Radiosensitizing effect of a novel CTSS inhibitor by enhancing BRCA1 protein stability in triple-negative breast cancer cells.

Triple-negative breast cancer (TNBC) patients harboring wild-type breast cancer susceptibility gene 1 (BRCA1) account for most TNBC patients but lack adequate targeted therapeutic options. Although radiotherapy (RT) is the primary treatment modality for TNBC patients, radioresistance is one of the major challenges. RT-induced increase in cathepsin S (CTSS) causes radioresistance through suppressing BRCA1-mediated apoptosis of tumor cells, which was induced by CTSS-mediated degradation of BRCA1. Targeting CTSS may provide a novel therapeutic opportunity for TNBC patients. Publicly available data and human tissue microarray slides were analyzed to investigate the relationship between CTSS and BRCA1 in breast cancer patients. A CTSS enzyme assay and in silico docking analysis were conducted to identify a novel CTSS inhibitor. RO5461111 was used first to confirm the concept of targeting CTSS for radiosensitizing effects. The MDA-MB-231 TNBC cell line was used for in vitro and in vivo assays. Western blotting, promoter assay, cell death assay, clonogenic survival assay, and immunohistochemistry staining were conducted to evaluate novel CTSS inhibitors. CTSS inhibitors were further evaluated for their additional benefit of inhibiting cell migration. A novel CTSS inhibitor, TS-24, increased BRCA1 protein levels and showed radiosensitization in TNBC cells with wild-type BRCA1 and in vivo in a TNBC xenograft mouse model. These effects were attributed by BRCA1-mediated apoptosis facilitated by TS-24. Furthermore, TS-24 demonstrated the additional effect of inhibiting cell migration. Our study suggests that employing CTSS inhibitors for the functional restoration of BRCA1 to enhance RT-induced apoptosis may provide a novel therapeutic opportunity for TNBC patients harboring wild-type BRCA1.

Significance of Soy-Based Fermented Food and Their Bioactive Compounds Against Obesity, Diabetes, and Cardiovascular Diseases.

Soybean-based fermented foods are commonly consumed worldwide, especially in Asia. These fermented soy-products are prepared using various strains of Bacillus, Streptococcus, Lactobacillus, and Aspergillus. The microbial action during fermentation produces and increases the availability of various molecules of biological significance, such as isoflavones, bioactive peptides, and dietary fiber. These dietary bio active compounds are also found to be effective against the metabolic disorders such as obesity, diabetes, and cardiovascular diseases (CVD). In parallel, soy isoflavones such as genistein, genistin, and daidzin can also contribute to the anti-obesity and anti-diabetic mechanisms, by decreasing insulin resistance and oxidative stress. The said activities are known to lower the risk of CVD, by decreasing the fat accumulation and hyperlipidemia in the body. In addition, along with soy-isoflavones fermented soy foods such as Kinema, Tempeh, Douchi, Cheonggukjang/Chungkukjang, and Natto are also rich in dietary fiber (prebiotic) and known to be anti-dyslipidemia, improve lipolysis, and lowers lipid peroxidation, which further decreases the risk of CVD. Further, the fibrinolytic activity of nattokinase present in Natto soup also paves the foundation for the possible cardioprotective role of fermented soy products. Considering the immense beneficial effects of different fermented soy products, the present review contextualizes their significance with respect to their anti-obesity, anti-diabetic and cardioprotective roles.

Dietary regulations for microbiota dysbiosis among post-menopausal women with type 2 diabetes.

