Lung transcriptome analysis for the identification of genes involved in the hypoxic adaptation of plateau pika (Ochotona curzoniae).

The plateau pika, a typical hypoxia-tolerant mammal lives 3000-5000 m above sea level on the Qinghai-Tibet Plateau, has acquired many physiological and morphological characteristics and strategies in its adaptation to sustained, high-altitude hypoxia. Blunted hypoxic pulmonary vasoconstriction is one such strategy, but the genes involved in this strategy have not been elucidated. Here, we investigated the genes involved and their expression profiles in the lung transcriptome of plateau pikas subjected to different hypoxic conditions (using low-pressure oxygen cabins). A slight, right ventricular hypertrophy was observed in pikas of the control group (altitude: 3200 m) vs. those exposed to 5000 m altitude conditions for one week. Our assembly identified 67,774 genes; compared with their expression in the control animals, 866 and 8364 genes were co-upregulated and co-downregulated, respectively, in pikas subjected to 5000 m altitude conditions for 1 and 4 w. We elucidated pathways that were associated with pulmonary vascular arterial pressure, including vascular smooth muscle contraction, HIF-1 signalling, calcium signalling, cGMP-PKG signalling, and PI3K-Akt signalling based on the differentially expressed genes; the top-100 pathway enrichments were found between the control group and the group exposed to 5000 m altitude conditions for 4 w. The mRNA levels of 18 candidate gene showed that more than 83% of genes were expressed and the number of transcriptome The up-regulated genes were EPAS1, Hbα, iNOS, CX40, CD31, PPM1B, HIF-1α, MYLK, Pcdh12, Surfactant protein B, the down-regulated genes were RYR2, vWF, RASA1, CLASRP, HIF-3α. Our transcriptome data are a valuable resource for future genomic studies on plateau pika.

Synthesis and biological evaluation of novel 8- substituted sampangine derivatives as potent inhibitor of Zn2+-Aß complex mediated toxicity, oxidative stress and inflammation.

A series of 8-substituted sampangine derivatives have been designed, synthesized and tested for their ability to inhibit cholinesterase and penetrate the blood-brain barrier. Their chelating ability toward Zn2+ and other biologically relevant metal ions was also demonstrated by isothermal titration calorimetry. The new derivatives exhibited high acetylcholinesterase inhibitory activity, high blood-brain barrier penetration ability and high chelating selectivity for Zn2+. Moreover, compound 10 with the strongest binding affinity to Zn2+ was selected for further research. Western blotting analysis, transmission electron microscopy, DCFH-DA assay and paralysis experiment indicated that compound 10 suppressed the formation of Zn2+-Aß complexes, alleviated the Zn2+ induced neurotoxicity and inhibited the production of ROS catalyzed by Zn2+ in Aß42 transgenic C. elegans. Furthermore, compound 10 also inhibited the expressions of pro-inflammatory cytokines, such as NO, TNF-α, IL-6 and IL-1ß, induced by Zn2+ + Aß1-42 in BV2 microglial cells. In general, this work provided new insights into the design and development of potent metal-chelating agents for Alzheimer's disease treatment.

Novel sampangine derivatives as potent inhibitors of Cu2+-mediated amyloid-ß protein aggregation, oxidative stress and inflammation.

A series of 11-substituted sampangine derivatives have been designed, synthesized, and tested for their ability to inhibit cholinesterase. Their chelating ability and selectivity for Cu2+ over other biologically relevant metal ions were demonstrated by isothermal titration calorimetry. Their blood-brain barrier permeability was also tested by parallel artificial membrane permeation assay. Among the synthesized derivatives, compound 11 with the strong anti-acetylcholinesterase activity, high blood-brain barrier penetration ability and high binding affinity to Cu2+ was selected for further research. Western blotting analysis, transmission electron microscopy, DCFH-DA assay and paralysis experiment indicated that compound 11 suppressed the formation of Cu2+-Aß complexes, alleviated the Cu2+ induced neurotoxicity and inhibited the production of ROS catalyzed by Cu2+ in Aß42 transgenic C. elegans. Moreover, compound 11 also inhibited the expressions of proinflammatory cytokines, such as NO, TNF-α, IL-6 and IL-1ß, induced by Cu2+ + Aß1-42 in BV2 microglial cells. In general, this work provided new insights into the design and development of potent metal-chelating agents for AD treatment.

