Correlation between monosaccharide, oligosaccharide, and microbial community profile changes in traditional soybean brick (meju) fermentation.

Meju is essential for making diverse traditional fermented soybean foods in Korea. To understand the changes in carbohydrates during fermentation, we aimed to identify autochthonous microorganisms from spontaneously fermented meju and compare the alterations in monosaccharides and oligosaccharides throughout the fermentation process. Microbial diversity was determined using a metabarcoding approach, and monosaccharide and oligosaccharide profiles were obtained by HPLC-Q-TOF MS and HPLC-MS/MS analyses, respectively. The dominant bacterial genera were Weissella, Lactobacillus, and Leuconostoc, while Mucor was highly abundant in the fungal community. The total monosaccharide content increased from Day 0 to Day 50, with the highest amount being 4.37 mg/g. Oligosaccharide profiling revealed the degradation of soybean dietary fiber during fermentation, and novel oligosaccharide structures were also discovered. Correlation analysis revealed that the fungus Mucor was positively related to pentose-containing oligosaccharides, galactose, and galacturonic acid, indicating that Mucor may degrade soybean dietary fibers such as xylogalacturonan, arabinogalactan, and rhamnogalacturonan. The negative relationships between the abundances of Weissella and oligo- and monosaccharides suggested that the bacteria may utilize saccharides for fermentation. These findings provide insights into the mechanisms underlying carbohydrate degradation and utilization; the key components involved in saccharide transformation that contribute to the characteristics of traditional meju were subsequently identified.

The LKB1-TSSK1B axis controls YAP phosphorylation to regulate the Hippo-YAP pathway.

The Hippo pathway's main effector, Yes-associated protein (YAP), plays a crucial role in tumorigenesis as a transcriptional coactivator. YAP's phosphorylation by core upstream components of the Hippo pathway, such as mammalian Ste20 kinase 1/2 (MST1/2), mitogen-activated protein kinase kinase kinase kinases (MAP4Ks), and their substrate, large tumor suppressor 1/2 (LATS1/2), influences YAP's subcellular localization, stability, and transcriptional activity. However, recent research suggests the existence of alternative pathways that phosphorylate YAP, independent of these core upstream Hippo pathway components, raising questions about additional means to inactivate YAP. In this study, we present evidence demonstrating that TSSK1B, a calcium/calmodulin-dependent protein kinase (CAMK) superfamily member, is a negative regulator of YAP, suppressing cellular proliferation and oncogenic transformation. Mechanistically, TSSK1B inhibits YAP through two distinct pathways. Firstly, the LKB1-TSSK1B axis directly phosphorylates YAP at Ser94, inhibiting the YAP-TEAD complex's formation and suppressing its target genes' expression. Secondly, the TSSK1B-LATS1/2 axis inhibits YAP via phosphorylation at Ser127. Our findings reveal the involvement of TSSK1B-mediated molecular mechanisms in the Hippo-YAP pathway, emphasizing the importance of multilevel regulation in critical cellular decision-making processes.

Taxonomic Variations of Bacterial and Fungal Communities depending on Fermentation Temperature in Traditional Korean Fermented Soybean Food, Doenjang.

Meju, a fermented soybean brick, is a key component in soybean foods like doenjang and ganjang, harboring a variety of microorganisms, including bacteria and fungi. These microorganisms significantly contribute to the nutritional and sensory characteristics of doenjang and ganjang. Amplicon-based next-generation sequencing was applied to investigate how the microbial communities of meju fermented at low and high temperatures differ and how this variation affects the microbial communities of doenjang, a subsequently fermented soybean food. Our metagenomic data showed distinct patterns depending on the fermentation temperature. The microbial abundance in the bacterial community was increased under both temperatures during the fermentation of meju and doenjang. Weissella was the most abundant genus before the fermentation of meju, however, it was replaced by Bacillus at high temperature-fermented meju and lactic acid bacteria such as Weissella and Latilactobacillus at low temperature-fermented meju. Leuconostoc, Logiolactobacillus, and Tetragenococcus gradually took over the dominant role during the fermentation process of doenjang, replacing the previous dominant microorganisms. Mucor was dominant in the fungal community before and after meju fermentation, whereas Debaryomyces was dominant under both temperatures during doenjang fermentation. The dominant fungal genus of doenjang was not affected regardless of the fermentation temperature of meju. Strong correlations were shown for specific bacteria and fungi linked to specific fermentation temperatures. This study helps our understanding of meju fermentation process at different fermentation temperatures and highlights different bacteria and fungi associated with specific fermentation periods which may influence the nutritional and organoleptic properties of the final fermented soybean foods doenjang.

