Identifying Candidate Polyphenols Beneficial for Oxidative Liver Injury through Multiscale Network Analysis.

Oxidative stress, a driver of liver pathology, remains a challenge in clinical management, necessitating innovative approaches. In this research, we delved into the therapeutic potential of polyphenols for oxidative liver injury using a multiscale network analysis framework. From the Phenol-Explorer database, we curated a list of polyphenols along with their corresponding PubChem IDs. Verified target information was then collated from multiple databases. We subsequently measured the propagative effects of these compounds and prioritized a ranking based on their correlation scores for oxidative liver injury. This result underwent evaluation to discern its effectiveness in differentiating between known and unknown polyphenols, demonstrating superior performance over chance level in distinguishing these compounds. We found that lariciresinol and isopimpinellin yielded high correlation scores in relation to oxidative liver injury without reported evidence. By analyzing the impact on a multiscale network, we found that lariciresinol and isopimpinellin were predicted to offer beneficial effects on the disease by directly acting on targets such as CASP3, NR1I2, and CYP3A4 or by modulating biological functions related to the apoptotic process and oxidative stress. This study not only corroborates the efficacy of identified polyphenols in liver health but also opens avenues for future investigations into their mechanistic actions.

Elucidating the callus-to-shoot-forming mechanism in Capsicum annuum 'Dempsey' through comparative transcriptome analyses.

BACKGROUND: The formation of shoots plays a pivotal role in plant organogenesis and productivity. Despite its significance, the underlying molecular mechanism of de novo regeneration has not been extensively elucidated in Capsicum annuum 'Dempsey', a bell pepper cultivar. To address this, we performed a comparative transcriptome analysis focusing on the differential expression in C. annuum 'Dempsey' shoot, callus, and leaf tissue. We further investigated phytohormone-related biological processes and their interacting genes in the C. annuum 'Dempsey' transcriptome based on comparative transcriptomic analysis across five species. RESULTS: We provided a comprehensive view of the gene networks regulating shoot formation on the callus, revealing a strong involvement of hypoxia responses and oxidative stress. Our comparative transcriptome analysis revealed a significant conservation in the increase of gene expression patterns related to auxin and defense mechanisms in both callus and shoot tissues. Consequently, hypoxia response and defense mechanism emerged as critical regulators in callus and shoot formation in C. annuum 'Dempsey'. Current transcriptome data also indicated a substantial decline in gene expression linked to photosynthesis within regenerative tissues, implying a deactivation of the regulatory system governing photosynthesis in C. annuum 'Dempsey'. CONCLUSION: Coupled with defense mechanisms, we thus considered spatial redistribution of auxin to play a critical role in the shoot morphogenesis via primordia outgrowth. Our findings shed light on shoot formation mechanisms in C. annuum 'Dempsey' explants, important information for regeneration programs, and have broader implications for precise molecular breeding in recalcitrant crops.

First report of soybean root rot caused by Fusarium falciforme in the Republic of Korea.