MiR-10a-5p restrains the aggressive phenotypes of ovarian cancer cells by inhibiting HOXA1.

MicroRNAs (miRNAs) are dysregulated in human ovarian carcinoma (OC). But the mechanism underlying miR-10a-5p in regulating the progression of OC need deeply explored. In the current study, we observed that miR-10a-5p was down-expressed in OC samples and OC cell lines. In addition, miR-10a-5p restrained the viability, colony formation, migration ability and invasiveness of OC cells. We further ascertained Homeobox A1 (HOXA1) was a downstream gene of miR-10a-5p. Furthermore, HOXA1 was distinctly upregulated in OC samples. Finally, upregulation of HOXA1 abolished the suppressive effects of miR-10a-5p on OC cells. These observations suggested that miR-10a-5p suppressed the aggressive phenotypes of OC cells via regulating HOXA1.

Increased lipopolysaccharide content is positively correlated with glucocorticoid receptor-beta expression in chronic rhinosinusitis with nasal polyps.

INTRODUCTION: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common and frequently occurring disease of the upper respiratory tract. The nasal instillation of the Gram-negative (G- ) bacterial product lipopolysaccharide (LPS) can induce not only acute sinusitis but also the development of CRSwNP in animal models. Nevertheless, the expression and distribution of LPS in patients with CRSwNP have not been investigated. And the study was to investigate the expression of LPS and its relationship with glucocorticoid receptors (GRs) in CRSwNP. METHODS: Multiple methods, including bacterial culture and immunohistochemistry, were used to detect and analyze nasal bacteria, plasma LPS content, and the levels of LPS and GR-α/ß, cluster of differentiation 68 (CD68), and myeloperoxidase (MPO) expression, as well as their relationship in CRSwNP. RESULTS: The number of G- bacteria and Escherichia coli (E. coli) was not significantly different between CRSwNP subjects and the controls. However, the positive rate of LPS was much higher than that of E. coli in CRSwNP subjects and was significantly higher in noneosinophilic CRSwNP subjects than in eosinophilic CRSwNP subjects. Moreover, the LPS levels were positively correlated with GR-ß but not GR-α expression in CRSwNP. Immunofluorescence assays showed that LPS was mainly detected in CD68+ macrophages and MPO+ neutrophils, in addition to histiocytes, in CRSwNP. CONCLUSIONS: Persistent LPS in CRSwNP can lead to unresolved mucosal inflammation, eventually leading to tissue remodeling and the development of CRSwNP. Our findings suggest that increased LPS content and possible resistance to glucocorticoids may be one of the important pathogenic mechanisms of G- bacteria in CRSwNP.

[Gene mutational analyses of cathepsin C gene in a family with Papillon-Lefèvre syndrome].

OBJECTIVE: This study aimed to investigate the gene mutational characteristics of cathepsin C (CTSC) gene in a Chinese patient with Papillon-Lefèvre syndrome (PLS) and further confirm the genetic basis for the phenotype of PLS. METHODS: Peripheral blood samples were obtained from the PLS proband and his family members (his parents and younger brother) for genomic DNA extraction. The coding region and exon boundaries of the CTSC gene were amplified and sequenced by polymerase chain reaction and direct sequencing of DNA. RESULTS: Compound heterozygous mutations of CTSC gene were identified in the patient. A heterozygous missense mutation occurred in the 800th base of exon 6, and the base T in the base pair was replaced by C (c.800T>C). The encoded amino acid leucine changed to proline (p. L267P). A heterozygous missense mutation occurred in the 1015th base of exon 7, and base C in the base pair was replaced by T (c.1015C>T). The encoded amino acid arginine changed to cysteine (p.R339C). Among the mutations, c.800T>C originated from the mother, c.1015C>T was identified from the father. No mutations were detected in the younger brother. CONCLUSIONS: Mutations of CTSC gene are responsible for the phenotype of PLS.

Structures and luminescent sensors of mixed-counterions based salen-type lanthanide coordination polymers.

