The CGG repeat expansion in RILPL1 is associated with oculopharyngodistal myopathy type 4.

Recent studies indicate that CGG repeat expansions in LRP12, GIPC1, and NOTCH2NLC are associated with oculopharyngodistal myopathy (OPDM) types 1, 2, and 3, respectively. However, some clinicopathologically confirmed OPDM cases continue to have unknown genetic causes. Here, through a combination of long-read whole-genome sequencing (LRS), repeat-primed polymerase chain reaction (RP-PCR), and fluorescence amplicon length analysis PCR (AL-PCR), we found that a CGG repeat expansion in the 5' UTR of RILPL1 is associated with familial and simplex OPDM type 4 (OPDM4). The number of repeats ranged from 139 to 197. Methylation analysis indicates that the methylation levels in RILPL1 were unaltered in OPDM4 individuals. Analyses of muscle biopsies suggested that the expanded CGG repeat might be translated into a toxic poly-glycine protein that co-localizes with p62 in intranuclear inclusions. Moreover, analyses suggest that the toxic RNA gain-of-function effects also contributed to the pathogenesis of this disease. Intriguingly, all four types of OPDM have been found to be associated with the CGG repeat expansions located in 5' UTRs. This finding suggests that a common pathogenic mechanism, driven by the CGG repeat expansion, might underlie all cases of OPDM.

Spinal histamine H4 receptor mediates chronic pruritus via p-ERK in acetone-ether-water (AEW)-induced dry skin mice.

Dry skin is common to many pruritic diseases and is difficult to improve with oral traditional antihistamines. Recently, increasing evidence indicated that histamine H4 receptor (H4R) plays an important role in the occurrence and development of pruritus. Extracellular signal-regulated kinase (ERK) phosphorylation activation in the spinal cord mediates histamine-induced acute and choric itch. However, whether the histamine H4 receptor regulates ERK activation in the dry skin itch remains unclear. In the study, we explore the role of the histamine H4 receptor and p-ERK in the spinal cord in a dry skin mouse model induced by acetone-ether-water (AEW). q-PCR, Western blot, pharmacology and immunofluorescence  were applied in the study. We established a dry skin itch model by repeated application of AEW on the nape of neck in mice. The AEW mice showed typically dry skin histological change and persistent spontaneous scratching behaviour. Histamine H4 receptor, instead of histamine H1 receptor, mediated spontaneous scratching behaviour in AEW mice. Moreover, c-Fos and p-ERK expression in the spinal cord neurons were increased and co-labelled with GRPR-positive neurons in AEW mice. Furthermore, H4R agonist 4-methyhistamine dihydrochloride (4-MH)induced itch. Both 4-MH-induced itch and the spontaneous itch in AEW mice were blocked by p-ERK inhibitor U0126. Finally, intrathecal H4R receptor antagonist JNJ7777120 inhibited spinal p-ERK expression in AEW mice. Our results indicated that spinal H4R mediates itch via ERK activation in the AEW-induced dry skin mice.

Expansion of GGC Repeat in GIPC1 Is Associated with Oculopharyngodistal Myopathy.