Type 2 diabetes (T2D) and T2D-associated comorbidities, such as obesity, are serious universally prevalent health issues among post-menopausal women. Menopause is an unavoidable condition characterized by the depletion of estrogen, a gonadotropic hormone responsible for secondary sexual characteristics in women. In addition to sexual dimorphism, estrogen also participates in glucose-lipid homeostasis, and estrogen depletion is associated with insulin resistance in the female body. Estrogen level in the gut also regulates the microbiota composition, and even conjugated estrogen is actively metabolized by the estrobolome to maintain insulin levels. Moreover, post-menopausal gut microbiota is different from the pre-menopausal gut microbiota, as it is less diverse and lacks the mucolytic Akkermansia and short-chain fatty acid (SCFA) producers such as Faecalibacterium and Roseburia. Through various metabolites (SCFAs, secondary bile acid, and serotonin), the gut microbiota plays a significant role in regulating glucose homeostasis, oxidative stress, and T2D-associated pro-inflammatory cytokines (IL-1, IL-6). While gut dysbiosis is common among post-menopausal women, dietary interventions such as probiotics, prebiotics, and synbiotics can ease post-menopausal gut dysbiosis. The objective of this review is to understand the relationship between post-menopausal gut dysbiosis and T2D-associated factors. Additionally, the study also provided dietary recommendations to avoid T2D progression among post-menopausal women.

Design, synthesis, and biological evaluation of novel HSP27 inhibitors to sensitize lung cancer cells to clinically available anticancer agents.

Expression of heat shock protein (HSP) correlates with the oncogenic status of malignant cells and plays an important role in tumorigenesis. HSP27 is constitutively expressed at specific stages of cancer development, and several clinical trials have reported correlations between HSP27 expression and tumor progression, metastasis, and chemoresistance in various types of cancer cells. These findings indicate that HSP27 is a major drug target, particularly in chemo-resistant cancers. As part of our ongoing efforts to improve the previously identified J2, a HSP27 cross-linker, we, in this study, report the identification of NK16 as a novel inducer of abnormal HSP27 dimers that did not affect the expression of HSP90 in an NCI-H460 lung cancer cell model. When NCI-H460 cells were treated with NK16 in combination with the anticancer drug cisplatin or paclitaxel, cleavage of PARP and caspase-3 was increased compared to administration of cisplatin or paclitaxel alone. Similar results were obtained in an NCI-H460-xenografted mouse model, in which tumor growth was suppressed more by co-administration of NK16 and paclitaxel than by paclitaxel alone. We propose NK16 as a meaningful strategy to improve the anticancer efficacy of cisplatin and paclitaxel.

Phylogenetic analysis and in-depth characterization of functionally and structurally diverse CE5 cutinases.

Cutinases are esterases that release fatty acids from the apoplastic layer in plants. As they accept bulky and hydrophobic substrates, cutinases could be used in many applications, ranging from valorization of bark-rich side streams to plastic recycling. Advancement of these applications, however, requires deeper knowledge of cutinases' biodiversity and structure-function relationships. Here, we mined over 3000 members from carbohydrate esterase family 5 for putative cutinases and condensed it to 151 genes from known or putative lignocellulose-targeting organisms. The 151 genes were subjected to a phylogenetic analysis, which showed that cutinases with available crystal structures were phylogenetically closely related. We then selected nine phylogenic diverse cutinases for recombinant production and characterized their kinetic activity against para-nitrophenol substrates esterified with consecutively longer alkyl chains (pNP-C2 to C16). Each investigated cutinase had a unique activity fingerprint against the tested pNP substrates. The five enzymes with the highest activity on pNP-C12 and C16, indicative of activity on bulky hydrophobic compounds, were selected for in-depth kinetic and structure-function analysis. All five enzymes showed a decrease in kcat values with increasing substrate chain length, whereas KM values and binding energies (calculated from in silico docking analysis) improved. Two cutinases from Fusarium solani and Cryptococcus sp. exhibited outstandingly low KM values, resulting in high catalytic efficiencies toward pNP-C16. Docking analysis suggested that different clades of the phylogenetic tree may harbor enzymes with different modes of substrate interaction, involving a solvent-exposed catalytic triad, a lipase-like lid, or a clamshell-like active site possibly formed by flexible loops.

Role, relevance, and possibilities of in vitro fermentation models in human dietary, and gut-microbial studies.

