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Cryptosporidium and Giardia duodenalis are common gastrointestinal protozoan parasites that cause diarrhea in humans and animals. Although dogs in animal shelters in South Korea can be reintroduced into human society as companions, no continuous investigations have been conducted on the prevalence and genetic characteristics of the protozoan parasites. In the present study, 345 fecal samples from dogs were obtained from animal shelters in six provinces between January and December 2022. The prevalence of Cryptosporidium and G. duodenalis were molecularly identified at the 18S rRNA gene. Cryptosporidium canis isolates were subtyped at the gp60 locus, and G. duodenalis assemblages were identified at the tpi, bg and gdh loci. Overall, 6.67% of the fecal samples tested positive for Cryptosporidium spp. and two species were identified: C. canis (5.51%) and Cryptosporidium parvum (1.16%). Significant regional differences in prevalence were identified for C. canis. Subtyping analysis of C. canis isolates revealed a predominance of the subtype families XXa and XXe over XXb, and XXc. G. duodenalis was detected in 17.68% of the samples, and significant regional differences were identified; its prevalence was also significantly highest in diarrhoeic animals. Molecular characterization of G. duodenalis reveal that most isolates belonged to the canine-specific assemblages C and D. The present results can contribute to further insights into the prevalence and genotypes of Cryptosporidium and G. duodenalis in shelter dogs in South Korea., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Nocardia farcinica is an opportunistic bacterium that causes bovine mastitis and pulmonary, cutaneous, and central nervous system infections in humans. Bovine abortion caused by N. farcinica has been sporadically reported. The purpose of this study was to analyze the pathological findings of bovine abortions caused by N. farcinica in the Republic of Korea and determine the antimicrobial resistance and genotypical characteristics of N. farcinica isolates., Case Presentation: Three cases of bovine abortions were submitted to the Animal and Plant Quarantine Agency for differential diagnosis. Grossly, one fetus showed severe lung consolidation following palpation of the entire lobes. Histologically, necrotizing granulomatous interstitial pneumonia was observed in all fetuses; a fetus with a gross lesion demonstrated necrotizing lymphadenitis in the mesenteric lymph nodes and necrotizing dermatitis in the ear. N. farcinica isolates were isolated from the abomasal contents and lungs of all fetuses. Finally, two cases were diagnosed as abortions due to N. farcinica , and one was diagnosed as an N. farcinica abortion coinfected with bovine viral diarrhea virus. According to the multilocus sequence analysis, all isolates were identified as N. farcinica and were determined to be genetically related to isolates from humans. Two N. farcinica isolates were resistant to trimethoprim-sulfamethoxazole, which is recommended as the first treatment for human nocardial infections., Conclusion: This is the first pathological report of bovine abortion caused by N. farcinica in the Republic of Korea. Further studies are needed to phenotypically and genotypically characterize N. farcinica isolates with various sources and continuously monitor antimicrobial resistance patterns., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kim, Yun, Bae, Lee, Moon, Lee, Jeoung, Ku and Kim.)

Summary: The design of two overlapping genes in a microbial genome is an emerging technique for adding more reliable control mechanisms in engineered organisms for increased stability. The design of functional overlapping gene pairs is a challenging procedure, and computational design tools are used to improve the efficiency to deploy successful designs in genetically engineered systems. GENTANGLE (Gene Tuples ArraNGed in overLapping Elements) is a high-performance containerized pipeline for the computational design of two overlapping genes translated in different reading frames of the genome. This new software package can be used to design and test gene entanglements for microbial engineering projects using arbitrary sets of user-specified gene pairs., Availability and Implementation: The GENTANGLE source code and its submodules are freely available on GitHub at https://github.com/BiosecSFA/gentangle. The DATANGLE (DATA for genTANGLE) repository contains related data and results and is freely available on GitHub at https://github.com/BiosecSFA/datangle. The GENTANGLE container is freely available on Singularity Cloud Library at https://cloud.sylabs.io/library/khyox/gentangle/gentangle.sif. The GENTANGLE repository wiki (https://github.com/BiosecSFA/gentangle/wiki), website (https://biosecsfa.github.io/gentangle/), and user manual contain detailed instructions on how to use the different components of software and data, including examples and reproducing the results. The code is licensed under the GNU Affero General Public License version 3 (https://www.gnu.org/licenses/agpl.html)., (Published by Oxford University Press 2024.)

Cell culture-based screening of a chemical library identified diphenoxylate as an antiviral agent against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The observed 50% effective concentrations ranged between 1.4 and 4.9 µM against the original wild-type strain and its variants. Time-of-addition experiments indicated that diphenoxylate is an entry blocker targeting a host factor involved in viral infection. Fluorescence microscopic analysis visualized that diphenoxylate prevented SARS-CoV-2 particles from penetrating the cell membrane and also impaired endo-lysosomal acidification. Diphenoxylate exhibited a synergistic inhibitory effect on SARS-CoV-2 infection in human lung epithelial Calu-3 cells when combined with a transmembrane serine protease 2 (TMPRSS2) inhibitor, nafamostat. This synergy suggested that efficient antiviral activity is achieved by blocking both TMPRSS2-mediated early and endosome-mediated late SARS-CoV-2 entry pathways. The antiviral efficacy of diphenoxylate against SARS-CoV-2 was reproducible in a human tonsil organoids system. In a transgenic mouse model expressing the obligate SARS-CoV-2 receptor, human angiotensin-converting enzyme 2, intranasal administration of diphenoxylate (10 mg/kg/day) significantly reduced the viral RNA copy number in the lungs by 70% on day 3. This study underscores that diphenoxylate represents a promising core scaffold, warranting further exploration for chemical modifications aimed at developing a new class of clinically effective antiviral drugs against SARS-CoV-2.

C-C motif chemokine ligand 2 (CCL2) has been reported to be expressed in the bovine endometrium during pregnancy. However, the details of its functions involved in the implantation mechanism are still not clear. The purpose of this study is to analyze the functional properties of CCL2 in the bovine endometrium and embryos. The expression of CCR2 was not different between the luteal phase and implantation phase of their endometrial tissues, but was significantly high in IFNa treated bovine endometrial stromal (BES) cells in vitro. The expressions of PGES1, PGES2, AKR1C4, and AKR1C4 were high at the implantation stage compared with the luteal stage. On the other hand, PGES2 and AKR1B1 in BEE and PGES3 and AKR1A1 in BES were significantly increased by CCL2 treatment, respectively. The expressions of PCNA and IFNt were found significantly high in the bovine trophoblastic cells (BT) treated with CCL2 compared to the control. CCL2 significantly increased the attachment rate of BT vesicles to BEE in in vitro co-culture system. The expression of OPN and ICAM-1 increased in BEE, and ICAM-1 increased in BT by CCL2 treatment, respectively. The present results indicate that CCL2 has the potential to regulate the synthesis of PGs in the endometrium and the embryo growth. In addition, CCL2 has the possibility to regulate the process of bovine embryo attachment to the endometrium by modulation of binding molecules expression., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

