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Jun Guo - Top 30 Publications

MiR-92a and miR-486 are potential diagnostic biomarkers for mercury poisoning and jointly sustain NF-κB activity in mercury toxicity.

Occupational and environmental exposure to mercury is a public health concern worldwide. Although the altered epigenetic regulatory features, such as microRNA, have been associated with mercury exposure, the underlying molecular mechanism is not well illuminated. This study aimed to confirm that hsa-miR-92a and hsa-miR-486 are novel diagnostic biomarkers of occupational mercury poisoning, and to explore the underlying mechanism of miR-92a and miR-486 in mercury toxicity. RT-qPCR assays and receiver operating characteristics curve analyses were conducted to confirm the diagnostic value of miR-92a and miR-486 as biomarkers of occupational mercury poisoning. Dual-luciferase assay was applied to confirm the target gene of miR-92a and miR-486 in vitro. Then, we established an in-vitro model where miR-92a and miR-486 were overexpressed or knocked down in HEK-293 and HUVEC cells. RT-qPCR and western blotting were used to analyze gene and protein expression levels. Cell apoptosis was determined by flow cytometry. Results show that miR-92a and miR-486 expression levels were up-regulated in workers exposed to occupational mercury. Upregulation of miR-92a and miR-486 may play a crucial role in mercury toxicity by jointly activating the NF-κB signaling pathway via targeting KLF4 and Cezanne, respectively.

Glycosylation stabilizes hERG channels on the plasma membrane by decreasing proteolytic susceptibility.

The human ether-a-go-go related gene (hERG)-encoded channel hERG undergoes N-linked glycosylation at position 598, which is located in the unusually long S5-pore linker of the channel. In other work we have demonstrated that hERG is uniquely susceptible to proteolytic cleavage at the S5-pore linker by proteinase K (PK) and calpain (CAPN). The scorpion toxin BeKm-1, which binds to the S5-pore linker of hERG, protects hERG from such cleavage. In the present study, our data revealed that, compared with normal glycosylated hERG channels, nonglycosylated hERG channels were significantly more susceptible to cleavage by extracellular PK. Furthermore, the protective effect of BeKm-1 on hERG from PK-cleavage was lost when glycosylation of hERG was inhibited. The inactivation-deficient mutant hERG channels S620T and S631A were resistant to PK cleavage, and inhibition of glycosylation rendered both mutants susceptible to PK cleavage. Compared with normal glycosylated channels, nonglycosylated hERG channels were also more susceptible to cleavage mediated by CAPN, which was present in the medium of human embryonic kidney cells under normal culture conditions. Inhibition of CAPN resulted in an increase of nonglycosylated hERG current. In summary, our results revealed that N-linked glycosylation protects hERG against protease-mediated degradation and thus contributes to hERG channel stability on the plasma membrane.-Lamothe, S. M., Hulbert, M., Guo, J., Li, W., Yang, T., Zhang, S. Glycosylation stabilizes hERG channels on the plasma membrane by decreasing proteolytic susceptibility.

Boosting Hot Electrons in Hetero-Superstructures for Plasmon-Enhanced Catalysis.

Hetero-nanostructures featured with both strong plasmon absorption and high catalytic activity are believed to be ideal platforms to realize efficient light-driven catalysis. However, in reality it remains great challenge to acquire high performance catalysis in such hetero-nanostructures due to poor generation and transfer of plamson-induced hot electrons. In this report, we demonstrate that Au [email protected] superstructures ([email protected] SSs), where the ordered Pd nanoarrays are precisely grown on Au nanorod surfaces via solution-based seed-mediated approach, would be an excellent solution for this challenge. Both experiment and theory disclose that the ordered arrangement of Pd on Au nanorod surfaces largely promotes hot electron generation and transfer via amplified local electromagnetic field and decreased electron-phonon coupling, respectively. Each effect is separately highlighted in experiment by the significant plasmon-enhanced catalytic activity of [email protected] SSs in two types of important reactions with distinct timescale of bond-dissociation event: molecular oxygen activation and carbon-carbon coupling reaction. This works opens the door to design and application of new generation photocatalysts.

Bacterial communities associated with the ectoparasitic mites Varroa destructor and Tropilaelaps mercedesae of honey bees (Apis mellifera).

