Single-cell RNA sequencing reveals recruitment of the M2-like CCL8high macrophages in Lewis lung carcinoma-bearing mice following hypofractionated radiotherapy.

BACKGROUND: Tumor-associated macrophages (TAMs) play a pivotal role in reshaping the tumor microenvironment following radiotherapy. The mechanisms underlying this reprogramming process remain to be elucidated. METHODS: Subcutaneous Lewis lung carcinoma (LLC) murine model was treated with hypofrationated radiotherapy (8 Gy × 3F). Single-cell RNA sequencing was utilized to identify subclusters and functions of TAMs. Multiplex assay and enzyme-linked immunosorbent assay (ELISA) were employed to measure serum chemokine levels. Bindarit was used to inhibit CCL8, CCL7, and CCL2. The infiltration of TAMs after combination treatment with hypofractionated radiotherapy and Bindarit was quantified with flow cytometry, while the influx of CD206 and CCL8 was assessed by immunostaining. RESULTS: Transcriptome analysis identified a distinct subset of M2-like macrophages characterized by elevated Ccl8 expression level following hypofractionated radiotherapy in LLC-bearing mice. Remarkbly, hypofractionated radiotherapy not only promoted CCL8high macrophages infiltration but also reprogrammed them by upregulating immunosuppressive genes, thereby fostering an immunosuppressive tumor microenvironment. Additioinally, hypofractionated radiotherapy enhanced the CCL signaling pathway, augmenting the pro-tumorigenic functions of CCL8high macrophages and boosting TAMs recruitment. The adjunctive treatment combining hypofractionated radiotherapy with Bindarit effectively reduced M2 macrophages infiltration and prolonged the duration of local tumor control. CONCLUSIONS: Hypofractionated radiotherapy enhances the infiltration of CCL8high macrophages and amplifies their roles in macrophage recruitment through the CCL signaling pathway, leading to an immunosuppressive tumor microenvironment. These findings highlight the potential of targeting TAMs and introduces a novel combination to improve the efficacy of hypofractionated radiotherapy.

STIC-HD live flow technology in the antenatal diagnosis of scimitar syndrome: A case report.

Scimitar syndrome (SS) is a rare entity with an incidence of approximately 1-3 in 200 000 people. It is typically characterized by complete or partial anomalous pulmonary venous drainage from the right lung into the systemic venous circulation, most commonly the inferior vena cava (IVC). For the first time, we report the diagnosis of SS in a fetus in utero using four-dimensional (4D) spatiotemporal image correlation combined with high-definition live flow rendering mode (STIC-HD live flow).

SIRT3-dependent mitochondrial redox homeostasis mitigates CHK1 inhibition combined with gemcitabine treatment induced cardiotoxicity in hiPSC-CMs and mice.

Administration of CHK1-targeted anticancer therapies is associated with an increased cumulative risk of cardiac complications, which is further amplified when combined with gemcitabine. However, the underlying mechanisms remain elusive. In this study, we generated hiPSC-CMs and murine models to elucidate the mechanisms underlying CHK1 inhibition combined with gemcitabine-induced cardiotoxicity and identify potential targets for cardioprotection. Mice were intraperitoneally injected with 25 mg/kg CHK1 inhibitor AZD7762 and 20 mg/kg gemcitabine for 3 weeks. hiPSC-CMs and NMCMs were incubated with 0.5 uM AZD7762 and 0.1 uM gemcitabine for 24 h. Both pharmacological inhibition or genetic deletion of CHK1 and administration of gemcitabine induced mtROS overproduction and pyroptosis in cardiomyocytes by disrupting mitochondrial respiration, ultimately causing heart atrophy and cardiac dysfunction in mice. These toxic effects were further exacerbated with combination administration. Using mitochondria-targeting sequence-directed vectors to overexpress CHK1 in cardiomyocyte (CM) mitochondria, we identified the localization of CHK1 in CM mitochondria and its crucial role in maintaining mitochondrial redox homeostasis for the first time. Mitochondrial CHK1 function loss mediated the cardiotoxicity induced by AZD7762 and CHK1-knockout. Mechanistically, mitochondrial CHK1 directly phosphorylates SIRT3 and promotes its expression within mitochondria. On the contrary, both AZD7762 or CHK1-knockout and gemcitabine decreased mitochondrial SIRT3 abundance, thus resulting in respiration dysfunction. Further hiPSC-CMs and mice experiments demonstrated that SIRT3 overexpression maintained mitochondrial function while alleviating CM pyroptosis, and thereby improving mice cardiac function. In summary, our results suggest that targeting SIRT3 could represent a novel therapeutic approach for clinical prevention and treatment of cardiotoxicity induced by CHK1 inhibition and gemcitabine.

