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Objectives: Riptolide (TPL) has been shown to have a good clinical effect on rheumatoid arthritis (RA). We designed TPL microspheres (TPL-MS) and investigated its metabolic behavior in human, dog, rabbit and rat liver microsomes (HLM, DLM, RLM and SDRLM) with UPLC- MS/MS method. Methods: First, a UPLC-MS/MS method was established to measure the concentration of TPL in samples. The sample was separated on a C18 column (2.1×100 mm, 1.8μm) and eluted with a gradient elution. The precursor ions/product ions were m/z 378.1/361.0 for TPL and 260.0/116.2 for the internal standard. Then T1/2, Vmax and CLint were calculated from the above data. Finally, the metabolites of TPL-MS were identified by high-resolution UPLC-MS/MS. The sample was separated on a C18 column (2.1×100 mm, 2.2 μm) and eluted with isocratic elution. Mass spectrometric detection was carried out on a thermo Q-exactive mass spectrometer with HESI. The scanning range of precursor ions was from m/z 50 to m/z 750. Results: Through several indicators including standard curve, precision, accuracy, stability, matrix effect and recovery rate, the enzymatic kinetics parameters including T1/2, Vmax and CLint were evaluated. Several metabolites of TPL-MS were identified. Discussion: UPLC-MS/MS method is an accurate and sensitive method for the determination of TPL in liver microsome samples with good precision, accuracy and stability. The variation of parameters indicated that the microspheres can delay the elimination of TPL in liver microsomes. Conclusion: The metabolism of TPL-MS varied among species, but no new metabolites appeared.

Alzheimer’s disease (AD) process is characterized classically by two hallmark pathologies: β-amyloid (Aβ) plaque deposition and neurofibrillary tangles of hyperphosphorylated tau. Aβ peptides play an important role in AD, but despite much effort the molecular mechanisms of how Aβ contributes to AD remain unclear. The present study evaluated the effects of the active components of Epimedium, Astragalus and Radix Puerariae induced HAMP on key enzymes in the hydrolysis of APP in HT22 cells. The active components of Epimedium, Astragalus and Radix Puerariae could effectively up-regulate the expression of HAMP, alleviate the iron overload in the brain tissues of mice, significantly improve the learning and memory ability of AD, down-regulate the expression of Aβ and reduce the deposition of SP in an APPswe/PS1ΔE9 transgenic mouse model of AD. HAMP and Aβ25–35 induced HT22 cells are used as AD cell models in this study to investigate the effect of the compound consisting of the effective components of Epimedium, Astragalus and Pueraria on the key enzymes in the hydrolysis of APP. After the administration of traditional Chinese medicine (TCM), the expression levels of ADAM10 and ADAM17 were increased while the expression level of BACE1 decreased. This indicates that TCM can promote the expression level of ADAM10 and ADAM17, inhibit the expression level of BACE1, thus further inhibiting the production of amyloid protein and reducing the production of Aβ and SP. Compared with RNAi group, the expression level of ADAM10 and ADAM17 in Aβ + RNAi group was decreased while the expression level of BACE1 increased. Compared with the Aβ + RNAi group the expression level of ADAM10 and ADAM17 in the Aβ + RNAi + TCM group was increased while the expression level of BACE1 was decreased. The present study indicated the effects of the active components of Epimedium, Astragalus and Radix Puerariae may alleviate AD by up-regulating the expression of HAMP, thus reducing brain iron overload, promoting the expression of ADAM10 and ADAM17, inhibiting the expression of BACE1, and reducing the deposition of Aβ.

C14H20CdCl2N4O4, monoclinic, P21/n (no. 14), a = 8.261(3) Å, b = 16.390(5) Å, c = 13.967(4) Å, β = 95.850(4)°, V = 1881.3(10) Å3, Z = 4, R gt (F) = 0.0342, wR ref (F 2) = 0.0873, T = 296 K.

Two bacterial strains SYSU G02173T and SYSU G03142 were isolated from hot springs in Tibet, China. Based on the results of nearly full-length 16S rRNA gene sequences and phylogenetic analyses, strains SYSU G02173T and SYSU G03142 were assigned to the family Sphingosinicellaceae, and were closest to Sandaracinobacter sibiricus RB16-17 T (96.04% and 96.12% similarity, respectively). Cells of the both new strains were observed to be motile rod-shape, Gram-staining negative. Growth occurred at pH 6–8 (optimal: pH 7.0) and 37–55 °C (optimal: 45 °C) with 0–1.0% (w/v) NaCl in T4 broth. The cells were found to be positive for oxidase and catalase activities. The major respiratory ubiquinone was Q-8. The major fatty acids were identified as summed feature 8 (C18:1 ω7c and/or C18:1 ω6c), C16:0, C14:0 2-OH. The major polar lipids were found to consist of sphingoglycolipid, phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, one unidentified phospholipid, one unidentified glycolipid, three unidentified aminolipids and two unidentified polar lipids. The DNA G + C contents of strains SYSU G02173T and SYSU G03142 were 71.8%. The average nucleotide identity (ANI) value between strain SYSU G02173T and SYSU G03142 was 99.98%. The amino acid identity (AAI) values between them and their closely related species were below 66.14%. The isolates are characterized by aerobic growth, a yellow endocellular pigment and a higher optimum growth temperature. The results showed that strains SYSU G02173T and SYSU G03142 represent a novel species of a novel genus in the family Sphingomonadaceae, and thus the name Thermaurantiacus tibetensis (type strain SYSU G02173T = KCTC 72052 T = CGMCC 1.16680 T) is proposed.