Oculopharyngodistal myopathy (OPDM) is an adult-onset inherited neuromuscular disorder characterized by progressive ptosis, external ophthalmoplegia, and weakness of the masseter, facial, pharyngeal, and distal limb muscles. The myopathological features are presence of rimmed vacuoles (RVs) in the muscle fibers and myopathic changes of differing severity. Inheritance is variable, with either putative autosomal-dominant or autosomal-recessive pattern. Here, using a comprehensive strategy combining whole-genome sequencing (WGS), long-read whole-genome sequencing (LRS), linkage analysis, repeat-primed polymerase chain reaction (RP-PCR), and fluorescence amplicon length analysis polymerase chain reaction (AL-PCR), we identified an abnormal GGC repeat expansion in the 5' UTR of GIPC1 in one out of four families and three sporadic case subjects from a Chinese OPDM cohort. Expanded GGC repeats were further confirmed as the cause of OPDM in an additional 2 out of 4 families and 6 out of 13 sporadic Chinese individuals with OPDM, as well as 7 out of 194 unrelated Japanese individuals with OPDM. Methylation, qRT-PCR, and western blot analysis indicated that GIPC1 mRNA levels were increased while protein levels were unaltered in OPDM-affected individuals. RNA sequencing indicated p53 signaling, vascular smooth muscle contraction, ubiquitin-mediated proteolysis, and ribosome pathways were involved in the pathogenic mechanisms of OPDM-affected individuals with GGC repeat expansion in GIPC1. This study provides further evidence that OPDM is associated with GGC repeat expansions in distinct genes and highly suggests that expanded GGC repeat units are essential in the pathogenesis of OPDM, regardless of the genes in which the expanded repeats are located.

Meroterpenoids with Immunosuppressive Activity from Edible Fungus Craterellus odoratus.

Two unusual polyketide-sesquiterpene metabolites, craterodoratins T (1) and U (2), along with the known compound craterellin A (3), were isolated from the higher fungus Craterellus odoratus. The structures of isolated compounds were characterized based on nuclear magnetic resonance (NMR) and mass spectrum (MS) spectroscopic analysis, while the absolute configuration of the compounds was determined by theoretical NMR and electronic circular dichroism (ECD) calculations. Compound 1 possessed a rare structure with two aromatic groups. Compounds 1 and 3 showed immunosuppressive activity with IC50 values ranging from 5.516 to 19.953 µM.

[Mechanism of Huangjing Qianshi Decoction in treatment of prediabetic mice based on transcriptome sequencing].

Based on transcriptome sequencing technology, the mouse model of prediabetes treated with Huangjing Qianshi Decoction was sequenced to explore the possible mechanism of treating prediabetes. First of all, transcriptome sequencing was performed on the normal BKS-DB mouse group, the prediabetic model group, and the Huangjing Qianshi Decoction treatment group(treatment group) to obtain differentially expressed genes in the skeletal muscle samples of mice. The serum biochemical indexes were detected in each group to screen out the core genes of Huangjing Qianshi Decoction in prediabetes. Gene Ontology(GO) database and Kyoto Encyclopedia of Genes and Genomes(KEGG) database were used to conduct signaling pathway enrichment analysis of differentially expressed genes, and real-time quantitative polymerase chain reaction(RT-qPCR) was used to verify them. The results showed that the levels of fasting blood glucose(FBG), fasting insulin(FINS), insulin resistance index(HOMA-IR), total cholesterol(TC), triglycerides(TG), and low-density lipoprotein cholesterol(LDL-C) in the mouse model were significantly decreased after treatment with Huangjing Qianshi Decoction. In the results of differential gene screening, there were 1 666 differentially expressed genes in the model group as compared with the normal group, and there were 971 differentially expressed genes in the treatment group as compared with the model group. Among them, interleukin-6(IL-6) and NR3C2 genes, which were closely related to the regulation of insulin resis-tance function, were significantly up-regulated between the model group and the normal group, and vascular endothelial growth factor A(VEGFA) genes were significantly down-regulated between the model group and the normal group. However, the expression results of IL-6, NR3C2, and VEGFA genes were adverse between the treatment group and the model group. GO functional enrichment analysis found that the biological process annotation mainly focused on cell synthesis, cycle, and metabolism; cell component annotation mainly focused on organelles and internal components; and molecular function annotation mainly focused on binding molecular functions. KEGG pathway enrichment analysis found that it involved the protein tyrosine kinase 6(PTK6) pathway, CD28-dependent phosphoinositide 3-kinase/protein kinase B(PI3K/AKT) pathway, p53 pathway, etc. Therefore, Huangjing Qianshi Decoction can improve the state of prediabetes, and the mechanism may be related to cell cycle and apoptosis, PI3K/AKT pathway, p53 pathway, and other biological pathways regulated by IL-6, NR3C2, and VEGFA.