Varroa and Tropilaelaps mites have been reported as serious ectoparasites of honey bees (Apis mellifera). In this study, bacterial communities associated with Varroa destructor and Tropilaelaps mercedesae from Northern Thailand were determined, using both culture-dependent and culture-independent approaches. Adult female mites were collected from apiaries in Chiang Mai and Lampang provinces. Culturable bacteria were isolated from individual mites. On average, we observed approximately 1340 and 1140 CFU/mite in Varroa and Tropilaelaps, respectively. All isolates were assigned to the genus Enterococcus. Six samples of genomic DNA from 30-50 mites were extracted and subjected to pyrosequencing of bacterial 16S rRNA amplicons. The resulting 81 717 sequences obtained from Varroa were grouped into 429 operational taxonomic units (OTUs). The most abundant bacteria in Varroa mites belonged to the family Enterobacteriaceae, especially the genera Arsenophonus, Enterobacter, and Proteus.For Tropilaelaps mites, 84 075 sequences were obtained and clustered into 166 OTUs, within which the family Enterococcaceae (particularly the genus Enterococcus) was predominant. Localization of bacteria in the mites using fluorescence in situ hybridization with two universal bacterial probes revealed that these bacteria were in the caecum of the mites.Taxon-specific Enterobacteriaceae and Arsenophonus probes also confirmed their localization in the caecum of Varroa.

VEGF secreted by mesenchymal stem cells mediates the differentiation of endothelial progenitor cells into endothelial cells via paracrine mechanisms.

Stem cell therapy is a promising treatment strategy for ischemic diseases. Mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) adhere to each other in the bone marrow cavity and in in vitro cultures. We have previously demonstrated that the adhesion between MSCs and EPCs is critical for MSC self‑renewal and their multi‑differentiation into osteoblasts and chondrocytes. In the present study, the influence of the indirect communication between EPCs and MSCs on the endothelial differentiation potential of EPCs was investigated, and the molecular mechanisms underlying MSC‑mediated EPC differentiation were explored. The effects of vascular endothelial growth factor (VEGF), which is secreted by MSCs, on EPC differentiation via paracrine mechanisms were examined via co‑culturing MSCs and EPCs. Reverse transcription-quantitative polymerase chain reaction and western blot analysis were used to detect the expression of genes and proteins of interest. The present results demonstrated that co‑culturing EPCs with MSCs enhanced the expression of cluster of differentiation 31 and von Willebrand factor, which are specific markers of an endothelial phenotype, thus indicating that MSCs may influence the endothelial differentiation of EPCs in vitro. VEGF appeared to be critical to this process. These findings are important for the understanding of the biological interactions between MSCs and EPCs, and for the development of applications of stem cell‑based therapy in the treatment of ischemic diseases.

Analysis of subcellular structural tension in axonal growth of neurons.

The growth and regeneration of axons are the core processes of nervous system development and functional recovery. They are also related to certain physiological and pathological conditions. For decades, it has been the consensus that a new axon is formed by adding new material at the growth cone. However, using the existing technology, we have studied the structural tension of the nerve cell, which led us to hypothesize that some subcellular structural tensions contribute synergistically to axonal growth and regeneration. In this review, we classified the subcellular structural tension, osmotic pressure, microfilament and microtubule-dependent tension involved controllably in promoting axonal growth. A squeezing model was built to analyze the mechanical mechanism underlying axonal elongation, which may provide a new view of axonal growth and inspire further research.

Postnatal deletion of β-catenin in osterix-expressing cells is necessary for bone growth and intermittent PTH-induced bone gain.

wnt/β-catenin signaling has been shown to influence bone homeostasis and is important for parathyroid hormone (PTH)-induced bone gain. To further understand the role of β-catenin in the early stages of osteoblastic lineage cells for postnatal bone homeostasis and the anabolic actions of PTH on bone, we examined mice with postnatal disruption of β-catenin in osterix-expressing cells (β-catenin KO mice) by mating floxed β-catenin mice with transgenic mice expressing cre under the control of the osterix promoter suppressible by doxycycline. After withdrawal of doxycycline, β-catenin KO mice developed progressive bone loss, ectopic cartilage formation, accumulation of mesenchymal stromal cells, and bone marrow adiposity. The β-catenin-defective osteoblasts sorted by flow cytometry from β-catenin KO mice exhibited decreased EdU incorporation, increased annexin V activity, and profound alterations in gene expression including wnt target genes, osteoclast regulators, and osteoblast markers. A dramatic increase in osteoclasts was observed in both neonatal and postnatal β-catenin KO mice. Intermittent administration of PTH for 4 weeks significantly increased bone mass in control mice; however, this anabolic effect of PTH was substantially blunted in β-catenin KO mice. Our data indicate that β-catenin in osterix-expressing cells is required for postnatal osteoblast differentiation, osteoblast proliferation, and bone resorption, and is essential for the anabolic actions of PTH in bone.

Fabry-Perot Cavity-Enhanced Optical Absorption in Ultrasensitive Tunable Photodiodes Based on Hybrid 2D Materials.