Dietary studies play a crucial role in determining the health-benefiting effects of most food substances, including prebiotics, probiotics, functional foods, and bioactive compounds. Such studies involve gastrointestinal digestion and colonic fermentation of dietary substances. In colonic fermentation, any digested food is further metabolized in the gut by the residing colonic microbiota, causing a shift in the gut microenvironment and production of various metabolites, such as short-chain fatty acids. These diet-induced shifts in the microbial community and metabolite production, which can be assessed through in vitro fermentation models using a donor's fecal microbiota, are well known to impact the health of the host. Although in vivo or animal experiments are the gold standard in dietary studies, recent advancements using different in vitro systems, like artificial colon (ARCOL), mini bioreactor array (MBRA), TNO in vitro model of the colon (TIM), Simulator of the Human Intestinal Microbial Ecosystem (SHIME), M-SHIME, Copenhagen MiniGut, and Dynamic Gastrointestinal Simulator, make it easy to study the dietary impact in terms of the gut microbiota and metabolites. Such a continuous in vitro system can have multiple compartments corresponding to different parts of the colon, that is, proximal, transverse, and distal colon, making the findings physiologically more significant. Furthermore, postfermentation samples can be analyzed using metagenomic, metabolomic, quantitative-polymerase chain reaction, and flow-cytometry approaches. Moreover, studies have shown that in vitro results are in accordance with the in vivo findings, supporting their relevance in dietary studies and giving confidence that shifts in metabolites are only due to microbes. This review meticulously describes the recent advancements in various fermentation models and their relevance in dietary studies.

Mulberry Leaf Supplements Effecting Anti-Inflammatory Genes and Improving Obesity in Elderly Overweight Dogs.

Overweight and obesity, associated with various health complications, refer to abnormal or excessive fat accumulation conditions that harm health. Like humans, obesity is a growing problem in dogs, which may increase the risk of serious diseases such as diabetes and cancer. Mulberry leaf has shown potential anti-obesity and anti-diabetes effects in several studies. Our research studied the impact of mulberry leaf supplements in healthy old overweight dogs for 12 weeks. Blood and fecal samples were collected from the dogs before and after treatment for different analyses, including whole transcriptome and gut microbiome analysis. The Body Condition Score (BCS) and blood glucose levels were significantly decreased in all mulberry treatment groups, which justifies the anti-obesity effect of mulberry leaf in dogs. Throughout the whole transcriptome study, the downregulation of PTX3 and upregulation of PDCD-1, TNFRSF1B, RUNX3, and TICAM1 genes in the high mulberry group were found, which have been associated with anti-inflammatory effects in the literature. It may be an essential gene expression mechanism responsible for the anti-inflammatory and, subsequently, anti-obesity effects associated with mulberry leaf treatment, as confirmed by real-time polymerase chain reaction analysis. In microbiome analysis, Papillibacter cinnamivorans, related to the Mediterranean diet, which may cause anti-inflammatory effects, were abundant in the same treatment group. Further studies may be required to establish the gene expression mechanism and role of abundant bacteria in the anti-obesity effect of mulberry supplements in dogs. Overall, we propose mulberry leaves as a portion of food supplements for improving blood glucose levels and the anti-inflammation of blood in companion dogs.

Review of the Current State of Freely Accessible Web Tools for the Analysis of 16S rRNA Sequencing of the Gut Microbiome.

Owing to the emergence and improvement of high-throughput technology and the associated reduction in costs, next-generation sequencing (NGS) technology has made large-scale sampling and sequencing possible. With the large volume of data produced, the processing and downstream analysis of data are important for ensuring meaningful results and interpretation. Problems in data analysis may be encountered if researchers have little experience in using programming languages, especially if they are clinicians and beginners in the field. A strategy for solving this problem involves ensuring easy access to commercial software and tools. Here, we observed the current status of free web-based tools for microbiome analysis that can help users analyze and handle microbiome data effortlessly. We limited our search to freely available web-based tools and identified MicrobiomeAnalyst, Mian, gcMeta, VAMPS, and Microbiome Toolbox. We also highlighted the various analyses that each web tool offers, how users can analyze their data using each web tool, and noted some of their limitations. From the abovementioned list, gcMeta, VAMPS, and Microbiome Toolbox had several issues that made the analysis more difficult. Over time, as more data are generated and accessed, more users will analyze microbiome data. Thus, the availability of free and easily accessible web tools can enable the easy use and analysis of microbiome data, especially for those users with less experience in using command-line interfaces.