Five Mesoporous Lanthanide Metal-Organic Frameworks: Syntheses, Structures, and Fluorescence Sensing of Fe3+, Cr2O72-, and H2O2 and Electrochemical Sensing of Trinitrophenol.

When a multicarboxylate aromatic ligand, 3,5-di(2',4'-dicarboxylphenyl)benzoic acid (H5L), was employed, five structurally similar lanthanide metal-organic frameworks (Ln-MOFs), {[Pr10L6(OH)3Cl(H2O)6]·4C2H8N}n (1), {[Nd10L6(OH)4 (H2O)9]·4C2H8N}n (2), {[Gd10L6(OH)4(H2O)3]·4C2H8N}n (3), {[Ho10L6(OH)4 (H2O)3]·4C2H8N}n (4) and {[Er10L6(OH)4(H2O)6]·4C2H8N}n (5), were synthesized and characterized. Single-crystal X-ray structural analyses disclosed that all five Ln-MOFs crystallize in the trigonal R3 space group. They have three-dimensional mesoporous structure featuring the coexistence of binuclear and tetranuclear species as inorganic building units. The mesoporous structure of 3 was verified by the gas adsorption experiment of N2. Fluorescence analysis showed that 3 can selectively detect Fe3+, Cr2O72-, and H2O2; furthermore, it can be used for the electrochemical detection of trinitrophenol. With the merit of an excellent highly sensitive detection performance, 3 has unpredictable application prospects in future research fields.

The GGC repeat expansion in NOTCH2NLC is associated with oculopharyngodistal myopathy type 3.

Oculopharyngodistal myopathy (OPDM) is an adult-onset neuromuscular disease characterized by progressive ocular, facial, pharyngeal and distal limb muscle involvement. Trinucleotide repeat expansions in LRP12 or GIPC1 were recently reported to be associated with OPDM. However, a significant portion of OPDM patients have unknown genetic causes. In this study, long-read whole-genome sequencing and repeat-primed PCR were performed and we identified GGC repeat expansions in the NOTCH2NLC gene in 16.7% (4/24) of a cohort of Chinese OPDM patients, designated as OPDM type 3 (OPDM3). Methylation analysis indicated that methylation levels of the NOTCH2NLC gene were unaltered in OPDM3 patients, but increased significantly in asymptomatic carriers. Quantitative real-time PCR analysis indicated that NOTCH2NLC mRNA levels were increased in muscle but not in blood of OPDM3 patients. Immunofluorescence on OPDM muscle samples and expressing mutant NOTCH2NLC with (GGC)69 repeat expansions in HEK293 cells indicated that mutant NOTCH2NLC-polyglycine protein might be a major component of intranuclear inclusions, and contribute to toxicity in cultured cells. In addition, two RNA-binding proteins, hnRNP A/B and MBNL1, were both co-localized with p62 in intranuclear inclusions in OPDM muscle samples. These results indicated that a toxic protein gain-of-function mechanism and RNA gain-of-function mechanism may both play a vital role in the pathogenic processes of OPDM3. This study extended the spectrum of NOTCH2NLC repeat expansion-related diseases to a predominant myopathy phenotype presenting as OPDM, and provided evidence for possible pathogenesis of these diseases.

[Mechanism of Huangjing Qianshi Decoction in treatment of prediabetes based on network pharmacology and molecular docking].