Monolayer two-dimensional (2D) transition metal dichalcogenides (TMDs) show interesting optical and electrical properties because of their direct bandgap. However, the low absorption of atomically thin TMDs limits their applications. Here, we report enhanced absorption and optoelectronic properties of monolayer molybdenum disulfide (MoS2) by using an asymmetric Fabry-Perot cavity. The cavity is based on a hybrid structure of MoS2/ hexagonal boron nitride (BN)/Au/SiO2 realized through layer-by-layer vertical stacking. Photoluminescence (PL) intensity of monolayer MoS2 is enhanced over 2 orders of magnitude. Theoretical calculations show that the strong absorption of MoS2 comes from photonic localization on the top of the microcavity at optimal BN spacer thickness. The n/n(+) MoS2 homojunction photodiode incorporating this asymmetric Fabry-Perot cavity exhibits excellent current rectifying behavior with an ideality factor of 1 and an ultrasensitive and gate-tunable external photo gain and specific detectivity. Our work offers an effective method to achieve uniform enhanced light absorption by monolayer TMDs, which has promising applications for highly sensitive optoelectronic devices.

Role of perforin secretion from CD8+ T-cells in neuronal cytotoxicity in multiple sclerosis.

Multiple sclerosis (MS) is the most prevalent autoimmune disease of the central nervous system, and is characterized by inflammation and myelin damage. The immune system initiates the autoimmune response, although the mechanisms of neuronal damage have not been elucidated. The purpose of the present study was to investigate autoreactive CD4+ and CD8(+) T lymphocytes, in conjunction with other inflammatory cells and cytokines in active MS lesions.

NKT-cell glycolipid agonist as adjuvant in synthetic vaccine.

NKT cells are CD1d-restricted, glycolipid antigen-reactive, immunoregulatory T lymphocytes that can serve as a bridge between the innate and adaptive immunities. NKT cells have a wide range of therapeutic application in autoimmunity, transplant biology, infectious disease, cancer, and vaccinology. Rather than triggering "danger signal" and eliciting an innate immune response, αGalCer-based NKT-cell agonist act via a unique mechanism, recruiting NKT cells which play a T helper-like role even without peptide as Th epitope. Importantly, the non-polymorphism of CD1d render glycolipid a universal helper epitope, offering the potential to simplify the vaccine construct capable of eliciting consistent immune response in different individuals. This review details recent advances in the design of synthetic vaccines using NKT-cell agonist as adjuvant, highlighting the role of organic synthesis and conjugation technique to enhance the immunological actives and to simplify the vaccine constructs.

Agronomic Traits and Molecular Marker Identification of Wheat-Aegilops caudata Addition Lines.

Aegilops caudata is an important gene source for wheat breeding. Intensive evaluation of its utilization value is an essential first step prior to its application in breeding. In this research, the agronomical and quality traits of Triticum aestivum-Ae. caudata additions B-G (homoeologous groups not identified) were analyzed and evaluated. Disease resistance tests showed that chromosome D of Ae. caudata might possess leaf rust resistance, and chromosome E might carry stem rust and powdery mildew resistance genes. Investigations into agronomical traits suggested that the introduction of the Ae. caudata chromosome in addition line F could reduce plant height. Grain quality tests showed that the introduction of chromosomes E or F into wheat could increase its protein and wet gluten content. Therefore, wheat-Ae. caudata additions D-F are all potentially useful candidates for chromosome engineering activities to create useful wheat-alien chromosome introgressions. A total of 55 EST-based molecular markers were developed and then used to identify the chromosome homoeologous group of each of the Ae. caudata B-G chromosomes. Marker analysis indicated that the Ae. caudata chromosomes in addition lines B to G were structurally altered, therefore, a large population combined with intensive screening pressure should be taken into consideration when inducing and screening for wheat-Ae. caudata compensating translocations. Marker data also indicated that the Ae. caudata chromosomes in addition lines C-F were 5C, 6C, 7C, and 3C, respectively, while the homoeologous group of chromosomes B and G of Ae. caudata are as yet undetermined and need further research.

Host-induced gene silencing of the MAPKK gene PsFUZ7 confers stable resistance to wheat stripe rust.

RNA interference (RNAi) is a powerful genetic tool to accelerate research in plant biotechnology and to control biotic stresses by manipulating target gene expression. However, the potential of RNAi in wheat to efficiently and durably control the devastating stripe rust fungus Puccinia striiformis f. sp. tritici (Pst), remained largely under explored, so far. To address this issue, we generated transgenic wheat lines expressing double-stranded RNA targeting PsFUZ7 transcripts of Pst. We analyzed expression of PsFUZ7 and related genes, and resistance traits of the transgenic wheat lines. We show that PsFUZ7 is an important pathogenicity factor which regulates infection and development of Pst. A PsFUZ7 RNAi construct stably expressed in two independent transgenic wheat lines confers strong resistance to Pst. Pst hyphal development is strongly restricted, and necrosis of plant cells in resistance responses was significantly induced. We conclude that trafficking of RNA molecules from wheat plants to Pst may lead to a complex molecular dialogue between wheat and the rust pathogen. Moreover, we confirm the RNAi-based crop protection approaches can be used as a novel control strategy against rust pathogens in wheat.