Controllable Nitric Oxide Storage and Release in Cu-BTC: Crystallographic Insights and Bioactivity.

Crystalline metal-organic frameworks (MOFs) are extensively used in areas such as gas storage and small-molecule drug delivery. Although Cu-BTC (1, MOF-199, BTC: benzene-1,3,5-tricarboxylate) has versatile applications, its NO storage and release characteristics are not amenable to therapeutic usage. In this work, micro-sized Cu-BTC was prepared solvothermally and then processed by ball-milling to prepare nano-sized Cu-BTC (2). The NO storage and release properties of the micro- and nano-sized Cu-BTC MOFs were morphology dependent. Control of the hydration degree and morphology of the NO delivery vehicle improved the NO release characteristics significantly. In particular, the nano-sized NO-loaded Cu-BTC (NO⊂nano-Cu-BTC, 4) released NO at 1.81 µmol·mg-1 in 1.2 h in PBS, which meets the requirements for clinical usage. The solid-state structural formula of NO⊂Cu-BTC was successfully determined to be [CuC6H2O5]·(NO)0.167 through single-crystal X-ray diffraction, suggesting no structural changes in Cu-BTC upon the intercalation of 0.167 equivalents of NO within the pores of Cu-BTC after NO loading. The structure of Cu-BTC was also stably maintained after NO release. NO⊂Cu-BTC exhibited significant antibacterial activity against six bacterial strains, including Gram-negative and positive bacteria. NO⊂Cu-BTC could be utilized as a hybrid NO donor to explore the synergistic effects of the known antibacterial properties of Cu-BTC.

Concurrence of quantum anomalous Hall and topological Hall effects in magnetic topological insulator sandwich heterostructures.

The quantum anomalous Hall (QAH) effect is a consequence of non-zero Berry curvature in momentum space. The QAH insulator harbours dissipation-free chiral edge states in the absence of an external magnetic field. However, the topological Hall (TH) effect, a hallmark of chiral spin textures, is a consequence of real-space Berry curvature. Here, by inserting a topological insulator (TI) layer between two magnetic TI layers, we realized the concurrence of the TH effect and the QAH effect through electric-field gating. The TH effect is probed by bulk carriers, whereas the QAH effect is characterized by chiral edge states. The appearance of the TH effect in the QAH insulating regime is a consequence of chiral magnetic domain walls that result from the gate-induced Dzyaloshinskii-Moriya interaction and occurs during the magnetization reversal process in the magnetic TI sandwich samples. The coexistence of chiral edge states and chiral spin textures provides a platform for proof-of-concept dissipationless spin-textured spintronic applications.

A large-scale metagenomic study for enzyme profiles using the focused identification of the NGS-based definitive enzyme research (FINDER) strategy.

Excavating the molecular details of many diverse enzymes from metagenomes remains challenging in agriculture, food, health, and environmental fields. We present a versatile method that accelerates metabolic enzyme discovery for highly selective gene capture in metagenomes using next-generation sequencing. Culture-independent enzyme mining of environmental DNA is based on a set of short identifying degenerate sequences specific for a wide range of enzyme superfamilies, followed by multiplexed DNA barcode sequencing. A strategy of 'focused identification of next-generation sequencing-based definitive enzyme research' enabled us to generate targeted enzyme datasets from metagenomes, resulting in minimal hands-on obtention of high-throughput biological diversity and potential function profiles, without being time-consuming. This method also provided a targeted inventory of predicted proteins and molecular features of metabolic activities from several metagenomic samples. We suggest that the efficiency and sensitivity of this method will accelerate the decryption of microbial diversity and the signature of proteins and their metabolism from environmental samples.