A thermophilic bacterium, designated SYSU G03088T, was isolated from Moincer hot spring, Tibet, PR China. Polyphasic taxonomic analyses and whole-genome sequencing were used to determine the taxonomic position and genomic profiles of the strain. Phylogenetic analysis using 16S rRNA gene sequence indicated that SYSU G03088T showed highest sequence similarity to Rhodobacter blasticus CGMCC 1.3365T (96.0 % sequence identity). The strain could be differentiated from most recognized species of the genus Rhodobacter by its slightly purple colony colour, distinct phenotypic characters and low ANI values. Cells were Gram-staining negative, and oval-to-rod shaped. Poly-β-hydroxybutyrate and vesicular intracytoplasmic membrane structures were formed inside cells. Growth occurred optimally at 45 °C and pH 7.0. Ubiquinone 10 was the only respiratory quinone. The major fatty acids (>10 %) were C18 : 0, C18 : 1ω7c 11-methyl and summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c). The detected polar lipids of SYSU G03088T included diphosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol and phosphatidylmethylethanolamine. The DNA G+C content of SYSU G03088T was 67.7 % (genome). On the basis of the differences in the phenotypic characteristics and phylogenetic analyses, SYSU G03088T is considered to represent a novel species of the genus Rhodobacter , for which the name Rhodobacter flagellatus sp. nov. is proposed. The type strain is SYSU G03088T (=CGMCC 1.16876T=KCTC 72354T).

A Gram-staining-positive, aerobic, non-motile, non-spore-forming and coccoid-shaped actinobacterial strain, designated YIM 730233T, was isolated from a sediment sample, collected from a hot spring in Tibet, China. Colonies were brownish, circular, smooth and convex. Strain YIM 730233T was able to grow in the temperature range of 20–50 °C, pH 6.5–8.0 and in the presence of up to 1.0 % (w/v) NaCl. A comparison of the 16S rRNA gene sequence of strain YIM 730233T with sequences of type strains of most closely related species of Marmoricola showed highest sequence similarities to Marmoricola bigeumensis MSL-05T (98.3%) and Marmoricola pocheonensis Gsoil 818T (98.1%). The draft genome of strain YIM 730233T had a size of 4 806 234 bp with a DNA G+C content of 72.1 mol%. The major fatty acids (>10 %) of strain YIM 730233T mainly consisted of iso-C16 : 0, anteiso-C17 : 0 and C18 : 1 ω9c, typical of the genus Marmoricola . Strain YIM 730233T had LL-2,6-diaminopimelic acid as the diagnostic diamino acid in the cell wall. The predominant isoprenoid quinone was MK-8(H4). The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, unidentified phospholipids and an unidentified lipid. DNA–DNA hybridizations between strain YIM 730233T and type strains of Marmoricola bigeumensis MSL-05T and Marmoricola pocheonensis Gsoil 818T resulted in similarity values of 21 and 19% respectively. Based on DNA–DNA hybridization results, together with the differentiating biochemical and chemotaxonomic features, showed that strain YIM 730233T represents a novel Marmoricola species, for which the name Marmoricola caldifontis sp. nov. (type strain YIM 730233T=KCTC 49192T=CGMCC 4.7521T), is proposed.

C28H22CuN2O4, monoclinic, C2/c (no. 15), a = 17.2971(3) Å, b = 14.4409(3) Å, c = 9.5617(2) Å, β = 90.580(2)°, V = 2388.25(8) Å3, Z = 4, R gt (F) = 0.0536, wR ref (F 2) = 0.1406, T = 293 K.

A β-glucosidase obtained from Thermobifida halotolerans YIM 90462T was expressed in Escherichia coli BL21 and subsequently characterized. The recombinant enzyme ThBGL1A showed optimal activity at 45 °C and pH 6, but also showed high activity from 40 to 55 °C and pH 5.6–6.6. Its half-life activity was 58 min at 50 °C. ThBGL1A exhibited notable cold-adapted activity, retaining 13.1%, 49.4%, and 83.5% of its optimal activity at 5, 25, and 30 °C, respectively. Kinetic characterization revealed an enzymatic turnover (Kcat) of 30 s−1 (cellobiose), 41.8 s−1 (p-nitrophenyl-β-d-glucopyranoside), and 52.6 s−1 (p-nitrophenyl-β-d-galactopyranoside). Moreover, ThBGL1A had high tolerance for salt, xylose, and glucose, which are extremely desirable features for industrial applications. Interestingly, its Ki for glucose was 932 mM and more than 80% of its optimal activity in the presence of 2000 mM xylose. After the addition of ThBGL1A (0.05 mg/ml) to a commercial cellulase reaction system, glucose yields from sugarcane bagasse were increased 20% and 18% after 1 day at 30 °C and 45 °C, respectively. Overall, this work identifies a cold-adapted, salt- and glucose-tolerant β-glucosidase with potential applications in commercial cellulose utilization and the bioenergy industry.

Thermus species are thermophilic heterotrophs, with most capable of using a variety of organic and inorganic electron donors for respiration. Here, a combined cultivation-independent and -dependent approach was used to explore the diversity of Thermus in Great Boiling Spring (GBS) and Little Hot Creek (LHC) in the US Great Basin. A cultivation-independent 16S rRNA gene survey of ten LHC sites showed that Thermus made up 0-3.5% of sequences and were predominately Thermus thermophilus. 189 Thermus isolates from GBS and LHC were affiliated with T. aquaticus (73.0%), T. oshimai (25.4%), T. sediminis (1.1%), and T. thermophilus (0.5%), with T. aquaticus and T. oshimai forming biogeographic clusters. 22 strains were selected for characterization, including chemolithotrophic oxidation of thiosulfate and arsenite, and reduction of ferric iron, polysulfide, and nitrate, revealing phenotypic diversity and broad respiratory capability within each species. PCR demonstrated the wide distribution of aerobic arsenite oxidase genes. A GBS sediment metaproteome contained sulfite oxidase and Fe3+ ABC transporter permease peptides, suggesting sulfur and iron transformations in situ. This study expands our knowledge of the physiological diversity of Thermus, suggesting widespread chemolithotrophic and anaerobic respiration phenotypes, and providing a foundation for better understanding the ecology of this genus in thermal ecosystems.