Three-Dimensional WO3 Nanoplate/Bi2S3 Nanorod Heterojunction as a Highly Efficient Photoanode for Improved Photoelectrochemical Water Splitting.

The rational design of semiconductor photoanodes with sufficient light absorption, efficient photogenerated carrier separation, and fast charge transport is crucial for photoelectrochemical (PEC) water splitting. Incorporating a small-band-gap semiconductor to a large-band-gap material with matched energy band position is a promising route to improve the light harvesting and charge transport. Herein, we report the fabrication of a three-dimensional heterojunction with uniform Bi2S3 nanorods on WO3 nanoplates by hydrothermal process and chemical bath deposition. The seed layer strategy was used to assist the growth of Bi2S3 nanorods for perfect interface contact between WO3 and Bi2S3. The as-prepared WO3/Bi2S3 composite exhibited a much enhanced photocurrent (5.95 mA/cm(2) at 0.9 V vs reversible hydrogen electrode), which is 35 and 1.4 times higher than those of pristine WO3 and WO3/Bi2S3 composite without a seed layer, respectively. In addition, higher incident photon-to-current conversion efficiency (68.8%) and photoconversion efficiency (1.70%) were achieved. The enhancement mechanism was investigated in detail, and the sufficient light absorption, efficient charge transport, and high carrier density simultaneously contribute to the improved PEC activity. These findings will open up new opportunities to develop other highly efficient heterostructures as photoelectrodes for PEC applications.

Self-Assembly of Chiral Gold Clusters into Crystalline Nanocubes of Exceptional Optical Activity.

Self-assembly of inorganic nanoparticles into ordered structures is of interest in both science and technology because it is expected to generate new properties through collective behavior; however, such nanoparticle assemblies with characteristics distinct from those of individual building blocks are rare. Herein we use atomically precise Au clusters to make ordered assemblies with emerging optical activity. Chiral Au clusters with strong circular dichroism (CD) but free of circularly polarized luminescence (CPL) are synthesized and organized into uniform body-centered cubic (BCC) packing nanocubes. Once the ordered structure is formed, the CD intensity is significantly enhanced and a remarkable CPL response appears. Both experiment and theory calculation disclose that the CPL originates from restricted intramolecular rotation and the ordered stacking of the chiral stabilizers, which are fastened in the crystalline lattices.

Stabilizing a Tubulysin Antibody-Drug Conjugate To Enable Activity Against Multidrug-Resistant Tumors.

The tubulysins are promising anticancer cytotoxic agents due to the clinical validation of their mechanism of action (microtubule inhibition) and their particular activity against multidrug-resistant tumor cells. Yet their high potency and subsequent systemic toxicity make them prime candidates for targeted therapy, particularly in the form of antibody-drug conjugates (ADCs). Here we report a strategy to prepare stable and bioreversible conjugates of tubulysins to antibodies without loss of activity. A peptide trigger along with a quaternary ammonium salt linker connection to the tertiary amine of tubulysin provided ADCs that were potent in vitro. However, we observed metabolism of a critical acetate ester of the drug in vivo, resulting in diminished conjugate activity. We were able to circumvent this metabolic liability with the judicious choice of a propyl ether replacement. This modified tubulysin ADC was stable and effective against multidrug-resistant lymphoma cell lines and tumors.

One-pot fabrication of N-doped graphene supported dandelion-like PtRu nanocrystals as efficient and robust electrocatalysts towards formic acid oxidation.

Engineering the architectures of metal nanocatalysts offers a valid approach for the development of electrocatalysts with greatly enhanced performances. Herein, we report the one-pot method to successfully fabricate the N-doped graphene (NG) supported dandelion-like PtRu nanocrystals. Such dandelion-like nanocrystals with different compositions can be readily tuned via the addition of different amounts of RuCl3. By virtue of the large accessible surface active areas, synergistic and electronic effect, as well as the successful introduction of NG, the as-obtained PtRu/NG with optimized compositions display outstandingly high electrocatalytic activity towards formic acid electrooxidation with the mass and specific activities of 1857.4mAmg(-1) and 18.3mAcm(-2), 6.3 and 3.3 times higher than those of commercial Pt/C, respectively. Moreover, the Pt1Ru1/NG can endure at least 500 cycles with less activity decay, showing a new class of Pt-based electrocatalysts with enhanced performance for fuel cells and beyond.

Random regression analyses to model the longitudinal measurements of yolk proportions in the laying chicken.