Adhaeribacter radiodurans sp. nov., isolated from the rhizospheric soil of Elymus tsukushiensis, a plant native to the Dokdo Islands, Republic of Korea.

KUDC8001T was isolated from the rhizosperic soil of Elymus tsukushiensis in the Dokdo Islands, Republic of Korea. Strain KUDC8001T was Gram-stain-negative, non-motile and rod-shaped. KUDC8001T was catalase- and oxidase-positive. This strain is capable of growing at 4-37 °C and pH 7.0-8.0 and exhibited optimal growth at 25 °C and pH 7.0. It could be grown in R2A, nutrient agar and ISP2 agar plates. The cell width ranged from 0.7 to 1.0 µm, and length ranged from 2.5 to 5.5 µm. The genomic G+C content was 40.8 mol%. Phylogenetic analysis, based on 16S rRNA gene sequences, revealed that the strain KUDC8001T belongs to the genus Adhaeribacter, which is most closely related to the strain A. pallidiroseus HMF7616T (97.5%). The DNA relatedness of KUDC8001T with the type strains of A. pallidiroseus HMF7616T, A. swui 17 mud1-7T and A. arboris HMF7605T was ≤80.3 % based on average nucleotide identity calculations and ≤86.9 % based on average amino acid identity calculations. In silico DNA-DNA hybridization values of the strain KUDC8001T with the most closely related strains were 22.1, 24.0 and 24.4 %. Based on its phenotypic, phylogenetic, genetic and chemotaxonomic features, the strain KUDC8001T should be considered as a novel species in the genus Adhaeribacter, for which we have proposed the name Adhaeribacter radiodurans sp. nov. The type strain is KUDC8001T (=KCTC 82078T=CGMCC 1.18475T).

Exploring functionality of the reverse ß-oxidation pathway in Corynebacterium glutamicum for production of adipic acid.

BACKGROUND: Adipic acid, a six-carbon platform chemical mainly used in nylon production, can be produced via reverse ß-oxidation in microbial systems. The advantages posed by Corynebacterium glutamicum as a model cell factory for implementing the pathway include: (1) availability of genetic tools, (2) excretion of succinate and acetate when the TCA cycle becomes overflown, (3) initiation of biosynthesis with succinyl-CoA and acetyl-CoA, and (4) established succinic acid production. Here, we implemented the reverse ß-oxidation pathway in C. glutamicum and assessed its functionality for adipic acid biosynthesis. RESULTS: To obtain a non-decarboxylative condensation product of acetyl-CoA and succinyl-CoA, and to subsequently remove CoA from the condensation product, we introduced heterologous 3-oxoadipyl-CoA thiolase and acyl-CoA thioesterase into C. glutamicum. No 3-oxoadipic acid could be detected in the cultivation broth, possibly due to its endogenous catabolism. To successfully biosynthesize and secrete 3-hydroxyadipic acid, 3-hydroxyadipyl-CoA dehydrogenase was introduced. Addition of 2,3-dehydroadipyl-CoA hydratase led to biosynthesis and excretion of trans-2-hexenedioic acid. Finally, trans-2-enoyl-CoA reductase was inserted to yield 37 µg/L of adipic acid. CONCLUSIONS: In the present study, we engineered the reverse ß-oxidation pathway in C. glutamicum and assessed its potential for producing adipic acid from glucose as starting material. The presence of adipic acid, albeit small amount, in the cultivation broth indicated that the synthetic genes were expressed and functional. Moreover, 2,3-dehydroadipyl-CoA hydratase and ß-ketoadipyl-CoA thiolase were determined as potential target for further improvement of the pathway.

Metabacillus elymi sp. nov., isolated from the Rhizosphere of Elymus tsukushiensis, a plant native to the Dokdo Islands, Republic of Korea.