A strictly anaerobic, Gram-stain-negative, catalase-negative, cocci-shaped, and propionate-producing bacterial strain, named Ds1651 T was isolated from the fecal sample collected from a South Korean infant. Through a comparison of 16S rRNA gene sequences, it was revealed that Ds1651 T had the highest phylogenetic affinity with Veillonella nakazawae KCTC 25297  T (99.86%), followed by Veillonella infantium KCTC 25370  T (99.80%), and Veillonella dispar KCTC 25309  T (99.73%) in the family Veillonellaceae. Average nucleotide identity values between Ds1651 T and three reference species were 95.48% for Veillonella nakazawae KCTC 25297  T , 94.46% for Veillonella infantium KCTC 25370  T , and 92.81% for Veillonella dispar KCTC 25309  T . The G + C content of Ds1651 T was 38.58 mol%. Major fermentation end-products were acetic and propionic acids in Trypticase peptone glucose yeast extract broth with 1% (v/v) sodium lactate. The predominant cellular fatty acids that account for more than 10% were summed in Feature 8 (C 17:1 ω8c and/or C 17:2 ) and C 13:0 . Based on the findings from phylogenetic, genomic, phenotypic, and chemotaxonomic studies, we propose that the type strain Ds1651 T (= KCTC 25477  T  = GDMCC 1.3707  T ) represents a novel bacterial species within the genus Veillonella, with the proposed name Veillonella faecalis sp. nov., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Chemical methods for the extraction and refinement of technologically critical rare earth elements (REEs) are energy-intensive, hazardous, and environmentally destructive. Current biobased extraction systems rely on extremophilic organisms and generate many of the same detrimental effects as chemical methodologies. The mesophilic methylotrophic bacterium Methylobacterium extorquens AM1 was previously shown to grow using electronic waste by naturally acquiring REEs to power methanol metabolism. Here we show that growth using electronic waste as a sole REE source is scalable up to 10 L with consistent metal yields without the use of harsh acids or high temperatures. The addition of organic acids increases REE leaching in a nonspecific manner. REE-specific bioleaching can be engineered through the overproduction of REE-binding ligands (called lanthanophores) and pyrroloquinoline quinone. REE bioaccumulation increases with the leachate concentration and is highly specific. REEs are stored intracellularly in polyphosphate granules, and genetic engineering to eliminate exopolyphosphatase activity increases metal accumulation, confirming the link between phosphate metabolism and biological REE use. Finally, we report the innate ability of M. extorquens to grow using other complex REE sources, including pulverized smartphones, demonstrating the flexibility and potential for use as a recovery platform for these critical metals.

Background: Blinatumomab is an immunotherapy agent used in pediatric oncology for the treatment of B-lineage acute lymphoblastic leukemia. Administration of blinatumomab, via continuous 28-day infusion cycles, can present multiple decision points and challenges related to patient care. Nurses are at the forefront of coordinating and delivering care for patients receiving blinatumomab., Objective: To describe the current state of practice across Children's Oncology Group (COG) member institutions regarding blinatumomab administration in both inpatient and home/outpatient settings., Methods: Between August and December 2021, a cross-sectional survey was used to determine current institutional practices related to blinatumomab administration. A single targeted respondent who was actively engaged in coordinating blinatumomab administration completed the survey on behalf of each COG institution., Results: Survey participation rate was 78% (150/192). During the first 28-day blinatumomab cycle, 71 institutions (53%) reported patient hospital stays between 73 hours and 7 days; 42 (31%) reported hospital stays ≤72 hours, and only 12 (9%) reported hospitalization for the full 28-day infusion. Small- to medium-size institutions were more likely to report longer hospitalizations (P = .03). Most blinatumomab administration occurred in the outpatient setting, with low rates of unplanned clinic/emergency room visits., Conclusions: The majority of COG institutions have navigated the complex coordination of care required for children to receive blinatumomab at home. Wide variations in practice were noted across institutions., Implications for Practice: This study describes current institutional practices surrounding administration of 28-day blinatumomab infusions in children with leukemia and offers a starting point for institutional benchmarking and standardization of practice., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Cryptosporidium , Cystoisospora , and Giardia duodenalis are gastrointestinal protozoa parasites that cause diarrhea in various animals. However, information regarding the detection and phylogenetic characterization of gastrointestinal protozoa parasites in cats is limited throughout South Korea. Therefore, this study aimed to determine the detection and identify subspecies of gastrointestinal protozoa parasites in cats from South Korea., Methods: A total of 290 fecal samples were collected from stray, companion, and shelter cats in six provinces. Cryptosporidium , Cystoisospora , and G. duodenalis were identified by PCR. All positive samples were subtyped by PCR and sequencing of gp60 , ITS-1 , tpi , bg , and gdh ., Results: The overall detection of gastrointestinal protozoan parasitic infection was 17.93%. G. duodenalis was the most prevalent, with 7.93%, followed by Cystoisospora spp. (7.24%) and Cryptosporidium spp. (4.48%). In addition, C. felis (n=10), C. parvum (n=2), C. ryanae (n=1), Cystoisospora felis (n=14), Cystoisospora suis (n=5), Cystoisospora ohioensis (n=1), Cystoisospora spp. were identified in subspecies analysis of positive samples. C. felis showed a significant association with diarrhea (7.81%) and living condition (6.04%), and Cystoisospora felis in diarreha (9.38%) according to detection. Through phylogenetic analysis of the tpi, bg, and gdh genes from 23 G. duodenalispositive samples, it was confirmed that the samples of present study belonged to assemblage A, B, C, and D., Discussion: South Korean cats have a high rate of gastrointestinal protozoan parasites infection with cat-specific Cryptosporidium and Cystoisospora, which are associated with living conditions and diarrhea symptoms. Moreover, zoonotic and other animal-specific subtype of protozoan parasites have been detected in cat feces., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yun, Moon, Lee, Kang, Ku and Hwang.)

Although numerous studies highlight the health benefits of tea, excessive consumption has been linked to toxic conditions. Thus, understanding the optimal consumption of tea is essential to minimize toxicity while maximizing its benefits. In this study, we investigated the effects of eight green tea samples (G1-G8) and eight black tea samples (R1-R8) from Camellia sinensis , the most popular teas in Asian culture, on RSC96 Schwann neural cells and embryonic cardiomyocyte H9c2 cells. The results showed that the IC 50 (mg/ml, weight/volume) of both tea types were inversely proportional to their polyphenol content, suggesting a relationship between toxicity and polyphenol levels in both green and black tea. Interestingly, green teas generally have higher polyphenol content than black teas. We also assessed the protective effects of tea in vitro by pretreating cells with the teas at indicated doses of polyphenol and subsequently exposing them to H 2 O 2 . Both tea types significantly reduced the decline in cell viability for both cell lines, and there was no significant difference in protective polyphenol concentrations for green (G3 & G7) and black (R3 & R8) teas at effective concentrations (EC20 and EC40). To evaluate the preventative effects of tea in vivo , we examined the impact of two green (G3 & G7) and two black (R3 & R8) teas with varying polyphenol content on dextran sulfate sodium (DSS)-induced inflammatory colitis in mice. Tea-treated groups exhibited significantly lower inflammatory scores (DAI) than the control group. DSS treatment in the control group led to shortened colorectal lengths in mice, while tea co-treatment partially prevented this loss. Histological analysis revealed that G7 and R3 (with a moderate polyphenol content) treatment improved colorectal crypt structure, decreased the severity of inflammatory ulcerative colitis, and significantly reduced histological scores compared to the control group. However, G3 and R8 (with high and low doses of polyphenol content, respectively) did not show these effects, suggesting that a moderate polyphenol level in both tea types is optimal for preventative benefits., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