Cubic spline function was used in a genetic evaluation to model the change of yolk proportion over the lay life. A total of 19,862 yolk proportion records of 2,324 hens was used. The evaluated submodels consisted of 3 to 6 knot models. The same knots were fitted for genetic and permanent environmental splines. The residual effects were specified to be independently and normally distributed, but with heterogeneous variance for each test week. (Co)variance components were estimated by the average information restricted maximum likelihood (AIREML) method. The best fitting random regression model (RRM) was a submodel with 4 knots at 32, 36, 52, and 72 wk of age for genetic and permanent environmental effects. The estimate of genetic variance was larger than that of permanent environmental variance at the same time point. The heritability of yolk proportion ranged from 0.32 to 0.55, and the repeatability ranged between 0.45 and 0.73. The genetic correlations between test wk were from moderate to unity. To the best of our knowledge, this was the first report on the use of a RRM to evaluate yolk proportion. The results of this study showed that random regression models with the spline function could be used for improvement of yolk proportion.

Cobalt-Catalyzed Asymmetric Sequential Hydroboration/Hydrogenation of Internal Alkynes.

A highly regio- and enantioselective cobalt-catalyzed hydroboration/hydrogenation of internal alkynes with HBpin and a hydrogen balloon in one pot was developed. A new type of chiral imidazoline iminopyridine (IIP) ligand was introduced for the first time in this novel and efficient strategy. This protocol used relatively simple and available starting materials with good functional group tolerance to construct more valuable chiral secondary organoboronates. The primary mechanistic studies illustrated that the cobalt-catalyzed regioselective hydroboration of alkynes did initially occur followed by HBpin-promoted and cobalt-catalyzed enantioselective hydrogenation of alkenylboronates.

LARP1 is regulated by the XIST/miR-374a axis and functions as an oncogene in non-small cell lung carcinoma.

La-related protein 1 (LARP1) is a conserved RNA-binding protein and is known to regulate 5'-terminal oligopyrimidine tract (TOP) mRNA translation. Dysregulated LARP1 has been reported to be related to the development of several cancers. However, the exact function and mechanism of LARP1 in non-small cell lung cancer (NSCLC) is largely unknown. In the present study, we found that the mRNA levels of LARP1 were increased in NSCLC cells compared to those in normal control cells. Knockdown of LARP1 inhibited cell proliferation, migration and invasion in NSCLC cells and tumourigenicity in H520 cells. Both in vitro and in vivo analyses confirmed that STAT3 signalling was inactivated by the knockdown of LARP1. Moreover, LARP1 was identified as a direct target of miR-374a. Overexpression of miR-374a attenuated the promotor effects of LARP1 by inhibiting proliferation, metastasis and STAT3 signalling. Clinically, LARP1 was markedly overexpressed in NSCLC tissues, and upregulated LARP1 was correlated with tumour progression and poor survival. The expression of miR-374a was negatively correlated with the expression of LARP1 in NSCLC tissues. Furthermore, we found that XIST functioned as a competing endogenous RNA to suppress miR-374a, which regulated its downstream target LARP1. In summary, we suggest that the dysfunction of the XIST/miR-374a/LARP1 axis contributes to NSCLC and may serve as a promising therapeutic strategy for treatment.

MNK1/2 inhibition limits oncogenicity and metastasis of KIT-mutant melanoma.

Melanoma can be stratified into unique subtypes based on distinct pathologies. The acral/mucosal melanoma subtype is characterized by aberrant and constitutive activation of the proto-oncogene receptor tyrosine kinase C-KIT, which drives tumorigenesis. Treatment of these melanoma patients with C-KIT inhibitors has proven challenging, prompting us to investigate the downstream effectors of the C-KIT receptor. We determined that C-KIT stimulates MAP kinase-interacting serine/threonine kinases 1 and 2 (MNK1/2), which phosphorylate eukaryotic translation initiation factor 4E (eIF4E) and render it oncogenic. Depletion of MNK1/2 in melanoma cells with oncogenic C-KIT inhibited cell migration and mRNA translation of the transcriptional repressor SNAI1 and the cell cycle gene CCNE1. This suggested that blocking MNK1/2 activity may inhibit tumor progression, at least in part, by blocking translation initiation of mRNAs encoding cell migration proteins. Moreover, we developed an MNK1/2 inhibitor (SEL201), and found that SEL201-treated KIT-mutant melanoma cells had lower oncogenicity and reduced metastatic ability. Clinically, tumors from melanoma patients harboring KIT mutations displayed a marked increase in MNK1 and phospho-eIF4E. Thus, our studies indicate that blocking MNK1/2 exerts potent antimelanoma effects and support blocking MNK1/2 as a potential strategy to treat patients positive for KIT mutations.

Shackling Effect Induced Property Differences in Metallo-Supramolecular Polymers.

