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Porcine deltacoronavirus (PDCoV) is a novel swine enteropathogenic coronavirus that causes watery diarrhea and induces proinflammatory cytokine responses in piglets. Our previous research showed that the specific-pathogen-free (SPF) chicks exhibited mild diarrhea and low fecal viral shedding, along with cecum lesions after PDCoV infection. Disturbances in the homeostasis of the gut microbiota have been associated with various diseases. We aimed to explore the effects of PDCoV infection on chick gut microbiota, short-chain fatty acid (SCFAs) production, and inflammatory cytokine expression in chicks, and also to investigate the relationship between gut microbiota and SCFAs or inflammatory cytokine expression of the PDCoV-infected chicks. Results obtained using 16S rRNA sequencing showed that infection with PDCoV strain HNZK-02 significantly altered the composition of chick gut microbiota, with the reduced abundance of Eisenbergiella and Anaerotruncus genera at 5 days post-inoculation (dpi) ( P < 0.05), and an increased abundance of Alistipes genus at 17 dpi ( P < 0.05). The production of SCFAs in the cecum of PDCoV HNZK-02-infected chicks, including acetic acid, propionic acid, and butyric acid, decreased in all cases. The expression of inflammatory cytokines (interferon-γ, tumor necrosis factor-α, and interleukin-10) was increased in the cecum tissue and serum of the PDCoV HNZK-02-infected chicks when detected by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Further analysis showed significant correlation between bacterial genera and SCFAs or inflammatory cytokines expression in cecum of the PDCoV infected chicks. These findings might provide new insight into the pathology and physiology of PDCoV in chicks., (Copyright © 2020 Li, Zhang, zhao, Wang, Wang and Wei.)

Glaucoma is a leading cause of irreversible blindness in the world. Intraocular pressure (IOP) plays a key role in glaucoma development and progression. Schlemm's canal (SC), an important structure of the anterior chamber angle, regulates the flow of aqueous humor and maintains IOP. Because of its special function of aqueous outflow, the SC has been intensive investigated recently. Several characteristics of SC in anatomy, physiology and pathophysiology have been revealed. Compare to normal, glaucomatous SC cells are more sensitive to substrate stiffness, have higher stiffness and and lower porosity leading to higher outflow resistance. And SC collapse caused by acute IOP increase is partially or totally reversal. With advanced inspection techniques, high-quality images of the SC can be obtained in vivo , which facilitates SC quantitative measurements clinically and allows us to investigate a new therapy paradigm for glaucoma. In this review, we summarize the basic and clinical research that focused on mechanisms of aqueous outflow resistance and SC changes in physiological, pathological, and post-treatment states., (International Journal of Ophthalmology Press.)

The plastid terminal oxidase (PTOX) - an interfacial diiron carboxylate protein found in the thylakoid membranes of chloroplasts - oxidizes plastoquinol and reduces molecular oxygen to water. It is believed to play a physiologically important role in the response of some plant species to light and salt (NaCl) stress by diverting excess electrons to oxygen thereby protecting photosystem II (PSII) from photodamage. PTOX is therefore a candidate for engineering stress tolerance in crop plants. Previously, we used chloroplast transformation technology to over express PTOX1 from the green alga Chlamydomonas reinhardtii in tobacco (generating line Nt-PTOX-OE). Contrary to expectation, growth of Nt-PTOX-OE plants was more sensitive to light stress. Here we have examined in detail the effects of PTOX1 on photosynthesis in Nt-PTOX-OE tobacco plants grown at two different light intensities. Under 'low light' (50 μmol photons m -2 s -1 ) conditions, Nt-PTOX-OE and WT plants showed similar photosynthetic activities. In contrast, under 'high light' (125 μmol photons m -2 s -1 ) conditions, Nt-PTOX-OE showed less PSII activity than WT while photosystem I (PSI) activity was unaffected. Nt-PTOX-OE grown under high light also failed to increase the chlorophyll a/b ratio and the maximum rate of CO 2 assimilation compared to low-light grown plants, suggesting a defect in acclimation. In contrast, Nt-PTOX-OE plants showed much better germination, root length, and shoot biomass accumulation than WT when exposed to high levels of NaCl and showed better recovery and less chlorophyll bleaching after NaCl stress when grown hydroponically. Overall, our results strengthen the link between PTOX and the resistance of plants to salt stress., (Copyright © 2020 Ahmad, Khan, Islam, Wei, McAusland, Lawson, Johnson and Nixon.)

An ongoing chemical investigation on n -BuOH extract of roots and rhizomes of Helleborus thibetanus afforded three new spirostanol glycosides ( 1 - 3 ). Their structures were elucidated by extensive analysis of 1 D, 2 D NMR spectra, together with IR and MS methods and acid hydrolysis. This is the first report of the isolation of spirostanol glycoside with xylose at C-24 of the aglycone in Helleborus .