The cell surface adsorption and intracellular uptake of mercuric mercury Hg(II) and methylmercury (MeHg) are important in determining the fate and transformation of Hg in the environment. However, current information is limited about their interactions with two important groups of microorganisms, i.e., methanotrophs and Hg(II)-methylating bacteria, in aquatic systems. This study investigated the adsorption and uptake dynamics of Hg(II) and MeHg by three strains of methanotrophs, Methylomonas sp. strain EFPC3, Methylosinus trichosporium OB3b, and Methylococcus capsulatus Bath, and two Hg(II)-methylating bacteria, Pseudodesulfovibrio mercurii ND132 and Geobacter sulfurreducens PCA. Distinctive behaviors of these microorganisms towards Hg(II) and MeHg adsorption and intracellular uptake were observed. The methanotrophs took up 55-80% of inorganic Hg(II) inside cells after 24 h incubation, lower than methylating bacteria (>90%). Approximately 80-95% of MeHg was rapidly taken up by all the tested methanotrophs within 24 h. In contrast, after the same time, G. sulfurreducens PCA adsorbed 70% but took up <20% of MeHg, while P. mercurii ND132 adsorbed <20% but took up negligible amounts of MeHg. These results suggest that microbial surface adsorption and intracellular uptake of Hg(II) and MeHg depend on the specific types of microbes and appear to be related to microbial physiology that requires further detailed investigation. Despite being incapable of methylating Hg(II), methanotrophs play important roles in immobilizing both Hg(II) and MeHg, potentially influencing their bioavailability and trophic transfer. Therefore, methanotrophs are not only important sinks for methane but also for Hg(II) and MeHg and can influence the global cycling of C and Hg., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Immunologists have activated T cells in vitro using various stimulation methods, including phorbol myristate acetate (PMA)/ionomycin and αCD3/αCD28 agonistic antibodies. PMA stimulates protein kinase C, activating nuclear factor-κB, and ionomycin increases intracellular calcium levels, resulting in activation of nuclear factor of activated T cell. In contrast, αCD3/αCD28 agonistic antibodies activate T cells through ZAP-70, which phosphorylates linker for activation of T cell and SH2-domain-containing leukocyte protein of 76 kD. However, despite the use of these two different in vitro T cell activation methods for decades, the differential effects of chemical-based and antibody-based activation of primary human T cells have not yet been comprehensively described. Using single-cell RNA sequencing (scRNA-seq) technologies to analyze gene expression unbiasedly at the single-cell level, we compared the transcriptomic profiles of the non-physiological and physiological activation methods on human peripheral blood mononuclear cell-derived T cells from four independent donors. Remarkable transcriptomic differences in the expression of cytokines and their respective receptors were identified. We also identified activated CD4 T cell subsets (CD55+) enriched specifically by PMA/ionomycin activation. We believe this activated human T cell transcriptome atlas derived from two different activation methods will enhance our understanding, highlight the optimal use of these two in vitro T cell activation assays, and be applied as a reference standard when analyzing activated specific disease-originated T cells through scRNA-seq.

Technologically critical rare-earth elements are notoriously difficult to separate, owing to their subtle differences in ionic radius and coordination number 1-3 . The natural lanthanide-binding protein lanmodulin (LanM) 4,5 is a sustainable alternative to conventional solvent-extraction-based separation 6 . Here we characterize a new LanM, from Hansschlegelia quercus (Hans-LanM), with an oligomeric state sensitive to rare-earth ionic radius, the lanthanum(III)-induced dimer being >100-fold tighter than the dysprosium(III)-induced dimer. X-ray crystal structures illustrate how picometre-scale differences in radius between lanthanum(III) and dysprosium(III) are propagated to Hans-LanM's quaternary structure through a carboxylate shift that rearranges a second-sphere hydrogen-bonding network. Comparison to the prototypal LanM from Methylorubrum extorquens reveals distinct metal coordination strategies, rationalizing Hans-LanM's greater selectivity within the rare-earth elements. Finally, structure-guided mutagenesis of a key residue at the Hans-LanM dimer interface modulates dimerization in solution and enables single-stage, column-based separation of a neodymium(III)/dysprosium(III) mixture to >98% individual element purities. This work showcases the natural diversity of selective lanthanide recognition motifs, and it reveals rare-earth-sensitive dimerization as a biological principle by which to tune the performance of biomolecule-based separation processes., (© 2023. The Author(s).)

This study aimed to investigate the pathogenicity of extraintestinal pathogenic Escherichia coli (ExPEC) isolated from dog and cat lung samples in South Korea. A total of 101 E. coli isolates were analyzed for virulence factors, phylogroups, and O-serogroups, and their correlation with bacterial pneumonia-induced mortality was elucidated. P fimbriae structural subunit (papA), hemolysin D (hlyD), and cytotoxic necrotizing factor 1 (cnf1) were highly prevalent in both species, indicating correlation with bacterial pneumonia. Phylogroups B1 and B2 were the most prevalent phylogroups (36.6% and 32.7%, respectively) and associated with high bacterial pneumonia-induced mortality rates. Isolates from both species belonging to phylogroup B2 showed high frequency of papA, hlyD, and cnf1. O-serogrouping revealed 21 and 15 serogroups in dogs and cats, respectively. In dogs, O88 was the most prevalent serogroup (n = 8), and the frequency of virulence factors was high for O4 and O6. In cats, O4 was the most prevalent serogroup (n = 6), and the frequency of virulence factors was high for O4 and O6. O4 and O6 serogroups were mainly grouped under phylogroup B2 and associated with high bacterial pneumonia-induced mortality. This study characterized the pathogenicity of ExPEC and described the probability of ExPEC pneumonia-induced mortality., (© 2023. The Author(s).)

A novel Gram-stain-negative, aerobic, rod-shaped, non-motile, cream-coloured strain (G124 T ) was isolated from ginseng soil collected in Yeongju, Republic of Korea. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain G124 T belongs to a distinct lineage within the genus Sphingomonas (family Sphingomonadaceae , order Sphingomonadales and class Alphaproteobacteria ). Strain G124 T was closely related to Sphingomonas rhizophila THG-T61 T (98.5 % 16S rRNA gene sequence similarity), Sphingomonas mesophila SYSUP0001 T (98.3 %), Sphingomonas edaphi DAC4 T (97.6 %) and Sphingomonas jaspsi TDMA-16 T (97.6 %). The strain contained ubiquinone 10 as the major respiratory quinone. The major polar lipid profile of strain G124 T comprised phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine and sphingoglycolipids. The predominant cellular fatty acids of strain G124 T were summed feature 8 (C 18 : 1  ω 7 c /C 18 : 1  ω 6 c ; 33.4 %), summed feature 3 (C 16 : 1  ω 6 c /C 16 : 1  ω 7 c ; 27.2 %) and C 16 : 0 (18.3 %). The genome size of strain G124 T was 2 549 305 bp. The genomic DNA G+C content is 62.0 mol%. The average nucleotide identity and digital DNA-DNA hybridization values between strain G124 T and other Sphingomonas species were in the range of 71.2-75.9 % and 18.7-19.9 %, respectively. Based on the polyphasic analysis such as biochemical, phylogenetic and chemotaxonomic characteristics, strain G124 T represents a novel species of the genus Sphingomonas , for which the name Sphingomonas cremea sp. nov. is proposed. The type strain is G124 T (=KACC 21691 T =LMG 31729 T ).