We demonstrate here the synthesis of a novel class of metallo-supramolecular polymers with shackled structure, via the coordination of cyclic di(bis-terpyridine-triphenyl ether ester) ligands with ruthenium(II) ions. The constraint from the ring topology via the shackling of ligands provides novel properties to these metallo-supramolecular polymers, including the formation of dendritic crystals, red-shift of absorption bands in the UV-vis spectra from interchain charge-transfer transitions, and a typical flash-type memory behavior.

Ciceribacter thiooxidans sp. nov., a novel nitrate-reducing thiosulfate-oxidizing bacterium isolated from sulfide-rich anoxic sediment.

Two facultative chemolithotrophic, nitrate-reducing thiosulfate-oxidizing strains, F43b(T) and F21, were isolated from the sulfide-rich anoxic sediment of an urban creek in Pearl River Delta, China. Both strains were Gram-negative, facultatively anaerobic, non-spore-forming and rod-shaped with a flagellum. Phylogenetic analyses of 16S rRNA genes and the thrC, recA, glnII and atpD housekeeping genes revealed that the type strain shared high sequence similarities to Ciceribacter lividus MSSRFBL1(T), with 98.8, 90.9, 94.8, 95.4 and 96.1 % identity, respectively. In addition, the major isoprenoid quinone (ubiquinone Q-10) and the DNA G+C content (66.0 mol%) of the type strain were similar to those of Ciceribacter lividus MSSRFBL1(T). These results strongly support the classification of strains F43b(T) and F21 into the genus Ciceribacter. However, these strains diverged markedly from strain MSSRFBL1(T) with respect to several physiological and biochemical properties such as their semi-translucent colonies and nitrate-reducing and simultaneous thiosulfate-oxidizing respiration. Furthermore, the predominant fatty acids of strain F43b(T) were summed feature 2 (C18 : 1ω9t and/or C18 : 1ω9c and/or C18 : 1ω11t), C14 : 0 3-OH, C18 : 0 and C16 : 0, and its polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidymonomethylethanolamine and an unidentified glycolipid, which represented another two significant differences from strain MSSRFBL1(T). Importantly, the DNA-DNA relatedness between strain F43b(T) and MSSRFBL1(T) was only 47.7 %. Based on the aforementioned polyphasic taxonomic results, the two isolates are suggested to represent a novel species of the genus Ciceribacter, for which the name Ciceribacterthiooxidans sp. nov. is proposed; the type strain is F43b(T) (=CCTCC AB 2016062(T)=KCTC 52231(T)).

Binostril endoscopic transsphenoidal neurosurgery for pituitary adenomas: experience with 42 patients.

Here we review the technical aspects of our experience with the neuroendoscopic bilateral nostril (binostril) transsphenoidal approach for pituitary adenomas. A total of 42 patients were treated in our hospital from September 2013 to December 2015. Total tumor resection was completed in 31 cases, nearly full resection was achieved in 9 cases, and partial resection was achieved in 2 cases. In most cases clinical symptoms were relieved after surgery. These included 18/22 cases with visual field and vision disorders; 19/25 cases with headaches; 11/15 cases where high baseline PRL returned to normal levels; 6/7 cases where elevated blood GH returned to normal levels; and 2/3 cases where elevated blood ACTH returned to normal levels after surgery. Postoperative complications were observed in 13 patients: 8 cases of diabetes insipidus, 4 cases of cerebrospinal fluid rhinorrhea, and 1 case of subarachnoid hemorrhage. Among the key advantages of the neuroendoscopic binostril transsphenoidal approach for pituitary adenoma resection are its minimally-invasive nature, clear exposure of the operative field, high full-excision rates, improved peri-operative safety, and minor patient trauma with fewer postoperative complications.

Face Recognition via Collaborative Representation: Its Discriminant Nature and Superposed Representation.

Collaborative representation methods, such as sparse subspace clustering (SSC) and sparse representation-based classification (SRC), have achieved great success in face clustering and classification by directly utilizing the training images as the dictionary bases. In this paper, we reveal that the superior performance of collaborative representation relies heavily on the sufficiently large class separability of the controlled face datasets such as Extended Yale B. On the uncontrolled or undersampled dataset, however, collaborative representation suffers from the misleading coefficients of the incorrect classes. To address this limitation, inspired by the success of linear discriminant analysis (LDA), we develop a superposed linear representation classifier (SLRC) to cast the recognition problem by representing the test image in term of a superposition of the class centroids and the shared intra-class differences. In spite of its simplicity and approximation, the new SLRC largely improves the generalization ability of collaborative representation, and competes well with more sophisticated dictionary learning techniques, on the experiments of AR and FRGC databases. Enforced with the sparsity constraint, SLRC achieves the state-of-the-art performance on FERET database using single sample per person.