Objective: To explore the transcriptional regulation mechanism of transforming growth factor β(1) (TGF-β(1)) on Meox1 and its effect on cell migration of adult human dermal fibroblasts (HDF-a). Methods: (1) HDF-a cells were cultured in RPMI 1640 complete medium (hereinafter referred to as routinely cultured). The cells were divided into TGF-β(1) stimulation group and blank control group. The cells in TGF-β(1) stimulation group were stimulated with 10 μL TGF-β(1) in the mass concentration of 1 mg/μL, while the cells in blank control group were stimulated with the equal volume of phosphate buffer solution. After 72 hours in culture, partial cells in both groups were collected for transcriptome sequencing. The genes with differential expression ratio greater than or equal to 2 and P <0.01 between the two groups were selected to perform enrichment analysis and analysis of metabolic pathways of the Kyoto Gene and Genome Encyclopedia with, and the expression value of Meox1 per million transcripts (TPM) was recorded ( n =3). Partial cells from the two groups were used to detect the Meox1 mRNA expression by real-time fluorescent quantitative reverse transcription polymerase chain reaction (RT-PCR) ( n =3). (2) Cultured HDF-a cells in the logarithmic growth phase (the same growth phase of cells below) were divided into empty plasmid group, Smad2 overexpression (OE) group, Smad3 OE group, and Smad4 OE group, which were transfected respectively with 2 μg empty pcDNA3.1 plasmid and pcDNA3.1 plasmids separately carrying Smad2, Smad3, and Smad4 for 6 hours, and then were routinely cultured for 48 hours. The Meox1 mRNA expression in the transfected cells of each group was detected by real-time fluorescent quantitative RT-PCR ( n =3). (3) HDF-a cells were routinely cultured and grouped the same as in experiment (1). After 72 hours in culture, the enrichment of Smad2, Smad3, and Smad4 protein on the Meox1 promoter in the cells of each group was detected by chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR) ( n =3). (4) HDF-a cells were routinely cultured and divided into negative interference group, small interference RNA (siRNA)-Smad2 group, siRNA-Smad3 group, siRNA-Smad4 group, empty plasmid group, Smad2 OE group, Smad3 OE group, and Smad4 OE group, which were transfected respectively with 50 μmol/L random siRNA, siRNA-Smad2, siRNA-Smad3, siRNA-Smad4, 2 μg empty pcDNA3.1 plasmid and pcDNA3.1 plasmids separately carrying Smad2, Smad3, and Smad4 for 6 hours and then routinely cultured for 48 hours. The enrichment of Smad2, Smad3, and Smad4 protein on the Meox1 promoter in the cells of corresponding group was detected by ChIP-qPCR ( n =3). (5) Two batches of HDF-a cells were cultured and divided into negative interference group, siRNA-Meox1 group, empty plasmid group, and Meox1 OE group, which were transfected respectively with 50 μmol/L random siRNA, siRNA-Meox1, 2 μg empty pcDNA3.1 plasmid and pcDNA3.1 plasmid carrying Meox1 for 6 hours and then routinely cultured for 24 hours. One batch of cells were subjected to scratch test with the scratch width being observed 24 hours after scratching and compared with the initial width for scratch wound healing; the other batch of cells were subjected to Transwell assay, in which the migrated cells were counted after being routinely cultured for 24 hours ( n =3). (6) From January 2018 to June 2019, 3 hypertrophic scar patients (2 males and 1 female, aged 35-56 years) were admitted to the First Affiliated Hospital of Army Medical University (the Third Military Medical University) 8-12 months after burns. The scar tissue and normal skin tissue along the scar margin resected during surgery were taken, and immunohistochemical staining was performed to observe the distribution of Meox1 protein expression. Data were statistically analyzed with one-way analysis of variance and independent sample t test. Results: (1) After 72 hours in culture, a total of 843 genes were obviously differentially expressed between the two groups, being related to tissue repair, cell migration, inflammatory cell chemotaxis induction process and potential signaling pathways such as tumor necrosis factor, interleukin 17, extracellular matrix receptor. The TPM value of Meox1 in the cells of blank control group was 45.9±1.9, which was significantly lower than 163.1±29.5 of TGF-β(1) stimulation group ( t =6.88, P <0.01) with RNA-sequencing. After 72 hours in culture, the Meox1 mRNA expression levels in the cells of blank control group was 1.00±0.21, which was significantly lower than 11.00±3.61 of TGF-β(1) stimulation group ( t =4.79, P <0.01). (2) After 48 hours in culture, the Meox1 mRNA expression levels in the cells of Smad2 OE group, Smad3 OE group, and Smad4 OE group were 198.70±11.02, 35.47±4.30, 20.27±2.50, respectively, which were significantly higher than 1.03±0.19 of empty plasmid group ( t =31.07, 13.80, 13.12, P <0.01). (3) After 72 hours in culture, the enrichment of Smad2, Smad3, and Smad4 protein on the promoter of Meox1 in the cells of TGF-β(1) stimulation group was significantly higher than that of blank control group respectively ( t =12.99, 41.47, 29.10, P <0.01). (4) After 48 hours in culture, the enrichment of Smad2 protein on the promoter of Meox1 in the cells of negative interference group was (0.200 000±0.030 000)%, significantly higher than (0.000 770±0.000 013)% of siRNA-Smad2 group ( t =11.67, P <0.01); the enrichment of Smad2 protein on the promoter of Meox1 in the cells of empty plasmid group was (0.200 000±0.040 000)%, significantly lower than (0.700 000±0.090 000)% of Smad2 OE group ( t =8.85, P <0.01). The enrichment of Smad3 protein on the promoter of Meox1 in the cells of negative interference group was (0.500 0±0.041 3)%, significantly higher than (0.006 0±0.001 3)% of siRNA-Smad3 group ( t =17.79, P <0.01); the enrichment of Smad3 protein on the promoter of Meox1 in the cells of empty plasmid group was (0.470 0±0.080 0)%, which was significantly lower than (1.100 0±0.070 0)% of Smad3 OE group ( t =9.93, P <0.01). The enrichment of Smad4 protein on the promoter of Meox1 in the cells of negative interference group was similar to that of siRNA-Smad4 group ( t =2.11, P >0.05); the enrichment of Smad4 protein on the promoter of Meox1 in the cells of empty plasmid group was similar to that of Smad4 OE group ( t =0.60, P >0.05). (5) Twenty-four hours after scratching, the scratch healing width of cells in siRNA-Meox1 group was narrower than that of negative interference group, while that of Meox1 OE group was wider than that of empty plasmid group. After 24 hours in culture, the number of migration cells in negative interference group was significantly higher than that in siRNA-Meox1 group ( t =9.12, P <0.01), and that in empty plasmid group was significantly lower than that in Meox1 OE group ( t =8.99, P <0.01). (6) The expression of Meox1 protein in the scar tissue was significantly higher than that in normal skin of patients with hypertrophic scars. Conclusions: TGF-β(1) transcriptionally regulates Meox1 expression via Smad2/3 in HDF-a cells, thus promoting cell migration.

Disturbances of sleep and the underlying circadian rhythm are related to many human diseases, such as obesity, diabetes, cardiovascular disorders, and cognitive impairments. Dysbiosis of the gut microbiome has also been reported to be associated with the pathologies of these diseases. Therefore, we proposed that disturbed sleep may regulate gut microbiota homeostasis. In this study, we mimicked the sleep-wake cycle shift, one typical type of circadian rhythm disturbances in young people, in recruited subjects. We used 16S rRNA gene amplicon sequencing to define microbial taxa from their fecal samples. Although the relative abundances of the microbes were not significantly altered, the functional-profile analysis of gut microbiota revealed functions enriched during the sleep-wake cycle shift. In addition, the microbial networks were quite distinct among baseline, shift, and recovery stages. These results suggest that an acute sleep-wake cycle shift may exert a limited influence on the gut microbiome, mainly including the functional profiles of the microbes and the microbial relationships within the microbial community. IMPORTANCE Circadian rhythm misalignment due to social jet lag, shift work, early morning starts, and delayed bedtimes is becoming common in our modern society. Disturbances of sleep and the underlying circadian rhythms are related to multiple human diseases, such as obesity, diabetes, cardiovascular disorders, and cognitive impairments. Given the crucial role of microbiota in the same pathologies as are caused by sleep disturbance, how the gut microbiota is affected by sleep is of increasing interest. The results of this study indicate that the acute circadian rhythm disturbance caused by sleep-wake shifts affect the human gut microbiota, especially the functional profiles of gut microbes and interactions among them. Further experiments with a longer-time-scale intervention and larger sample size are needed to assess the effects of chronic circadian rhythm disruption on the gut microbiome and to guide possible microbial therapies for clinical intervention in the related diseases., (Copyright © 2020 Liu et al.)