Ubiquitin E3 ligases in cancer: somatic mutation and amplification.

Defects in DNA double-strand break (DSB) repair signaling permit cancer cells to accumulate genomic alterations that confer their aggressive phenotype. Nevertheless, tumors depend on residual DNA repair abilities to survive the DNA damage induced by genotoxic stress. This is why only isolated DNA repair signaling is inactivated in cancer cells. DNA DSB repair signaling contributes to general mechanism for various types of lesions in diverse cell cycle phases. DNA DSB repair genes are frequently mutated and amplified in cancer; however, limited data exist regarding the overall genomic prospect and functional result of these modifications. We list the DNA repair genes and related E3 ligases. Mutation and expression frequencies of these genes were analyzed in COSMIC and TCGA. The 11 genes with a high frequency of mutation differed between cancers, and mutations in many DNA DSB repair E3 ligase genes were related to a higher total mutation burden. DNA DSB repair E3 ligase genes are involved in tumor suppressive or oncogenic functions, such as RNF168 and FBXW7, by assisting the functionality of these genomic alterations. DNA damage response-related E3 ligases, such as RNF168, FBXW7, and HERC2, were generated with more than 10% mutation in several cancer cells. This study provides a broad list of candidate genes as potential biomarkers for genomic instability and novel therapeutic targets in cancer. As a DSB related proteins considerably appear the possibilities for targeting DNA repair defective tumors or hyperactive DNA repair tumors. Based on recent research, we describe the relationship between unstable DSB repairs and DSB-related E3 ligases. [BMB Reports 2023; 56(5): 265-274].

Identification of the antibacterial action mechanism of diterpenoids through transcriptome profiling.

Effective antibacterial substances of Aralia continentalis have anti-biofilm and bactericidal activity to the oral pathogen Streptococcus mutans. In this study, three compounds extracted from A. continentalis were identified as acanthoic acid, continentalic acid, and kaurenoic acid by NMR and were further investigated how these diterpenoids affect the physiology of the S. mutans. When S. mutans was exposed to individual or mixed fraction of diterpenoids, severe growth defects and unique morphology were observed. The proportion of unsaturated fatty acids in the cell membrane was increased compared to that of saturated fatty acids in the presence of diterpenoids. Genome-wide gene expression profiles with RNA-seq were compared to reveal the mode of action of diterpenoids. Streptococcus mutans commonly enhanced the expression of 176 genes in the presence of the individual diterpenoids, whereas the expression of 232 genes was considerably reduced. The diterpenoid treatment modulated the expression of genes or operon(s) involved in cell membrane synthesis, cell division, and carbohydrate metabolism of S. mutans. Collectively, these findings provide novel insights into the antibacterial effect of diterpenoids to control S. mutans infection, which causes human dental caries.

Transcriptome Analysis of Halotolerant Staphylococcus saprophyticus Isolated from Korean Fermented Shrimp.