This study analyzed the molecular mechanism of Huangjing Qianshi Decoction(HQD) in the treatment of prediabetes based on network pharmacology and molecular docking. The active components of HQD were identified and screened based on Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP, http://Lsp.nwu.edu.cn/tcmsp.php) and then the targets of the components and the genes related to prediabetes were retrieved, followed by identifying the common targets of the decoction and the disease. The medicinal component-target network was constructed by Cytoscape to screen key components. The protein-protein interaction(PPI) network was established by STRING and hub genes were identified by Cytoscape-CytoNCA, followed by Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) of the hub genes with R-clusterProfi-ler. Thereby, the possible signaling pathways were predicted and the molecular mechanism was deduced. A total of 79 active components of HQD and 785 diabetes-related targets of the components were screened out. The hub genes mainly involved the GO terms of tricarboxylic acid cycle, peptide binding, amide binding, hydrolase activity, and kinase activity regulation, and the KEGG pathways of AGE-RAGE signaling pathway, TNF signaling pathway, AMPK signaling pathway, IL-17 signaling pathway, and insulin signaling pathway. Western blot result showed that HQD-containing serum significantly reduced the expression of AKT1, AGE, and RAGE proteins in insulin resistance model cells. HQD's treatment of prediabetes is characterized by multiple pathways, multiple targets, and multiple levels. The main mechanism is that the components zhonghualiaoine, baicalein, kaempferol, and luteolin act on AKT1 and inhibit the AGE-RAGE axis.

Glycomyces salinus sp. nov., an actinomycete isolated from a hypersaline habitat.

A Gram-stain-positive, aerobic, nonmotile actinobacterium, designated strain YIM 93776T, was isolated from a saline sediment sample collected from Aiding Lake in Xinjiang Uygur Autonomous Region, Northwest China. Phylogenetic analysis based on the 16S rRNA gene sequences showed that strain YIM 93776T was affiliated to the genus Glycomyces and was closely related to Glycomyces albus TRM 49136T (97.6% sequence similarity), Glycomyces lacisalsi XHU 5089T (97.0%) and Glycomyces anabasis EGI 6500139T (96.2%). The cell wall contained meso-diaminopimelic acid and the whole-cell hydrolysates sugars were galactose, mannose, arabinase, glucose and ribose. The predominant menaquinones were MK-9 (H4) and MK-10 (H4). Diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, two phosphatidylglyceride, two unidentified phospholipids and two unidentified polar lipids were detected in the polar lipid extracts. Major fatty acids were anteiso-C17:0, iso-C15:0, iso-C16:0, anteiso-C15:0 and anteiso C17:1 A. The draft genome sequence of strain YIM 93776T was 5.37 Mbp in size with 69.5% DNA G + C content. The dDDH and ANI values between strain YIM 93776T and related neighbours were 25.0-34.3% and 77.3-79.8%, respectively. On the basis of morphological, chemotaxonomic and phylogenetic evidence, strain YIM 93776T; therefore, represents a novel species, for which the name Glycomyces salinus sp. nov. is proposed. The type strain is YIM 93776T (= KCTC 49430T = CGMCC 4.7685T).

Oceanobacillus salinisoli sp. nov., a bacterium isolated from saline soil of Turpan city in Xinjiang province, north-west China.

YIM B00359T, a novel bacterial strain was isolated from the saline soil of Turpan city in Xinjiang province, north-west China. The strain was Gram-stain-positive, motile, aerobic, produced oval subterminal endospores in swollen sporangia. The whole-cell hydrolysates contain meso-diaminopimelic acid as the cell-wall diamino acid, with xylose, glucose, and ribose as the major whole-cell sugars. The phospholipids are diphosphatidylglycerol, phosphatidylglycerol, unidentified phospholipids, unidentified glycolipids, and one unidentified glycophospholipid. The predominant menaquinone is MK-7. The major fatty acids are anteiso-C15:0, iso-C14:0, iso-C15:0, and iso-C16:0. The DNA G + C content of the type strain is 37.5 mol%. Phylogenetic analysis indicated that the isolate belongs to the genus Oceanobacillus. However, it differed from its closest relatives, Oceanobacillus halophilus DSM 23996 T and Oceanobacillus senegalensis Marseille-P3587T in many physiological and chemotaxonomic characteristics. Based on comparative analysis of polyphasic taxonomic data, strain YIM B00359T represents a novel species of the genus Oceanobacillus, for which the name Oceanobacillus salinisoli sp. nov. is proposed. The type strain is YIM B00359T (= CGMCC 1.17509T = KCTC 43185T).