Insulin reduces pyroptosis-induced inflammation by PDHA1 dephosphorylation-mediated NLRP3 activation during myocardial ischemia-reperfusion injury.

BACKGROUND: Previous studies proved that pyrin domain-containing protein 3 (NLRP3)-induced pyroptosis plays an important role in Myocardial ischemia-reperfusion injury (MIRI). Insulin can inhibit the activation of NLRP3 inflammasome, although the exact mechanism remains unclear. The aim of this study was to determine whether insulin reduces NLRP3-induced pyroptosis by regulating pyruvate dehydrogenase E1alpha subunit (PDHA1) dephosphorylation during MIRI. METHODS: Rat hearts were subject to 30 min global ischemia followed by 60 min reperfusion, with or without 0.5 IU/L insulin. Myocardial ischemia-reperfusion injury was evaluated by measuring myocardial enzymes release, Cardiac hemodynamics, pathological changes, infarct size, and apoptosis rate. Cardiac aerobic glycolysis was evaluated by measuring ATP, lactic acid content, and pyruvate dehydrogenase complex (PDHc) activity in myocardial tissue. Recombinant adenoviral vectors for PDHA1 knockdown were constructed. Pyroptosis-related proteins were measured by Western blotting analysis, immunohistochemistry staining, and ELISA assay, respectively. RESULTS: It was found that insulin significantly reduced the area of myocardial infarction, apoptosis rate, and improved cardiac hemodynamics, pathological changes, energy metabolism. Insulin inhibits pyroptosis-induced inflammation during MIRI. Subsequently, Adeno-associated virus was used to knock down cardiac PDHA1 expression. Knockdown PDHA1 not only promoted the expression of NLRP3 but also blocked the inhibitory effect of insulin on NLRP3-mediated pyroptosis in MIRI. CONCLUSIONS: Results suggest that insulin protects against MIRI by regulating PDHA1 dephosphorylation, its mechanism is not only to improve myocardial energy metabolism but also to reduce the NLRP3-induced pyroptosis.

MNK2-eIF4E axis promotes cardiac repair in the infarcted mouse heart by activating cyclin D1.

Adult mammals have limited potential for cardiac regeneration after injury. In contrast, neonatal mouse heart, up to 7 days post birth, can completely regenerate after injury. Therefore, identifying the key factors promoting the proliferation of endogenous cardiomyocytes (CMs) is a critical step in the development of cardiac regeneration therapies. In our previous study, we predicted that mitogen-activated protein kinase (MAPK) interacting serine/threonine-protein kinase 2 (MNK2) has the potential of promoting regeneration by using phosphoproteomics and iGPS algorithm. Here, we aimed to clarify the role of MNK2 in cardiac regeneration and explore the underlying mechanism. In vitro, MNK2 overexpression promoted, and MNK2 knockdown suppressed cardiomyocyte proliferation. In vivo, inhibition of MNK2 in CMs impaired myocardial regeneration in neonatal mice. In adult myocardial infarcted mice, MNK2 overexpression in CMs in the infarct border zone activated cardiomyocyte proliferation and improved cardiac repair. In CMs, MNK2 binded to eIF4E and regulated its phosphorylation level. Knockdown of eukaryotic translation initiation factor (eIF4E) impaired the proliferation-promoting effect of MNK2 in CMs. MNK2-eIF4E axis stimulated CMs proliferation by activating cyclin D1. Our study demonstrated that MNK2 kinase played a critical role in cardiac regeneration. Over-expression of MNK2 promoted cardiomyocyte proliferation in vitro and in vivo, at least partly, by activating the eIF4E-cyclin D1 axis. This investigation identified a novel target for heart regenerative therapy.

