeutic effect of 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol on chemically induced atopic dermatitis.

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease worldwide. However, it is still urgent to develop innovative treatments that can effectively manage refractory patients with unpredictable chronic disease courses. In this study, we evaluated the therapeutic efficacy of 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) as a novel agent for AD treatment using a human-like mouse model of AD. PLAG significantly improved 2,4-dinitrochlorobenzene (DNCB)-induced AD skin lesions compared to those in mice treated with DNCB alone. PLAG substantially modulated the AD-induced infiltration of monocytes and eosinophils into skin lesions and humoral systemic responses involving immunoglobulin E (IgE), interleukin (IL)-4, and IL-13, restoring them to a normal state. Next, we compared the therapeutic efficacy of PLAG and abrocitinib for severe AD treatment. PLAG exhibited a significant therapeutic effect on AD skin lesions compared to abrocitinib. Unlike abrocitinib, PLAG significantly reduced AD-induced eosinophil infiltration to a level similar to that observed in untreated negative controls. Notably, both PLAG and abrocitinib downregulated IgE, IL-4, and IL-13 in a similar pattern, reaching levels similar to those in the untreated negative controls. Our findings strongly suggest that PLAG may serve as a therapeutic agent for AD with an efficacy comparable to that of abrocitinib.

Genomic patterns in the schizophrenia brain.

Somatic noncoding mutations likely contribute to schizophrenia development.

Integrating visual and community environments in a motorcycle crash and casualty estimation.

Motorcycle crashes pose a serious problem because their probability of causing casualties is greater than that of passenger vehicle crashes. Therefore, accurately identifying the factors that influence motorcycle crashes is essential for enhancing traffic safety and public health. The aim of this study was to address three major research gaps: first, existing studies have relatively overlooked the built environment in relation to visual factors; second, existing crash prediction models have not fully reflected the differences in built environment characteristics between areas with frequent motorcycle crashes and areas with frequent casualties; and third, multidimensional analysis for variable selection is limited, and the interpretability of the models is insufficient. Therefore, this study proposes a comprehensive framework for motorcycle crash and casualty estimation. The framework uses a data cube model incorporating OLAP operations to provide deeper insights into crash influencing factors at different levels of abstraction. We also utilized the XGBoost model to predict motorcycle high crash spots and casualty risk and integrate visual factors extracted from Google Street View images and community-level urban environments into the model. SHAP techniques were used to analyze and interpret the global and local feature importance of the models. Our results revealed that the factors affecting areas with frequent motorcycle crashes and the factors that affect casualties differ. In particular, visual factors such as vegetation and the sky ratio are important for estimating casualties. We aim to provide practical guidelines for a safe environment for motorcycle crashes.

Mitochondrial transplantation attenuates lipopolysaccharide-induced acute respiratory distress syndrome.

BACKGROUND: The mitochondria are essential organelles not only providing cellular energy in the form of ATP, but also regulating the inflammatory response and the cell death program. Mitochondrial dysfunction has been associated with various human diseases, including metabolic syndromes as well as inflammatory and neurodegenerative diseases. Acute respiratory distress syndrome (ARDS) is an acute pulmonary disorder characterized by uncontrolled alveolar inflammation, apoptotic lung epithelial/endothelial cells, and pulmonary edema. Despite the high mortality of ARDS, an effective pharmacotherapy to treat this disease has not been established yet. Therefore, identifying a novel targeted therapy for ARDS is important. Recently, exogenous mitochondrial transplantation was reported to be beneficial for treating mitochondrial dysfunction. The current study aimed to investigate the therapeutic effect of mitochondrial transplantation on ARDS in vitro and in vivo. METHODS: Mitochondria were isolated from human stem cells. For in vitro efficacy of mitochondrial transplantation on the inflammation and cell death, murine alveolar macrophages MH-S and human pulmonary microvascular endothelial cells HPMECs were exposed to LPS, respectively. The ARDS mice model established by a single intratracheal instillation of LPS was used for in vivo efficacy of intravenously treated mitochondria. RESULTS: Our results showed that the mitochondria isolated from human stem cells exhibited an anti-inflammatory effect against alveolar macrophages and an anti-apoptotic effect against the alveolar epithelial cells. Furthermore, intravenous mitochondrial treatment was associated with the attenuation of lung injury in the LPS-induced ARDS mice. CONCLUSION: Dual effects of mitochondria on anti-inflammation and anti-apoptosis support the potential of mitochondrial transplantation as a novel therapeutic strategy for ARDS.

Comparison of the accuracy of implant placement using a simple guide device and freehand surgery.