Saeu-jeotgal, a Korean fermented shrimp food, is commonly used as an ingredient for making kimchi and other side dishes. The high salinity of the jeotgal contributes to its flavor and inhibits the growth of food spoilage microorganisms. Interestingly, Staphylococcus saprophyticus was discovered to be capable of growth even after treatment with 20% NaCl. To elucidate the tolerance mechanism, a genome-wide gene expression of S. saprophyticus against 0%, 10%, and 20% NaCl was investigated by RNA sequencing. A total of 831, 1314, and 1028 differentially expressed genes (DEGs) were identified in the 0% vs. 10%, 0% vs. 20%, and 10% vs. 20% NaCl comparisons, respectively. The Clusters of Orthologous Groups analysis revealed that the DEGs were involved in amino acid transport and metabolism, transcription, and inorganic ion transport and metabolism. The functional enrichment analysis showed that the expression of the genes encoding mechanosensitive ion channels, sodium/proton antiporters, and betaine/carnitine/choline transporter family proteins was downregulated, whereas the expression of the genes encoding universal stress proteins and enzymes for glutamate, glycine, and alanine synthesis was upregulated. Therefore, these findings suggest that the S. saprophyticus isolated from the saeu-jeotgal utilizes different molecular strategies for halotolerance, with glutamate as the key molecule.

Effect of different ceramic materials and substructure designs on fracture resistance in anterior restorations.

STATEMENT OF PROBLEM: Materials have been developed to reduce the chipping of ceramic veneer and improve the esthetics of anterior ceramic veneered restorations. However, studies of the effects of material and substructure design on fracture resistance are sparse. PURPOSE: The purpose of this in vitro study was to investigate the fracture resistance of metal-ceramic (MC), zirconia-feldspathic porcelain (ZC), and zirconia-lithium disilicate (ZL) anterior restorations and evaluate the effect of material and substructure design. MATERIAL AND METHODS: After preparing and scanning artificial maxillary central incisor teeth, titanium abutments and restoration specimens (n=90) were fabricated. MC, ZC, and ZL materials were prepared with substructure designs A (two-third coverage of the palatal surface) and B (one-third coverage of the palatal surface). After cementation, the specimens were thermocycled (10 000 cycles, 5 and 55 °C). Fracture load measurements, failure mode analysis, energy dispersive X-ray spectroscopy (EDS), line scan analysis, fractography, finite element analysis (FEA), and Weibull analysis were performed. Two-way ANOVA was used to identify the effects of material and substructure design on fracture load. One-way ANOVA was used to identify significant differences of fracture load (α=.05). RESULTS: MC and ZL showed significantly higher fracture load than ZC (P<.05). MC_A showed a significantly higher fracture load than MC_B (P<.05). ZC_A exhibited the lowest Weibull modulus. FEA revealed that the maximum principal stress occurred near the loading area of the veneer. ZL displayed the lowest maximum principal stress among all the materials. CONCLUSIONS: ZL and MC_A exhibited more favorable fracture resistance. The substructure design of MC, with increased metal coverage of the palatal surface, improved fracture resistance significantly.

Development of a yoga posture coaching system using an interactive display based on transfer learning.

Yoga is a form of exercise that is beneficial for health, focusing on physical, mental, and spiritual connections. However, practicing yoga and adopting incorrect postures can cause health problems, such as muscle sprains and pain. In this study, we propose the development of a yoga posture coaching system using an interactive display, based on a transfer learning technique. The 14 different yoga postures were collected from an RGB camera, and eight participants were required to perform each yoga posture 10 times. Data augmentation was applied to oversample and prevent over-fitting of the training datasets. Six transfer learning models (TL-VGG16-DA, TL-VGG19-DA, TL-MobileNet-DA, TL-MobileNetV2-DA, TL-InceptionV3-DA, and TL-DenseNet201-DA) were exploited for classification tasks to select the optimal model for the yoga coaching system, based on evaluation metrics. As a result, the TL-MobileNet-DA model was selected as the optimal model, showing an overall accuracy of 98.43%, sensitivity of 98.30%, specificity of 99.88%, and Matthews correlation coefficient of 0.9831. The study presented a yoga posture coaching system that recognized the yoga posture movement of users, in real time, according to the selected yoga posture guidance and can coach them to avoid incorrect postures.

Identification and Characterization of a Novel Thermostable GDSL-Type Lipase from Geobacillus thermocatenulatus.