Qaidamihabitans albus gen. nov., sp. nov., a new member of the family Pseudonocardiaceae, and transfer of Prauserella shujinwangii to Qaidamihabitans gen. nov. as Qaidamihabitans shujinwangii comb. nov.

A novel mycelium-forming actinomycete strain, designated YIM S01255T were isolated from a salt lake. Optimal growth occurred in the presence of 0-5.0% (w/v) NaCl, at pH 7.0-8.0, and at 37 °C. Strain YIM S01255T contained meso-diaminopimelic acid as the diagnostic diamino acid, and glucose, galactose and arabinose as the whole-cell sugars. The major fatty acid (> 5.0%) were iso-C16:0, iso-C16:1H and iso-C15:0. The major menaquinone were MK-9(H4) and MK-8(H4). The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylmonomethylethanolamine, phosphatidylinositolmannoside and phosphatidylinositol. The DNA G + C content was 70.7 mol%. The 16S rRNA gene sequence of the strain showed high similarity to members of genera in the family Pseudonocardiaceae with values less than 95.8%, and most closely related to the genus Amycolatopsis. Both of phylogenetic analysis based on 16S rRNA gene sequences and the up-to-date bacterial genome sequences analysis revealed that strains YIM S01255T and Prauserella shujinwangii XJ46T formed a distinct monophyletic clade and was separated from the other members within the family Pseudonocardiaceae. The average nucleotide identity (ANI) values and digital DNA-DNA hybridization (dDDH) between the two strains were 81.0% and 40.6%, respectively. The distinctive polyphasic evidences differentiated YIM S01255T from members of the family Pseudonocardiaceae, so strain YIM S01255T is considered to represent a novel species of a novel genus of the family Pseudonocardiaceae, for which the name Qaidamihabitans albus gen. nov., sp. nov. is proposed. The type strain of genus Qaidamihabitans is YIM S01255T (= KCTC 49476T = CGMCC 4.7684T). Moreover, Prauserella shujinwangii is also proposed to being transferred into the genus Qaidamihabitans as Qaidamihabitans shujinwangii comb. nov. (type strain XJ46T = CGMCC 4.7125T = JCM 19736T).

Lentibacillus saliphilus. sp. nov., a moderately halophilic bacterium isolated from a saltern in Korea.

A novel moderately halophilic bacterial strain, designated YIM 93176T, was isolated from a saltern in Korea and subjected to a polyphasic taxonomic study. This isolate YIM 93176T was observed to grow in the presence of 0-22% (w/v) NaCl and at pH 6.0-10.0 and 10-45 °C; optimum growth was observed with 5-10% (w/v) NaCl and at pH 7.0-9.0 and 28-37 °C. Based on 16S rRNA gene sequences analysis, the nearest relatives were Lentibacillus alimentarius M2024T (96.5% similarity), followed by Virgibacillus carmonensis LMG 20964T (96.0%) and the other type strains of the family Bacillaceae, but phylogenetic analysis indicated that strain YIM 93176T belonged to the cluster comprising type species of the genus Lentibacillus. Genome sequencing of strain YIM 93176T revealed a genome size of 3.2 Mb and a DNA G + C content of 40.5 mol%. The major fatty acids were anteiso-C15:0 (40.7%) and iso-C15:0 (26.4%), while the predominant respiratory quinone was menaquinone 7. The polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine. These genotypic and chemotaxonomic characteristics supported affiliation of strain YIM 93176T to the genus Lentibacillus. In addition, phenotypic characteristics could distinguish strain YIM 93176T from its closely related species in genus Lentibacillus. Based on the cumulative evidences from the polyphasic taxonomic study, strain YIM 93176T represents a novel species of the genus Lentibacillus, for which name Lentibacillus saliphilus sp. nov. (type strain YIM 93176T = CCTCC AB 208139T = DSM 21375T) is proposed.