In this work, a novel thermoresponsive switching transistor is developed through the rational design of active materials based on the typical field-effect transistor (FET) device configuration, where the active material is composed of a blend of a thermal expansion polymer and a polymeric semiconductor. Herein, polyethylene (PE) is employed as the thermal expansion polymer because of its high volume expansion coefficient near its melting point (90-130 °C), which similarly corresponds to the overheating point that would cause damage or cause fire in the devices. It is revealed that owing to the thermistor property of PE, the FET characteristics of the derived device will be largely decreased at high temperatures (100-120 °C). It is because the high volume expansion of PE at such high temperature (near its T m ) effectively increases the distance of the crystalline domains of poly(3-hexylthiophene-2,5-diyl) to result in a great inhibition of current. Besides, the performance of this device will recover back to its original value after cooling from 120 to 30 °C owing to the volume contraction of PE. The reversible FET characteristics with temperature manifest the good thermal sensitivity of the PE-based device. Our results demonstrate a facile and promising approach for the development of next-generation overheating shutdown switches for electrical circuits., Competing Interests: The authors declare no competing financial interest., (Copyright © 2019 American Chemical Society.)

The hypoxia-inducible factor-1α (HIF-1α) pathway has been implicated in tumor angiogenesis, growth, and metastasis. Therefore, the inhibition of this pathway is an important therapeutic target for the treatment of various types of cancers. Here, we designed and synthesized 31 ursolic acid (UA) derivatives containing a tetrazole moiety and evaluated them for their potential anti-tumor activities as HIF-1α transcriptional inhibitors. Of these, compound 14d (IC 50 0.8 ± 0.2 µM) displayed the most potent activity and compounds 14a (IC 50 4.7 ± 0.2 µM) exhibited the most promising biological profile. Analysis of the structure-activity relationships of these compounds with HIF-1α suggested that the presence of a tetrazole group located at C-28 of the UA derivatives was critical for their inhibitory activities., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Silver nanowires are widely used in catalysts, surface enhanced Raman scattering, microelectronic equipment, thin film solar cells, microelectrodes and biosensors for their excellent conductivity, heat transfer, low surface resistance, high transparency and good biocompatibility. However, the optical nonlinearity of silver nanowires has not been further explored yet. In this paper, three silver nanowire samples with different concentrations are produced via a typical hydrothermal method. Their applications to fiber lasers are implemented to prove the optical nonlinearity of silver nanowires for the first time. Based on three kinds of silver nanowires, the mode-locked operation of fiber lasers is successfully realized. Moreover, the fiber laser based on the silver nanowire with a concentration of 2 mg/L demonstrates the shortest pulse duration of 149.3 fs. The experiment not only proves the optical nonlinearity of silver nanowires, but also has some enlightenment on the selection of the optimum concentration of silver nanowires in the consideration of ultrashort pulse output.

Covalent organic frameworks (COFs), an emerging class of organic porous materials, have attracted intense attention due to their versatile applications. However, the deliberate fabrication of COF-based nanomaterials for nanomedical application remains challenging due to difficulty in their size- and structure-controlled synthesis and poor aqueous dispersibility. Herein, we report two boron-dipyrromethene (BODIPY)-decorated nanoscale COFs (NCOFs), which were prepared by the Schiff-base condensation of the free end -CHO (bonding defects in COFs) on the established imine-based NCOFs with the amino-substituted organic photosensitizer BODIPY via "bonding defects functionalization" approach. Thus BODIPY has been successfully nanocrystallized via the NCOF platform, and can be used for photodynamic therapy (PDT) to treat tumors. These NCOF-based PDT agents featured nanometer size (∼110 nm), low dark toxicity, and high phototoxicity as evidenced by in vitro and in vivo experiments. Moreover, the "bonding defects functionalization" approach might open up new avenues for the fabrication of additional COF-based platforms for biomedical treatment., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Competing Interests: The authors declare no conflict of interest.

The infection of ruminants by Fasciola spp. always induces a non-protective Th2-type immune response. However, little is known about changes in the local and systemic immune environment during F. gigantica migration in buffalo. In this study, native swamp buffaloes were each infected with 500 viable F. gigantica metacercariae. Mesenteric lymph node (MLN), hepatic lymph node (HLN), spleen, and serum samples were collected from control and infected buffaloes at 3, 10, 28, 42, 70, and 98 days post-infection (DPI). The mRNA expression levels of the Th1- and Th2-related cytokines IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p40, IFN-γ, TNF-α, and CD4 were measured during different infection stages in the MLNs, spleens, and HLNs using quantitative real-time PCR (qRT-PCR). Levels of the specific anti-ESP isotype antibodies IgG, IgG1, and IgG2 were used to reflect changes in humoral immunity. The results of this study indicated that swamp buffaloes were susceptible to F. gigantica infection, and that susceptibility to this infection was closely related to the cytokine environment associated with the Th2-type immune response. The MLNs showed a mixed Th1- and Th2-type immune response during the acute infection stages, after which the production of these cytokines returned to normal. Cytokine expression in the HLNs also expressed a mixed Th1- and Th2-type immune response during the early infection stages. When the infection became chronic, the typical Th2 immune response was induced in the HLNs. At the acute infection stages, the spleen exhibited a Th2 immune response. Nevertheless, cytokines associated with the Th1 and Th2 immune responses were upregulated at 98 DPI. In addition, the total IgG and IgG1 of the parasite-specific antibodies increased. This suggested that the Th2-related cytokines and IgG1 induced by F. gigantica infection might mediate successful F. gigantica infection in the natural host, swamp buffalo., (Copyright © 2019 Elsevier B.V. All rights reserved.)