Separate neural subsystems support goal-directed speech listening.

How do humans excel at tracking the narrative of a particular speaker with a distracting noisy background? This feat places great demands on the collaboration between speech processing and goal-related regulatory functions. Here, we propose that separate subsystems with different cross-task dynamic activity properties and distinct functional purposes support goal-directed speech listening. We adopted a naturalistic dichotic speech listening paradigm in which listeners were instructed to attend to only one narrative from two competing inputs. Using functional magnetic resonance imaging with inter- and intra-subject correlation techniques, we discovered a dissociation in response consistency in temporal, parietal and frontal brain areas as the task demand varied. Specifically, some areas in the bilateral temporal cortex (SomMotB_Aud and TempPar) and lateral prefrontal cortex (DefaultB_PFCl and ContA_PFCl) always showed consistent activation across subjects and across scan runs, regardless of the task demand. In contrast, some areas in the parietal cortex (DefaultA_pCunPCC and ContC_pCun) responded reliably only when the task goal remained the same. These results suggested two dissociated functional neural networks that were independently validated by performing a data-driven clustering analysis of voxelwise functional connectivity patterns. A subsequent meta-analysis revealed distinct functional profiles for these two brain correlation maps. The different-task correlation map was strongly associated with language-related processes (e.g., listening, speech and sentences), whereas the same-task versus different-task correlation map was linked to self-referencing functions (e.g., default mode, theory of mind and autobiographical topics). Altogether, the three-pronged findings revealed two anatomically and functionally dissociated subsystems supporting goal-directed speech listening.

Synthesis and Evaluation of 18F-Labeled Boramino Acids as Potential New Positron Emission Tomography Agents for Cancer Management.

Boron neutron capture therapy (BNCT) is a promising cancer treatment strategy that utilizes boron-containing ligands. In this report, a series of substituted boramino acids were synthesized and evaluated, aiming to obtain metabolically stable boron-derived agents that could integrate positron emission tomography (PET) with BNCT (a theranostic agent). Based on the phenylalanine (Phe) core structure, the impact of substitution groups on tumor accumulation was studied. The agents were labeled with fluorine-18 in 27.2-66.8% yield via the 18F-19F isotope exchange reaction. In B16-F10 tumor-bearing mice, [18F]-(R)-(1-ammonio-2-(4-methoxyphenyl) ethyl) trifluoroborate (R-[18F]-5a) demonstrated the best tumor uptake (5.54 ± 2.32% ID/g based on ex vivo biodistribution and 3.5 ± 0.04% ID/g based on PET imaging with the tumor-to-muscle ratio up to 2.6) and stability compared with other tested agents. Together, R-[18F]-5a is a promising agent that could potentially integrate PET and BNCT, whose treatment efficacy is worth further evaluation in the future.

CT-based radiomics signatures can predict the tumor response of non-small cell lung cancer patients treated with first-line chemotherapy and targeted therapy.

OBJECTIVES: The goal of this study was to evaluate the effectiveness of radiomics signatures on pre-treatment computed tomography (CT) images of lungs to predict the tumor responses of non-small cell lung cancer (NSCLC) patients treated with first-line chemotherapy, targeted therapy, or a combination of both. MATERIALS AND METHODS: This retrospective study included 322 NSCLC patients who were treated with first-line chemotherapy, targeted therapy, or a combination of both. Of these patients, 224 were randomly assigned to a cohort to help develop the radiomics signature. A total of 1946 radiomics features were obtained from each patient's CT scan. The top-ranked features were selected by the Minimum Redundancy Maximum Relevance (MRMR) feature-ranking method and used to build a lightweight radiomics signature with the Random Forest (RF) classifier. The independent predictive (IP) features (AUC > 0.6, p value < 0.05) were further identified from the top-ranked features and used to build a refined radiomics signature by the RF classifier. Its prediction performance was tested on the validation cohort, which consisted of the remaining 98 patients. RESULTS: The initial lightweight radiomics signature constructed from 15 top-ranked features had an AUC of 0.721 (95% CI, 0.619-0.823). After six IP features were further identified and a refined radiomics signature was built, it had an AUC of 0.746 (95% CI, 0.646-0.846). CONCLUSIONS: Radiomics signatures based on pre-treatment CT scans can accurately predict tumor response in NSCLC patients after first-line chemotherapy or targeted therapy treatments. Radiomics features could be used as promising prognostic imaging biomarkers in the future. KEY POINTS: The radiomics signature extracted from baseline CT images in patients with NSCLC can predict response to first-line chemotherapy, targeted therapy, or both treatments with an AUC = 0.746 (95% CI, 0.646-0.846). The radiomics signature could be used as a new biomarker for quantitative analysis in radiology, which might provide value in decision-making and to define personalized treatments for cancer patients.