Proteasome inhibitors with γ-lactam structure, such as lactacystin and salinosporamide A, have been isolated from actinomycetes and have attracted attention as lead compounds for anticancer drugs. Previously, we identified a unique enzyme TAS1, which is the first reported fungal NRPS-PKS hybrid enzyme, from the filamentous fungus Pyricularia oryzae for the biosynthesis of a mycotoxin tenuazonic acid, a tetramic acid compound without γ-lactam structure. Homologues of TAS1 have been identified in several fungal genomes and classified into four groups (A-D). Here, we show that the group D TAS1 homologues from two filamentous fungi can biosynthesize γ-lactam compounds, taslactams A-D, with high similarity to actinomycete proteasome inhibitors. One of the γ-lactam compounds, taslactam C, showed potent proteasome inhibitory activity. In contrast to actinomycete γ-lactam compounds which require multiple enzymes for biosynthesis, the TAS1 homologue alone was sufficient for the biosynthesis of the fungal γ-lactam compounds.

A Gram-negative, obligate anaerobic, non-motile, non-spore-forming, rod-shaped bacterial strain designated AGMB00274 T was isolated from swine faeces. An 16S rRNA gene analysis indicated that strain AGMB00274 T belonged to the genus Parabacteroides, with the highest similarity to Parabacteroides johnsonii (P. johnsonii) DSM 18315 T (sequence similarity of 94.9%). The genome size of strain AGMB00274 T was 4,308,683 bp, with a DNA G+C content of 42.5 mol%. The biochemical analysis of strain AGMB00274 T showed that it was positive for gelatin hydrolysis and α-fucosidase, but negative for the acid production from D-glucose, D-mannitol, D-maltose, salicin, glycerol, D-cellobiose, D-mannose, D-melezitose, D-sorbitol, D-trehalose, and negative for α-arabinosidase, glutamic acid decarboxylase, and pyroglutamic acid arylamidase. The dominant cellular fatty acids (> 10%) of the isolate were anteiso-C 15: 0 (23.2%), iso-C 15: 0 (16.6%), C 18: 1 ω9c (16.4%), summed feature 11 (iso-C 17: 0 3-OH and/or C 18: 2 DMA) (12.5%), and C 16: 0 (11.3%). The major respiratory quinones of strain AGMB00274 T were MK-9 (55.4%) and MK-10 (44.6%). The major polar lipid was phosphatidylethanolamine. Based on phylogenetic, genetic, physiological, and chemotaxonomic analyses, as a novel species of the genus Parabacteroides, strain AGMB00274 T was proposed with the name Parabacteroides faecalis sp. nov. The type strain used was AGMB00274 T (= KCTC 25286 T  = GDMCC 1.2742 T )., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The aim of this study was to design an image restoration algorithm that combined denoising and deblurring and to confirm its applicability in positron emission tomography (PET) images of patients with Alzheimer's disease (AD). PET images of patients with AD obtained using 18 F-AV-45, which have a lot of noise, and 18 F-FDG, which have a lot of blurring, were available in the Alzheimer's Disease Neuroimaging Initiative open dataset. The proposed framework performed image restoration incorporating blind deconvolution after noise reduction using a non-local means (NLM) approach to improve the PET image quality. We found that the coefficient of variation result after denoising and deblurring of the 18 F-AV-45 image was improved 1.34 times compared to that for the degraded image. In addition, the profile result of the 18 F-FDG PET image of patients with AD, which had a relatively large amount of blurring, showed a gentle shape when deblurring was performed after denoising. The overall no-reference-based evaluation results showed different results according to the degree of noise and blurring in the PET images. In conclusion, the applicability of the deconvolution deblurring algorithm to AD PET images after NLM denoising processing was demonstrated in this study., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

The genome of Methylocystis sp. strain SB2, which was previously isolated from a spring bog in southeast Michigan, was sequenced using long-read sequencing technology. This new sequencing and assembly effort yielded a complete assembly of the genome in a single contig.

The acute stress response is a natural and fundamental reaction that balances the physiological conditions of the brain. To maintain homeostasis in the brain, the response is based on changes over time in hormones and neurotransmitters, which are related to resilience and can adapt successfully to acute stress. This increases the need for dynamic analysis over time, and new approaches to examine the relationship between metabolites have emerged. This study investigates whether the constructed metabolic network is a realistic or a random network and is affected by acute stress. While the metabolic network in the control group met the criteria for small-worldness at all time points, the metabolic network in the stress group did not at some time points, and the small-worldness had resilience after the fifth time point. The backbone metabolic network only met the criteria for small-worldness in the control group. Additionally, creatine had lower local efficiency in the stress group than the control group, and for the backbone metabolic network, creatine and glutamate were lower and higher in the stress group than the control group, respectively. These findings provide evidence of metabolic imbalance that may be a pre-stage of alterations to brain structure due to acute stress., (© 2022. The Author(s).)

Alzheimer's disease (AD) is the most common progressive neurodegenerative disease. 18 F-fluorodeoxyglucose positron emission tomography ( 18 F-FDG PET) is widely used to predict AD using a deep learning model. However, the effects of noise and blurring on 18 F-FDG PET images were not considered. The performance of a classification model trained using raw, deblurred (by the fast total variation deblurring method), or denoised (by the median modified Wiener filter) 18 F-FDG PET images without or with cropping around the limbic system area using a 3D deep convolutional neural network was investigated. The classification model trained using denoised whole-brain 18 F-FDG PET images achieved classification performance (0.75/0.65/0.79/0.39 for sensitivity/specificity/F1-score/Matthews correlation coefficient (MCC), respectively) higher than that with raw and deblurred 18 F-FDG PET images. The classification model trained using cropped raw 18 F-FDG PET images achieved higher performance (0.78/0.63/0.81/0.40 for sensitivity/specificity/F1-score/MCC) than the whole-brain 18 F-FDG PET images (0.72/0.32/0.71/0.10 for sensitivity/specificity/F1-score/MCC, respectively). The 18 F-FDG PET image deblurring and cropping (0.89/0.67/0.88/0.57 for sensitivity/specificity/F1-score/MCC) procedures were the most helpful for improving performance. For this model, the right middle frontal, middle temporal, insula, and hippocampus areas were the most predictive of AD using the class activation map. Our findings demonstrate that 18 F-FDG PET image preprocessing and cropping improves the explainability and potential clinical applicability of deep learning models.

Methanobactins (MBs) are ribosomally synthesized and posttranslationally modified peptides (RiPPs) produced by methanotrophs for copper uptake. The posttranslational modification that defines MBs is the formation of two heterocyclic groups with associated thioamines from X-Cys dipeptide sequences. Both heterocyclic groups in the MB from Methylosinus trichosporium OB3b (MB-OB3b) are oxazolone groups. The precursor gene for MB-OB3b is mbnA , which is part of a gene cluster that contains both annotated and unannotated genes. One of those unannotated genes, mbnC , is found in all MB operons and, in conjunction with mbnB , is reported to be involved in the formation of both heterocyclic groups in all MBs. To determine the function of mbnC , a deletion mutation was constructed in M. trichosporium OB3b, and the MB produced from the Δ mbnC mutant was purified and structurally characterized by UV-visible absorption spectroscopy, mass spectrometry, and solution nuclear magnetic resonance (NMR) spectroscopy. MB-OB3b from the Δ mbnC mutant was missing the C-terminal Met and was also found to contain a Pro and a Cys in place of the pyrrolidinyl-oxazolone-thioamide group. These results demonstrate MbnC is required for the formation of the C-terminal pyrrolidinyl-oxazolone-thioamide group from the Pro-Cys dipeptide, but not for the formation of the N-terminal 3-methylbutanol-oxazolone-thioamide group from the N-terminal dipeptide Leu-Cys. IMPORTANCE A number of environmental and medical applications have been proposed for MBs, including bioremediation of toxic metals and nanoparticle formation, as well as the treatment of copper- and iron-related diseases. However, before MBs can be modified and optimized for any specific application, the biosynthetic pathway for MB production must be defined. The discovery that mbnC is involved in the formation of the C-terminal oxazolone group with associated thioamide but not for the formation of the N-terminal oxazolone group with associated thioamide in M. trichosporium OB3b suggests the enzymes responsible for posttranslational modification(s) of the two oxazolone groups are not identical.