As a saturable absorption material, the heterostructure with the van der Waals structure has been paid much attention in material science. In general, the heterogeneous combination is able to neutralize, or even exceed, the individual material's advantages in some aspects. In this paper, which describes the magnetron sputtering deposition method, the tapered fiber is coated by the MoS 2 -WS 2 heterostructure, and the MoS 2 -WS 2 heterostructure saturable absorber (SA) is fabricated. The modulation depth of the prepared MoS 2 -WS 2 heterostructure SA is measured to be 19.12%. Besides, the theoretical calculations for the band gap and carrier mobility of the MoS 2 -WS 2 heterostructure are provided. By employing the prepared SA, a stable and passively erbium-doped fiber laser is implemented. The generated pulse duration of 154 fs is certified to be the shortest among all fiber lasers based on transition mental dichalcogenides. Results in this paper provide the new direction for the fabrication of ultrafast photon modulation devices.

Longshengzhi capsule consisting of 12 herbs is widely used in clinically treating cerebral ischemia during recovery period.In this study,in order to investigate the consistency of different batches of Longshengzhi capsules,a high performance liquid chromatography coupled to triple quadrupole mass spectrometry method(HPLC-QQQ/MS) was developed for the determination of 19 representative components in Longshengzhi Capsules within 9 min. Methodology validation indicated this method was simple,rapid,accurate,highly sensitive and reproducible,and it could be used for the content determination of components in Longshengzhi Capsules. The consistency analysis results showed that paeoniflorin and calycosin-7-glucoside in Longshengzhi Capsules had the highest content; RSD value of total content of 19 compounds was 5. 2% and the RSD value of main compounds such as astragaloside and calycosin-7-glucoside was all less than 15%,reflecting good consistency among different batches. This study has provided a scientific method and basis for the quality control and consistency evaluation of Longshengzhi Capsules.

Background: Excess energy intake contributes to metabolic disorders. However, the relationship between excess sugar and fat in their contributions to metabolic abnormalities remains to be further elucidated. Here we conducted a prospective feeding experiment to evaluate effects of dietary fat-to-sugar ratio on diet-induced metabolic abnormalities in adult cynomolgus monkeys., Methods: Four groups of adult cynomolgus monkeys were fed regular chow plus emulsion with combinations of high sugar (HS) or low sugar (HS) and low fat (LF) or high fat (HF) for 7 months. Plasma levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG) and blood glucose were measured for all the four groups of animals during the experiment., Results: Plasma levels of TC and LDL-C gradually increased in all 4 diets groups, with the highest increase found in the LSHF group compared to the other three groups (P = 0.0018 and P = 0.0005 respectively). HF induced increased fasting glucose (P = 0.0077) and HS induced higher TG (P = 0.0227) respectively. Intriguingly, HSHF led to dramatically smaller magnitude of increase in LDL-C and TC levels compared to LSHF, while such difference was absent between the LSLF and LSHF groups. Our findings thus indicate interactive effects of HS and HF on TC and LDL-C. In addition, HF exhibited stronger effects on lipid abnormalities than HS., Conclusions: In the current study, our prospective feeding experiment in adult cynomolgus monkeys revealed effects of different fat-to-sugar ratios on diet-induced metabolic abnormalities. Furthermore, our findings suggest that not only excess dietary energy but also the balance of dietary fat-to-sugar ratio matters in diet-induced lipid abnormalities.

Deoxynivalenol (DON) is a kind of natural pollutant belonging to the trichothecenes family. The aim of this study is to use diverse assays to evaluate oxidative damage as well as translocation of nuclear factor erythroid 2-related factor 2 (Nrf2), and to investigate their mechanisms in DON-induced toxicities on a placenta and embryo. Pregnant C57BL/6 mice were randomly assigned to three groups with different doses of DON: 0, 1.0, 2.5 mg/(kg·day). In gestation day (GD) 12.5 d and 18.5 d, DON induced an elevated resorption rate of the embryos as well as structural and functional damage of the placenta. In the placenta, altered levels of the antioxidant enzymes malondialdehyde, superoxide dismutase and glutathione indicated remarkable oxidative stress. Furthermore, an elevated level of heme oxygenase-1 (HO-1) and the translocation of Nrf2 from nucleus to cytoplasm indicated Nrf2/HO-1 pathway activation in DON-L group (1.0 mg/(kg·day)). It is noteworthy that the results in this experiment in GD 12.5 d were similar to those in GD 18.5 d. In conclusion, DON-induced placental oxidative damage and Nrf2 translocation were similar in GD 12.5 d and GD 18.5 d. Oxidative stress is one of the most important molecular mechanisms for embryotoxicity induced by DON, and Nrf2 translocation may play a substantial role against it.

Objective: Data on dietary patterns in relation to the risk of metabolic syndrome (MetS) in a middle-aged Chinese population are sparse. The present study was performed to determine the major dietary patterns among a population aged 45-59 years and to evaluate their associations with MetS risk in China., Design: Cross-sectional examination of the association between dietary patterns and MetS. Face-to-face interviews were used to assess dietary intake using a validated semi-quantitative FFQ. OR and 95 % CI for MetS were calculated across quartiles of dietary pattern scores using multivariate logistic regression analysis models., Setting: City of Linyi, Shandong Province, China., Subjects: Adults (n 1918) aged 45-59 years., Results: Three major dietary patterns were identified: traditional Chinese, animal food and high-energy. After adjustment for potential confounders, individuals in the highest quartile of the traditional Chinese pattern had a reduced risk of MetS relative to the lowest quartile (OR=0·72, 95 % CI 0·596, 0·952; P<0·05). Compared with those in the lowest quartile, individuals in the highest quartile of the animal food pattern had a greater risk of MetS (OR=1·28; 95 % CI 1·103, 1·697; P<0·05). No significant association was observed between the high-energy pattern and risk of MetS., Conclusions: These findings indicate that the traditional Chinese pattern was associated with a reduced risk, while the animal food pattern was associated with increased risk of MetS. Given the cross-sectional nature of our study, further prospective studies are warranted to confirm these findings.