Phytopathogenic Fusarium species causing root and stem rot diseases in susceptible soybean (Glycine max (L.) Merrill) are a major threat to soybean production worldwide. Several Fusarium species have been reported to infect soybean plants in the Republic of Korea, including F. solani, F. oxysporum, F. fujikuroi, and F. graminearum (Cho et al., 2004; Choi et al., 2019; Kang et al., 2020). During the nationwide survey of soybean diseases in 2015, soybean plants showing symptoms of leaf chlorosis, wilting, and shoot death were found in soybean fields in Seosan, Chungnam. Fusarium isolates were obtained from the margins of sterilized necrotic symptomatic and asymptomatic regions of the stem tissues of diseased samples by culturing on potato dextrose agar (PDA). To examine the morphological characteristics, isolates were cultured on PDA at 25°C in the darkness for 10 days. Colonies produced white aerial mycelia with apricot pigments in the medium. Macroconidia were hyaline, slightly curved in shape with 3 or 4 septa, and their average length and width were 34.6± 0.56 µm (31.4 to 37.8 µm) and 4.7±0.16 µm (4.1 to 5.8 µm), respectively (n = 20). Microconidia were elongated, oval with 0 or 1 septum, and their average length and width were 11.4±0.87 and 5.2±0.32 µm, respectively (n = 20). The colonies and conidia exhibited morphological similarities to those of F. falciforme (Xu et al., 2022). Using the primers described by O'Donnell et al. (2008), identity of a representative strain '15-110' was further confirmed by sequencing portions of two genes, the translation elongation factor 1-alpha (EF-1α) and the second largest subunit of RNA polymerase II (RPB2). The two sequences (GenBank accession No. OQ992718 and OR060664) of 15-110 were 99% similar to those of two F. falciforme strains, 21BeanYC6-14 (GenBank accession nos. ON375419 and ON331931), and 21BeanYC6-16 (GenBank accession nos. ON697187 and ON331933). To test the pathogenicity, a single-spore isolate was cultured on carnation leaf agar (CLA) at 25℃ for 10 days. Pathogenicity test was performed by root-cutting assays using 14-day-old soybean seedlings of 'Daewon' and 'Taekwang'. Ten-day-old mycelia of 15-110 were collected from the CLA plates by scraping with distilled water, and the spore suspension was filtered and diluted to 1 × 106 conidia/mL. The roots of the soybean seedlings were partially cut and inoculated by soaking in the diluted spore suspension for two hours. The seedlings were then transplanted into 12 cm plastic pots (11 cm in height) and grown in a growth chamber at 25°C, 14h light/10h dark for 2 weeks. The infected plants exhibited wilting, observed brown discoloration on the root, and eventually died within 2 weeks, whereas the control plants inoculated with sterile water remained healthy. F. falciforme 15-110 was reisolated from infected plants, but not from the uninoculated controls. The morphology of the re-isolated fungus on PDA and its target gene sequences were identical to those of the original colony. To the best of our knowledge, this is the first report of root rot in soybean caused by F. falciforme in the Republic of Korea. Fusarium spp. induce a range of diseases in soybean plants, including root rot, damping-off, and wilt. Given the variable aggressiveness and susceptibility to fungicides among different Fusarium species, it is imperative to identify the Fusarium species posing a threat to soybean production. This understanding is crucial for developing a targeted and tailored disease management strategy to control Fusarium diseases.

First report of soybean root rot caused by Fusarium proliferatum in the Republic of Korea.