Alkalibacillus aidingensis sp. nov., an Bacterium Isolated from Aiding Lake in Xinjiang Province, North-West China.

A bacterial strain, Gram staining negative, aerobic, long rod, motile bacterium with flagellum, designated strain YIM 98829T, was isolated from the Aiding Lake in Xinjiang province, North-West China. The isolate produced oval subterminal endospores in swollen sporangia. The predominant menaquinone was MK-7. The cell wall peptidoglycan contained ornithine, serine, aspartic acid, glutamic acid, and alanine, while diaminopimelic acid could not be detected. The major whole-cell sugars contained xylose, glucose, galactose, and mannose. Diphosphatidylglycerol, phosphatidylglycerol, one unknown phospholipid, and two unidentified aminophospholipids were part of the polar lipid profile. Iso-C15:0 and anteiso-C15:0 were the major fatty acids. The DNA G + C content of the type strain was 38.0 mol%. Phylogenetic analysis indicated that the isolate belongs to the genus Alkalibacillus. However, it differed from its closest relatives, A. haloalkaliphilus DSM 5271T (97.04%), A. filiformis 4AGT (96.99%), and A. silvisoli BM2T (96.95%) in some physiological characteristics. DNA-DNA hybridization result indicated low levels of relatedness between strain YIM 98829T and A. haloalkaliphilus JCM 12303T (16.9%). On the basis of physiological, phenotypic, and chemotaxonomic data, strain YIM 98829T represents a novel species of genus Alkalibacillus, for which the name Alkalibacillus aidingensis sp. nov. is proposed. The type strain is YIM 98829T (= NBRC 114103T = CGMCC 1.17260T = DSM 112470T).

Individualized predictions of early isolated distal deep vein thrombosis in patients with acute ischemic stroke: a retrospective study.

BACKGROUND: Although isolated distal deep vein thrombosis (IDDVT) is a clinical complication for acute ischemic stroke (AIS) patients, very few clinicians value it and few methods can predict early IDDVT. This study aimed to establish and validate an individualized predictive nomogram for the risk of early IDDVT in AIS patients. METHODS: This study enrolled 647 consecutive AIS patients who were randomly divided into a training cohort (n = 431) and a validation cohort (n = 216). Based on logistic analyses in training cohort, a nomogram was constructed to predict early IDDVT. The nomogram was then validated using area under the receiver operating characteristic curve (AUROC) and calibration plots. RESULTS: The multivariate logistic regression analysis revealed that age, gender, lower limb paralysis, current pneumonia, atrial fibrillation and malignant tumor were independent risk factors of early IDDVT; these variables were integrated to construct the nomogram. Calibration plots revealed acceptable agreement between the predicted and actual IDDVT probabilities in both the training and validation cohorts. The nomogram had AUROC values of 0.767 (95% CI: 0.742-0.806) and 0.820 (95% CI: 0.762-0.869) in the training and validation cohorts, respectively. Additionally, in the validation cohort, the AUROC of the nomogram was higher than those of the other scores for predicting IDDVT. CONCLUSIONS: The present nomogram provides clinicians with a novel and easy-to-use tool for the prediction of the individualized risk of IDDVT in the early stages of AIS, which would be helpful to initiate imaging examination and interventions timely.

Peripheral nerve pathology in VAPB-associated amyotrophic lateral sclerosis with dysautonomia in a Chinese family.