Copper is an important component of methanotrophic physiology, as it controls the expression and activity of alternative forms of methane monooxygenase (MMO). To collect copper, some methanotrophs secrete a chalkophore- or copper-binding compound called methanobactin (MB). MB is a ribosomally synthesized posttranslationally modified polypeptide (RiPP) that, after binding copper, is collected by MbnT, a TonB-dependent transporter (TBDT). Structurally different forms of MB have been characterized, and here, we show that different forms of MB are collected by specific TBDTs. Further, we report that in the model methanotroph, Methylosinus trichosporium OB3b, expression of the TBDT required for uptake of a different MB made by Methylocystis sp. strain SB2 (MB-SB2) is induced in the presence of MB-SB2, suggesting that methanotrophs have developed specific machinery and regulatory systems to actively take up MB from other methanotrophs for copper collection. Moreover, the canonical "copper switch" in M. trichosporium OB3b that controls expression of alternative MMOs is apparent if one of the two TBDTs required for MB-OB3b and MB-SB2 uptake is knocked out, but is disrupted if both TBDTs are knocked out. These data indicate that MB uptake, including the uptake of exogenous MB, plays an important role in the copper switch in M. trichosporium OB3b and, thus, overall activity. Based on these data, we propose a revised model for the copper switch in this methanotroph that involves MB uptake. IMPORTANCE In this study, we demonstrate that different TBDTs in the model methanotroph Methylosinus trichosporium OB3b are responsible for uptake of either endogenous MB or exogenous MB. Interestingly, the presence of exogenous MB induces expression of its specific TBDT in M. trichosporium OB3b, suggesting that this methanotroph is able to actively take up MB produced by others. This work contributes to our understanding of how microbes collect and compete for copper and also helps inform how such uptake coordinates the expression of different forms of methane monooxygenase. Such studies are likely to be very important to develop a better understanding of methanotrophic interactions via synthesis and secretion of secondary metabolites such as methanobactin and thus provide additional means whereby these microbes can be manipulated for a variety of environmental and industrial purposes.

Aerobic methanotrophy is strongly controlled by copper, and methanotrophs are known to use different mechanisms for copper uptake. Some methanotrophs secrete a modified polypeptide-methanobactin-while others utilize a surface-bound protein (MopE) and a secreted form of it (MopE*) for copper collection. As different methanotrophs have different means of sequestering copper, competition for copper significantly impacts methanotrophic activity. Herein, we show that Methylomicrobium album BG8, Methylocystis sp. strain Rockwell, and Methylococcus capsulatus Bath, all lacking genes for methanobactin biosynthesis, are not limited for copper by multiple forms of methanobactin. Interestingly, Mm. album BG8 and Methylocystis sp. strain Rockwell were found to have genes similar to mbnT that encodes for a TonB-dependent transporter required for methanobactin uptake. Data indicate that these methanotrophs "steal" methanobactin and such "theft" enhances the ability of these strains to degrade methylmercury, a potent neurotoxin. Further, when mbnT was deleted in Mm. album BG8, methylmercury degradation in the presence of methanobactin was indistinguishable from when MB was not added. Mc. capsulatus Bath lacks anything similar to mbnT and was unable to degrade methylmercury either in the presence or absence of methanobactin. Rather, Mc. capsulatus Bath appears to rely on MopE/MopE* for copper collection. Finally, not only does Mm. album BG8 steal methanobactin, it synthesizes a novel chalkophore, suggesting that some methanotrophs utilize both competition and cheating strategies for copper collection. Through a better understanding of these strategies, methanotrophic communities may be more effectively manipulated to reduce methane emissions and also enhance mercury detoxification in situ., (© 2021. The Author(s), under exclusive licence to International Society for Microbial Ecology.)

Little is known about the modulatory capacity of the microbiota in early intestinal development. We examined various intestinal models that respond to gut microbial metabolites based on human pluripotent stem cell-derived human intestinal organoids (hIOs): physiologically relevant in vitro fetal-like intestine, intestinal stem cell, and intestinal disease models. We found that a newly isolated Limosilactobacillus reuteri strain DS0384 accelerated maturation of the fetal intestine using 3D hIO with immature fetal characteristics. Comparative metabolomic profiling analysis revealed that the secreted metabolite N-carbamyl glutamic acid (NCG) is involved in the beneficial effect of DS0384 cell-free supernatants on the intestinal maturation of hIOs. Experiments in an intestinal stem cell spheroid model and hIO-based intestinal inflamed model revealed that the cell-free supernatant from DS0384 comprising NCG promoted intestinal stem cell proliferation and was important for intestinal protection against cytokine-induced intestinal epithelial injury. The probiotic properties of DS0384 were also evaluated, including acid and bile tolerance and ability to adhere to human intestinal cells. Seven-day oral administration of DS0384 and cell-free supernatant promoted the intestinal development of newborn mice. Moreover, NCG exerted a protective effect on experimental colitis in mice. These results suggest that DS0384 is a useful agent for probiotic applications and therapeutic treatment for disorders of early gut development and for preventing intestinal barrier dysfunction.

Filamentous fungi have many secondary metabolism genes and produce a wide variety of secondary metabolites with complex and unique structures. However, the role of most secondary metabolites remains unclear. Moreover, most fungal secondary metabolism genes are silent or poorly expressed under laboratory conditions and are difficult to utilize. Pyricularia oryzae, the causal pathogen of rice blast disease, is a well-characterized plant pathogenic fungus. P. oryzae also has a large number of secondary metabolism genes and appears to be a suitable organism for analyzing secondary metabolites. However, in case of this fungus, biosynthetic genes for only four groups of secondary metabolites have been well characterized. Among two of the four groups of secondary metabolites, biosynthetic genes were identified by activating secondary metabolism. These secondary metabolites include melanin, a polyketide compound required for rice infection; tenuazonic acid, a well-known mycotoxin produced by various plant pathogenic fungi and biosynthesized by a unique nonribosomal peptide synthetase-polyketide synthase hybrid enzyme; nectriapyrones, antibacterial polyketide compounds produced mainly by symbiotic fungi, including plant pathogens and endophytes, and pyriculols, phytotoxic polyketide compounds. This review mainly focuses on the biosynthesis and biological functions of the four groups of P. oryzae secondary metabolites., (© The Author(s) 2021. Published by Oxford University Press on behalf of Society of Industrial Microbiology and Biotechnology.)