The structural and electronic properties of Cu3O3- and Cu3O4- were investigated using mass-selected anion photoelectron spectroscopy in combination with density functional theoretical calculations. The vertical detachment energies of Cu3O3- and Cu3O4- were measured to be 3.48 ± 0.08 and 3.54 ± 0.08 eV, respectively. Their geometrical structures were determined by comparison of the theoretical calculations with the experimental results. The most stable structure of Cu3O3- can be characterized as a C3v symmetric six-membered ring structure with alternating Cu-O bonds, in which the plane of the three O atoms is slightly above that of the three Cu atoms. The most stable structure of Cu3O4- can be viewed as a Cs symmetric seven-membered ring with a peroxo unit. The bond order and molecular orbital analyses indicate that the Cu-Cu interactions in Cu3O3- and Cu3O4- are weak. The calculated NICS(0) and NICS(1) values of Cu3O3- are -25.0 ppm and -19.2 ppm, respectively, and those of Cu3O4- are -18.6 ppm and -10.5 ppm, respectively, indicating that they both are significantly aromatic.

To explore the drug-induced constituents in vivo of Polygonum multiflorum extract (PM). This study was the first to study the drug-induced constituents in target organ liver. Agilent MassHunter qualitative analysis software and Metabolite ID software were applied for the analysis of retention time, exact relative molecular mass, primary and secondary mass spectrum information based on ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and targeted-MS/MS. By comparison with literature and standards, a total of 5 prototypes and 6 metabolites were identified or tentatively elucidated from the liver samples. In addition, the drug-induced constituents in plasma and PM were also analyzed in this study and 8 prototypes and 19 metabolites were detected from the plasma samples, while 30 compounds were detected from the extract of PM. Emodin oxidative acetylation metabolites, hydroxyl methylation metabolites, carboxylation glucuronidation metabolites and ketone glucuronidation metabolites in this study were first reported. Through the comparative analysis between the in vivo and in vitro constituents of PM, the study preliminarily revealed the drug-induced constituents (prototypes and metabolites) in liver and clarified the transfer process and transmutation rules of constituents in PM, blood and liver, which would further deepen our understanding on constituents of PM in vivo ., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Ursolic acid derivatives containing oxadiazole, triazolone, and piperazine moieties were synthesized in an attempt to develop potent anti-inflammatory agents. Structures of the synthesized compounds were elucidated by 1 H NMR, 13 C NMR, and HRMS. Most of the synthesized compounds showed pronounced anti-inflammatory effects at 100 mg/kg. In particular, compound 11b, which displayed the most potent anti-inflammatory activity of all of the compounds prepared, with 69.76% inhibition after intraperitoneal administration, was more potent than the reference drugs indomethacin and ibuprofen. The cytotoxicity of the compounds was also assessed by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, and no compounds showed any appreciable cytotoxic activity (IC 50 >100 μmol/L). Furthermore, molecular docking studies of the synthesized compounds were performed to rationalize the obtained biological results. Overall, the results indicate that compound 11b could be a therapeutic candidate for the treatment of inflammation., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Glucocorticoids (GCs) are the most common cause of atraumatic osteonecrosis of the femoral head (ONFH) because their effect compromises the osteogenic capability of bone marrow‑derived mesenchymal stem cells (BMSCs). Valproic acid (VPA) is a widely used anti‑epileptic and anti‑convulsant drug. Previous studies have reported that VPA promotes osteogenic differentiation of MSCs in vitro and osteogenesis in vivo as a histone deacetylase (HDAC) inhibitor. The purpose of the present study was to investigate the efficacy of VPA as a precautionary treatment of ONFH after GC treatment in rats. In vitro, the effect of VPA, dexamethasone or a combination treatment of the two on the proliferation and osteogenic differentiation of human BMSCs was assessed using a Cell Counting Kit‑8 and apoptosis assays, and by measuring the expression of proteins associated with osteogenesis. In vivo, a GC‑induced ONFH model was established in rats and VPA was added during GC treatment to investigate the preventive effect of VPA against ONFH. Rat BMSCs were also extracted to investigate the osteogenic capacity. The results of micro‑computed tomography scanning, angiography of the femoral head and histological and immunohistochemical analyses indicated that 11 of 15 rats induced with methylprednisolone (MP) presented with ONFH, while only 2 of 15 rats treated with a combination of MP and VPA developed ONFH. VPA produced beneficial effects on subchondral bone trabeculae in the femoral head with significant preservation of bone volume and blood supply, as well as improved osteogenic capability of BMSCs compared with those in rats treated with GC alone. In conclusion, VPA attenuated the inhibitory effect of GC on BMSC proliferation and osteogenesis by inhibiting apoptosis and elevating the expression of proteins associated with osteogenesis, which may contribute to the prevention of GC‑induced ONFH in rats.

Inactivated transmissible gastroenteritis virus (TGEV) vaccines are widely used in swine herds in China. These are limited, however, by the need to elicit both humoral and cellular immunity, as well as the efficiency of adjuvants. In this study, a 70-nm nano silicon particle was applied with inactivated TGEV vaccine in mice, and its immune-enhancing effects and mechanism of action investigated. We found that nano silicon applied with inactivated TGEV vaccine induced high antibody titers, increase IL-6, TNF-α and IFN-γ expression, and stimulate CD3+ T cell proliferation with a high CD4+/CD8+ T lymphocyte ratio. Nano silicon could quickly activate innate and adaptive immunity by stimulating Toll-like receptor signaling pathways, indicating that the nano silicon adjuvant enhanced long-term humoral and early cellular immune responses when combined with inactivated TGEV vaccine. Nano silicon could be considered for use as an antigen- carrier and adjuvant for veterinary vaccines., (Copyright © 2018 Elsevier Inc. All rights reserved.)

This study aims to explore the role of long noncoding RNA (lncRNA)-HOX transcript antisense intergenic RNA (HOTAIR) in the occurrence and progression of glioma. Fresh glioma and normal brain tissues were classified into a glioma group (n = 67) and a normal group (n = 64) respectively. U87 cells were assigned into the blank, sh-NC, and sh-HOTAIR groups. Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to determine HOTAIR expression. Cell proliferation, cell cycle and cell apoptosis rates were detected by cell counting kit-8 (CCK-8) and flow cytometry (FCM). Scratch test and transwell assay were conducted for cell migration and invasion. Orthotopic glioma tumor model in nude mice was established by inoculating tumor cell suspension. Hematoxylin-Eosin (HE) staining was used to observe the growth and invasion of orthotopic glioma tumors. The expression of HOTAIR and cell viability was found to be lowest in the sh-HOTAIR group among the three groups. The sh-HOTAIR group exhibited a higher apoptotic rate and lower number of cell migration compared with the blank and sh-NC groups. Additionally, the speed of wound healing was slower, the migration distance decreased and the survival time of nude mice was extended in the sh-HOTAIR compared to the other groups. Moreover, the sh-HOTAIR group demonstrated reduced lesion sizes and inflammation, no convulsions or hemiplegia and lesser number of satellite metastases. Our findings support that down-regulation of HOTAIR could inhibit cell proliferation, promote cell apoptosis as well as suppress cell invasion and migration in the progression of glioma., (© 2017 Wiley Periodicals, Inc.)