Fusarium species are widespread soilborne pathogens that can cause damping-off, root rot, and wilting in soybean [Glycine max (L.) Merrill], subsequently leading to significant yield suppression. Several Fusarium spp. have already been documented for their pathogenicity on soybean plants in the Republic of Korea. The nationwide monitoring of soybean diseases continues to identify new pathogenic Fusarium spp. In 2016, five plant samples at R3-R4 growth stages, showing symptoms of wilting in the upper parts and root rot, were collected in Suwon, Gyeonggi, Republic of Korea. Fungal colonies were obtained from the diseased root samples, with the surface sterilized in 1% sodium hypochlorite for 2 min, rinsed thrice with sterile distilled water, and placed on water agar at 25°C. Five isolates were collected and purified by single-spore isolation. The fungal mycelium was subsequently cultivated on potato dextrose agar for ten days. The isolates produced abundant, aerial, and white mycelium and became purple in old cultures. Macroconidia were slender, falcate to almost straight, usually 3 to 5 septated, and thin-walled. Microconidia were formed in chains from polyphalides, clavate or oval, usually single-celled with a flattened base. These characteristics of isolates were consistent with the description of F. proliferatum (Leslie and Summerrell 2006), and the representative isolate 16-19 was selected for molecular identification to confirm its identity as F. proliferatum. Two evolutionarily conserved genes, the translation elongation factor 1-alpha (EF-1α) and the second-largest subunit of RNA polymerase II (RPB2) genes, were partially amplified using the primers described by O'Donnell et al. (2008), resulting in nucleotide sequences of 680 and 382 base pairs, respectively. These two sequences (GenBank accession numbers: OQ992720 and OR060666) showed 100 and 99.5% identity to the EF-1α and RPB2 of F. proliferatum A40 (GenBank accession numbers: KP964907 and KP964842). For the Petri-dish pathogenicity assay (Broders et al. 2007), five surface-sterilized seeds were placed on water agar media with either sterile water or actively growing '16-19' culture. After 7 days of incubation in a growth chamber (25°C; 12-hour photoperiod), brown lesions were observed on the roots of the inoculated plants, while no symptoms were observed in the sterile water-treated controls. The experiment was conducted three times. For root-cut pathogenicity assay, conidial suspension (1×106 conidia/ml) of the isolate '16-19' was prepared with harvested mycelia cultured on PDA for 10 days with sterile water. The roots of 10-day-old soybean seedlings were partially cut and soaked in either the suspension or sterile water for 2 hours. The seedlings were transplanted into 12 cm plastic pots (11 cm in height) and grew in a greenhouse (26 ± 3°C, 13-h photoperiod). The experiment followed a completely randomized design with three replicates (i.e. three plants in a pot), and it was repeated twice. The inoculated plants began to wilt 7 days after inoculation, while the sterile water-treated controls remained healthy. Ten days after inoculation, all plants were collected, washed under running tap water, and evaluated for the presence and severity of root rot using a 0-4 scale (Chang et al. 2015). The inoculated plants exhibited reduced vigor and developed dark brown lesions on their roots. F. proliferatum was reisolated from symptomatic root tissues of the infected plants, while not from those of the controls. Its colony and spores were morphologically identical to those of the original isolate. F. proliferatum was previously reported as a causative agent of soybean root rot in the United States (Díaz Arias et al. 2011) and Canada (Chang et al. 2015). This is the first report of soybean root rot caused by F. proliferatum in the Republic of Korea. This finding implies that F. proliferatum may potentially threaten soybean production in the Republic of Korea and suggests that effective disease management strategies should be established for soybean protection against the disease, along with continuous surveillance.

Linking void and interphase evolution to electrochemistry in solid-state batteries using operando X-ray tomography.

Despite progress in solid-state battery engineering, our understanding of the chemo-mechanical phenomena that govern electrochemical behaviour and stability at solid-solid interfaces remains limited compared to at solid-liquid interfaces. Here, we use operando synchrotron X-ray computed microtomography to investigate the evolution of lithium/solid-state electrolyte interfaces during battery cycling, revealing how the complex interplay among void formation, interphase growth and volumetric changes determines cell behaviour. Void formation during lithium stripping is directly visualized in symmetric cells, and the loss of contact that drives current constriction at the interface between lithium and the solid-state electrolyte (Li10SnP2S12) is quantified and found to be the primary cause of cell failure. The interphase is found to be redox-active upon charge, and global volume changes occur owing to partial molar volume mismatches at either electrode. These results provide insight into how chemo-mechanical phenomena can affect cell performance, thus facilitating the development of solid-state batteries.

Developing a best practice framework for clinical competency education in the traditional East-Asian medicine curriculum.

BACKGROUND: While clinical competency is crucial for traditional East-Asian medical education, available studies on the educational system for fostering clinical performance are scarce. This study aimed to review the educational system, curriculum, facilities, and management of current traditional East-Asian medicine in a well-established university of Korea and develop a Best Practice Framework (BPF) of clinical competency education. METHODS: The clinical competency education system in Pusan National University School of Korean Medicine was systematically described through 5 steps of governance of the educational system, competency of the graduates, educational resources, assessment strategies and tools, and gaps in the curriculum. We also reviewed the experiences in education and the points to be improved. RESULTS: The Office of Traditional Korean Medicine Education governs the development, implementation, and evaluation of the educational curriculum for cultivating students' clinical competency. Medical students have undertaken 39 modules of clinical biomedicine and 21 of traditional medicine during the clinical clerkship courses in an affiliated hospital, Clinical Skill Practice Center, clinical research center, practice lab for medical herb, and other locations. After training, 15 modules of simulated clinical training using standardized patients, students' clinical competency are evaluated by a Clinical Performance Test using a Clinical Performance Examination (CPX) and an Objective Structured Clinical Examination (OSCE) for biomedical and traditional medical skills. CONCLUSIONS: A clinical competency framework is required for a qualified physician of traditional East-Asian medicine. This study reviewed the current well-organized educational system of Korean traditional medicine in detail, which can be used for the BPF of competency-based clinical education. We expect the current study to be a representative reference for establishing an educational system of traditional medicine such as acupuncture and medical herbs in other countries.