A moderately thermophilic, aerobic, Gram-stain-negative, non-spore-forming, rod-shaped and yellow-pigmented bacterium, designated strain SYSU G00007T, was isolated from a hot spring slurry sample. Optimum growth was observed at 37–45 °C and pH 7. Pairwise comparison of the 16S rRNA gene sequence of strain SYSU G00007T and other Novosphingobium species showed sequence similarities ranging from 93.7 to 97.9 %. Strain SYSU G00007T showed highest sequence identity to Novosphingobium subterraneum DSM 12447T (97.9 %). The average nucleotide identities and digital DNA–DNA hybridization values between strain SYSU G00007T and its closely related phylogenetic neighbours were below 81 and 31 %, respectively, indicating that strain SYSU G00007T represented a novel species of the genus Novosphingobium . The DNA G+C content of strain SYSU G00007T was 64.3 % (genome). The major respiratory quinone was ubiquinone Q-10. The polar lipid profile included diphosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, two sphingoglycolipids, two unidentified phospholipids, two unidentified aminophospholipids and two unidentified polar lipids. Spermidine was the only polyamine detected. The major fatty acids were C19 : 0cyclo ω8c, summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c) and C16 : 0. The results obtained from phylogenetic, chemotaxonomic and phenotypic analyses support the conclusion that strain SYSU G00007T represents a novel species of the genus Novosphingobium , for which we proposed the name Novosphingobium meiothermophilum sp. nov. The type strain is SYSU G00007T (=KCTC 52672T=CCTCC AB2017010T).

An efficient copper-catalyzed intramolecular C-H alkoxylation of 1,4-disubstituted 1,2,3-triazoles has been developed. The chemistry was applied to a wide range of substrates, generating tricyclic benzoxazine-fused 1,2,3-triazoles in good yields. Mechanistic studies suggest that a radical pathway may be involved in this transformation. The triazole products were found to exhibit strong antifungal activity against ginseng root-rot disease, demonstrating their potential as a scaffold in medicinal chemistry research.

A gene encoding a β-xylosidase (designated as Thxyl43A) was cloned from strain Thermobifida halotolerans YIM 90462T. The open reading frame of this gene encodes 550 amino acid residues. The gene was over-expressed in Escherichia coli and the recombinant protein was purified. The monomeric Thxyl43A protein presented a molecular mass of 61.5 kDa. When p-nitrophenyl-β-d-xylopyranoside was used as the substrate, recombinant Thxyl43A exhibited optimal activity at 55 °C and pH 4.0 to 7.0, being thermostable by maintaining 47% of its activity after 30 h incubation at 55 °C. The recombinant enzyme retained more than 80% residual activity after incubation at pH range of 4.0 to 12.0 for 24 h, respectively, which indicated notable thermostability and pH stability of Thxyl43A. Moreover, Thxyl43A displayed high catalytic activity (> 60%) in presence of 5–35% NaCl (w/v) or 1–20% ionic liquid (w/v) or 1–50 mM xylose. These properties suggest that Thxyl43A has potential for promoting hemicellulose degradation and other industrial applications.

Thermus species are widespread in natural and artificial thermal environments. Two new yellow-pigmented strains, L198T and L423, isolated from Little Hot Creek, a geothermal spring in eastern California, were identified as novel organisms belonging to the genus Thermus. Cells are Gram-negative, rod-shaped, and non-motile. Growth was observed at temperatures from 45 to 75 °C and at salinities of 0–2.0% added NaCl. Both strains grow heterotrophically or chemolithotrophically by oxidation of thiosulfate to sulfate. L198T and L423 grow by aerobic respiration or anaerobic respiration with arsenate as the terminal electron acceptor. Values for 16S rRNA gene identity (≤ 97.01%), digital DNA–DNA hybridization (≤ 32.7%), OrthoANI (≤ 87.5%), and genome-to-genome distance (0.13) values to all Thermus genomes were less than established criteria for microbial species. The predominant respiratory quinone was menaquinone-8 and the major cellular fatty acids were iso-C15:0, iso-C17:0 and anteiso-C15:0. One unidentified phospholipid (PL1) and one unidentified glycolipid (GL1) dominated the polar lipid pattern. The new strains could be differentiated from related taxa by β-galactosidase and β-glucosidase activity and the presence of hydroxy fatty acids. Based on phylogenetic, genomic, phenotypic, and chemotaxonomic evidence, the novel species Thermus sediminis sp. nov. is proposed, with the type strain L198T (= CGMCC 1.13590T = KCTC XXX).

Cilia loss is common in cancer, and its roles remain unknown. Deng et al. show that cilia loss sensitizes cells to transformation by activating a mevalonate pathway through β-catenin–TCF signaling. The mevalonate pathway inhibitor statin blocks the progression of pancreatic cancer., Although cilia loss and cell transformation are frequently observed in the early stage of tumorigenesis, the roles of cilia in cell transformation are unknown. In this study, disrupted ciliogenesis was observed in cancer cells and pancreatic cancer tissues, which facilitated oncogene-induced transformation of normal pancreatic cells (HPDE6C7) and NIH3T3 cells through activating the mevalonate (MVA) pathway. Disruption of ciliogenesis up-regulated MVA enzymes through β catenin–T cell factor (TCF) signaling, which synchronized with sterol regulatory element binding transcription factor 2 (SREBP2), and the regulation of MVA by β-catenin–TCF signaling was recapitulated in a mouse model of pancreatic ductal adenocarcinoma (PDAC) and human PDAC samples. Moreover, disruption of ciliogenesis by depleting Tg737 dramatically promoted tumorigenesis in the PDAC mouse model, driven by KrasG12D, which was inhibited by statin, an inhibitor of the MVA pathway. Collectively, this study emphasizes the crucial roles of cilia in governing the early steps of the transformation by activating the MVA pathway, suggesting that statin has therapeutic potential for pancreatic cancer treatment.