Tenuazonic acid (TeA) is a toxin produced by the rice blast fungus Pyricularia oryzae. Although knockout of the TeA biosynthetic gene TAS1 did not affect the virulence of P. oryzae, constitutive TAS1 expression suppressed its infection. TAS1 expression was induced alongside transition of P. oryzae infection behavior. The results suggested that controlling TeA biosynthesis is important for P. oryzae infection., (© The Author(s) 2021. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

A Gram-stain-negative, non-motile, non-spore-forming, aerobic, rod-shaped and yellow-pigmented bacterium, designated strain Gsoil 183 T , was isolated from ginseng-cultivation soil sampled in Pocheon Province, Republic of Korea. This bacterium was characterized to determine its taxonomic position by using a polyphasic approach. Strain Gsoil 183 T grew at 10-37 °C and at pH 5.0-9.0 on tryptic soy agar. Strain Gsoil 183 T had β -glucosidase activity, which was responsible for its ability to convert ginsenoside Rb1 (one of the dominant active components of ginseng) to F2. Based on 16S rRNA gene sequencing, strain Gsoil 183 T clustered with species of the genus Chryseobacterium and appeared to be closely related to Chryseobacterium sediminis LMG 28695 T (99.1 % sequence similarity), Chryseobacterium lactis NCTC 11390 T (98.6%), Chryseobacterium rhizoplanae LMG 28481 T (98.6%), Chryseobacterium oncorhynchi CCUG 60105 T (98.5%), Chryseobacterium viscerum CCUG 60103 T (98.4%) and Chryseobacterium joostei DSM 16927 T (98.3%). Menaquinone MK-6 was the predominant respiratory quinone and the major fatty acids were iso-C 15 : 0 , iso-C 17 : 0 -3OH and summed feature 3 (C 16 : 1  ω 6 c and/or C 16 : 1  ω 7 c ). The polar lipids were phosphatidylethanolamine, six unidentified glycolipids, five unidentified aminolipids and three unidentified lipids. The G+C content of the genomic DNA was 36.6 mol%. Digital DNA-DNA hybridization between strain Gsoil 183 T and the type strains of C. sediminis , C. lactis , C. rhizoplanae , C. oncorhynchi , C. viscerum and C. joostei resulted in values below 70 %. Strain Gsoil 183 T could be differentiated genotypically and phenotypically from the recognized species of the genus Chryseobacterium . The isolate therefore represents a novel species, for which the name Chryseobacterium panacisoli sp. nov. is proposed, with the type strain Gsoil 183 T (=KACC 15033 T =LMG 23397 T ).

Glandular epithelial cells (GE) in the endometrium are thought to support the elongation and survival of ruminant embryos by secreting histotrophs. In the present study, the gene expression of bovine endometrial epithelial cells cultured in matrigel was analyzed and examined whether it could be an in vitro model of GE. Bovine endometrial epithelial cells (BEE) and stromal cells (BES) were isolated from the slaughterhouse uteri and cultured in DMEM/F12 + 10% FBS. BEE showed the gland-like structure morphological changes when cultured in 15% matrigel but could not be identified in higher concentrations of the matrigel (30% or 60%). The expression of typical genes expressed in GE, SERPINA14 and GRP, was substantially high in matrigel-cultured BEE than in monolayer (P  <  0.05). P4 and INFα have no significant effect on the SERPINA14 expression of BEE cultured in matrigel without co-culture with BES. On the other hand, when BEE were co-cultured with BES in matrigel culture, the expression of FGF13 was increased by the P4 treatment (P  <  0.05). Furthermore, SERPINA14 and TXN expressions were increased by P4 + IFNα treatment (P  <  0.05). These results demonstrate the appropriate conditions for BEE to form glandular structures in matrigel and the effect of co-culture with BES. The present study highlighted the possible use of matrigel for the culture of BEE to investigate the expression of cell-specific glandular epithelial genes as well as P4 and type-I IFN as factors controlling endometrial function during the implantation period., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Ceramics are non-metallic inorganic materials fabricated from natural or high-purity raw materials through heating and cooling processes. Urethane is a three-dimensional plastic with both elasticity and chemical resistance; moreover, it is used as a rubber substitute. The use of both materials in various applications is gradually increasing. However, as ceramics and urethane have distinctly different properties, this prompted questions regarding the properties of a material that is fabricated using both materials. Therefore, we studied the characteristics of a composite material fabricated through physical foaming using a batch process. The process was conducted with gas saturation, foaming, cooling, and curing. When a specimen of 2 mm thickness was saturated in 5 MPa of CO 2 for 2 h, the solubility was 6.43%; when foaming was carried out at a temperature of 150 °C in boiled glycerin, the foaming ratio, cell size, cell density, and void fraction were found to be 43.62%, 24.40 µm, 9.1 × 10⁷ cells/cm 2 , and 22.11%, respectively. Furthermore, the volume increased by 102.96%, color changed from dark to light gray, hardness decreased by 24%, thermal diffusivity increased by 0.046 mm 2 /s at 175 °C, and friction coefficient decreased to 0.203. Thus, the microcellular foamed ceramic urethane exhibits a larger volume, lighter weight, and improved thermal conductivity and friction coefficient.

The genomes of Methylomonas sp. strain EFPC1 and Methylococcus sp. strain EFPC2, isolated from a mercury-contaminated stream in Oak Ridge, Tennessee, were sequenced., (Copyright © 2021 Kang-Yun et al.)

Interferon tau (IFNT) is thought to have essential functions in maternal recognition and establishment of pregnancy in ruminants. There, however, is a lack of research on embryonic factors that affect pregnancy other than IFNT. The present study was conducted to determine what are other embryo-derived factors involved in pregnancy recognition and to identify effects on endometrial cells using an in vitro culture system. With use of LC-MS/MS procedures to evaluate the supernatant of elongating embryos of cattle in culture, there was detection of 78 secretary proteins including five cytokines and two growth factors. Then there was analysis for up-regulated genes using ingenuity pathway procedure, IFNT and MIF were identified as upstream regulators of 37 and five genes, respectively. The mRNA transcript of MIF receptors was identified in endometrial cells, however, not in embryos. Among genes induced by MIF, CCL2, IL7 and IL23A transcripts were identified in endometrial cells. When endometrial cells were treated with interferon alpha (IFNA) and MIF, the CCL2 transcript was in a larger abundance of endometrial epithelial and polymorphonuclear neutrophil cells, and there was a larger abundance of there mRNA transcripts as a result of MIF treatment of peripheral blood mononuclear cells. In conclusion, MIF secreted by elongating embryos of cattle synergistically regulates relative abundances of specific mRNA transcripts of endometrial cells when there is treatment with IFNA, indicating further there are several factors other than IFNT that have effects on gene expression in the endometrium during early stages of gestation in cattle., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Mutations in the isocitrate dehydrogenase 1 (IDH1) gene are frequently found in various cancer types. IDH1 mutants produce 2-hydroxyglutarate (2-HG), an oncometabolite, from alpha-ketoglutarate (α-KG). This 2-HG plays a key role in tumorigenesis via inhibition of α-KG dependent enzymes. For this reason, IDH1 mutant could be an ideal target for the treatment of cancer., Materials and Methods: To find a new IDH1 inhibitor, 8,364 compounds were obtained from Korea Chemical Bank. Using high-throughput screening (HTS) of a chemical library, we unveiled a compound that could inhibit the IDH1 mutant., Results: According to the enzyme assay, our compound (KRC-09) effectively inhibited the activity of IDH1 R132H mutant. In addition, KRC-09 decreased the concentration of intracellular 2-HG in the U-87 MG cell line harboring IDH1 R132H., Conclusion: In this article, we present a novel chemical scaffold that suppresses the activity of an IDH1 mutant., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Many microbial secondary metabolites are produced by multienzyme complexes comprising nonribosomal peptide synthetases (NRPSs) and polyketide synthases (PKSs). The ketosynthase (KS) domains of polyketide synthase normally catalyze the decarboxylative Claisen condensation of acyl and malonyl blocks to extend the polyketide chain. However, the terminal KS domain in tenuazonic acid synthetase 1 (TAS1) from the fungus Pyricularia oryzae conducts substrate cyclization. Here, we report on the unique features of the KS domain in TAS1. We observed that this domain is monomeric, not dimeric as is typical for KSs. Analysis of a 1.68-Å resolution crystal structure suggests that the substrate cyclization is triggered via proton abstraction from the active methylene moiety in the substrate by a catalytic His-322 residue. Additionally, we show that TAS1 KS promiscuously accepts aminoacyl substrates and that this promiscuity can be increased by a single amino acid substitution in the substrate-binding pocket of the enzyme. These findings provide insight into a KS domain that accepts the amino acid-containing substrate in an NRPS-PKS hybrid enzyme and provide hints to the substrate cyclization mechanism performed by the KS domain in the biosynthesis of the mycotoxin tenuazonic acid., Competing Interests: Conflict of interest—The authors declare that they have no conflicts of interest with the contents of this article., (© 2020 Yun et al.)