Size Dependence Unveiling the Adsorption Interaction of High-Density Lipoprotein Particles with PEGylated Gold Nanoparticles in Biomolecular Corona Formation.

Apolipoproteins have been often found to be highly enriched in the serum protein coronas produced on various engineered nanoparticles (NPs), which is also known to greatly influence the behaviors of protein corona NPs in the biological systems. As most of the apolipoproteins in blood are associated with lipoproteins, it suggests the active involvement of lipoproteins in the formation of biomolecular coronas on NPs. However, the interactions of lipoprotein complexes with NPs in the corona formation have been rarely understood. In this study, to obtain insights into the interactions, the formation of biomolecular coronas of high-density lipoproteins (HDLs) on the PEGylated gold NPs (PEG-AuNPs) of various sizes (20-150 nm dia.) was investigated as a model system. The results of this study revealed a noticeable size dependence, which is a drastic increase in the affinity of HDL for larger NPs and thus less-curved NP surfaces. For example, only a few HDLs per NP, which correspond to 5% surface coverage, were found to constitute the hard coronas of HDLs on 20 nm PEG-AuNPs, whereas 73% surface coverage was assessed for larger 150 nm PEG-AuNPs. However, the relative affinities of HDL and apolipoprotein A-1 (APOA1) examined in competition with human serum albumin exhibited the opposite size dependences, which suggests that the adsorption of HDLs is not driven by the constituent protein, APOA1. In fact, the total strength of non-covalent intermolecular interactions between a HDL particle and a NP relies on the physical contact between the two particles, which thus depends on the varying curvatures of spherical NPs in this case. Therefore, it was concluded that it is whole HDL complex that interacts with the spherical PEG-AuNPs in the initial stage of adsorption toward biomolecular coronas, which is unveiled by the distinct size dependence observed in this study.

Morinda citrifolia noni water extract enhances innate and adaptive immune responses in healthy mice, ex vivo, and in vitro.

Although Morinda citrifolia (noni) has long been used in traditional medicines for human diseases, its molecular and cellular mechanism of immunostimulatory ability to improve human health under normal healthy conditions is not fully elucidated. This study aimed to investigate the in vitro and in vivo immunostimulatory activity of M. citrifolia fruit water extract treated with enzymes (Mc-eWE). In vitro studies revealed that Mc-eWE stimulated the cells by inducing nitric oxide (NO) production and the expression of inflammatory cytokines, such as interleukin (IL)-1ß, IL-6, IL-12, tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ). The immunostimulatory activity was mediated by activation of NF-κB and AP-1. Ex vivo studies showed that Mc-eWE stimulated splenocytes isolated from mice by inducing NO production and expression of immunostimulatory cytokines and by downregulating the expression of the immunosuppressive cytokine IL-10 without cytotoxicity. In vivo demonstrated that Mc-eWE induced immunostimulation by modulating populations of splenic immune cells, especially by increasing the population of IFN-γ+ NK cells. Mc-eWE enhanced the expression of inflammatory genes and immunostimulatory cytokines and inhibited the expression of IL-10 in the mouse splenocytes and sera. Taken together, these results suggest that Mc-eWE plays an immunostimulatory role by activating innate and adaptive immune responses.

Seeded Nanowire and Microwire Growth from Lithium Alloys.