Reactions of N,N'-bis (salicylidene)-1,2-cyclohexanediamine (H2 L) with mixed lanthanide counterions of LnCl3 ·6H2 O and Ln (NO3 )3 ·6H2 O afford six H2 L lanthanide coordination polymers, e.g. {[Pr(H2 L)2 (NO3 )2 Cl]·2CH2 Cl2 }n (1); {[Ln(H2 L)1.5 (NO3 )3 ]2 ·5CHCl3 ·mCH3 OH}n [Ln = Sm (2), Eu (3), Gd (4), Tb (5) and Yb (6); m = 1 (2-5); m = 0 (6)]. X-ray crystallographic analysis reveals that complex 1 exhibits three-dimensional diamondoid topologic structure and complexes 2-6 are of two-dimensional structure. Luminescent spectra show that complexes 1 and 6 have characteristic near-infrared (NIR) emission of praseodymium (III) and ytterbium (III) ions and complexes 2-5 emit luminescence in the visible region. Complexes 3 and 6 reveal sensitive luminescence responses to formaldehyde.

Evaluation of sensory function and recovery after replantation of fingertips at Zone I in children.

Sensory function is the most significant criterion when evaluating the prognosis of replanted fingers. Current clinical research has focused on surgical techniques and indications for finger replantation; however, few studies have focused on recovery of finger sensory function after replantation. This study retrospectively assessed data of eight patients who had undergone nine Zone I replantations of the fingertips in the First Affiliated Hospital of Sun Yat-sen University of China from July 2014 to January 2016. Variations in the extent of damage, with the residual vessels or nerves in some fingers being too short or even missing, prevented tension-free suture repair in some patients. Thus, repair of four of the nine fingertips included arteriovenous anastomosis, the remaining five undergoing arterial anastomosis during replantation of the amputated fingers. Three patients underwent nerve repair, whereas the remaining six cases did not. Fingertip replantations were successful in all eight patients. Compared with the patients without vascular anastomosis, no obvious atrophy was visible in the fingertips of patients who did undergo vascular anastomosis during replantation and their sensory function did recover. Fingertip replantation provides good sensory function and cosmetic outcomes when good artery and vein anastomoses have been created, even when digital nerves have not been repaired.

Glyoxalase I is differentially expressed in cutaneous neoplasms and contributes to the progression of squamous cell carcinoma.

Glyoxalase I (GLO1) is a methylglyoxal detoxification enzyme being implicated in the progression of multiple malignancies. However, currently, the role of GLO1 in human nonmelanoma skin tumors remains unclear. To explore the expression of GLO1 in cutaneous neoplasms and its role in the pathogenesis of skin cancers, we determined the GLO1 expression in multiple subtypes of cutaneous neoplasms and cell lines harboring different tumorigenicity. Also, the GLO1 siRNA transfection was performed in squamous cell carcinoma (SCC)-13 cells or SCC in the xenograft model. The results show that GLO1 was overexpressed by SCC, basal cell carcinoma, and verrucous carcinoma but weakly expressed by several benign neoplasms. Human papilloma virus 16 E6/E7-transfected keratinocytes expressed more GLO1 than did normal keratinocytes, although both of them had lower levels of GLO1 than SCC-13 cells. Moreover, the knockdown of GLO1 by siRNA was related to enhanced apoptosis of SCC-13 cells in the presence of tumor necrosis factor-related apoptosis-inducing ligand and inhibited cell invasion and migration, which was mirrored by the suppressed growth of SCC xenografts in mice. Finally, the GLO1 regulation of SCC-13 cells might be relevant to methylglyoxal-induced p53 translocation. Therefore, GLO1 is prevailingly expressed in cutaneous neoplasms of higher malignancy and contributes to the progression of SCC.

Near-IR luminescence and field-induced single molecule magnet of four salen-type ytterbium complexes.