Two putative genes, lip29 and est29, encoding lipolytic enzymes from the thermophilic bacterium Geobacillus thermocatenulatus KCTC 3921 were cloned and overexpressed in Escherichia coli. The recombinant Lip29 and Est29 were purified 67.3-fold to homogeneity with specific activity of 2.27 U/mg and recovery of 5.8% and 14.4-fold with specific activity of 0.92 U/mg and recovery of 1.3%, respectively. The molecular mass of each purified enzyme was estimated to be 29 kDa by SDSPAGE. The alignment analysis of amino acid sequences revealed that both enzymes belonged to GDSL lipase/esterase family including conserved blocks with SGNH catalytic residues which was mainly identified in plants before. While Est29 showed high specificity toward short-chain fatty acids (C4-C8), Lip29 showed strong lipolytic activity to long-chain fatty acids (C12-C16). The optimal activity of Lip29 toward p-nitrophenyl palmitate as a substrate was observed at 50°C and pH 9.5, respectively, and its activity was maintained more than 24 h at optimal temperatures, indicating that Lip29 was thermostable. Lip29 exhibited high tolerance against detergents and metal ions. The homology modeling and substrate docking revealed that the long-chain substrates showed the greatest binding affinity toward enzyme. Based on the biochemical and in silico analyses, we present for the first time a GDSL-type lipase in the thermophilic bacteria group.

A Methodological Quality Assessment of Meta-Analysis Studies in Dance Therapy Using AMSTAR and AMSTAR 2.

Although earlier meta-analysis studies have provided evidence-based information useful for decision-making, debate regarding their quality continues. This study aimed to evaluate the quality of meta-analysis studies in the field of dance therapy (DT) using the Assessment of Multiple Systematic Reviews (AMSTAR) and AMSTAR 2 assessment tools. Meta-analysis studies on DT were collected from various databases. Seven meta-analysis studies were selected for this study. Our findings showed that the quality level of the meta-analysis studies related to DT was "High" on the AMSTAR evaluation, but their quality decreased to "Low" on the AMSTAR 2 evaluation. Moreover, using AMSTAR 2, 71.43% of the studies fell within the category of "Moderate" or below. There was no statistically significant difference in the quality scores of the characteristics of these studies. Our results suggest that (1) education on meta-analysis guidelines is required to improve the quality of DT-related meta-analysis studies, and (2) methodological caution is warranted, since different outcomes in evaluation scores for each tool may be obtained when using AMSTAR and AMSTAR 2. Based on this study, it is expected that common and specific guidelines for meta-analysis in DT can be established.

Salt Stress Response of Sulfolobus acidocaldarius Involves Complex Trehalose Metabolism Utilizing a Novel Trehalose-6-Phosphate Synthase (TPS)/Trehalose-6-Phosphate Phosphatase (TPP) Pathway.

The crenarchaeon Sulfolobus acidocaldarius has been described to synthesize trehalose via the maltooligosyltrehalose synthase (TreY) and maltooligosyltrehalose trehalohydrolase (TreZ) pathway, and the trehalose glycosyltransferring synthase (TreT) pathway has been predicted. Deletion mutant analysis of strains with single and double deletions of ΔtreY and ΔtreT in S. acidocaldarius revealed that in addition to these two pathways, a third, novel trehalose biosynthesis pathway is operative in vivo: the trehalose-6-phosphate (T6P) synthase/T6P phosphatase (TPS/TPP) pathway. In contrast to known TPS proteins, which belong to the GT20 family, the S. acidocaldarius TPS belongs to the GT4 family, establishing a new function within this group of enzymes. This novel GT4-like TPS was found to be present mainly in the Sulfolobales The ΔtreY ΔtreT Δtps triple mutant of S. acidocaldarius, which lacks the ability to synthesize trehalose, showed no altered phenotype under standard conditions or heat stress but was unable to grow under salt stress. Accordingly, in the wild-type strain, a significant increase of intracellular trehalose formation was observed under salt stress. Quantitative real-time PCR showed a salt stress-mediated induction of all three trehalose-synthesizing pathways. This demonstrates that in Archaea, trehalose plays an essential role for growth under high-salt conditions.IMPORTANCE The metabolism and function of trehalose as a compatible solute in Archaea was not well understood. This combined genetic and enzymatic approach at the interface of microbiology, physiology, and microbial ecology gives important insights into survival under stress, adaptation to extreme environments, and the role of compatible solutes in Archaea Here, we unraveled the complexity of trehalose metabolism, and we present a comprehensive study on trehalose function in stress response in S. acidocaldarius This sheds light on the general microbiology and the fascinating metabolic repertoire of Archaea, involving many novel biocatalysts, such as glycosyltransferases, with great potential in biotechnology.