Although vapor-liquid-solid (VLS) growth of nanowires from alloy seed particles is common in various semiconductor systems, related wire growth in all-metal systems is rare. Here, we report the spontaneous growth of nano- and microwires from metal seed particles during the cooling of Li-rich bulk alloys containing Au, Ag, or In. The as-grown wires feature Au-, Ag-, or In-rich metal tips and LiOH shafts; the results indicate that the wires grow as Li metal and are converted to polycrystalline LiOH during and/or after growth due to exposure to H2O and O2. This new process is a simple way to create nanostructures, and the findings suggest that metal nanowire growth from alloy seeds is possible in a variety of systems.

Antioxidant and Cytoprotective Effects of (-)-Epigallocatechin-3-(3″-O-methyl) Gallate.

Reactive oxygen species (ROS) are generated from diverse cellular processes or external sources such as chemicals, pollutants, or ultraviolet (UV) irradiation. Accumulation of radicals causes cell damage that can result in degenerative diseases. Antioxidants remove radicals by eliminating unpaired electrons from other molecules. In skin health, antioxidants are essential to protect cells from the environment and prevent skin aging. (-)-Epigallocatechin-3-(3″-O-methyl) gallate (3″Me-EGCG) has been found in limited oolong teas or green teas with distinctive methylated form, but its precise activities have not been fully elucidated. In this study, we examined the antioxidant roles of 3″Me-EGCG in keratinocytes (HaCaT cells). 3″Me-EGCG showed scavenging effects in cell and cell-free systems. Under H2O2 exposure, 3″Me-EGCG recovered cell viability and increased the expression of heme oxygenase 1 (HO-1). Under ultraviolet B (UVB) and sodium nitroprusside (SNP) exposure, 3″Me-EGCG protected keratinocytes and regulated the survival protein AKT1. By regulating the AKT1/NF-κB pathway, 3″Me-EGCG augmented cell survival and proliferation in HaCaT cells. These results indicate that 3″Me-EGCG exhibits antioxidant properties, resulting in cytoprotection against various external stimuli. In conclusion, our findings suggest that 3″Me-EGCG can be used as an ingredient of cosmetic products or health supplements.

Tabetri™ (Tabebuia avellanedae Ethanol Extract) Ameliorates Atopic Dermatitis Symptoms in Mice.

Tabebuia avellanedae has been traditionally used as an herbal remedy to alleviate various diseases. However, the plant's pharmacological activity in allergic and inflammatory diseases and its underlying mechanism are not fully understood. Therefore, we investigated the pharmacological activity of Tabetri (T. avellanedae ethanol extract (Ta-EE)) in the pathogenesis of AD. Its underlying mechanism was explored using an AD mouse model and splenocytes isolated from this model. Ta-EE ameliorated the AD symptoms without any toxicity and protected the skin of 2,4-dinitrochlorobenzene- (DNCB-) induced AD mice from damage and epidermal thickness. Ta-EE reduced the secreted levels of allergic and proinflammatory cytokines, including histamine, immunoglobulin E (IgE), interleukin- (IL-) 4, and interferon-gamma (IFN-γ) in the DNCB-induced AD mice. Ta-EE suppressed the mRNA expression of T helper 2-specific cytokines, IL-4 and IL-5, and the proinflammatory cytokine IFN-γ in the atopic dermatitis skin lesions of AD mice. Moreover, Ta-EE suppressed the mRNA expression of IL-4, IL-5, IFN-γ, and another proinflammatory cytokine, IL-12, in the Con A-stimulated splenocytes. It also suppressed IL-12 and IFN-γ in the LPS-stimulated splenocytes. Taken together, these results suggest that Ta-EE protects against the development of AD through the inhibition of mRNA expression of T helper 2-specific cytokines and other proinflammatory cytokines.

Skin Protective Effect of Epigallocatechin Gallate.