A series of rigid hexadentate salen-type (H2L) ytterbium complexes, namely, [Yb2L3(CH3OH)]·3CH3CN (1), [Yb2LL'L″(CH3OH)(H2O)2](ClO4)2·CH3OH·H2O (2), [Yb2L(OAc)4(CH3OH)2]·2CH3OH (3), and {[Yb2L(OAc)4]·3H2O}n (4) (H2L = N,N'-bis(2-oxy-3-methoxybenzylidene)-1,2-phenylenediamine, HL' = 2-(2'-hydroxy-3'-methyloxy-phenyl)benzimidazole and HL" = 3-methoxysalicylaldehyde) have been synthesized by reactions of H2L with multifarious Yb(3+) salts. X-ray crystallographic analyses demonstrate that complex 1 is of a triple-decker sandwich-type Yb2L3 structure with a ratio of H2L/Yb = 3:2, 2 and 3 possess the unique Yb2 core with a ratio of H2L/Yb = 2:2 and 1:2, respectively, 4 exhibits one dimensional coordination polymers in which the polymeric structures are formed by acetate (OAc(-)) groups. All complexes 1-4 exhibit near-IR luminescence, which can be rationalized on the basis of the disparate structural effects. The magnetic analysis unveils that all complexes 1-4 are of field-induced single-molecule magnet behavior with the energy barriers (Ueff/kB) of 14.5, 2.0, 9.5, and 2.4 K at 3 kOe direct current fields, respectively.

Imbalance between oxidative and antioxidative systems: toward an understanding of visible light-induced titanium dioxide nanoparticles toxicity.

The broad application of titanium dioxide nanoparticles (TiO(2) NPs) has resulted in the release of substantial quantities of untreated TiO(2) NPs into aquatic systems, which serve as the terminal sink for nanomaterials. These TiO(2) NPs may induce some unexpected toxic effects to aquatic systems. The objectives of this research were to evaluate toxic effects of low dosage TiO(2) NPs on Tetrahymena pyriformis under visible-light illumination conditions and further discuss possible mechanisms. The results showed that TiO(2) NPs accumulated as aggregates in cytosolic vesicles of T. pyriformis. Cell numbers and viability of TiO(2) NPs-exposed groups decreased to (20.2 ± 1.8)% and (17.3 ± 1.9)% after 24h continuous 12000 Lx illumination. Compared with the dark control, the intracellular reactive oxygen species (ROS) levels increased (1.9-fold) by the combination of 5 mg L(-1) TiO(2) NPs and 12000 Lx illumination. Even incubation in the dark for 6h after 12h illumination, superoxide dismutase (SOD) activity of TiO(2) NPs exposed groups still maintained at the high level (about 3.9-fold of dark control). Meanwhile, illumination-induced TiO(2) NPs led to a reduction of scavenging hydroxyl radicals (OH) activity with an average of (14.3 ± 6.5)%. Under illumination conditions, overproduction of reactive oxygen species (ROS) by TiO(2) NPs exceeded the scavenging capability of T. pyriformis and then led to the breakdown of oxidative/anti-oxidative systems, further resulting in cell growth delay and mitochondria dysfunction. All the results revealed that via visible light excitation, oxidative injury may be responsible for the toxic effects of TiO(2) NPs on T. pyriformis.

Combined toxicity of ferroferric oxide nanoparticles and arsenic to the ciliated protozoa Tetrahymena pyriformis.

Fe3O4 nanoparticles (NPs) have a high affinity for arsenic. As a result of this association, Fe3O4 NPs loaded with high concentration of arsenic can enter into organisms and produce locally high concentrations of arsenic, which may lead to some unexpected toxicity to aquatic organisms. The objectives of this research were to investigate the toxic effect of Fe3O4 NPs in combination with As(V). Cultured Tetrahymena pyriformis was chosen as a research model organism to evaluate the toxic effects of the combined agents. The results showed that after 24 h of As(V) exposure, the median effective concentration of As(V) to T. pyriformis was 1.29 mg/L. Fe3O4 NPs alone were not only non-toxic, but actually promoted the growth of T. pyriformis at the experimental doses. After 24 h exposure, the cell number increased by 32.2% at an exposure level of 3mg/L Fe3O4 NPs. After 24h exposure to 1.0 mg/L As(V), the survival rate increased from 60.5% in the absence of Fe3O4 NPs to 73.8% and 83.8% in the presence of 13 mg/L and 19 mg/L Fe3O4 NPs, respectively. However, after 30 h, the combined toxic effect of As(V) and Fe3O4 NPs on T. pyriformis was significantly enhanced and the survival rates for co-exposure to 1.5 mg/L As(V) and 13 mg/L Fe3O4 NPs decreased from 92.3% after 18 h to 45.3% after 30 h. After 18 h of exposure to Fe3O4 NPs alone, the intracellular ROS levels were markedly increased and achieved steady state. Compared with the control group, the intracellular ROS levels were significantly increased (2.56-fold) by the combination of 19 mg/L Fe3O4 NPs and 1.0 mg/L As(V). Accumulation of As(V) in T. pyriformis led to an increase in trivalent arsenics as a result of the saturation of the cellular arsenic methylation capability or/and redox reactions. These exposures also resulted in an imbalance between oxidants and antioxidants, resulting in oxidative damage and cell death.