A comparison of surgical outcomes between robot and laparoscopy-assisted adenomyomectomy.

We aimed to investigate the feasibility of robotic adenomyomectomy and compared surgical outcomes between laparoscopic and robotic approaches for adenomyomectomy.We retrospectively reviewed the data of women who were diagnosed with adenomyosis and underwent adenomyomectomy through a minimally invasive approach between January 2014 and March 2018 at the CHA Gangnam Medical Center, Seoul, Republic of Korea. Patient demographics and operation-related outcomes were compared between the robotic and laparoscopic surgery groups.We evaluated 43 women who underwent adenomyomectomy through a minimally invasive approach (21 underwent a laparoscopic and 22 underwent a robotic adenomyomectomy). All 22 women who had originally been scheduled to undergo robotic adenomyomectomy could successfully undergo the robotic surgery without requiring conversion to laparotomy and/or serious complications. No statistically significant differences in patient demographics were observed between the robotic and the laparoscopic surgery groups. No significant intergroup difference was observed in the operative time, estimated blood loss, weight of the resected nodule, and length of hospitalization (160.0 vs 212.5 min, P = .106; 500.0 vs 300.0 mL, P = .309; 60.0 vs 70.0 g, P = .932; and 5.0 vs 6.0 days, P = .277). No serious perioperative complications were observed in either group.Robotic adenomyomectomy is feasible for women with adenomyosis. Surgical outcomes of robotic adenomyomectomy were comparable to those of a laparoscopic approach. There was, however, no superiority of robotic adenomyomectomy in terms of surgical outcomes. Further multicenter prospective studies using standardized surgical procedures are needed to confirm the conclusion of this study.

Effect of liners and primers on tensile bond strength between zirconia and resin-based luting agent.

PURPOSE: The effect of silica-based glass-ceramic liners on the tensile bond strength between zirconia and resin-based luting agent was evaluated and compared with the effect of 10-methacryloyloxydecyl dihydrogen phosphate (MDP)-containing primers. MATERIALS AND METHODS: Titanium abutments and zirconia crowns (n = 60) were fabricated, and the adhesive surfaces of the specimens were treated by airborne-particle abrasion. The specimens were divided into 5 groups based on surface treatment: a control group, 2 primer groups (MP: Monobond Plus; ZP: Z Prime Plus), and 2 liner groups (PL: P-containing Liner; PFL: P-free Liner). All specimens were cemented with self-adhesive resin-based luting agent. After 24-hour water storage and thermocycling (5,000 cycles, 5℃/55℃), the tensile bond strength was measured using a universal testing machine. Failure mode analysis and elemental analysis on the bonding interface were performed. The data were analyzed using Kruskal-Wallis test, Dunn's post hoc test, and Fisher's exact test. RESULTS: The liner groups and primer groups showed significantly higher tensile bond strengths than that of the control group (P<.05). PFL showed a significantly higher tensile bond strength than the primer groups (P<.05). The percentage of mixed failure was higher in the primer groups than in the control group (P<.001), and all the specimens showed mixed failure in the liner groups (P<.001). A chemical reaction area was observed at the bonding interface between zirconia and liner. CONCLUSION: The application of liner significantly increased the tensile bond strength between zirconia and resin-based luting agent. PFL was more effective than MDP-containing primers in improving the tensile bond strength with the resin-based luting agent.

Analysis of gold and silver nanoparticles internalized by zebrafish (Danio rerio) using single particle-inductively coupled plasma-mass spectrometry.