Dokdo islands in Republic of Korea, is not suited to survive plant because strong wind, low organic content and high salinity. Nevertheless, 64 taxa of plants have a symbiotic relationship with microbe. The Metabacillus elymi KUDC1714T was isolated from the rhizosphere of Elymus tsukushiensis collected from Dokdo Islands. This bacterial strain was Gram-stain positive, non-motile, non-spore forming, aerobic and rod-shape bacteria with 0.4-0.5 × 2.5-3.0 µm in size. Colonies were smooth, yellowish-white circular and 2.0-3.0 mm in diameter. KUDC1714T was capable of growing at 10-45 °C (optimum, 30 °C), pH 7-11 (optimum, pH 8) and 0-8.0% (w/v) NaCl (optimum, 1.0-2.0%). Flagella were not observed by transmission electron microscopy. Phylogenetic analyses, based on 16S rRNA gene sequences, showed that KUDC1714T belonged to the genus Metabacillus formed a phyletic lineage within the genus Metabacillus of the family Bacillaceae. The strain KUDC1714T was most closely related to Metabacillus sediminilitoris DSL-17 T (98.2%), Metabacillus litoralis SW-211 T (98.2%) and Metabacillus halosaccharovorans E33T (97.7%) based on 16S rRNA gene sequence. In silico DNA-DNA hybridization using genome-to-genome distance calculator were analysed at 25.8% and 23.5% in strain KUDC1714T and Metabacillus sediminilitoris DSL-17 T, and strain KUDC1714T and Metabacillus litoralis SW-211 T, respectively. Strain KUDC1714T and its closet type strain were all below cut-off point of the average nucleotide identity and average amino acid identity values. The genome contains 5197 CDSs, 3 rRNAs, 118 tRNAs, 5 ncRNAs. The genomic DNA G + C content was 34.8 mol%. Its polar lipids were diphosphatidylglycerol, phosphatidylglycerol and its major fatty acids were anteiso-C15:0 and iso-C15:0. The strain KUDC1714T contained menaquinone-7 as major isoprenoid quinone. Based on its genetic data, physiological and biochemical characteristics, strain KUDC1714T should be considered a novel species of the genus Metabacillus, for which we propose the name Metabacillus elymi sp. nov. the type strain is KUDC1714T (= KCTC 33222 T, = DSM 27608 T).

Pseudomyopia with paradoxical accommodation: a case report.

BACKGROUND: Pseudomyopia is caused by increased refractive power by ciliary muscle spasm. Most patients cannot overcome pseudomyopia spontaneously; therefore, treatment of pseudomyopia is fastidious and needs a multidisciplinary approach. We report a case of unusual pseudomyopia with paradoxical accommodation, straining eyes to induce emmetropia at far distance and relaxing eyes to focus at near objects, contrary to physiological accommodation. CASE PRESENTATION: A 33-year-old woman experienced intermittent distant vision discomfort. This occurred at least a few hundred times daily. She could see near objects clearly; however, distant objects could be seen clearly only when she strained her eyes. Uncorrected distance visual acuity was 20/20 and manifest refraction (MR) in both eyes in the relaxed state was approximately - 2.5 D. MR changed to approximately - 0.5 D when she grimaced and strained her eyes when attempting to focus on distant letters. Her response was contrary to the physiological accommodative response. Cycloplegic refraction was approximately 0.0 D. Binocular autorefractor/keratometer was used to objectively evaluate her refractive response and pupil reaction according to accommodative stimulation. The IOL Master was used to evaluate the anterior chamber depth (ACD), lens thickness (LT), and pupil diameter with relaxed and strained eyes. For stepwise static accommodative stimuli (1-5 D), the refractive responses were correspondingly stepwise, similar to those elicited by healthy individuals. However, contrary to physiological accommodation, she strained her eyes to see distant objects and relaxed them to see near objects. There was no change in pupil diameter despite the accommodative stimuli being maximum. Biometry results showed that ACD deepened and LT flattened with eye strain, which were contrary to those during physiological accommodation. CONCLUSIONS: We report a rare case with reverse of physiological accommodative response. When patients complain of unusual distant visual discomfort, pseudomyopia with paradoxical accommodation should be considered.