Background: Epidermoid cysts are benign tumors derived from the infundibular portion of hair follicles and thus have a flattened surface epithelium and keratohyaline granules. They can occur at any age but are most frequently reported in adults, and more often occur in men than women. Most epidermoid cyst operations are performed for cosmetic purposes, or to relieve inflammation. The definitive treatment is complete excision or destruction of the cyst. The aim of this study was to improve understanding of epidermoid cysts., Methods: We analyzed 432 cases of epidermoid cyst in 398 patients that underwent complete excision and biopsy between April 2001 and March 2020, according to patient age, patient gender, and lesion location., Results: From all epidermoid cyst excisions performed, 17.6% were for patients in their 40s and 50s, 16.8% for those in their 20s, 16.1% for those in their 30s, 14.6% for those aged 60 or older, 5.0% for teenagers, and 0.5% for those under 10 years. Cases of epidermoid cysts occurred at a men-to-women ratio of about 3:2, with 59.5% of cases in men and 40.5% in women. By lesion location, 65.0% of cases were on the face, 10.9% on the trunk, 7.9% on the scalp, 7.9% on the neck, 4.3% on lower extremities, 3.9% on upper extremities, and 0.2% on genitalia. On the face, 20.8% of cases were on the cheek, 12.7% on the periauricular area, 10.9% on the periorbital area, 6.0% on the frontal area, 5.6% on the mental area, 3.7% on the perioral area, 2.8% on the nasal area, and 2.5% on the temporal area., Conclusion: The proportion of women with epidermoid cysts was higher in our study than in previous studies. Moreover, the results showed that surgery has been on the rise in recent years, with facial surgery being the most common.

A Gram stain negative, motile, non-spore-forming, rod-shaped, strictly aerobic, beige-pigmented bacterium, designated strain BO-7 T , was isolated from soil of cattle farm, in Seosan, Republic of Korea. On the basis of 16S rRNA gene sequencing, strain BO-7 T clustered with species of the genus Ochrobactrum and appeared closely related to O. haematophilum CCUG 38531 T (98.9%), O. daejeonense KCTC 22458 T (98.1%), O. rhizosphaerae DSM 19824 T (98.1%), O. pituitosum DSM 22207 T (98.0%), and O. pecoris DSM 23868 T (98.0%). The digital DNA-DNA hybridization and average nucleotide identity between strain BO-7 T and the closely related strains were 21.9-39.1%, 78.5-89.5%, respectively, indicating that BO-7 T is a novel species of the genus Ochrobactrum. The DNA G + C content of the genomic DNA was 57.1 mol%, and ubiquinone Q-10 was the predominant respiratory quinone. The polar lipids consisted of phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, phosphatidylmonomethyl-ethanolamine, di-phosphatidylglycerol, the major polyamines were spermidine, putrescine, and sym-homospermidine. The major cellular fatty acids (> 5%) were C 16:0 , C 19:0 cycle ω7c, and C 18:1 ω7c and/or C 18:1 ω6c (summed feature 8). ANI calculation, digital DNA-DNA hybridization, physiological and biochemical characteristics indicated that strain BO-7 T represents a novel species of the genus Ochrobactrum, for which the name Ochrobactrum soli sp. nov. is proposed. The type strain is BO-7 T (= KACC 19676 T  = LMG 30809 T ).

Shrinkage and warpage of injection-molded parts can be minimized by applying microcellular foaming technology to the injection molding process. However, unlike the conventional injection molding process, the optimal conditions of the microcellular foam injection molding process are elusive because of core differences such as gas injection. Therefore, this study aims to derive process conditions to minimize the shrinkage and warpage of microcellular foam injection-molded parts made of glass fiber reinforced polyamide 6 (PA6/GF). Process factors and levels were first determined, with experiments planned accordingly. We simulated designed experiments using injection molding analysis software, and the results were analyzed using the Taguchi method, analysis of variance (ANOVA), and response surface methodology (RSM), with the ANOVA analysis being ultimately demonstrating the influence of the factors. We derived and verified the optimal combination of process factors and levels for minimizing both shrinkage and warpage using the Taguchi method and RSM. In addition, the mechanical properties and cell morphology of PA6/GF, which change with microcellular foam injection molding, were confirmed., Competing Interests: The authors declare no conflict of interest.

Aerobic methane-oxidizing bacteria of the Alphaproteobacteria have been found to express a novel ribosomally synthesized post-translationally modified polypeptide (RiPP) termed methanobactin (MB). The primary function of MB in these microbes appears to be for copper uptake, but MB has been shown to have multiple capabilities, including oxidase, superoxide dismutase and hydrogen peroxide reductase activities, the ability to detoxify mercury species, as well as acting as an antimicrobial agent. Herein, we describe the diversity of known MBs as well as the genetics underlying MB biosynthesis. We further propose based on bioinformatics analyses that some methanotrophs may produce novel forms of MB that have yet to be characterized. We also discuss recent findings documenting that MBs play an important role in controlling copper availability to the broader microbial community, and as a result can strongly affect the activity of microbes that require copper for important enzymatic transformations, e.g. conversion of nitrous oxide to dinitrogen. Finally, we describe procedures for the detection/purification of MB, as well as potential medical and industrial applications of this intriguing RiPP., (© FEMS 2020.)

We investigated the shape-recovery characteristics of thermoplastic polyurethane (TPU) with a microcellular foaming process (MCP). Additionally, we investigated the correlation between changes in the microstructure and the shape-recovery characteristics of the polymers. TPU was selected as the base material, and the shape-recovery characteristics were confirmed using a universal testing machine, by manufacturing dog-bone-type injection-molded specimens. TPUs are reticular polymers with both soft and hard segments. In this study, we investigated the shape-memory mechanism of foamed polymers by maximizing the shape-memory properties of these polymers through a physical foaming process. Toward this end, TPU specimens were prepared by varying the gas pressure, foaming temperature, and type of foaming gas in the batch MCP. The effects of internal structural changes were investigated. These experimental variables affected the microstructure and shape-recovery characteristics of the foamed polymer. The generated cell density changed, which affected the shape-recovery characteristics. In general, a higher cell density corresponded to a higher shape-recovery ratio.