A novel Gram-stain-positive, obligately anaerobic and thermophilic bacterium, strain SYSU GA15001T, was isolated from a sample collected from a hot spring located in Tengchong, China. Phylogenetic analysis based on the 16S rRNA gene sequence indicated that strain SYSU GA15001T belonged to the family Eubacteriaceae , and was closely related to ‘ Irregularibacter muris ’ 2PG-426-CC4.2T (93.6 % similarity), Garciella nitratireducens DSM 15102T (93.2 %) and Alkalibacter saccharofermentans Z-78920T (89.7 %). Cells were rods and motile by means of a subpolar flagellum. Spores were formed in old cultures. Optimum growth was observed at 45 °C, at pH 7 and in the presence of 1.5 % (w/v) NaCl. The strain utilized d-arabinose, dulcitol, d-galactose, glucose, lactose, maltose, d-mannose, raffinose, l-rhamnose, d-sorbitol, xylitol, l-alanine, l-arginine, glycine, l-isoleucine, l-leucine, dl-methionine, NH4Cl, l-proline and l-threonine as sole carbon/nitrogen sources. Additionally, complex substrates including beef extract, peptone, starch and yeast extract can also be used as sole energy sources. The major fatty acid methyl esters were C14 : 0, anteiso-C15 : 0 and C18 : 0. The polar lipid profile consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, an unidentified polar lipid, three unidentified phospholipids and an unidentified glycolipid. The DNA G+C content was determined to be 35.6 mol%. Strain SYSU GA15001T was physiologically and phylogenetically distinguishable from its closely related genera, and merits assignment as representing the type species of a new genus Rhabdanaerobium, with the name Rhabdanaerobium thermarum gen. nov., sp. nov. The type strain of the type species is SYSU GA15001T (=CGMCC 1.5219T=KCTC 15623T).

Clustered regularly interspaced short palindromic repeats (CRISPR)-associated proteins (Cas), such as Cas9 and Cpf1, are RNA-guided endonucleases that target and degrade nucleic acids, providing powerful genomic editing and molecular diagnostic tools. Cas12b enzymes are distinct effectors; however, their features and catalytic boundaries require further characterization. We identified BrCas12b from the thermophile bacterium Brevibacillus sp. SYSU G02855 as a novel ortholog of cas12b. Biochemical analyses revealed that BrCas12b is a dual-RNA-guided endonuclease with higher optimum reaction temperature than that of other reported members of Cas12b. The seed sequence of BrCas12b is only 4 nt in length, indicating that it has greater target mismatch tolerance than that of previously reported Cas effectors; however, it contains a compensatory effect at the position of the cleavage site. Using fluorescence-based detection method to evaluate target cleavage efficiency, we showed that BrCas12b has robust enzymatic cleavage activity (Kcat/Km (s−1 M−1) = 8.80 × 1011), which is significantly higher than that of AacCas12b (Kcat/Km (s−1 M−1) = 7.56 × 108) from Alicyclobacillus acidoterrestris. The results increase our understanding of the catalytic mechanism of Cas12b family members and suggest that BrCas12b might be useful in the application of genomic editing and molecular diagnosis.

One thermophilic bacterium, designated strain SYSU G02662T, was isolated from hot spring sediment sampled in Tibet, PR China. Polyphasic taxonomic analyses and whole-genome sequencing were used to determine the taxonomy position of the strain. Phylogenetic analysis using 16S rRNA gene sequences indicated that strain SYSU G02662T showed the highest sequence similarity to Actinomarinicola tropica SCSIO 58843T (95.1 %). The strain could be differentiated from other species of the family Iamiaceae by its distinct phenotypic and genotypic characteristics. Cells of strain SYSU G02662T were aerobic, Gram-staining-positive and short rodshaped. Growth occurred optimally at 45 °C and pH 7.0. In addition, meso-diaminopimelic acid was the diagnostic diamino acid in the cell-wall peptidoglycan. The respiratory quinone was MK-9 (H8), while the major fatty acids (>10 %) were C16 : 0, C17 : 0, C18 : 0 and iso-C16 : 0. The detected polar lipids included diphosphatidylglycerol, phosphatidylinositol mannoside and phosphatidylinositol. The G+C content of the genomic DNA was 70.5 % based on the draft genomic sequence. On the basis of phenotypic, genotypic and phylogenetic data, strain SYSU G02662T represents a novel species of a novel genus in the family Iamiaceae , for which the name Rhabdothermincola sediminis gen. nov., sp. nov. is proposed. The type strain of the proposed novel species is SYSU G02662T (=CGMCC 4.7688T=KCTC 49500T).

A xylanase gene (TrXyn10) from Thermoactinospora rubra YIM 77501T was cloned and expressed in Escherichia coli. The amino acid sequence displayed 78% homology with Microbispora mesophila xylanase (WP_062413927.1). The recombinant xylanase (TrXyn10), with MW 46.1 kDa, could hydrolyse beechwood, birchwood and oatspelt xylan. Based on the sequence, enzymatic properties and tertiary structure of the protein, TrXyn10 belongs to glycoside hydrolase family 10 (GH10). The optimal pH and temperature for the recombinant enzyme were determined to be 7.0 and 55 °C, respectively. TrXyn10 was stable over a wide pH range, and it retained more than 45% of the total activity at pH 6.0–12.0 for 12 h. In addition, the activity was greatly promoted, by approximately 200% of the initial activity, after incubation at pH 6.0 and 7.0 for 12 h. Based on enzymatic properties and product analysis, we showed that TrXyn10 is a neutral endoxylanase.

The ortho- C–H bonds at C(4)-aryl of 1, 4-disubstituted 1, 2, 3-triazoles were regioselectively alkoxylated in good to excellent yields with under the directing of the triazole ring. Some products were found to exhibit strong antifungal capacity to fight against root-rot disease of Panax notoginseng by testing the minimum inhibitory concentration (MIC).