Epigallocatechin gallate (EGCG) is a catechin and an abundant polyphenol in green tea. Although several papers have evaluated EGCG as a cosmetic constituent, the skin hydration effect of EGCG is poorly understood. We aimed to investigate the mechanism by which EGCG promotes skin hydration by measuring hyaluronic acid synthase (HAS) and hyaluronidase (HYAL) gene expression and antioxidant and anti-pigmentation properties using cell proliferation assay, Western blotting analysis, luciferase assay, 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, and reverse transcription polymerase chain reaction (RT-PCR) analysis. RT-PCR showed that EGCG increased the expression of natural moisturizing factor-related genes filaggrin (FLG), transglutaminase-1, HAS-1, and HAS-2. Under UVB irradiation conditions, the expression level of HYAL was decreased in HaCaT cells. Furthermore, we confirmed the antioxidant activity of EGCG and also showed a preventive effect against radical-evoked apoptosis by downregulation of caspase-8 and -3 in HaCaT cells. EGCG reduced melanin secretion and production in melanoma cells. Together, these results suggest that EGCG might be used as a cosmetic ingredient with positive effects on skin hydration, moisture retention, and wrinkle formation, in addition to radical scavenging activity and reduction of melanin generation.

Cytoprotective Effect of Epigallocatechin Gallate (EGCG)-5'-O-α-Glucopyranoside, a Novel EGCG Derivative.

Epigallocatechin gallate (EGCG) is a well-studied polyphenol with antioxidant effects. Since EGCG has low solubility and stability, many researchers have modified EGCG residues to ameliorate these problems. A novel EGCG derivative, EGCG-5'-O-α-glucopyranoside (EGCG-5'Glu), was synthesized, and its characteristics were investigated. EGCG-5'Glu showed antioxidant effects in cell and cell-free systems. Under SNP-derived radical exposure, EGCG-5'Glu decreased nitric oxide (NO) production, and recovered ROS-mediated cell viability. Moreover, EGCG-5'Glu regulated apoptotic pathways (caspases) and cell survival molecules (phosphoinositide 3-kinase (PI3K) and phosphoinositide-dependent kinase 1 (PDK1)). In another radical-induced condition, ultraviolet B (UVB) irradiation, EGCG-5'Glu protected cells from UVB and regulated the PI3K/PDK1/AKT pathway. Next, the proliferative effect of EGCG-5'Glu was examined. EGCG-5'Glu increased cell proliferation by modulating nuclear factor (NF)-κB activity. EGCG-5'Glu protects and repairs cells from external damage via its antioxidant effects. These results suggest that EGCG-5'Glu could be used as a cosmetics ingredient or dietary supplement.

Tabetri™ (Tabebuia avellanedae Ethanol Extract) Ameliorates Osteoarthritis Symptoms Induced by Monoiodoacetate through Its Anti-Inflammatory and Chondroprotective Activities.

Although osteoarthritis (OA), a degenerative joint disease characterized by the degradation of joint articular cartilage and subchondral bones, is generally regarded as a degenerative rather than inflammatory disease, recent studies have indicated the involvement of inflammation in OA pathogenesis. Tabebuia avellanedae has long been used to treat various diseases; however, its role in inflammatory response and the underlying molecular mechanisms remain poorly understood. In this study, the pharmacological effects of Tabetri (Tabebuia avellanedae ethanol extract (Ta-EE)) on OA pathogenesis induced by monoiodoacetate (MIA) and the underlying mechanisms were investigated using experiments with a rat model and in vitro cellular models. In the animal model, Ta-EE significantly ameliorated OA symptoms and reduced the serum levels of inflammatory mediators and proinflammatory cytokines without any toxicity. The anti-inflammatory activity of Ta-EE was further confirmed in a macrophage-like cell line (RAW264.7). Ta-EE dramatically suppressed the production and mRNA expressions of inflammatory mediators and proinflammatory cytokines in lipopolysaccharide-stimulated RAW264.7 cells without any cytotoxicity. Finally, the chondroprotective effect of Ta-EE was examined in a chondrosarcoma cell line (SW1353). Ta-EE markedly suppressed the mRNA expression of matrix metalloproteinase genes. The anti-inflammatory and chondroprotective activities of Ta-EE were attributed to the targeting of the nuclear factor-kappa B (NF-κB) and activator protein-1 (AP-1) signaling pathways in macrophages and chondrocytes.