Aqueous humor cytokine levels through microarray analysis and a sub-analysis based on optical coherence tomography in wet age-related macular degeneration patients.

BACKGROUND: To identify disease-specific cytokine and growth factor profile differences in the aqueous humor between wet age-related macular degeneration (AMD) patients and age-matched controls and to correlate their levels with the optical coherence tomography (OCT) findings. METHODS: Aqueous humors were obtained from 13 wet AMD eyes and 10 control eyes. Twenty cytokines and growth factors were measured using a RayBio antibody microarray technology in wet AMD and control eyes. RESULTS: The samples obtained from wet AMD patients exhibited a significantly increased expression of MCP-1, MIP-1α, MIP-1ß, and vascular endothelial growth factor (VEGF). Subretinal fluid (SRF) patients showed significantly lower levels of proinflammatory cytokines, such as IL-1α and GM-CSF, than those without SRF. Pigment epithelial detachments (PED) patients showed lower levels of inflammatory cytokines, such as GM-CSF, IFN-γ, and TNF-α, than those without PED. Subretinal tissue (SRT) patients showed a higher level of IFN-γ than those without SRT. Compared with the controls, type 1 macular neovascularization (MNV) patients showed increased levels of MCP-1, MIP-1α, and MIP-1ß, but not VEGF (p = 0.083). However, type 2 MNV patients showed increased levels of MCP-1 and VEGF (p = 0.040 and p = 0.040). CONCLUSION: Inflammatory cytokines varied according to the type of AMD- and OCT-based parameters. Our observation of low levels of VEGF in patients with type 1 MNV implies that the inhibition of VEGF alone appears to be insufficient treatment for these patients and that cytokines such as MCP-1, MIP-1α, and MIP-1ß should be modulated. And the presence of SRF in MNV may be associated with a positive prognosis because we found relatively low levels of proinflammatory cytokines.

Microbial production of 4-amino-1-butanol, a four-carbon amino alcohol.

4-Amino-1-butanol (4AB) serves as an important intermediate compound for drugs and a precursor of biodegradable polymers used for gene delivery. Here, we report for the first time the fermentative production of 4AB from glucose by metabolically engineered Corynebacterium glutamicum harboring a newly designed pathway comprising a putrescine (PUT) aminotransferase (encoded by ygjG) and an aldehyde dehydrogenase (encoded by yqhD) from Escherichia coli, which convert PUT to 4AB. Application of several metabolic engineering strategies such as fine-tuning the expression levels of ygjG and yqhD, eliminating competing pathways, and optimizing culture condition further improved 4AB production. Fed-batch culture of the final metabolically engineered C. glutamicum strain produced 24.7 g/L of 4AB. The strategies reported here should be useful for the microbial production of primary amino alcohols from renewable resources.

Microlunatus elymi sp. nov., a novel actinobacterium isolated from rhizospheric soil of the wild plant Elymus tsukushiensis.

An actinobacterial strain, designated KUDC0627T, was isolated from rhizospheric soil that contained Elymus tsukushiensis on the Dokdo Islands, Republic of Korea. Cells were Gram-stain-positive, facultative anaerobic, non-motile and non-endospore-forming cocci. Results of phylogenetic analysis based on 16S rRNA gene sequences indicated that strain KUDC0627T belongs to the genus Microlunatus and is most closely related to Microlunatus soli DSM 21800T (98.5 %), Microlunatus endophyticus DSM 100019T (97.7 %) and Microlunatus ginsengisoli Gsoil 633T (96.5 %). The average nucleotide identity scores and average amino acid identity values were all below the 95.0 % cut-off point. In silico DNA-DNA hybridization, using the Genome-to-Genome Distance Calculator, estimated that there is 22.3 % DNA relatedness between KUDC0627T and M. soli DSM 21800T. The genomic DNA G+C content was 66.9 mol%. The major menaquinone was MK-9(H4) and the major diagnostic diamino acid in the cell-wall peptidoglycan was ll-diaminopimelic acid. The polar lipid profile included diphosphatidylglycerol, phosphatidylglycerol, unidentified phospholipids, unidentified glycolipids and unidentified lipids. The major cellular fatty acids were iso-C15 : 0, anteiso-C15 : 0 and iso-C16 : 0. Based on phenotypic, chemotaxonomic, and phylogenetic data, strain KUDC0627T (=KCTC 39853T=JCM 32702T) represents a novel species, for which the name Microlunatus elymi sp. nov. is proposed.