The bioconversion of lignocellulose in various industrial processes, such as biofuel production, requires the degradation of cellulose. Actinomadura amylolytica YIM 77502T is an aerobic, Gram-positive actinomycete that can efficiently degrade crystalline cellulose by extracellular cellulases. Genomic analysis of A. amylolytica identified 9 cellulase and 11 β-glucosidase genes that could potentially encode proteins that digest cellulose. Extracellular proteome characterization of A. amylolytica cell-free culture supernatant by liquid chromatography tandem mass spectrometry analysis revealed that 4 of these cellulases and 2 of these β-glucosidases functioned during cellulose hydrolysis. Thin-layer chromatography analysis revealed extracellular β-glucosidases play a major role in carboxyl methyl cellulose (CMC) degradation of products in culture supernatants. In this study, 2 of the identified secreted β-glucosidases, AaBGL1 and AaBGL2, were functionally expressed in Escherichia coli and found to have β-glucosidase activity with wide substrate specificities, including for p-nitrophenyl β-D-glucopyranoside (pNPG), p-nitrophenyl-beta-D-cellobioside (pNPC), and cellobiose. Moreover, AaBGL1 and AaBGL2 had high tolerances for glucose. After adding these β-glucosidases to commercial cellulases, the degradation rates of CMC, Avicel, birch sawdust, and corncob powder increased by 37, 42, 33, and 9%, respectively. Overall, this work identifies an alternative potential source of β-glucosidases with potential applications in commercial cellulose utilization and the bioenergy industry.

An ovoid to rod-shaped, phototrophic, purple non-sulfur bacterium was isolated from a sediment sample of a hot spring in Tibet, China. Cells of strain YIM 73036T were Gram-stain negative, non-motile and multiplied by binary fission. Strain YIM 73036T grew optimally at pH 7.0–7.5 at 37–45 °C. Growth occurred in 0.5–3.5% (w/v) NaCl. Vitamins were not required for growth. The presence of photosynthesis genes pufL and pufM were shown and photosynthesis pigments were formed. Bacteriochlorophyll α, the bacteriopheophytin and carotenoids were present as photosynthetic pigments. Internal cytoplasmic membranes were of the lamellar type. The organism YIM 73036T was able to grow chemo-organoheterophically, chemo-lithoautotrophically and photo-organoheterotrophically but photo-lithoautotrophic and fermentative growth were not demonstrated. Phylogenetic analysis on the basis of 16S rRNA gene sequences showed that strain YIM 73036T is closely related to Rhodobacter blasticus ATCC 33485T (96.65% sequence similarity) and clustered with species of the genus Rhodobacter of the family Rhodobacteraceae. Whole-genome sequence analyses based on the average nucleotide BLAST identity (ANI

Thermoactinospora rubra YIM 77501T is an aerobic, Gram-positive, spore-formingand cellulose degrading thermophilic actinomycete isolated from a sandy soil sample of a volcano. Its growth temperature range is 28 to 60°C. The genomic sequence of this strain revealed that there are 27 cellulase genes belonging to six glycoside hydrolase families. To understand the strategy that this strain uses to utilize carbon sources such as cellulose at different temperatures, comparative transcriptomics analysis of T. rubra YIM 77501T was performed by growing it with cellulose (CMC) and without cellulose (replaced with glucose) at 30°C, 40°C and 50°C, respectively. Transcriptomic analyses showed four cellulase genes (TrBG2, TrBG3, TrBG4 and ThrCel6B) were up-regulated at 30°C, 40°C and 50°C. The rate of gene expression of TrBG2, TrBG3, TrBG4 and ThrCel6B were 50°C > 30°C > 40°C. One cellulase gene (TrBG1) and two cellulase genes (TrBG5 and ThrCel6A) were up-regulated only at 30°C and 50°C, respectively. These up-regulated cellulase genes were cloned and expressed in Escherichia coli. The enzymatic properties of up-regulated cellulases showed a variety of responses to temperature. Special up-regulated cellulases TrBG1 and ThrCel6A displayed temperature acclimation for each growth condition. These expression patterns revealed that a hybrid strategy was used by T. rubra to utilize carbon sources at different temperatures. This study provides genomic, transcriptomics and experimental data useful for understanding how microorganisms respond to environmental changes and their application in enhancing cellulose hydrolysis for animal feed and bioenergy production.

A facile, efficient, and low energy consumption detonation method to prepare few-layered graphene nanosheets has been developed using graphite oxide as a precursor at detonation induced temperature as low as 100 °C . The composition and structure of as-produced few-layered graphenes were characterized by X-Ray Diffraction (XRD), Scanning Electron Microscope (SEM), Fourier Transform Infrared (FTIR), Specific Surface (BET), Transmission Electron Microscopy (TEM), Raman Microscope, and Atomic Force Microscope (AFM). Results showed that the as-produced graphenes were transparent and few-layered with a high specific surface area (225.9 m2/g). The investigation opens a new road to prepare few-layered graphene nanosheets at low exfoliation temperature in a low-cost and facile way.

nanozinc oxide (n-ZnO) was synthesized by sol-gel method. The surface of n-ZnO was modified by a silane coupling agent. The modified n-ZnO was then used as rubber vulcanizing activator and nanofiller for BR/SBR blends. The size and morphology of n-ZnO were characterized by X-ray diffraction (XRD) and transmission electron microscopy (TEM). The effects of modified n-ZnO on cure characteristics, mechanical properties and thermal conductivity of BR/SBR blends were tested and analyzed. The use of modified n-ZnO resulted in less optimum cure time (t90), higher mechanical properties (anti-abrasion, tear strength, tensile strength, tensile modulus) and thermal conductivity at lower content compared to the conventional micro ZnO(c-ZnO).