Hydroquinone suppresses IFN-ß expression by targeting AKT/IRF3 pathway.

Previous studies have demonstrated the role of hydroquinone (HQ), a hydroxylated benzene metabolite, in modulating various immune responses; however, its role in macrophage-mediated inflammatory responses is not fully understood. In this study, the role of HQ in inflammatory responses and the underlying molecular mechanism were explored in macrophages. HQ down-regulated the expression of interferon (IFN)-ß mRNA in LPS-stimulated RAW264.7 cells without any cytotoxicity and suppressed interferon regulatory factor (IRF)-3-mediated luciferase activity induced by TIR-domain-containing adapter-inducing interferon-ß (TRIF) and TANK-binding kinase 1 (TBK1). A mechanism study revealed that HQ inhibited IRF-3 phosphorylation induced by lipopolysaccharide (LPS), TRIF, and AKT by suppressing phosphorylation of AKT, an upstream kinase of the IRF-3 signaling pathway. IRF-3 phosphorylation is highly induced by wild-type AKT and poorly induced by an AKT mutant, AKT C310A, which is mutated at an inhibitory target site of HQ. We also showed that HQ inhibited IRF-3 phosphorylation by targeting all three AKT isoforms (AKT1, AKT2, and AKT3) in RAW264.7 cells and suppressed IRF-3-mediated luciferase activities induced by AKT in HEK293 cells. Taken together, these results strongly suggest that HQ inhibits the production of a type I IFN, IFN-ß, by targeting AKTs in the IRF-3 signaling pathway during macrophage-mediated inflammation.

Sizing by weighing: characterizing sizes of ultrasmall-sized iron oxide nanocrystals using MALDI-TOF mass spectrometry.

We present a rapid and reliable method for determining the sizes and size distributions of <5 nm-sized iron oxide nanocrystals (NCs) using matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometry (MS). MS data were readily converted to size information using a simple equation. The size distribution obtained from the mass spectrum is well-matched with the data from transmission electron microscopy, which requires long and tedious analysis work. The size distribution obtained from the mass spectrum is highly resolved and can detect size differences of only a few angstroms. We used this MS-based technique to investigate the formation of iron oxide NCs, which is not easy to monitor with other methods. From ex situ measurements, we observed the transition from molecular precursors to clusters and then finally to NCs.

Comparative transcriptomics reveals the role of altered energy metabolism in the establishment of single-cell C4 photosynthesis in Bienertia sinuspersici.

Single-cell C4 photosynthesis (SCC4) in terrestrial plants without Kranz anatomy involves three steps: initial CO2 fixation in the cytosol, CO2 release in mitochondria, and a second CO2 fixation in central chloroplasts. Here, we investigated how the large number of mechanisms underlying these processes, which occur in three different compartments, are orchestrated in a coordinated manner to establish the C4 pathway in Bienertia sinuspersici, a SCC4 plant. Leaves were subjected to transcriptome analysis at three different developmental stages. Functional enrichment analysis revealed that SCC4 cycle genes are coexpressed with genes regulating cyclic electron flow and amino/organic acid metabolism, two key processes required for the production of energy molecules in C3 plants. Comparative gene expression profiling of B. sinuspersici and three other species (Suaeda aralocaspica, Amaranthus hypochondriacus, and Arabidopsis thaliana) showed that the direction of metabolic flux was determined via an alteration in energy supply in peripheral chloroplasts and mitochondria via regulation of gene expression in the direction of the C4 cycle. Based on these results, we propose that the redox homeostasis of energy molecules via energy metabolism regulation is key to the establishment of the SCC4 pathway in B. sinuspersici.

Variations in metabolite profiles of serum coronas produced around PEGylated liposomal drugs by surface property.