The prognostic significance of survivin expression in patients with HNSCC: a systematic review and meta-analysis.

BACKGROUND: Survivin has been recently identified as a promising novel therapeutic target and prognostic marker in different types of cancer. Here we conducted a comprehensive meta-analysis to better clarify they the precise prognostic and diagnostic value of survivin in head and neck squamous cell carcinoma (HNSCC). METHODS: Database of PubMed (Medline), Embase, and Web of Science were systematically searched for related published literature up to September 2020. Pooled hazards ratios (HR) and related 95% confidence intervals (CI) were used to estimate the association of survivin expression and survival outcomes in HNSCC patients. RESULTS: Twenty eight studies with 4891 patients were finally included in this meta-analysis, the pooled analysis indicated that the survivin expression was significantly correlated with poorer overall survival (OS) (HR, 2.02; 95% CI, 1.65-2.47, P < 0.001), and poorer disease-free survival (DFS)/ disease-specific survival (DSS) (HR = 2.03, 95%CI: 1.64-2.52, P < 0.001; HR = 1.92, 95%CI: 1.41-2.60, P < 0.001, receptively). Similar results were observed in subgroup analysis stratified by different cancer types, such as laryngeal squamous cell carcinoma (LSCC) (HR = 1.35, 95%CI: 1.05-1.74, P < 0.001), oral squamous cell carcinomas (OSCC) (HR = 2.45, 95%CI: 1.89-3.17, P < 0.001), nasopharyngeal carcinoma (NPC) (HR = 2.53, 95%CI: 1.76-3.62, P < 0.001) and HNSCC (HR = 1.52, 95%CI: 1.25-1.86, P < 0.001). Furthermore, ethnicity-stratified analysis indicated that survivin was significantly associated with poorer OS among both Asian and Non- Asian HNSCC patients (HR = 2.16, 95%CI: 1.76-2.66; HR = 1.56, 95%CI: 1.33-1.82, respectively). CONCLUSIONS: Our results suggested that survivin is predictors of worse prognosis in HNSCC patients. Hence, survivin is a potential therapeutic target for HNSCC.

Identification of a 3,3-difluorinated tetrahydropyridinol compound as a novel antitumor agent for hepatocellular carcinoma acting via cell cycle arrest through disturbing CDK7-mediated phosphorylation of Cdc2.

Tetrahydropyridinol derivatives were recently reported to exhibit good biological activities, and the incorporation of fluorine into organic molecules may have profound effects on their physical and biological properties. Therefore, we investigated the anticancer activities of six fluorinated tetrahydropyridinol derivatives that we synthesized previously. We found that only one compound, 3,3-difluoro-2,2-dimethyl-1,6-diphenyl-5-tosyl-1,2,3,6-tetrahydropyridin-4-ol, showed significant antiproliferative activity on human hepatocellular carcinoma HepG2 and HMCCLM3 cells (the IC50 values were 21.25 and 29.07 µM, respectively). We also found that this compound mediated cell cycle arrest in the G0/G1 phase at 30-40 µM. Western blot analysis demonstrated that the cell cycle arrest induced by this compound in HepG2 and HMCCLM3 cells was associated with a significant decrease in Cdc2 and cyclin B1, which led to the accumulation of the phosphorylated-Tyr15 (inactive) form of Cdc2 and low expression of M phase-promoting factor (cyclin B1/Cdc2). Moreover, cells treated with this compound exhibited decreased expression of cyclin-dependent kinase (CDK)-activating kinase (CDK7/cyclin H). This compound also induced cell apoptosis via activation of caspase-3. A xenograft model in nude mice demonstrated anti-liver cancer activity and the mechanism of action of this compound. These findings indicated that the anticancer effect of this compound was partially due to G0/G1 cell cycle arrest via inhibition of CDK7-mediated expression of Cdc2, and this compound may be a promising anticancer candidate for further investigation.