Oriental lacquer collected from lacquer trees is widely used as surface coatings for centuries. The lacquer with little activity of laccase is called dead lacquer vividly which cannot be cured automatically. In this study, the cheap copper chloride dihydrate (K2CuCl4·2H2O) was used as a novel catalyst to cure the dead lacquer at room temperature. The redox property of K2CuCl4·2H2O was studied by cyclic voltammetry. The process of oxidative polymerization of urushiol was confirmed by FT-IR, 1H NMR, UV–vis, and electron spin-resonance spectroscopy. At 75% relative humidity, the dead lacquer film with the gloss of 101.0% and hardness of 0.84 (glass value) could be obtained when the K2CuCl4·2H2O content was 0.6 wt%. The results of the thermal properties and the chemical resistance tests showed that the dead lacquer film catalyzed by K2CuCl4·2H2O had better thermal stability and chemical resistance than those of the raw lacquer film catalyzed by laccase.

Chemical investigation of one entomopathogenic fungus Paecilomyces cateniobliquus YMF1.01799 led to the isolation and identification of six metabolites, which include three new compounds (2-3, and 5) and three known metabolites. Their structures were established by spectroscopic studies such as 1D and 2D NMR and MS analysis. Insect growth experiments suggested that polyketide-derived compound 1 showed significant inhibitory effect on the growth of cotton bollworm Helicoverpa armigera, while terpenoid-derived metabolite 5 promoted the growth of the larvae. The findings revealed that the entomopathogenic fungus P. cateniobliquus could produce different types of metabolites to regulate growth of the insect.

With the increasing of mechanization of coal mining, the fine coal content in raw coal is more and more, which makes the work of dewatering difficult. The constant voltage and constant current electro-osmosis, combined with vacuum filtration were adopted to dewater the fine coal. The dewatering efficiency can be improved and the moisture of cake can be reduced when the electric field was imposed. When the initial electric field strength is less than 40 V/cm, the precipitation rate of constant voltage electro-osmosis dewatering (EOD) higher than the constant current EOD, can reach 30%. When the initial electric field higher than 40 V/cm, the Precipitation rate of constant current EOD higher than the constant voltage EOD, can reach 55%.

Investigation into the temperature programmed reduction (TPR) of bulk or γ-Al2O3 supported molybdenum trioxide using n-hexane as a carbon source in hydrogen was carried out. The resulting catalyst was evaluated using dibenzothiophene (DBT) as a model compound for the hydrodesulfurization (HDS). The results show that the utilization of n-hexane can lower the temperature, to fulfill carburization to some extent. For DBT HDS, however, there exists an optimal temperature at which carburization is carried out, leading to a high activity of the resulting catalyst. In these experiments, it has been found that the resulting catalyst exhibits the highest DBT HDS activity if the precursor, MoO3/γ-Al2O3, with 30% theoretic loading, is carburized at 620°C under atmospheric pressure and 0.025 mol ratio of n-hexane to hydrogen in carburizing reagents.

The effects of two-stage aging and retrogression and reaging heat treatment on the fracture toughness and stress corrosion cracking resistance of 7475 alloy were studied. The fracture toughness, conductivity and strength of samples of nine groups under duplex aging conditions and three retrogression and reaging heat treatments were also measured. Incorporating the microstructure and property, we found that when the condition of the first order aging kept identical, the fracture toughness and stress corrosion cracking resistance increase with aging time and the second aging temperature. The optimal treatment conditions are (115°C×7h+185°C×13h) among all tested two-stage aging treatments. Although the 7475 alloy treated by RRA method shows the highest strength and its stress corrosion cracking resistance after twenty minutes retrogression can also reach the same level as those by the optimal treatment of (115°C×7h+185°CsX13h), the fracture toughness is even low.

The interfacial dilational viscoelastic properties of hydrophobically associating block copolymer composed of acrylamide (AM) and a low amount of 2‐ethylhexyl acrylate (EHA) (

Background & Aims Iron is an essential metal for fundamental metabolic processes, but little is known regarding the involvement of iron in other nutritional disorders. In the present study, we investigated disordered iron metabolism in a murine model of hereditary tyrosinemia type I (HT1), a disease of the tyrosine degradation pathway. Methods We analysed the status of iron accumulation following NTBC withdrawal from Fah −/− mice, a murine model for HT1. Liver histology and serum parameters were used to assess the extent of liver injury and iron deposition. To determine the physiological significance of iron accumulation, mice were subjected to a low-iron food intake to reduce the iron accumulation. Mechanistic studies were performed on tissues and cells using immunoblotting, qRT-PCR, adenovirus transfection and other assays. Results Severe iron overload was observed in the murine model of HT1 with dramatically elevated hepatic and serum iron levels. Mechanistic studies revealed that downregulation and dysfunction of Tfr2 decreased hepcidin, leading to iron overload. The Fah −/− hepatocytes lost the ability of transferrin-sensitive induction of hepcidin. Forced expression of Tfr2 in the murine liver reduced the iron accumulation. Moreover, transcription factor Sp1 was downregulated and identified as a new regulator of Tfr2 here. Additionally, low-iron food intake effectively reduced the iron deposits, protected the liver and prolonged the survival in these mice. Conclusions Iron was severely overloaded in the HT1 mice via the Sp1/Tfr2/Hepcidin axis. The iron overload induced liver injury in the HT1 mice, and reduction of the iron accumulation ameliorated liver injury. Lay summary Primary and secondary iron overload is an abnormal status affecting millions of people worldwide. Here, we reported severe iron overload in a murine model of HT1, a disease of the tyrosine degradation pathway, and elucidated the mechanistic basis and the physiological significance of iron overload in HT1. These studies are of general interest not only with respect to secondary iron-induced liver injury in HT1 but also are important to elucidate the crosstalk between the two metabolic pathways.