With the increase in the application of nano-consumer products containing engineered nanoparticles (NPs), the unintended environmental exposure to NPs has been inevitable. Because of the bioaccumulation of NPs, concern about their potential cytotoxicity to aquatic organisms is also growing. Although measuring tools for analyzing particle size and/or concentration of NPs in intracellular uptake of tissues have been well developed, a simultaneous analysis of the two characteristics is difficult. The objective of this study was to use single particle-inductively coupled plasma-mass spectrometry (sp-ICP-MS) to measure the bioaccumulation and particle size changes of NPs exposed to zebrafish (Danio rerio) for 7 days. The uptake of NPs in the liver, intestine, and gill tissues was confirmed by electron microscopic (EM) analysis. However, the primary particle size of NPs in tissues could not be determined by the EM analysis. Therefore, sp-ICP-MS coupled with alkaline digestion was used for the easy extraction and immediate analysis of NPs from tissues. Zebrafish were exposed to four NPs (30 and 80 nm gold/silver NPs; AuNPs/AgNPs). Uptake amounts of AgNPs in the liver and intestine were significantly higher than those of AuNPs. Although larger NPs were finally accumulated in the liver and intestine tissues, most of the smaller NPs were filtered in the gills. The sp-ICP-MS method coupled with alkaline digestion enabled the accurate analysis of size, size distribution, and mass concentration of NPs in an aquatic organism.

LRRK2 functions as a scaffolding kinase of ASK1-mediated neuronal cell death.

Leucine-rich repeat kinase 2 (LRRK2), a multi-domain protein, is a key causative factor in Parkinson's disease (PD). Identification of novel substrates and the molecular mechanisms underlying the effects of LRRK2 are essential for understanding the pathogenesis of PD. In this study, we showed that LRRK2 played an important role in neuronal cell death by directly phosphorylating and activating apoptosis signal-regulating kinase 1 (ASK1). LRRK2 phosphorylated ASK1 at Thr832 that is adjacent to Thr845, which serves as an autophosphorylation site. Moreover, results of binding and kinase assays showed that LRRK2 acted as a scaffolding protein by interacting with each components of the ASK1-MKK3/6-p38 MAPK pathway through its specific domains and increasing the proximity to downstream targets. Furthermore, LRRK2-induced apoptosis was suppressed by ASK1 inhibition in neuronal stem cells derived from patients with PD. These results clearly indicate that LRRK2 acts as an upstream kinase in the ASK1 pathway and plays an important role in the pathogenesis of PD.

Parkin mediates neuroprotection through activation of Notch1 signaling.

Parkin, an E3 ubiquitin ligase, is the most frequently mutated gene in hereditary Parkinson's disease. Inactivation of Parkin leads to impairment of the ubiquitin-proteasome system, resulting in the accumulation of misfolded or aggregated proteins and ensuing neurodegeneration. In this study, we show that Parkin positively regulates the Notch1 signaling pathway. Overexpression of Parkin stabilized Notch1-IC protein levels, whereas knockdown of Parkin decreased Notch1-IC protein stability. Notably, overexpression of Parkin disrupted oxidative stress-induced apoptosis in neuronal cells. However, knockdown of Notch1 inhibited Parkin-induced neuronal cell survival. Together, these results indicate that Parkin is a novel regulator of the Notch1 signaling pathway, which promotes neuronal cell survival.

Characterization of silver nanoparticle aggregates using single particle-inductively coupled plasma-mass spectrometry (spICP-MS).

The single particle-inductively coupled plasma-mass spectrometry was applied to characterize the aggregates of AgNPs. was applied to characterize the aggregates of AgNPs. Two sizes of citrate-AgNPs and PVP-AgNPs were used at relatively high and predicted environmental concentrations under various ionic strengths. Citrate-AgNP aggregated with increases in the ionic strength, whereas PVP-AgNPs were sterically stable. The critical coagulation concentrations were 85 mM and 100 mM NaNO3 for 60 nm and 100 nm citrate-AgNPs at 2 mg L-1 as total Ag obtained by dynamic light scattering (DLS). At 2 mg L-1 as total Ag, the mass of an aggregate gradually increased with increasing ionic strength for both citrate-AgNP during spICP-MS analyses. The average number of single particles derived from the mass in an aggregate was calculated to be 8.68 and 5.95 for 60 nm and 100 nm citrate-AgNPs at 85 mM and 100 mM NaNO3, respectively after 2 h. The mass fractal dimensions were determined to be 2.97 and 2.83, further implying that the aggregate structures were very rigid and compact. Only marginal increases in the average mass and number of single particles in the aggregate units were found during 24 h under environmentally relevant AgNP concentrations. The average number of single particles constituting an aggregate unit for 60 nm and 100 nm citrate-AgNPs was 1.24 and 1.37 after 24 h at a high ionic strength. These results indicate that under environmentally relevant conditions, the collision frequency is predominant in the aggregation and that NPs are likely to encounter natural colloids such as clay and organic matter to form hetero-aggregates.