Background/purpose: In clinical settings, there may be a need for a guide device that is simple and enhances the positioning accuracy of prosthetics. This study aimed to compare the accuracy of implant positioning using two methods: implant placement with a simple guide device (SGD) and freehand surgery. Materials and methods: A total of 103 patients were randomly assigned to the control or study group. In the control group, implant placement was performed using the freehand technique. In the study group, implant placement was conducted with an SGD. Implant positioning accuracy was assessed by measuring how much the central position, fixture angulation, and fixture position differed from the ideal implant position based on periapical radiographs and cone-beam computed tomography images. In patients with double implants, parallelism between the two fixtures was also measured. Results: There were 124 subjects, with 84 having single implants (42 in the control group and 42 in the study group) and 40 having double implants (20 in the control group and 20 in the study group). Utilization of the SGD for both single and double implant placement improved the accuracy of the central position, fixture angulation, and fixture position (P < 0.05). Additionally, in double implantation cases, it significantly enhanced parallelism between the two fixtures (P < 0.001). Conclusion: These findings suggest that use of an SGD leads to more accurate implant placement compared with freehand surgery taking into account the final prosthetic restoration.

Cold Plasma Ameliorates Imiquimod-Induced Psoriasis-Like Skin Inflammation in Mice.

OBJECTIVES: Cold plasma has shown efficacy in various dermatological applications by reduces inflammatory responses and modulating cytokine expression. Therefore, this study aimed to investigate the therapeutic effects of cold plasma on psoriasis. METHODS: In psoriasis HaCaT cells with cold plasma, we confirmed the expression of inflammatory cytokines involved in psoriasis formation and MAPK pathway, cell cycle, and apoptosis-related factors. In psoriasis-like BALB/c mice model, the effects of cold plasma treatment on skin were visually assessed. The expression of psoriasis-related factors was confirmed through qPCR, Western blotting, and Immunohistochemistry. RESULTS: Cold plasma led to a reduction in inflammatory cytokines including IL-17A, IL-23A, IL-24, IL-1ß, and TNF-α in the psoriasis cell line. It also modulated factors involved in the MAPK pathway and the cell cycle. In the psoriasis-like mice model, cold plasma resulted in improvements in skin thickness, erythema, scaling, and PASI. Additionally, decreases in inflammatory cytokines like INF-γ, IL-23, and S100a7 were observed, along with improvements in MAPK pathway activation, apoptosis, and other psoriasis-related factors. CONCLUSION: Through in vitro and in vivo studies, our research highlights the potential of cold plasma as a novel therapeutic approach for psoriasis. Furthermore, cold plasma could serve as an adjunctive treatment for skin immunological diseases.

Genome-wide association study and polygenic risk score analysis for schizophrenia in a Korean population.

Although large-scale genome-wide association studies (GWASs) have revealed the genetic architecture of schizophrenia, these studies have mainly focused on populations of European ancestry. This study aimed to identify common genetic variants associated with schizophrenia in the Korean population and evaluate the performance of polygenic risk scores (PRSs) derived from large-scale GWASs across ancestries. In the Korean psychiatric GWAS project (KPGP), seven academic institutes and their affiliated hospitals across South Korea recruited a cohort of 1670 patients with DSM-IV-defined schizophrenia and 2271 healthy controls. A total of 6690,822 SNPs were tested for association with schizophrenia. We identified one previously unreported genome-wide significant locus rs2423464 (P = 2.83 × 10-11; odds ratio = 1.65; 95 % confidence interval = 1.43-1.91, minor allele frequency = 0.126). This variant was also associated with increased lysosomal-associated membrane protein family member 5 (LAMP5) gene expression. The PRS derived from the meta-analysis results of East Asian and European GWASs explained a larger proportion of the phenotypic variance in the Korean schizophrenia sample than the PRS of an East Asian or European GWAS. (R2 = 0.073 for meta-analysis; 0.028 for East Asian GWAS; 0.037 for European GWAS). GWASs involving diverse ethnic groups will expand our understanding of the genetic architecture of schizophrenia.

Factors associated with generalized anxiety disorder in adolescents with cultural diversity: secondary data analysis.

BACKGROUND: The number of culturally diverse adolescents in South Korea has reached 290,000 and is increasing every year; however, they still represent only 2.5% of the total adolescent population in middle and high schools, making them a minority. Adolescents experiencing cultural diversity are psychologically vulnerable because they grow up in bicultural environments and experience prejudice. Given the nature of generalized anxiety disorder, which can be exacerbated by stress, these adolescents may face an increased risk of developing the disorder not only because of developmental stress but also because of the stress of cultural adaptation. To identify the prevalence of generalized anxiety disorder among adolescents with cultural diversity, we analyzed related factors. Based on the results, strategies have been proposed to reduce anxiety in adolescents with cultural diversity and generalized anxiety disorders. METHODS: This study used data from the 16th - 18th Korea Youth Risk Behavior Survey. Factors associated with generalized anxiety disorders were identified based on the social determinants of the health framework. Statistical analyses were conducted using IBM SPSS 25.0, and statistical methods were used for complex samples. RESULTS: Among adolescents with cultural diversity, 12.8% exhibited generalized anxiety disorders. Among the structural factors, economic status, mother's education level, and gender were significantly associated with the disorder, whereas among the psychosocial factors, suicidal ideation, depressive mood, loneliness, perceived stress level, and subjective health status were significant factors influencing it. CONCLUSION: The factors identified in our research can be used as a resource for the early identification of culturally diverse adolescents who are vulnerable to generalized anxiety disorders. To prevent generalized anxiety disorder among adolescents with cultural diversity, school or community nurses can implement interventions to reduce loneliness or stress management programs.