Exiguobacterium flavidum sp. nov., isolated from the Red Maple Lake.

A Gram-stain-positive, motile, facultatively anaerobic, non-sporing, and rod-shaped bacterial strain, designated HF60T, was isolated from the Red Maple Lake of Guizhou Province, China. The DNA G+C content of the strain HF60T was 55.0 %. The predominant isoprenoid quinones were identified as MK-7 (56.4 %) and MK-8 (35.7 %). The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol and aminophosphoglycolipid. The major fatty acids were anteiso-C13 : 0, iso-C15 : 0, C16 : 0 and iso-C13 : 0. The strain had cell wall peptidoglycan type A3α l-Lys-Gly. Phylogenetic analyses based on 16S rRNA gene sequences indicated that strain HF60T belonged to the genus Exiguobacterium and was most closely related to Exiguobacterium sibiricum JCM 13490T (97.2 % 16S rRNA gene sequence similarity), followed by Exiguobacterium undae DSM 14481T (97.1 %), Exiguobacterium antarcticum DSM 14480T (96.9 %) and Exiguobacterium aurantiacum NBRC 14763T (94.5 %). The differential phenotypic properties, together with the phylogenetic and genetic distinctiveness indicated that strain HF60T can be considered to represent a novel species of the genus Exiguobacterium, for which the name Exiguobacterium flavidum sp. nov. is proposed, The type strain is HF60T (=MCCC 1H00336T=KCTC 33987T).

Tichowtungia aerotolerans gen. nov., sp. nov., a novel representative of the phylum Kiritimatiellaeota and proposal of Tichowtungiaceae fam. nov., Tichowtungiales ord. nov. and Tichowtungiia class. nov.

Kiritimatiellaeota is widespread and ecologically important in various anoxic environments. However, the portion of culturable bacteria within this phylum is quite low and, in fact, there is only one currently described species. In this study, a novel anaerobic, non-motile, coccoid, Gram-stain-negative bacterial strain, designated S-5007T, was isolated from surface marine sediment. The 16S rRNA gene sequence was found to have very low 16S rRNA gene sequence similarity to the nearest known type strain, Kiritimatiella glycovorans L21-Fru-ABT (84.9 %). The taxonomic position of the novel isolate was investigated using a polyphasic approach and comparative genomic analysis. Phylogenetic analyses based on 16S rRNA genes and genomes indicated that strain S-5007T branched within the radiation of the phylum Kiritimatiellaeota. Different from the type strain, strain S-5007T can grow under microaerobic conditions, and the genomes of strain S-5007T and the other strains in its branch have many more antioxidant-related genes. Meanwhile, other different metabolic features deduced from genome analysis supported the separate evolution of the proposed class (strain S-5007T branch) and K. glycovorans L21-Fru-ABT. Based on phylogenetic and phenotypic characterization studies, Tichowtungia aerotolerans gen. nov., sp. nov. is proposed with S-5007T (=MCCC 1H00402T=KCTC 15876T) as the type strain, as the first representative of novel taxa, Tichowtungiales ord. nov., Tichowtungiaceae fam. nov. in Tichowtungiia class. nov.

Lutibacter citreus sp. nov., isolated from Arctic surface sediment.