The identification of network targets is one of the core issues used to reveal the molecular mechanism of traditional Chinese medicine (TCM) and is also the grand challenge of modernization of TCM. In this study, a protein-protein interaction (PPI) network was constructed based on the integration of network pharmacology and metabolomics, which was used as an effective approach to elucidate the relationship between disease pathway proteins and the targets of active small-molecule compounds. The intermolecular transfer process of the drug effect of active compounds in Salvia miltiorrhiza (SM) was revealed and visualized using the PPI network. Our study indicates that PTGS2 was the most important disease protein regulated by the active compounds in SM. Furthermore, the drug targets that can be linked to PTGS2 were regarded as direct targets and the direct targets of the active compounds were identified, respectively. Western blot and co-immuno precipitation (Co-IP) were used to verify the results of the network analysis and reveal the intermolecular transfer process of the effect of Tan IIA. Biological validation revealed that Tan IIA-EDN1-PTGS2-anandamide was a major intervention way of Tan IIA on early atherosclerosis (AS). This work provides a new perspective for the discovery of drug targets and the specific approaches regulated by the active compounds in SM on disease pathway proteins, which is beneficial for understanding the mechanism of action of bioactive compounds and expanding their clinical applications., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Glioma is the most common primary tumor in the brain, accounting for about 40~50% of intracranial primary tumors. Most chemotherapeutic drugs have difficulty in penetrating the blood-brain barrier, and their clinical applications are greatly limited. We evaluated the effects of methylmercury-L-cysteine (MeHg-L-cys) and methylmercury chloride (MMC) on apoptosis of C6 glioma cells. L-type amino acid transporter (LAT1) was used to investigate the targeted transport function and cytotoxicity of MeHg- L-cys in glioma. MeHg-L-cys enhanced the ability of targeting glioma cells and reduced the adverse reactions to normal brain tissues. Therefore, it is significantly important to develop new anti-glioma drugs targeting the blood-brain barrier.

Background: Determining the mechanisms involved in the immune-pathogenesis of the tropical liver fluke, Fasciola gigantica, is crucial to the development of any effective therapeutic intervention. Here, we examined the differential gene expression of cytokines and transcription factors in the liver of F. gigantica-infected buffaloes, over the course of infection., Methods: Water buffaloes (swamp type) were infected orally with 500 F. gigantica encysted metacercariae. Liver tissue samples were collected 3, 10, 28, 42, 70 and 98 days post-infection (dpi). Levels of gene expression of nine cytokines (IFN-γ, TGF-β, IL-1β, IL-4, IL-6, IL-10, IL-12B, IL-13 and IL-17A) and four transcription factors (T-bet, GATA-3, Foxp3 and ROR-γτ) were determined using quantitative real-time PCR (qRT-PCR). We evaluated any correlation between gene expression of these immune-regulatory factors and the severity of liver pathology., Results: Histopathological examination revealed that cellular infiltration, hemorrhage and fibrosis without calcification in the liver parenchyma of infected buffaloes, increased over the course of infection. This progressive pathology was attributed to dysregulated and excessive inflammatory responses induced by infection. The early infection phase (3-10 dpi) was marked by a generalized immunosuppression and elevated TGF-β expression in order to facilitate parasite colonization. A mixed Th1/Th2 immune response was dominant from 28 to 70 dpi, to promote parasite survival while minimizing host tissue damage. During late infection (98 dpi), the response was biased towards Th1/Treg in order to inhibit the host's Th2 protective response and promote chronic infection. Both IL-10 and IL-17A and the Th17/Treg balance, played key roles in mediating the inflammatory and immunoregulatory mechanisms in the liver during chronic fasciolosis., Conclusions: Our data showed distinct CD4 + T helper (Th) polarization and cytokine dysregulation in response to F. gigantica infection in water buffaloes over the course of infection. Characterizing the temporal expression profiles for host immune genes during infection should provide important information for defining how F. gigantica adapts and survives in the liver of buffaloes and how host immune responses influence F. gigantica pathogenicity.

Hypoxia-inducible factor-1α (HIF-1α), a key mediator in tumor metastasis and angiogenesis, is associated with poor patient prognosis and has been recognized as an important cancer drug target. In this work, four novel series of ursolic acid derivatives containing oxadiazole, triazolone, and piperazine moieties were designed, synthesized, and evaluated for anti-tumor activity as HIF-1α inhibitors. The majority of the compounds showed an excellent ability to inhibit the expression of HIF-1α. In particular, 11b inhibited HIF-1α transcriptional activity under hypoxic conditions with IC 50 =36.9μM. The cytotoxicity of these compounds was also assessed in human colon cancer cell HCT116 cells by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, and no compounds showed any appreciable cytotoxic activity (IC 50 >100μmol/L), which was lower than that of ursolic acid (IC 50 =23.8μmol/L). The mechanism of action of the representative compound 11b was also investigated., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: This research was applied to case-control studies of the association between pancreatitis and SPINK1 gene to assess the joint evidence for the association, the influence of individual studies, and evidence for publication bias., Methods: MEDLINE and Embase were searched to identify longitudinal studies evaluating pancreatitis and SPINK1. Odds ratios (ORs) and 95% confidence interval (CI) were pooled using random-effect models and calculated using Carlin method. Publication bias was assessed using Egger et al's approach (A famous statistic method by Egger et al). Sensitivity, heterogeneity, and trim and fill analyses were conducted., Results: Based on the results, we found that (1) the results support for the association between pancreatitis and SPINK1, when analyzed totally and by subdivision (total [OR, 7.771; 95% CI, 5.232-11.543; P < 0.000]; European [OR,6.400; 95% CI, 4.346-9.426; P < 0.000]; Asian [OR, 11.823; 95% CI, 4.612-30.310; P < 0.000]; American [OR, 3.777; 95% CI, 1.596-8.939; P = 0.002]; mixed: [OR, 13.566; 95% CI, 2.322-79.252, P = 0.004]); (2) no evidence indicates that this association is accounted for by any one study, and no evidence indicates any publication bias exists., Conclusions: The results indicated that SPINK1 gene, particularly the N34S mutation, has a genetic association with the development of pancreatitis.