Mutations of the vesicle-associated membrane protein-associated protein B (VAPB) gene have been identified in familial amyotrophic lateral sclerosis (ALS) with dysautonomia. Here we report the peripheral nerve pathology in ALS with dysautonomia caused by the p.Pro56Ser mutation of the VAPB gene in a Chinese family. The clinical features in all patients were camptocormia, fasciculation, and weakness in all limbs. Two patients developed symptoms of dysautonomia, including abdominal bloating, orthostatic hypotension, constipation, frequent urination, decreased sweating, and burning feet. Electromyography showed widespread neuropathic damage. The sympathetic skin response was absent in the soles of the feet. Sural nerve biopsy revealed loss of nerve fibers, especially unmyelinated fibers. Electron microscopy revealed regional loss of unmyelinated fibers with numerous collagen pockets. This report indicates that VAPB-associated ALS may be accompanied by multifocal autonomic nerve damage.

Sural nerve pathology in TFG-associated motor neuron disease with sensory neuropathy.

The tropomyosin-receptor kinase fused gene (TFG) functions in vesicles formation and egress at the endoplasmic reticulum (ER). A heterozygous missense mutation c.854C > T (p.Pro285Leu) within TFG has been reported as causative for hereditary motor and sensory neuropathy with proximal predominance. Here, we describe two unrelated Chinese pedigrees with 13 affected members harboring the same variant. The clinical, electrophysiological and pathological findings are consistent with motor neuron disease with sensory neuropathy. The main symptoms were painful muscle cramps, slowly progressive proximal predominant weakness, muscle atrophy, fasciculation and distal sensory disturbance. Electromyography revealed widespread denervation and reinnervation. Sural nerve biopsy revealed severe loss of myelinated fibers. Electron microscopy revealed aggregation of ER with enlarged lumen and small vesicles in the remaining myelinated and unmyelinated axons. The mitochondria are smaller in Schwann cells and axons. Some unmyelinated axons showed disappearance of neurofilament and microtubular structures. This is the first report of c.854C > T mutation within TFG in Chinese population. Our findings not only extend the geographical and phenotypic spectrum of TFG-related neurological disorders, but also confirm the abnormalities of ER and mitochondria in sural nerves.

Aidingibacillus halophilus gen. nov., sp. nov., a novel member of the family Bacillaceae.

A Gram-positive, non-motile, asporogenous and aerobic bacterium, designated YIM 98012T, was isolated from a salt lake in China. Strain YIM 98012T was found to be catalase and oxidase positive. Optimal growth of strain YIM 98012T was observed at 37 °C and pH 7.0 and it was found to grow in the presence of 5-20% (w/v) NaCl (optimum 10% NaCl). Phylogenetic analysis based on the 16S rRNA gene sequence indicated that the novel strain is affiliated with the family Bacillaceae of the phylum Firmicutes and that it shares high (94.7%) sequence similarity with Alteribacillus persepolensis DSM 21632T and does not show sequence similarities of more than 94.0% to known members of other related genera. The major fatty acids (> 10%) were identified as anteiso-C15:0, anteiso-C17:0, iso-C16:0 and C16:0. The genomic DNA G+C content was determined to be 41.0 mol% and the dominated respiratory quinone was identified as MK-7. The cell wall peptidoglycan of strain YIM 98012T was found to contain meso-diaminopimelic acid, while the polar lipids profile was found to include diphosphatidylglycerol, phosphatidylglycerol and phosphatidylcholine. Based on physiological and chemotaxonomic characteristics, strain YIM 98012T is concluded to be the type strain of the type species of a novel genus in the family Bacillaceae for which the name Aidingibacillus halophilus gen. nov., sp. nov. is proposed. The type strain is YIM 98012T (= KCTC 33868T = DSM 104332T).

Complete Chloroplast Genomes from Sanguisorba: Identity and Variation Among Four Species.