A Gram-stain-negative, aerobic, non-motile, non-gliding, yellow-pigmented and rod-shaped bacterial strain, designated 1KV19T, was isolated from a surface sediment sample collected near a bay in the Arctic. Growth of strain 1KV19T occurred in 1-4 % (w/v) NaCl (optimum, 2 %), at 4-35 °C (optimum, 25-30 °C) and at pH 6.5-8.0 (optimum, pH 7.0-7.5). The phylogenetic trees based on the 16S rRNA gene sequences showed that strain 1KV19T was associated with the genus Lutibacter and had the highest 16S rRNA gene sequence similarity to Lutibacter oceani 325-5T with 98.1 % similarity. Similarity values between strain 1KV19T and the type strains of other Lutibacter species were in the range 95.9-97.6 %. The average nucleotide identity and digital DNA-DNA hybridization values between strain 1KV19T and related species of the genus Lutibacter were 76.4-79.1 and 19.9-22.3 %, respectively. The major cellular fatty acids of strain 1KV19T were iso-C15 : 0 3-OH, iso-C15 : 0 and iso-C16 : 1 H. The respiratory quinone was MK-6. The major polar lipids of strain 1KV19T were phosphatidylethanolamine, one unidentified aminolipid and two unidentified polar lipids. The phenotypic, genotypic and chemotaxonomic differences between strain 1KV19T and its phylogenetic relatives indicate that strain 1KV19T should be regarded as representing a novel species in the genus Lutibacter, for which the name Lutibacter citreus sp. nov. is proposed. The type strain is 1KV19T (=KCTC 62595T=MCCC 1H00307T).

Tessaracoccus antarcticus sp. nov., a rhodopsin-containing bacterium from an Antarctic environment and emended description of the genus Tessaracoccus.

A Gram-stain-positive, facultatively anaerobic bacterium, strain JDX10T, was isolated from a soil sample of Fildes Peninsula, Antarctica. Cells of the strain were irregular rod-shaped and non-motile. Cells grew at 4-40 °C (optimum, 28 °C), at pH 6.0-9.0 (optimum, 7.5) and with 0.0-3.0 % (w/v) NaCl (optimum, 1.0 %). According to phylogenetic analysis based on 16S rRNA gene sequences, strain JDX10T was associated with the genus Tessaracoccus, and showed highest similarities to Tessaracoccus rhinocerotis CCTCC AB 2013217T (97.2 %), Tessaracoccus flavescens SST-39T (96.9 %) and Tessaracoccus terricola JCM 32157T (96.9 %). The average nucleotide identity scores of strain JDX10T to T. rhinocerotis CCTCC AB 2013217T and T. bendigoensis JCM 13525T were 74.8 and 73.3 %, respectively and the Genome-to-Genome Distance Calculator scores were 19.2 and 18.7 %, respectively. The major (>10.0 %) cellular fatty acid was anteiso-C15 : 0. The predominant isoprenoid quinone was MK-10(H4). The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol and one unidentified glycolipid. The phylogenetic analysis and physiological and biochemical data showed that strain JDX10T should be classified as representing a novel species in the genus Tessaracoccus, for which the name Tessaracoccus antarcticus sp. nov. is proposed. The type strain is JDX10T (=MCCC 1H00351T=KCTC 49242T).

Dokdonia sinensis sp. nov., a flavobacterium isolated from surface seawater.

A taxonomic study was carried out on strain SH27T, which was isolated from seawater collected around Xiaoshi Island, PR China. Cells of strain SH27T were Gram-stain-negative, non-motile, rod-shaped, orange-pigmented and grew at 15-37 °C (optimum, 28 °C), at pH 6.0-8.0 (pH 7.0) and in 1.0-7.0 % (w/v) NaCl (2.0-3.0 %). The isolate was positive for catalase, but negative for nitrate reduction, oxidase, indole production and urease. Carotenoid pigment was produced. Phylogenetic analysis based on the 16S rRNA gene placed strain SH27T in the genus Dokdonia with the closest relative being Dokdonia donghaensis KCTC 12391T, exhibiting 96.7 % 16S rRNA gene pairwise similarity. The results of genomic comparisons, including average nucleotide identity and digital DNA-DNA hybridization, showed 72.9 and 19.2 % identity to D. donghaensis KCTC 12391T, respectively. The major cellular fatty acids were iso-C15 : 0, iso-C15 : 1 G and iso-C17 : 0 3-OH. The major polar lipids were phosphatidylethanolamine and two unidentified lipids. Menaquinone-6 was the only respiratory quinone. The G+C content of the genomic DNA was 32.9 mol%. On the basis of the phenotypic and phylogenetic data, strain SH27T represents a novel species of the genus Dokdonia, for which the name Dokdonia sinensis sp. nov. is proposed, with the type strain SH27T (MCCC 1H00358T=CCTCC AB 2018323T=KCTC 62962T).