The n-3 PUFAs have many beneficial effects on human health, including roles in immunity, neurodevelopment, and preventing cardiovascular disease. In this study, we established reliable model fat-1 transgenic cattle using transgenic technology and performed a systematic investigation to examine the function of n-3 PUFAs. Our results showed that expression of the fat-1 gene improved several biochemical parameters related to liver function and to plasma glucose and plasma lipid metabolism. Results of global gene and plasma protein expression analysis showed that 310 genes and 13 plasma proteins differed significantly in the blood of fat-1 transgenic cattle compared with WT cattle, reflecting their regulatory roles in the immune and cardiovascular systems. Finally, changes in the gut microflora were also noted in the fat-1 transgenic cattle, suggesting novel roles for n-3 PUFAs in the metabolism of glucose and lipids, as well as anti-stress properties. To the best of our knowledge, this is the first report using multiple parallel analyses to investigate the role of n-3 PUFAs using models such as fat-1 transgenic cattle. This study provides novel insights into the regulatory mechanism of fat-1 in the immune and cardiovascular systems, as well as its anti-stress role., (Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.)

Porcine parvovirus virus (PPV) is an animal virus that has caused high economic losses for the swine industry worldwide. Previous studies demonstrated that PPV infection induced significant production of interleukin 6 (IL-6) in vitro and in vivo. However, the inflammatory cytokines and specific signaling pathways induced during PPV infection remain largely unknown. In the present study, we analyzed the expression levels of IL-6 in PPV-infected porcine kidney 15 (PK-15) and the results showed that PPV infection induced the increase of IL-6 mRNA expression in a dose-dependent manner. We also detected the expression of toll-like receptor 9 (TLR9) signaling proteins in the mRNA expressing level, when compared with the control group, the TLR9 expression in mRNA level increased at 24h in PK-15 cells after PPV infection and reached the peak level at 48h. In addition, the transcript profile of nuclear factor kappa B (NF-κB) signal pathway relating genes (MyD88, IRAK1, TRAF6, TAK1α, IκBκB and NF-κB) expression levels increased at different times. Furthermore, to verify the IL-6 expression was specific with the TLR9 expression and then by activating the NF-κB signal pathway, TLR9 and NF-κB specific inhibitors were applied during PPV infection, separately, the result indicated that the expression of IL-6 was decreased after inhibitor treatment. Taken together, PPV infection significantly induced IL-6 expression and this induction depended on NF-κB activation and TLR9 signaling pathways in PK-15 cell., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The methyltransferase-like 21C gene (METTL21C), which is mainly expressed in muscle, can promote the differentiation of myoblasts to myotubes and reduce glucocorticoid-induced apoptosis of osteocytes. The purpose of this study was to explore the association between single nucleotide polymorphisms of METTL21C and peak bone mineral density (BMD), body mass index, total fat mass (TFM), and total lean mass (TLM) in Chinese young men. Fifteen tagging single nucleotide polymorphisms were genotyped, and haplotype blocks were derived in 400 Chinese male nuclear families. The peak BMD of the lumbar and hip, TFM, and TLM were measured by dual-energy X-ray absorptiometry. The association analyses were performed by a quantitative transmission disequilibrium test. Both TLM and TFM had a significant positive effect on peak BMD, but the positive regulation of TLM was stronger than that of TFM. After 1000 permutations, significant within-family associations were found between rs9585961 and lumbar spine BMD and femoral neck BMD, rs9518810 and femoral neck BMD, and rs599976 and body mass index, TFM, and percentage fat mass (all P < 0.05). The association analyses with haplotypes showed that haplotype AG in block 1 was significantly associated with TFM (P = 0.031) and haplotype CAG in block 2 was significantly associated with lumbar spine BMD (P = 0.020). Our study, for the first time, demonstrates that the polymorphisms and haplotypes of METTL21C contribute to the peak BMD and TFM in Chinese males, which suggests that as a quantitative trait locus with potential pleiotropy it may have an influence on osteoporosis and obesity.

In an attempt to search for more potent positive inotropic agents, two series of [1,2,4]triazolo[4,3- a ] quinoxaline derivatives bearing substituted benzylpiperazine and benzoylpiperazine moieties were synthesized and their positive inotropic activities evaluated by measuring left atrial stroke volume in isolated rabbit heart preparations. Several compounds showed favorable activities compared with the standard drug, milrinone. Compound 6c was the most potent agent, with an increased stroke volume of 12.53% ± 0.30% (milrinone: 2.46% ± 0.07%) at 3 × 10 -5 M. The chronotropic effects of compounds having considerable inotropic effects were also evaluated.

Quantum coherence is the most distinguished feature of quantum mechanics. It lies at the heart of the quantum-information technologies as the fundamental resource and is also related to other quantum resources, including entanglement. It plays a critical role in various fields, even in biology. Nevertheless, the rigorous and systematic resource-theoretic framework of coherence has just been developed recently, and several coherence measures are proposed. Experimentally, the usual method to measure coherence is to perform state tomography and use mathematical expressions. Here, we alternatively develop a method to measure coherence directly using its most essential behavior-the interference fringes. The ancilla states are mixed into the target state with various ratios, and the minimal ratio that makes the interference fringes of the "mixed state" vanish is taken as the quantity of coherence. We also use the witness observable to witness coherence, and the optimal witness constitutes another direct method to measure coherence. For comparison, we perform tomography and calculate l&#95;{1} norm of coherence, which coincides with the results of the other two methods in our situation. Our methods are explicit and robust, providing a nice alternative to the tomographic technique.

In this study, four novel series of 4-phenyl-1H-1,2,4-triazol-5(4H)-one derivatives containing triazole or piperazine moieties were designed, synthesized, and evaluated for negative inotropic activity by measuring the left atrium stroke volume in isolated rabbit heart preparations. Almost all of the compounds showed an ability to moderate the cardiac workload by decreasing the heart rate and contractility. Among them, 7h was found to be the most potent with a change in stroke volume of -48.22 ± 0.36% at a concentration of 3 × 10 -5  mol/L (metoprolol: -9.74 ± 0.14%). The cytotoxicity of these compounds was evaluated using the human cervical cancer cell line HeLa, the liver cancer cell line Hep3B, and the human normal hepatic cell line LO2. A preliminary study of the mechanism of action for the compound 7h on the regulation of atrial dynamics with ATP-sensitive K + channel and L-type Ca 2+ channel blockers glibenclamide and nifedipine was performed in the isolated perfused beating rabbit atria., (© 2016 John Wiley & Sons A/S.)