Reproductive and Developmental Toxicity Screening Test of Ethyl Hydrogen Adipate in Rats.

This study aimed to evaluate the potential toxicity and safety of ethyl hydrogen adipate (EHA) by determining its effect on the reproductive function and development of Sprague-Dawley (SD) rats at dose levels of 0 (control), 200, 400, and 800 mg/kg/day. One male and five females of the 800 mg/kg/day died. Body weight loss was observed in the males of the 800 mg/kg/day and in females of the 400 and 800 mg/kg/day. In addition, mating indices decreased and pre-implantation loss rates increased in parental animals of the 400 and 800 mg/kg/day. The gestation index decreased in the male and female rats of the 800 mg/kg/day. Moreover, the body weight of the pups from the 800 mg/kg/day group decreased on post-parturition day 4. These results indicated that the no-observed-adverse-effect level of EHA for parental males and females was 400 mg/kg/day and 200 mg/kg/day, respectively, and that for pups was 400 mg/kg/day.

Autophagy negatively regulates tumor cell proliferation through phosphorylation dependent degradation of the Notch1 intracellular domain.

Autophagy is a highly conserved mechanism that degrades long-lived proteins and dysfunctional organelles, and contributes to cell fate. In this study, autophagy attenuates Notch1 signaling by degrading the Notch1 intracellular domain (Notch1-IC). Nutrient-deprivation promotes Notch1-IC phosphorylation by MEKK1 and phosphorylated Notch1-IC is recognized by Fbw7 E3 ligase. The ubiquitination of Notch1-IC by Fbw7 is essential for the interaction between Notch1-IC and p62 and for the formation of aggregates. Inhibition of Notch1 signaling prevents the transformation of breast cancer cells, tumor progression, and metastasis. The expression of Notch1 and p62 is inversely correlated with Beclin1 expression in human breast cancer patients. These results show that autophagy inhibits Notch1 signaling by promoting Notch1-IC degradation and therefore plays a role in tumor suppression.

Developmental toxicity of intravenously injected zinc oxide nanoparticles in rats.

Recent toxicity studies of zinc oxide nanoparticles by oral administration showed relatively low toxicity, which may be resulted from low bioavailability. So, the intrinsic toxicity of zinc oxide nanoparticles needs to be evaluated in the target organs by intravenous injection for full systemic concentration of the administered dosage. Although the exposure chance of injection route is low compared to oral and/or inhalation route, it is important to see the toxicity with different exposure routes to get better risk management tool. In this study, the effects of zinc oxide nanoparticles on dams and fetuses were investigated in rats after intravenous injection (5, 10, and 20 mg/kg) from gestation day 6 to 20. Two of 20 dams in the 20 mg/kg treatment group died during the treatment period. Hematological examination and serum biochemistry showed dose-dependent toxicity in treated dams. Histopathological analysis of treated dams revealed multifocal mixed cell infiltration and thrombosis in lung, tubular dilation in kidneys, and extramedullary hemopoiesis in liver. Total dead fetuses (post-implantation loss) were increased and the body weight of fetus was decreased in the 20 mg/kg treatment group. Statistical differences in corpora lutea, resorption, placental weight, morphological alterations including external, visceral and skeletal malformations were not observed in treated groups. Based on the data, lowest observed adverse effect level of injection route was suggested to be 5 mg/kg in dams and no observed adverse effect level was suggested to be 10 mg/kg in fetal developmental toxicity.