Nocardioides sambongensis sp. nov., isolated from Dokdo Islands soil.

Strain KUDC5002T was isolated from soil sampled on the Dokdo Islands, Republic of Korea. This bacterial strain was Gram stain-positive, non-motile, rod-shaped, capable of growing at 25-37°C and pH 5.0-12.0, and showed optimal growth at 30 °C and pH 7.0-8.0. Strain KUDC5002T could be grown in tryptic soy broth containing less than 7.0 % NaCl (w/v). The cell width ranged from 0.5 to 0.6 µm and length ranged from 0.8 to 1.0 µm. Strain KUDC5002T was catalase- and oxidase-positive. Its genomic G+C content was 72.2 mol%. Its major fatty acids were C18 : 1 ω9c (17.3 %), iso-C16 : 0 (16.0 %) and iso-C17 : 0 (11.4 %). Phylogenetic analysis, based on 16S rRNA gene sequences, showed that strain KUDC5002T belongs to the genus Nocardioides and is most closely related to strain Nocardioides humi DCY24T (97.0 %). Based on its phenotypic, phylogenetic, genetic and chemotaxonomic features, strain KUDC5002T should be considered a novel species in the genus Nocardioides, for which we have proposed the name Nocardioides sambongensis sp. nov. The type strain is KUDC5002T (=KCTC 39855T=DSM 106604T).

Quality of science and reporting of radiomics in oncologic studies: room for improvement according to radiomics quality score and TRIPOD statement.

OBJECTIVES: To evaluate radiomics studies according to radiomics quality score (RQS) and Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) to provide objective measurement of radiomics research. MATERIALS AND METHODS: PubMed and Embase were searched for studies published in high clinical imaging journals until December 2018 using the terms "radiomics" and "radiogenomics." Studies were scored against the items in the RQS and TRIPOD guidelines. Subgroup analyses were performed for journal type (clinical vs. imaging), intended use (diagnostic vs. prognostic), and imaging modality (CT vs. MRI), and articles were compared using Fisher's exact test and Mann-Whitney analysis. RESULTS: Seventy-seven articles were included. The mean RQS score was 26.1% of the maximum (9.4 out of 36). The RQS was low in demonstration of clinical utility (19.5%), test-retest analysis (6.5%), prospective study (3.9%), and open science (3.9%). None of the studies conducted a phantom or cost-effectiveness analysis. The adherence rate for TRIPOD was 57.8% (mean) and was particularly low in reporting title (2.6%), stating study objective in abstract and introduction (7.8% and 16.9%), blind assessment of outcome (14.3%), sample size (6.5%), and missing data (11.7%) categories. Studies in clinical journals scored higher and more frequently adopted external validation than imaging journals. CONCLUSIONS: The overall scientific quality and reporting of radiomics studies is insufficient. Scientific improvements need to be made to feature reproducibility, analysis of clinical utility, and open science categories. Reporting of study objectives, blind assessment, sample size, and missing data is deemed to be necessary. KEY POINTS: • The overall scientific quality and reporting of radiomics studies is insufficient. • The RQS was low in demonstration of clinical utility, test-retest analysis, prospective study, and open science. • Room for improvement was shown in TRIPOD in stating study objective in abstract and introduction, blind assessment of outcome, sample size, and missing data categories.