Effects of gnotobiotic fermentation on global gene expression of germ-free vegetables.

Existing research has underscored the vital interplay between host organisms and their associated microbiomes, which affects health and function. In both plants and animals, host factors critically shape microbial communities and influence growth, health, and immunity. Post-harvest plants, such as those used in kimchi, a traditional Korean dish, offer a unique avenue for exploring host-microbe dynamics during fermentation. Despite the emphasis on lactic acid bacteria (LAB) in fermentation studies, the roles of host factors remain unclear. This study aimed to investigate the influence of these factors on plant transcriptomes during kimchi fermentation. We individually inoculated nine LAB strains into germ-free kimchi to generate LAB-mono-associated gnotobiotic kimchi and performed RNA-sequencing analysis for the host vegetables during fermentation. The transcriptomes of post-harvest vegetables in kimchi change over time, and microbes affect the transcriptome profiles of vegetables. Differentially expressed gene analyses revealed that microbes affected the temporal expression profiles of several genes in the plant transcriptomes in unique directions depending on the introduced LAB strains. Cluster analysis with other publicly available transcriptomes of post-harvest vegetables and fruits further revealed that the plant transcriptome is more profoundly influenced by the environment harboring the host than by host phylogeny. Our results bridge the gap in understanding the bidirectional relationship between host vegetables and microbes during food fermentation, illuminating the complex interplay between vegetable transcriptomes, fermentative microbes, and the fermentation process in food production. The different transcriptomic responses elicited by specific LAB strains suggest the possibility of microbial manipulation to achieve the desired fermentation outcomes.

A leucine-rich-repeat receptor-like kinase regulates pollen aperture formation in rice.

Apertures in pollen grains exhibit species-specific patterns and provide an ideal model for studying cell-surface patterning. Pollen apertures are critical for cereal crop fertility, and while DEFECTIVE IN APERTURE FORMATION1 (OsDAF1) and INAPERTURATE POLLEN1 (OsINP1) have been documented to participate in pollen aperture formation in rice (Oryza sativa), the molecular transduction pathway regulating aperture formation is largely unknown. Here, we report that a leucine-rich-repeat receptor-like kinase (LRR-RLK), AM1, plays a key role in rice pollen aperture formation. Mutations of OsAM1 lead to complete sterility due to disappearance of the pollen aperture and failure in pollen tube germination. OsAM1 encodes a LRR-RLK that belongs to the STRUBBELIG-receptor family. Similar to other reported aperture regulators, OsAM1 assembles to future aperture sites on tetrads after meiosis to regulate aperture formation. The extracellular and intracellular domain of OsAM1 interacts with OsINP1 and OsDAF1, respectively. However, despite their interaction and the absence of aperture formation in osam1 pollen grains, OsINP1 and OsDAF1 localize to future aperture sites at the tetrad stage. Mutation of OsINP1, however, disrupts normal localization of OsAM1, indicating that OsAM1 acts downstream of OsINP1. Our findings reveal the role of a LRR-RLK protein in pollen aperture formation and shed light on the regulatory network of pollen aperture formation.

SiMPl-GS: Advancing Cell Line Development via Synthetic Selection Marker for Next-Generation Biopharmaceutical Production.

Rapid and efficient cell line development (CLD) process is essential to expedite therapeutic protein development. However, the performance of widely used glutamine-based selection systems is limited by low selection efficiency, stringency, and the inability to select multiple genes. Therefore, an AND-gate synthetic selection system is rationally designed using split intein-mediated protein ligation of glutamine synthetase (GS) (SiMPl-GS). Split sites of the GS are selected using a computational approach and validated with GS-knockout Chinese hamster ovary cells for their potential to enable cell survival in a glutamine-free medium. In CLD, SiMPl-GS outperforms the wild-type GS by selectively enriching high producers. Unlike wild-type GS, SiMPl-GS results in cell pools in which most cells produce high levels of therapeutic proteins. Harnessing orthogonal split intein pairs further enables the selection of four plasmids with a single selection, streamlining multispecific antibody-producing CLD. Taken together, SiMPl-GS is a simple yet effective means to expedite CLD for therapeutic protein production.