[Relationship between longevity and soil environment in Xiayi County, Henan Province, China].

Based on field investigation and laboratory analysis, exploration was done of distribution of macro and micro elements in the soils and distribution of longevity population in Xiayi County, Henan Province, China, and relationship between the spatial variation of the distribution of soil elements and the distribution of the longevity population. It was found that longevity population was distributed in a belt running across Xiayi county from northeast to southwest. In the northeast part, the longevity rate (over 95 years old) reached 187 per million and while in the northwest part, it was only 83. The concentrations of heavy metals such as Cd, Cr, Cu, Ni, Pb, Zn in Xiayi soils were (0.177 +/- 0.057), (63.9 +/- 7.48), (23.6 +/- 5.63), (29.5 +/- 3.80), (21.8 +/- 3.37) and (64.80 +/- 8.81) mg x kg(-1), respectively, all up to the criteria for grade II soils in the National Standard for Soil Environment Quality of China; Moreover, the soils in longevous areas were rich in Cr, Zn, K and Mg. K and Mg in Xiayi soils were 1.30 and 1.79 as times as high as the background value of Henan Province and 1.21 and 2.62 times that of the country, respectively. In Liji, Huodian and Zhongfeng where the centenarian rate was relatively low, the soils were low in Cu, Se and Zn, but high in Na. The findings clearly indicate that the soil rich in Cr, Zn, K and Mg and free of any heavy metal pollution is a major contributor to the longevity in the area, while uneven distribution of Se, Zn, Cu and Na in the soil is the key factor affecting the distribution of longevity population in Xiayi County.

Genome-wide association study identifies two new susceptibility loci for atopic dermatitis in the Chinese Han population.

Atopic dermatitis is a chronic, relapsing form of inflammatory skin disorder that is affected by genetic and environmental factors. We performed a genome-wide association study of atopic dermatitis in a Chinese Han population using 1,012 affected individuals (cases) and 1,362 controls followed by a replication study in an additional 3,624 cases and 12,197 controls of Chinese Han ethnicity, as well as 1,806 cases and 3,256 controls from Germany. We identified previously undescribed susceptibility loci at 5q22.1 (TMEM232 and SLC25A46, rs7701890, P(combined) = 3.15 × 10(-9), odds ratio (OR) = 1.24) and 20q13.33 (TNFRSF6B and ZGPAT, rs6010620, P(combined) = 3.0 × 10(-8), OR = 1.17) and replicated another previously reported locus at 1q21.3 (FLG, rs3126085, P(combined) = 5.90 × 10(-12), OR = 0.82) in the Chinese sample. The 20q13.33 locus also showed evidence for association in the German sample (rs6010620, P = 2.87 × 10(-5), OR = 1.25). Our study identifies new genetic susceptibility factors and suggests previously unidentified biological pathways in atopic dermatitis.

[Study on the technique of ultrasonic wave extraction of triterpeneclucoside].

The extraction technique of ultrasonic wave on increasing the triterpeneclucoside was studied. Based on single factor experiments and the orthogonal design introduced,the optimized extracting conditions of triterpeneclucoside were investigated. The results showed that the best extraction technique conditons are 65% alcohol-water, the ratio of solid to liquid 1:30,dousing over 30 minutes,ultrasonic wave lasting for 40 minutes, ultrasonic frequency 26.8 KHZ, ultrasonic (output) power 1080 kw and extraction temperature 40 degrees C, respectively.