Understanding biomolecular coronas that spontaneously occur around nanocarriers (NCs) in biological fluids is critical to nanomedicine as the coronas influence the behaviors of NCs in biological systems. In contrast to extensive investigations of protein coronas over the past decades, understanding of the coronas of biomolecules beyond proteins, e.g., metabolites, has been rather limited despite such biochemicals being ubiquitously involved in the coronas, which may influence the bio-nano interactions and thus exert certain biological impacts. In this study, serum biomolecular coronas, in particular the coronas of metabolites including lipids, around PEGylated doxorubicin-loaded liposomes with different surface property were investigated. The surface properties of liposomal drugs varied in terms of surface charge and PEGylation density by employing different ionic lipids such as DOTAP and DOPS and different concentrations of PEGylation lipids in liposome formulation. Using the liposomal drugs, the influence of the surface property on the serum metabolite profiles in the coronas was traced for target molecules of 220 lipids and 88 hydrophilic metabolites. From the results, it was found that metabolites rather than proteins mainly constitute the serum coronas on the liposomal drugs. Most of the serum metabolites were found to be retained in the coronas but with altered abundances. Depending on their class, lipids exhibited a different dependence on the surface property. However, overall, lipids appeared to favor corona formation on more negatively charged and PEGylated surfaces. Hydrophilic metabolites also exhibited a similar propensity for corona formation. This study on the surface dependence of metabolite corona formation provides a fundamental contribution toward attaining a comprehensive understanding of biomolecular coronas, which will be critical to the development of efficient nanomedicine.

Genome-wide identification of a novel Na+ transporter from Bienertia sinuspersici and overexpression of BsHKT1;2 improved salt tolerance in Brassica rapa.

Salt stress is an ever-increasing stressor that affects both plants and humans. Therefore, developing strategies to limit the undesirable effects of salt stress is essential. Sodium ion exclusion is well known for its efficient salt-tolerance mechanism. The High-affinity K+ Transporter (HKT) excludes excess Na+ from the transpiration stream. This study identified and characterized the HKT protein family in Bienertia sinuspersici, a single-cell C4 plant. The HKT and Salt Overly Sensitive 1 (SOS1) expression levels were examined in B. sinuspersici and Arabidopsis thaliana leaves under four different salt stress conditions: 0, 100, 200, and 300 mM NaCl. Furthermore, BsHKT1;2 was cloned, thereby producing stable transgenic Brassica rapa. Our results showed that, compared to A. thaliana as a glycophyte, the HKT family is expanded in B. sinuspersici as a halophyte with three paralogs. The phylogenetic analysis revealed three paralogs belonging to the HKT subfamily I. Out of three copies, the expression of BsHKT1;2 was higher in Bienertia under control and salt stress conditions than in A. thaliana. Stable transgenic plants overexpressing 35S::BsHKT1;2 showed higher salt tolerance than non-transgenic plants. Higher biomass and longer roots were observed in the transgenic plants under salt stress than in non-transgenic plants. This study demonstrates the evolutionary and functional differences in HKT proteins between glycophytes and halophytes and associates the role of BsHKT1;2 in imparting salt tolerance and productivity.

Aluminum foil negative electrodes with multiphase microstructure for all-solid-state Li-ion batteries.

Metal negative electrodes that alloy with lithium have high theoretical charge storage capacity and are ideal candidates for developing high-energy rechargeable batteries. However, such electrode materials show limited reversibility in Li-ion batteries with standard non-aqueous liquid electrolyte solutions. To circumvent this issue, here we report the use of non-pre-lithiated aluminum-foil-based negative electrodes with engineered microstructures in an all-solid-state Li-ion cell configuration. When a 30-µm-thick Al94.5In5.5 negative electrode is combined with a Li6PS5Cl solid-state electrolyte and a LiNi0.6Mn0.2Co0.2O2-based positive electrode, lab-scale cells deliver hundreds of stable cycles with practically relevant areal capacities at high current densities (6.5 mA cm-2). We also demonstrate that the multiphase Al-In microstructure enables improved rate behavior and enhanced reversibility due to the distributed LiIn network within the aluminum matrix. These results demonstrate the possibility of improved all-solid-state batteries via metallurgical design of negative electrodes while simplifying manufacturing processes.