Diaminonaphthalene Boronic Acid (DANBA): New Approach for Peroxynitrite Sensing Site.

Selective detection of reactive oxygen species (ROS) is vital for studying their role in brain diseases. Fluorescence probes can distinguish ONOO- species from other ROS; however, their selectivity toward ONOO- species depends on the ONOO- recognition group. Aryl-boronic acids and esters, which are common ONOO- recognition groups, are not selective for ONOO- over H2O2. In this study, we developed a diaminonaphthalene (DAN)-protected boronic acid as a new ONOO- recognition group that selectively reacts with ONOO- over H2O2 and other ROS. Three DAN-protected boronic acid (DANBA)-based fluorophores that emit fluorescence over visible to near-infrared (NIR) regions, Cou-BN, BVP-BN, and HDM-BN, and their aryl-boronic acid-based counterparts (Cou-BO, BVP-BO, and HDM-BO), were developed. The DANBA-based probes exhibited enhanced selectivity toward ONOO- over that of their control group, as well as universality in solution assays and in vitro experiments with PC12 cells. The NIR-emissive HDM-BN was optimized to delineate in vivo ONOO- levels in mouse brains with Parkinson's disease. This DAN-protected boronic acid belongs to a new generation of recognition groups for developing ONOO- probes, and this strategy could be extended to other common hydroxyl-containing dyes to detect ONOO- levels in complex biological systems and processes.

Optimization of Sodium Iodide-Based Root Filling Material for Clinical Applications: Enhancing Physicochemical Properties.

Premature loss of root canal-treated primary teeth has long been a concern in dentistry. To address this, researchers developed a sodium iodide-based root canal-filling material as an alternative to traditional iodoform-based materials. The goal of this study was to improve the physicochemical properties of the sodium iodide-based material to meet clinical use standards. To resolve high solubility issues in the initial formulation, researchers adjusted component ratios and added new ingredients, resulting in a new paste called L5. This study compared L5 with L0 (identical composition minus lanolin) and Vitapex as controls, conducting physicochemical and antibacterial tests. Results showed that L5 met all ISO 6876 standards, demonstrated easier injection and irrigation properties than Vitapex, and exhibited comparable antibacterial efficacy to Vitapex, which is currently used clinically. The researchers conclude that if biological stability is further verified, L5 could potentially be presented as a new option for root canal-filling materials in primary teeth.

Novel Variant of FDXR as a Molecular Etiology of Postlingual Post-synaptic Auditory Neuropathy Spectrum Disorder via Mitochondrial Dysfunction: Reiteration of the Correlation between Genotype and Cochlear Implantation Outcomes.

OBJECTIVES: FDXR encodes mitochondrial ferredoxin reductase, which is associated with auditory neuropathy spectrum disorder (ANSD) and optic atrophy. To date, only two studies have described FDXR-related hearing loss. The auditory rehabilitation outcomes of this disease entity have not been investigated, and the pathophysiological mechanisms remain incompletely understood. Here we report a hearing-impaired individual with co-segregation of the FDXR variant and post-synaptic type ANSD, who underwent cochlear implantation (CI) with favorable outcomes. We suggest a possible pathophysiological mechanism of adult-onset ANSD involving mitochondrial dysfunction. METHODS: A 35-year-old woman was ascertained to have ANSD. Exome sequencing identified the genetic cause of hearing loss, and a functional study measuring mitochondrial activity was performed to provide molecular evidence of pathophysiology. Expression of FDXR in the mouse cochlea was evaluated by immunohistochemistry. Intraoperatively, electrically evoked compound action potential (ECAP) responses were measured, and the mapping parameters were adjusted accordingly. Audiological outcomes were monitored for over 1 year. RESULTS: In lymphoblastoid cell lines (LCLs) carrying a novel FDXR variant, decreased ATP levels, reduced mitochondrial membrane potential, and increased reactive oxygen species levels were observed compared to control LCLs. These dysfunctions were restored by administering mitochondria isolated from umbilical cord mesenchymal stem cells, confirming the pathogenic potential of this variant via mitochondrial dysfunction. Partial ECAP responses during CI and FDXR expression in the mouse cochlea indicate that FDXR-related ANSD is post-synaptic. As a result of increasing the pulse width during mapping, the patient's CI outcomes showed significant improvement over 1-year post-CI. CONCLUSION: A novel FDXR variant associated with mitochondrial dysfunction and post-synaptic ANSD was first identified in a Korean individual. Additionally, 1-year post-CI outcomes were reported for the first time in the literature. Excellent audiologic. RESULTS: were obtained, and our. RESULTS: reiterate the correlation between genotype and CI outcomes in ANSD.