PAK signalling drives acquired drug resistance to MAPK inhibitors in BRAF-mutant melanomas.

Targeted BRAF inhibition (BRAFi) and combined BRAF and MEK inhibition (BRAFi and MEKi) therapies have markedly improved the clinical outcomes of patients with metastatic melanoma. Unfortunately, the efficacy of these treatments is often countered by the acquisition of drug resistance. Here we investigated the molecular mechanisms that underlie acquired resistance to BRAFi and to the combined therapy. Consistent with previous studies, we show that resistance to BRAFi is mediated by ERK pathway reactivation. Resistance to the combined therapy, however, is mediated by mechanisms independent of reactivation of ERK in many resistant cell lines and clinical samples. p21-activated kinases (PAKs) become activated in cells with acquired drug resistance and have a pivotal role in mediating resistance. Our screening, using a reverse-phase protein array, revealed distinct mechanisms by which PAKs mediate resistance to BRAFi and the combined therapy. In BRAFi-resistant cells, PAKs phosphorylate CRAF and MEK to reactivate ERK. In cells that are resistant to the combined therapy, PAKs regulate JNK and β-catenin phosphorylation and mTOR pathway activation, and inhibit apoptosis, thereby bypassing ERK. Together, our results provide insights into the molecular mechanisms underlying acquired drug resistance to current targeted therapies, and may help to direct novel drug development efforts to overcome acquired drug resistance.

Geometry-Modulated Magnetoplasmonic Optical Activity of Au Nanorod-Based Nanostructures.

Comprehension and modulation of optical activity at nanoscale have attracted tremendous interest in the past decades due to its potential application in many fields including chemical/biological sensing, artificial metamaterials, asymmetric catalysis, and so forth. As for the conventional molecular materials, magnetic field is among the most effective routes in inducing and manipulating their optical activity; whereas the magnetic optical activity at nanoscale calls for deeper understanding, especially for anisotropic noble metal nanoparticles. In this work, distinctly different magnetic circular dichroism (MCD) responses are demonstrated in gold nanorods (GNRs) with a derivative-shaped MCD signal corresponding to the transverse surface plasmon resonance (TSPR) band and a Gaussian-shaped signal at the position of the longitudinal surface plasmon resonance (LSPR) band. Furthermore, changing the aspect ratio of GNRs easily regulates such magnetoplasmonic CD response. More interestingly, GNR assemblies with different geometric configuration (end-to-end and side-by-side) show structure-sensitive magnetoplasmonic CD response. Armed with theoretical calculation, we clearly elucidate the intrinsic relationship of the resultant magnetoplasmonic CD response with the optical symmetry and geometry factor inside one-dimensional GNRs. This work not only greatly benefits our understanding toward the nature of SPR mode in anisotropic plasmonic nanostructures but also opens the way to achieve tunable magnetoplasmonic response, which will significantly advance the design and application of optical nanodevices.

Biocompatible 60/70 Fullerenols: Potent Defense against Oxidative Injury Induced by Reduplicative Chemotherapy.

Chemotherapy as a conventional cancer treatment suffers from critical systemic side effects, which is generally considered as the consequence of reactive oxygen species (ROS). Fullerenes have been widely studied for their excellent performance in radicals scavenging. In the present study, we report a solid-liquid reaction to synthesize fullerenols and their application as ROS scavengers in chemotherapy protection. The solid-liquid reaction is carried out without catalyst and suitable for mass production. The novel [60]/[70] fullerenols show a high stability in water, and the [70] fullerenols (C70-OH) exhibit radical scavenging capability superior to that of [60] fullerenols (C60-OH) in chemotherapy protection. The mouse model for single and reduplicative chemotherapy-induced liver injury demonstrates their protective effects in the chemotherapeutic process, which is confirmed by histopathological examinations and hematological index. The increase of the hepatic l-glutathione (GSH) level and downregulated expression of the cytochrome P-450 2E1 (CYP2E1) give the possible mechanism associated with the impact of fullerenols on the metabolism of doxorubicin. The novel fullerenols may be promising protective agents to satisfy the demand for future clinical chemotherapy.

Effects of Zinc Alpha2 Glycoprotein on Lipid Metabolism of Liver in High-Fat Diet-Induced Obese Mice.