The genus Sanguisorba, which contains about 30 species around the world and seven species in China, is the source of the medicinal plant Sanguisorba officinalis, which is commonly used as a hemostatic agent as well as to treat burns and scalds. Here we report the complete chloroplast (cp) genome sequences of four Sanguisorba species (S. officinalis, S. filiformis, S. stipulata, and S. tenuifolia var. alba). These four Sanguisorba cp genomes exhibit typical quadripartite and circular structures, and are 154,282 to 155,479 bp in length, consisting of large single-copy regions (LSC; 84,405⁻85,557 bp), small single-copy regions (SSC; 18,550⁻18,768 bp), and a pair of inverted repeats (IRs; 25,576⁻25,615 bp). The average GC content was ~37.24%. The four Sanguisorba cp genomes harbored 112 different genes arranged in the same order; these identical sections include 78 protein-coding genes, 30 tRNA genes, and four rRNA genes, if duplicated genes in IR regions are counted only once. A total of 39⁻53 long repeats and 79⁻91 simple sequence repeats (SSRs) were identified in the four Sanguisorba cp genomes, which provides opportunities for future studies of the population genetics of Sanguisorba medicinal plants. A phylogenetic analysis using the maximum parsimony (MP) method strongly supports a close relationship between S. officinalis and S. tenuifolia var. alba, followed by S. stipulata, and finally S. filiformis. The availability of these cp genomes provides valuable genetic information for future studies of Sanguisorba identification and provides insights into the evolution of the genus Sanguisorba.

Plasma level of miR-93 is associated with higher risk to develop type 2 diabetic retinopathy.

PURPOSE: MicroRNA-93 (miR-93) usually acts as a promoter of tumor progression in several human carcinomas. It has been found distinctly high in eyes with proliferative diabetic retinopathy (DR). The present study aims to investigate the role of plasma miR-93 in the progression of type 2 diabetic retinopathy (T2DR). METHODS: Our study subjects were made up of 140 type 2 diabetes mellitus (T2DM) patients who were assigned into DR (DR patients, n = 75), NDR (non-DR patients, n = 65), and control (healthy individuals, n = 127) groups. Levels of fasting blood glucose (FBG), fasting plasma glucose (FPG), triglyceride (TG), glycosylated hemoglobin (HbA1c), total cholesterol (TC), blood urea nitrogen (BUN), creatinine (Cr), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and fasting insulin (FIsn) were detected by automatic biochemical analyzer. Enzyme-linked immunosorbent assay (ELISA) was performed for the levels of interleukin (IL)-1, IL-6, tumor necrosis factor (TNF)-α and vascular endothelial growth factor (VEGF), qRT-PCR for the miR-93 expression in plasma, and mRNA expressions of IL-1, IL-6, TNF-α and VEGF; receiver operating characteristic (ROC) curve for the diagnostic performance of miR-93 to T2DR, Pearson correlation analysis for correlation analysis between miR-93 and other indexes detected before and multivariate logistic regression analyses for the risk factors for T2DR. RESULTS: The DR and NDR groups exhibited elevated course of disease, and decreased levels of FBG, FPG, TG, HbA1c, TC, BUN, Cr, HDL-C, FIsn, IL-1, IL-6, TNF-α and VEGF but declined LDL-C level as compared to the control group. The course of disease was longer and the levels of FBG, FPG, HbA1c, IL1, IL6 and VEGF were higher in the DR group than those in the NDR group (all P < 0.05). The miR-93 expression and RNA expressions of IL-1, IL-6, TNF-α and VEGF were higher in the DR group than those in the NDR group (P < 0.05). The best cutoff for miR-93 to assess T2DR was 1.31, with a Youden index of 0.63, sensitivity of 73.33%, specificity of 89.24%, and area under the curve (AUC) of 0.866. Pearson correlation analysis indicated that miR-93 expression was positively associated with course of disease, the levels of FPG, HbA1c, TNF-α and VEGF. T2DM patients with longer disease course, higher levels of FBG, HbA1c, VEGF and miR-93 expression were risk factors for developing DR. CONCLUSION: Our study demonstrates that plasma miR-93 is associated with the progression of T2DR and it can sever as a diagnostic marker for T2DR.