Sorafenib is a specific adenosine triphosphate–competitive RAF inhibitor used as a first-line treatment of advanced hepatocellular carcinoma (HCC). However, the responses are variable, reflecting heterogeneity of the disease, while the resistance mechanism remains poorly understood. Here, we report that sorafenib treatment can exacerbate disease progression in both patient-derived xenografts and cell line–derived xenografts and that the therapeutic effect of the drug inversely covaries to the ratio of epithelial cell adhesion molecule–positive cells, which may be tumor initiating cells in HCC. The TSC2-AKT cascade mediates this sorafenib resistance. In response to sorafenib treatment, formation of the TSC1/2 complex is enhanced, causing increased phosphorylation of AKT, which contributes to up-regulation of “stemness”-related genes in epithelial cell adhesion molecule–positive cells and enhancement of tumorigenicity. The expression of TSC2 negatively correlated with prognosis in clinical sorafenib therapy. Furthermore, all-trans retinoic acid decreased AKT activity, reduced the epithelial cell adhesion molecule–positive cell population enriched by sorafenib, and potentiated the therapeutic effect of sorafenib in the patient-derived xenograft model. Conclusion: Our findings suggest that a subtype of HCC is not suitable for sorafenib therapy; this resistance to sorafenib can be predicted by the status of TSC2, and agents inducing differentiation of tumor initiating cells (e.g., all-trans retinoic acid) should improve the prognosis of this subtype of HCC.(Hepatology 2015;62:1791–1803)

Two aerobic, Gram-positive actinomycetes, designated YIM 77502(T) and YIM 77510(T), were isolated from geothermally heated soil of Tengchong county, Yunnan province, south-west China. The taxonomic position of strains YIM 77502(T) and YIM 77510(T) were investigated by a polyphasic approach. Phylogenetic analyses based on 16S rRNA gene sequences showed that strains YIM 77502(T) and YIM 77510(T) belong to the genus Actinomadura. Both strains form extensively-branched substrate and aerial mycelia which differentiated into short spore chains. The cell wall of the two strains contained meso-diaminopimelic acid, while the whole-cell sugars detected were glucose, madurose, mannose and rhamnose. The polar lipid profile of strain YIM 77502(T) was found to consist of diphosphatidylglycerol, phosphatidylinositol mannoside, phosphatidylinositol, two unidentified phospholipids and an unidentified polar lipid, while strain YIM 77510(T) consisted of diphosphatidylglycerol, phosphatidylinositol mannoside and phosphatidylinositol. The respiratory quinones of strains YIM 77502(T) and YIM 77510(T) were MK-9(H6) and MK-9(H8). The major fatty acids (10 %) of strain YIM 77502(T) were C17:0, iso-C16:0, C17:010-methyl and iso-C18:0, and those of strain YIM 77510(T) were iso-C16:0, C17:010-methyl and iso-C18:0. The G+C contents of strains YIM 77502(T) and YIM 77510(T) were determined to be 71.3 and 70.2 mol%, respectively. The DNA-DNA hybridization values of strains YIM 77502(T), YIM 77510(T) and their closest phylogenetic neighbours Actinomadura echinospora BCRC 12547(T) and Actinomadura umbrina KCTC 9343(T) were less than 70 %. Based on the morphological and physiological properties, and phylogenetic analyses, strains YIM 77502(T) and YIM 77510(T) are considered to represent two novel species of the genus Actinomadura, for which the names Actinomadura amylolytica sp. nov. (type strain YIM 77502(T) = DSM 45822(T) = CCTCC AA 2012024(T)) and Actinomadura cellulosilytica sp. nov. (type strain YIM 77510(T) = DSM 45823(T) = CCTCC AA 2012023(T)) are proposed.

A novel endoglucanase gene was cloned from Thermobifida halotolerans YIM 90462T, designated as thcel6A for being a member of glycoside hydrolase family 6. The gene was 1332 bp long and encoded a 443-amino-acid protein with a molecular mass of 45.9 kDa. The purified recombinant endoglucanase had optimal activity at 55 °C and pH 8.5. Thcel6A showed high hydrolytic activities at 25–55 °C and retained 58 % of initial activity after incubation at 90 °C for 1 h. It retained more than 80 % of activity after incubation for 12 h at pH values from 4 to 12. Thcel6A displayed higher hydrolytic activities in 5–15 % NaCl (w/v) than at 0 % NaCl. Activity increased 2.5-fold after incubation with 20 % (w/v) NaCl at 37 °C for 10 min. These properties suggest that this novel endoglucanase has potential for specific industrial application.

Chinese bamboo flour was chemically modified by acetylation with acetic anhydride by using trichloroacetic acid as an activation agent and the optimized condition for acetylation of bamboo flour was determined as the trichloroacetic acid amount 6.0 g per 1.5-g bamboo flour, ultrasosonication duration 40 min and the reaction time 1 h at 65°C. The composition, microstructure and thermal behavior of acetylated bamboo flour were preliminarily characterized by FT-IR, DSC and SEM etc. The acetylated bamboo flour can be molded into sheets at 130°C and 10 MPa, indicating the modified bamboo flour possesses thermalplastic performance.

C28H22N2O8Pb, orthorhombic, Pbcn (no. 60), a = 18.691(2) Å, b = 12.611(1) Å, c = 11.092(1) Å, V = 2614.7 Å3, Z = 4, Rgt(F) = 0.0220, wRref(F2) = 0.0671, T = 296 K.

The transcription factor NF-κB plays a pivotal role in innate immunity in response to a variety of stimuli, and the coordinated regulation of this pathway determines the proper host responses to extracellular signals. In this study, we identified RACK1 as a novel negative regulator of NF-κB signaling, NF-κB-mediated cytokine induction and inflammatory reactions. RACK1 physically associates with the IKK complex in a TNF-triggered manner. This interaction interferes with the recruitment of the IKK complex to TRAF2, which is a critical step for IKK phosphorylation and subsequent activation triggered by TNF. By modulating the interaction between TRAF2 and IKK, RACK1 regulates the levels of NF-κB activation in response to different intensities of stimuli. Our findings suggest that RACK1 plays an important role in controlling the sensitivity of TNF-triggered NF-κB signaling by regulating IKK activation and provide new insight into the negative regulation of inflammatory reactions.