Zinc alpha2 glycoprotein (ZAG) is a new type of adipokine involved in adipose tissue mobilization, however, little is known about its lipid metabolism effect in liver. Therefore, we investigated the effects of ZAG in the regulation of hepatic lipid accumulation. Mice were randomly divided into two groups; one was fed a normal diet and another was fed a high-fat diet for eight weeks to establish obesity model. After that, the normal diet group was divided into ND (injection of pcDNA3.1) and NDZ (injection of ZAG recombinant plasmid) and the high-fat diet group was divided into HF (injection of pcDNA3.1) and HFZ (injection of ZAG recombinant plasmid). The mice were weighed once per week and injected with plasmid once every three days for eight times. The results showed that body weight and hepatic TG content were decreased dramatically in HFZ group compared with HF group. The stearoyl-CoAdesaturase1 (SCD1) and Acyl-CoA Synthetase-1 (ACSS1) protein levels in HFZ group were significantly decreased. Furthermore, phosphorylated hormone sensitive lipase (P-HSL) was significantly higher in HFZ group. In HFZ group, hepatic fatty acid translocase (CD36) and fatty acids binding protein-1 (FABP1) protein levels were reduced. In addition, the expression of phosphorylated protein kinase A (PPKA) in HFZ group was higher than the HF group. Meanwhile, NDZ group showed significantly decreased body weight and increased P-HSL level though the hepatic TG content showed no significantly changes compared with the ND group. Therefore, we conclude that ZAG may be beneficial for preventing high-fat-diet-induced hepatic lipid metabolic disorders.

Mutations in BRAF codons 594 and 596 predict good prognosis in melanoma.

B-Raf proto-oncogene serine/threonine kinase (BRAF) V600E is the most common kinase-activating mutation and is associated with poor prognosis in melanoma. However, the clinical significance of kinase-impairing mutations remains unclear. The present study aimed to analyze kinase-impairing mutations in BRAF codons 594 and 596 in non-Caucasian patients with melanoma and to investigate their possible clinical significance. To detect hotspot mutations, exon 15 of the BRAF gene was amplified using polymerase chain reaction in samples from 1,554 patients with melanoma. Among these patients, a total of 912 valid follow-up data were obtained. These patients were divided into three groups according to their BRAF activation status: BRAF wild-type (n=752), BRAF V600E (n=147); and BRAF D594/G596 (n=13). Then the correlation between BRAF activation status, and the clinicopathological features and overall survival (OS) of the patients were analyzed. The prevalence of BRAF mutations in non-Caucasian patients with melanoma was 24.3% (377/1554). Three patients carried two mutations simultaneously. The overall mutation frequencies of kinase-activating mutations, kinase-impairing mutations, and mutations with unknown effects were 93.4 (355/380), 3.4 (13/380), and 3.2% (12/380), respectively. BRAF V600E was identified to be associated with a poor prognosis. Patients with BRAF mutations in codons 594 and 596 had a longer OS time compared with those with a BRAF V600E mutation [median OS, 45 vs. 25 months; HR, 0.45 (95% confidence interval, 0.31-0.97); P=0.043]. To the best of our knowledge, this is the first study to examine a large number of samples from non-Caucasian patients with melanoma and report the characteristics of BRAF mutations according to mutant kinase activity. Melanoma arising from a mutation in BRAF codon 594 or 596 can be differentiated from BRAF V600E-induced melanoma, and mutations in these codons may be good prognostic factors for melanoma. The results of the present study are thus of significance for the development of accurate personalized medicine to treat melanoma.

Chinese Sacbrood virus infection in Asian honey bees (Apis cerana cerana) and host immune responses to the virus infection.

Chinese Sacbrood virus (CSBV) is a positive-stranded RNAvirus that infects both the European honey bee (Apis mellifera) and the Asian honey bee (A. cerana). However, CSBV has much more devastating effects on Asian honey bees than on European honey bees, posing a serious threat to the agricultural and natural ecosystems that rely on A. cerana for pollination service. Using quantitative RT-PCR method, we conducted studies to examine the CSBV infection in Asian honey bee colonies and immune responses of individual bees in response to CSBV infection. Our study showed that CSBV could cause infection in different developmental stages of workers including eggs, larvae, pupae, newly emerged workers, and foraging workers. In addition, evaluating the tissue tropism and transmission of CSBV in infected bees showed that CSBV was detected in the ovaries, spermatheca, and feces of queens as well as semen of drones of the same colonies, suggesting an existence of vertical transmission of CSBV in Asian honey bees. Further, the detection of CSBV in colony food suggests that healthy bees could pick the infection by the virus-contaminated food, and therefore, a possible existence of a food-borne transmission pathway of CSBV in Asian bee colonies. The expression analysis of transcripts (defensin, abaecin, apidaecin, and hymenoptaecin) involving innate antiviral immune pathways showed that CSBV infection could induce significant immune responses in infected bees. However, the immune responses to CSBV infection varied among different development stages with eggs exhibiting the lowest level of immune expression and forager workers exhibiting the highest level of immune gene expression. The results obtained in the study yield important insights into the mechanisms underlying disease pathogenesis of CSBV infections in Asian honey bees and provide valuable information for a rational design of disease control measures.