Pelagivirga dicentrarchi sp. nov., a member of the family Rhodobacteraceae isolated from the gut microflora of sea bass (Dicentrarchus labrax L.).

A Gram-stain negative, aerobic, non-flagellated, non-gliding, rod-shaped bacterium, designated strain YLY04T, was isolated from the gut microflora of a sea bass (Dicentrarchus labrax L.) collected from the coast of Yuanyao Wharf, Weihai, China. Growth was found to occur at pH 6.0-9.0 (optimum, 7.0-8.0), 4-37 °C (optimum, 28-30 °C) in the presence of 0-11.0% (w/v) NaCl (optimum, 3.0-4.0%). Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain YLY04T is closely related to Pelagivirga sediminicola BH-SD19T and Roseovarius antarcticus M-S13-148T. Strain YLY04T contains ubiquinone-10 as the sole respiratory quinone and summed feature 8 (C18:1ω7c and/or C18:1ω6c), cyclo-C19:0ω8c, C16:0 and 11-methyl-C18:1ω7c as the major fatty acids. The polar lipids of strain YLY04T were found to consist of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, an unidentified aminolipid, an unidentified phospholipid and three unidentified lipids. The DNA G+C content was determined to be 62.7 mol%. The phenotypic, chemotaxonomic and phylogenetic properties, and genome analysis, indicated that strain YLY04T represents a novel species within the genus Pelagivirga, for which the name Pelagivirga dicentrarchi sp. nov. is proposed. The type strain is YLY04T (= MCCC 1H00334T = KCTC 62452T).

MicroRNA-133b suppresses bladder cancer malignancy by targeting TAGLN2-mediated cell cycle.

MicroRNAs (miRNAs), a group of small noncoding RNAs, are widely involved in the regulation of gene expression via binding to complementary sequences at 3'-untranslated regions (3'-UTRs) of target messenger RNAs. Recently, downregulation of miR-133b has been detected in various human malignancies. Here, the potential biological role of miR-133b in bladder cancer (BC) was investigated. In this study, we found the expression of miR-133b was markedly downregulated in BC tissues and cell lines (5637 and T24), and was correlated with poor overall survival. Notably, transgelin 2 (TAGLN2) was found to be widely upregulated in BC, and overexpression of TAGLN2 also significantly increased risks of advanced TMN stage. We further identified that upregulation of miR-133b inhibited glucose uptake, invasion, angiogenesis, colony formation and enhances gemcitabine chemosensitivity in BC cell lines by targeting TAGLN2. Additionally, we showed that miR-133b promoted the proliferation of BC cells, at least partially through a TAGLN2-mediated cell cycle pathway. Our results suggest a novel miR-133b/TAGLN2/cell cycle pathway axis controlling BC progression; a molecular mechanism which may offer a potential therapeutic target.

Coraliomargarita sinensis sp. nov., isolated from a marine solar saltern.

A Gram-stain negative, spherical, obligately aerobic bacterium, designated strain WN38T, was isolated from a marine solar saltern on the coast of Weihai, China. Optimal growth occurred at 33 °C, pH 7.0-7.5 and in the presence of 3-4 % (w/v) NaCl. The genome of strain WN38T was found to contain the genes necessary for arsenate reductase and related proteins, indicating that it may have potential in bioremediation of heavy metal polluted environments. Comparative 16S rRNA gene sequence analysis showed that strain WN38T represented a member of the genus Coraliomargarita, and was related most closely to Coraliomargarita akajimensis KCTC 12865T (95.7 %). Pairwise sequence similarities to all other type strains of species were below 90 %. Genome-based calculations (average nucleotide identity, genome-to-genome distance and DNA G+C percentage) and results of pairwise amino acid identity (AAI >60 %) and percentage of conserved proteins (POCP >50 %) also indicated clearly that strain WN38T represents a novel species within this genus. Different phenotypic analyses, such as the detection of a quinone system composed of the sole respiratory quinone was menaquinone-7 (MK-7) and a fatty acid profile with iso-C14 : 0, C18 : 0 and C18 : 1ω9c as major components, supported this finding at the same time as contributing to a comprehensive characterization of strain WN38T. On the basis of its phenotypic and genotypic properties, strain WN38T represents a novel species of the genus Coraliomargarita, for which the name Coraliomargaritasinensis sp. nov. is proposed. The type strain is WN38T (=KCTC 62602T=MCCC 1H00313T).