In the title compound, C4H6N4S·0.5H2O, there are two independent pyrimidinethione units, both of which lie across mirror planes in the space groupCmca. Hence, the H atoms bonded to the ring N atoms in each molecule are disordered over two symmetry-related sites, each having an occupancy of 0.5. The water molecule lies across a twofold rotation axis parallel to [010]. The molecular components of (I) are linked by seven independent hydrogen bonds, of N—H...N, N—H...S, N—H...O and O—H...S types. A combination of disordered N—H...N hydrogen bonds and ordered N—H...S hydrogen bonds links the pyrimidinethione units into a continuous tubular structure. The water molecule acts as both a double donor of hydrogen bonds and a double acceptor, forming hydrogen bonds with components of four distinct pyrimidinethione tubes, thus linking these tubes into a three-dimensional structure.

A new approach to the synthesis of 3,5-disubstituted thiohydantoins, which uses a functionalized ionic liquid as soluble support, is described.

The reaction between hydrogen peroxide and sodium chlorate in presence of aqueous sulfuric acid was studied at various temperatures and molar concentrations of hydrogen peroxide, chlorate and sulfuric acid. The reaction rate law was established by analyzing the consumption of chlorate or hydrogen peroxide. Reaction had been found 0.5 and 1 order with respect to hydrogen peroxide and chlorate concentration, respectively. Reaction order was found about 5.99 with respect to molar concentration of sulfuric acid but it reduced to 1.64 when acidity function, h-, was substituted in place of molar concentration. The temperature dependence of the reaction was also investigated and pre-exponential Arrhenius parameter as well as activation energy were determined. Reaction mechanism compatible with the reaction kinetics was proposed.

In the crystal of the title compound, C11H15NO4, the molecules are linked into sheets by N—H...O and C—H...O hydrogen bonds. Within the molecule, the 1,4-dihydropyridine ring exhibits a distinctive planar conformation [r.m.s. deviation from the mean plane of 0.009 (3)Å], and the other non-H atoms are almost coplanar [r.m.s. deviation = 0.021 (3) Å] with the 1,4-dihydropyridine ring. The conformation of the latter is governed mainly by two intramolecular C—H...O non-classical interactions.

In 1-(4-chloroanilinomethyl)-5-(4-chlorophenyl)-1,3,5-triazinane-2-thione, C(16)H(16)Cl(2)N(4)S, there are two independent molecules in the asymmetric unit which form inversion dimers via two weak N-H...S hydrogen bonds. The dimers are then linked into C(9)C(14) chains by a C-H...S hydrogen bond and a C-H...Cl contact. In 1-(anilinomethyl)-5-phenyl-1,3,5-triazinane-2-thione, C(16)H(18)N(4)S, molecules are linked into complex sheets via a combination of N-H...S and C-H...pi hydrogen bonds.

In this paper, we describe a novel technology for three dimensional (3D) microstructure manufacture, which is based on the laser-induced thermoplastic expansion. A thermoplastic material melted by laser heating grows in the surrounding space filled with liquid, and after the laser irradiation is switched off, it immediately solidifies into a protuberant shape because of the heat release to the liquid surroundings. The size of 3D microstructure is controlled by the parameter of laser irradiation, including focal spot diameter, power density and irradiation time. This technology does not require expensive equipments or complicated steps, like molding, masking or bonding. We can fabricate microstructures swiftly, with a low cost. We have developed the experiment setup, which consists of laser, optical components and liquid container. And paraffin dots have been manufactured with this experiment setup.

Polyhedral copper oxide (CuO) nanoparticles were successfully prepared by a molten-salt method without any surfactant or template. Scanning electron microscopy images of the copper oxide samples demonstrated that the as-prepared nanoparticles have a polyhedral structure. The catalytic performances of copper oxide on the degradation of Rhodamine B in the presence of hydrogen peroxide were investigated. The results show that the polyhedral copper oxide nanoparticles exhibited much better catalytic performance in the degradation of Rhodamine B with hydrogen peroxide than commercial nano particles, even with smaller specific surface area. The possible reason can be attributed to the synergistic effect of high crystallinity and the exposed facets formed by polyhedral structure.

Ba0.7Sr0.3TiO3 (BST) nanocatalysts were prepared by a Sol-Gel method at pH of 2.4 and 4, respectively, both of which were presented as tetragonal phase. TEM images indicated that the BST sample obtained at pH = 2.4 was nanoparticles with an average size of about 100 nm, while that obtained at pH = 4 was gridding structures composed of nanocubes with a mean size of 100 nm. The photocatalytic behavior of BST in the degradation of Rhodamine B (RhB) was investigated. It was found that the BST catalysts with gridding structures showed much better photocatalytic performance than the BST nanoparticles. This could be attributed to the fact that the photo-generated carriers can migrate easily through the gridding-structured BST sample, which would enhance the photocatalytic activity during the degradation process. It was also found that both BST photocatalysts in this work showed good catalytic stability.

This article reports a novel color tuning technology based on micro-nano structure and metal nanolayer. On the basis of theoretical analysis, a color tuning model is established. Aluminum(Al) metal nanolayers are magnetron-sputtered on the surfaces of porour alumina (PA) templates with the pore-depths of 250 nm and 410 nm, and their pictures and reflective interference spectra show clearly green and red colors, respectively. These results indicate that different colors can be achieved just by controlling the pore-depth in PA templates. As comparison, a nanolayer of chromium(Cr) metal is magnetron-sputtered on the surface of PA template about 410 nm in pore-depth, the reflective interference spectra show that color tuning can also be achieved in the visible spectrum by changing the material and the thickness of the metal nanolayer. Moreover, a color pattern is further prepared based on mask and local sputtering method. Theoretical and experimental results validate the feasibility of this color tuning method.