Hepatitis B virus (HBV) remains a major health concern with 260 million people having been infected globally, and approximately 680,000 deaths have occurred annually from cirrhosis and liver cancer. The modulation of HBV capsid assembly has emerged as a promising therapeutic approach for curing chronic HBV infection. Small-molecule capsid assembly modulators (CAMs) can broadly be classified as heteroaryldihydropyrimidines and sulfamoylbenzamides (SBAs). SBAs are capsid activators that inhibit viral replication by achieving capsid assembly before polymerase encapsulation. Herein, we report a novel series of HBV CAMs based on NVR 3-778 , a potent CAM belonging to the SBA class. The lead compound ( KR-26556 ) exhibited improved pharmacological activity and was examined through molecular docking studies., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

NAD + synthetase is an essential enzyme of de novo and recycling pathways of NAD + biosynthesis in Mycobacterium tuberculosis but not in humans. This bifunctional enzyme couples the NAD + synthetase and glutaminase activities through an ammonia tunnel but free ammonia is also a substrate. Here we show that the Homo sapiens NAD + synthetase (hsNadE) lacks substrate specificity for glutamine over ammonia and displays a modest activation of the glutaminase domain compared to tbNadE. We report the crystal structures of hsNadE and NAD + synthetase from M. tuberculosis (tbNadE) with synthetase intermediate analogues. Based on the observed exclusive arrangements of the domains and of the intra- or inter-subunit tunnels we propose a model for the inter-domain communication mechanism for the regulation of glutamine-dependent activity and NH 3 transport. The structural and mechanistic comparison herein reported between hsNadE and tbNadE provides also a starting point for future efforts in the development of anti-TB drugs.

Because juvenile hormone (JH) controls insect development and its analogs are used as insecticides, juvenile hormone disruptors (JHDs) represent potential sources from which novel pesticides can be developed. Many plant species harbor JHD activity, which has previously been attributed plant secondary metabolites (i.e., diterpenes) that disrupt insect development by interfering with the JH-mediated heterodimer formation of insect juvenile receptor complexes. The results of the present study indicate that plant JHD activity is also concentrated in certain plant groups and families and that plant metabolites have insect group-specific activity. These findings suggest that reciprocal diversification has occurred between plants and insects through the evolution of the plant metabolites and JH receptors, respectively, and that plant metabolites could be developed into insect group-specific pesticides with limited effects on non-target species.

Bromodomain-containing protein 4 (Brd4) is known to play a key role in tumorigenesis. It binds acetylated histones to regulate the expression of numerous genes. Because of the importance of brd4 in tumorigenesis, much research has been undertaken to develop brd4 inhibitors with therapeutic potential. As a result, various scaffolds for bromodomain inhibitors have been identified. To discover new scaffolds, we performed mid-throughput screening using two different enzyme assays, alpha-screen and ELISA. We found a novel bromodomain inhibitor with a unique scaffold, aristoyagonine. This natural compound showed inhibitory activity in vitro and tumor growth inhibition in a Ty82-xenograft mouse model. In addition, we tested Brd4 inhibitors in gastric cancer cell lines, and found that aristoyagonine exerted cytotoxicity not only in I-BET-762-sensitive cancer cells, but also in I-BET-762-resistant cancer cells. This is the first paper to describe a natural compound as a Brd4 bromodomain inhibitor., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Tenuazonic acid (TeA) is a mycotoxin produced by the rice blast fungus Pyricularia oryzae and some plant pathogenic fungi. We previously demonstrated that TeA is biosynthesized in P. oryzae by TeA synthetase 1 (TAS1) and that its production is induced by osmo-sensory MAPK-encoding gene (OSM1) deletion or the addition of 1% DMSO to cultures; however, the regulatory mechanisms of TeA production were unknown. Here, we identify a Zn(II) 2 -Cys 6 -type transcription factor in the upstream region of TAS1, which is encoded by TAS2 and regulates TeA production. We also find PoLAE1, which is a homologue of LaeA, a regulator of fungal secondary metabolism. Analysis of PoLAE1 deletion and overexpression strains indicate that PoLAE1 drives TeA production. We also demonstrate that two TeA-inducing signals, 1% DMSO addition and OSM1 deletion, were transmitted through PoLAE1. Our results indicate that TeA production is regulated by two specific regulators, TAS2 and PoLAE1, in P. oryzae.

The objective of this study was to evaluate the permeability of small molecules into the brain via the blood-brain barrier in zebrafish and to investigate the possibility of using this animal model as a screening tool during the early stages of drug discovery. Fifteen compounds were used to understand the permeation into the brain in zebrafish and mice. The ratio of brain-to-plasma concentration was compared between the two animal models. The partition coefficient (K p,brain ), estimated using the concentration ratio at designated times (0.167, 0.25, 0.5, or 2 h) after oral administrations (per os, p.o), ranged from 0.099 to 5.68 in zebrafish and from 0.080 to 11.8 in mice. A correlation was observed between the K p,brain values obtained from the zebrafish and mice, suggesting that zebrafish can be used to estimate K p,brain to predict drug penetration in humans. Furthermore, in vivo transport experiments to understand the permeability glycoprotein (P-gp) transporter-mediated behavior of loperamide (LPM) in zebrafish were performed. The zebrafish, K p,brain,30min of LPM was determined to be 0.099 ± 0.069 after dosing with LPM alone, which increased to 0.180 ± 0.115 after dosing with LPM and tariquidar (TRQ, an inhibitor of P-gp). In mouse, the K p,brain,30min of LPM was determined to be 0.080 ± 0.004 after dosing with LPM alone and 0.237 ± 0.013 after dosing with LPM and TRQ. These findings indicate that the zebrafish could be used as an effective screening tool during the discovery stages of new drugs to estimate their distribution in the brain.

Diterpene resin acids (DRAs) are important components of oleoresin and greatly contribute to the defense strategies of conifers against herbivorous insects. In the present study, we determined that DRAs function as insect juvenile hormone (JH) antagonists that interfere with the juvenile hormone-mediated binding of the JH receptor Methoprene-tolerant (Met) and steroid receptor coactivator (SRC). Using a yeast two-hybrid system transformed with Met and SRC from the Indian meal moth Plodia interpunctella, we tested the interfering activity of 3704 plant extracts against JH III-mediated Met-SRC binding. Plant extracts from conifers, especially members of the Pinaceae, exhibited strong interfering activity, and four active interfering DRAs (7α-dehydroabietic acid, 7-oxodehydroabietic acid, dehydroabietic acid, and sandaracopimaric acid) were isolated from roots of the Japanese pine Pinus densiflora. The four isolated DRAs, along with abietic acid, disrupted the juvenile hormone-mediated binding of P. interpunctella Met and SRC, although only 7-oxodehydroabietic acid disrupted larval development. These results demonstrate that DRAs may play a defensive role against herbivorous insects via insect endocrine-disrupting activity.

In this study, a series of novel 2,4-diaminopyrimidines bearing fused tricyclic ring moiety was described for ALK inhibitor. The pyrazole, imidazole, 1,2,4-triazole, piperazine and phenanthridine moieties were employed at the 2-position of pyrimidine. Among the compounds synthesized, 28, 29, 36, and 42 showed promising anti-ALK activities in enzymatic- and cell-based assays. In vivo H3122 xenograft model study showed that compound 29 effectively suppressed ALK-driven tumor growth, similar to the extent of ceritinib, suggesting that it could be used for a novel ALK inhibitor development., (Copyright © 2017. Published by Elsevier Ltd.)