Pedobacter chinensis sp. nov., a cellulose-decomposing bacterium from Arctic tundra soil.

A novel bacterial strain, JDX94T, was isolated from tundra soil sampled north of the Yellow River station, Arctic. Cells were Gram-stain-negative, non-spore-forming, short rod-shaped and aerobic. The strain displayed growth at 4-37 °C with an optimum at 28 °C, with 0-1.0 % (w/v) NaCl (optimum, 0%) and at pH 6.0-9.0 (optimum, pH 7.0-7.5). Cells contained summed feature 3 (comprising C16 : 1ω7c and/or C16 : 1ω6c), iso-C15 : 0 and iso-C17 : 0 3-OH as its major cellular fatty acids and menaquinone-7 as the only respiratory quinone. The polar lipid profile of strain JDX94T consisted of phosphatidylethanolamine, two unidentified aminolipids and four unknown polar lipids. The DNA G+C content was 37.5 mol%. On the basis 16S rRNA gene sequence comparison, strain JDX94T showed the highest sequence similarity (96.7 %) to Pedobacteragri JCM 15120T, followed by Pedobacteralluvionis DSM 19624T (96.3 %). Furthermore, the average nucleotide identity and digital DNA-DNA hybridization values between strain JDX94T and related species of the genus Pedobacter were 74.6-79.2 % and 18.9-24.5 %, respectively. Based on the presented results, we propose a novel species for which the name Pedobacterchinensis sp. nov. is suggested, with the type strain JDX94T (=MCCC 1H00335T= KCTC 62850T).

Oceaniglobus ichthyenteri sp. nov., isolated from the gut microflora of sea bass (Dicentrarchus labrax L.) and emended description of the genus Oceaniglobus.

A Gram-stain-negative, non-flagellated, catalase-positive, oxidase-positive bacterial strain, designated YLY08T, was isolated from the gut microflora of sea bass (Dicentrarchus labrax L.) collected from the coast of Yuanyao Wharf, Weihai, PR China, and subjected to a polyphasic taxonomic study. Strain YLY08T grew optimally at 28-30 °C, at pH 7.0-7.5 and in the presence of 2.0-3.0 % (w/v) NaCl. Poly-ß-hydroxybutyrate granules were produced. Neighbour-joining, maximum-likelihood and maximum-parsimony phylogenetic trees based on 16S rRNA gene sequences revealed that strain YLY08T clustered with the type strain of Oceaniglobus indicus, with which it exhibited 95.3 % sequence similarity, while the similarity to other genera was below 95.0 %. Genomic analyses, including average nucleotide identity and the digital DNA-DNA hybridization, clearly separated YLY08T from O. indicus MCCC 1A11863T with values below the thresholds for species delineation. The major cellular fatty acid was summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c). The sole respiratory quinone detected was Q-10. The polar lipid profile consisted of phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, phosphatidyldimethylethanolamine, diphosphatidylglycerol, one unidentified aminolipid and one unidentified phospholipid. The genome of strain YLY08T, with 38 assembled contigs, was 3.9 Mb long with a G+C content of 59.0 mol%. The results of the phenotypical, phylogenetic and biochemical analyses between the strain YLY08T and the related type strain indicated that this strain represents a novel species in genus Oceaniglobus within the family Rhodobacteraceae, for which the name Oceaniglobus ichthyenteri sp. nov. is proposed. The type strain is YLY08T (=MCCC 1H00318T=KCTC 62182T).