Three novel series of chalcone derivatives containing an aminoguanidine or acylhydrazone moiety were designed, synthesized and evaluated in terms of their antibacterial, antifungal and anti-inflammatory activities. Most of the synthesized compounds showed potent inhibitory activity towards various bacteria and one fungus with minimum inhibitory concentrations (MICs) ranging from 1 to 8μg/mL. Compared with our previously reported chalcone derivatives (MICs >64μg/mL), these compounds exhibited improved antibacterial activities (MICs=2μg/mL) against Gram-negative bacterial strains (Escherichia coli 1924 and 1356). Compounds 4f and 4h were found to be the most potent with an MIC value of 1μg/mL against the Gram-negative bacterial strains Salmonella typhimurium 1926 and the fungus Candida albicans 7535. In addition, compound 4f displayed the most potent anti-inflammatory activity of all of the compounds prepared in the current study with 92.45% inhibition after intraperitoneal administration, making it more potent than the reference drugs indomethacin and ibuprofen. The cytotoxic activity of the compound 4f was assessed in HeLa, Hep3B and L02 cells., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Myelination of Schwann cells in the peripheral nervous system is an intricate process involving myelin protein trafficking. Recently, the role and mechanism of the endosomal/lysosomal system in myelin formation were emphasized. Our previous results demonstrated that a small GTPase Rab27a regulates lysosomal exocytosis and myelin protein trafficking in Schwann cells. In this present study, we established a dorsal root ganglion (DRG) neuron and Schwann cell co-culture model to identify the signals associated with Rab27a during myelination. First, Slp2-a, as the Rab27a effector, was endogenously expressed in Schwann cells. Second, Rab27a expression significantly increased during Schwann cell myelination. Finally, Rab27a and Slp2-a silencing in Schwann cells not only reduced myelin protein expression, but also impaired formation of myelin-like membranes in DRG neuron and Schwann cell co-cultures. Our findings suggest that the Rab27a/Slp2-a complex affects Schwann cell myelination in vitro ., Competing Interests: Conflicts of Interest: None declared.

As there are multiple factors causing hydrocephalus subsequent to intraventricular hemorrhage (IVH), it is difficult to achieve the best treatment effect using a single drug alone. In the present study, the protective effect of combination treatment with granulocyte-colony stimulating factor (G-CSF) and lithium chloride against hydrocephalus after IVH was investigated. A total of 130 adult male Sprague-Dawley rats were divided into five groups, including the IVH control, G-CSF treatment, lithium chloride treatment, combination treatment and sham surgery groups. An IVH rat model was established in order to examine the effect of combination treatment on hydrocephalus incidence. A TUNEL assay was performed to detect neuronal apoptosis in the five groups. In addition, the protein expression levels of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) were detected by western blot analysis. The differentiation of nerve cells in the brain tissue obtained from the five rat groups was also determined with double immunofluorescence staining. The results demonstrated that administration of G-CSF or lithium chloride alone was able to only partly relieve the incidence of hydrocephalus after IVH. By contrast, combination treatment with G-CSF and lithium chloride significantly attenuated the development of hydrocephalus following IVH. TUNEL assay showed that neuronal apoptosis was significantly reduced by the combination treatment with G-CSF and lithium chloride. Furthermore, the expression of Bcl-2 was upregulated, whereas Bax expression was downregulated in the combination treatment group. The results also detected the highest expression of BrdU/GFAP, BrdU/NeuN and BrdU/PSA-NCAM in the combination treatment group. In conclusion, the combination of endogenous neural stem cell mobilization (using G-CSF) and lithium chloride treatment resulted in highly reduced incidence of hydrocephalus after IVH by inhibiting neuronal apoptosis.

During the process of embryonic development in mammals, epigenetic modifications must be erased and reconstructed. In particular, the trimethylation of histone 3 lysine 27 (H3K27me3) is associated with gene-specific transcriptional repression and contributes to the maintenance of the pluripotent embryos. In this study, we determined that the global levels of the H3K27me3 marker were elevated in MII oocyte chromatin and decrease to minimal levels at the 8-cell and morula stages. When the blastocyst hatched, H3K27me3 was re-established in the inner cell mass. We also determined that H3K27me3-specific demethylases, UTX and JMJD3, were observed at high transcript and protein levels in mouse preimplantation embryos. In the activated oocytes, when the H3K27me3 disappeared at the 8-cell stage, the UTX (but not JMJD3) protein levels were undetectable. Using RNA interference, we suppressed UTX and JMJD3 gene expression in the embryos and determined that the functions of UTX and JMJD3 were complementary. When JMJD3 levels were decreased by RNA interference, the embryo development rate and quality were improved, but the knockdown of UTX produced the opposite results. Understanding the epigenetic mechanisms controlling preimplantation development is critical to comprehending the basis of embryonic development and to devise methods and approaches to treat infertility.

A key step in the repair of photoinactivated oxygen-evolving photosystem II (PSII) complexes is the selective recognition and degradation of the damaged PSII subunit, usually the D1 reaction center subunit. FtsH proteases play a major role in D1 degradation in both cyanobacteria and chloroplasts. In the case of the cyanobacterium Synechocystis sp. PCC 6803, analysis of an N-terminal truncation mutant of D1 lacking 20 amino-acid residues has provided evidence that FtsH complexes can remove damaged D1 in a processive reaction initiated at the exposed N-terminal tail. To test the importance of the N-terminal D1 tail in higher plants, we have constructed the equivalent truncation mutant in tobacco using chloroplast transformation techniques. The resulting mutant grew poorly and only accumulated about 25% of wild-type levels of PSII in young leaves which declined as the leaves grew so that there was little PSII activity in mature leaves. Truncating D1 led to the loss of PSII supercomplexes and dimeric complexes in the membrane. Extensive and rapid non-photochemical quenching (NPQ) was still induced in the mutant, supporting the conclusion that PSII complexes are not required for NPQ. Analysis of leaves exposed to high light indicated that PSII repair in the truncation mutant was impaired at the level of synthesis and/or assembly of PSII but that D1 could still be degraded. These data support the idea that tobacco plants possess a number of back-up and compensatory pathways for removal of damaged D1 upon severe light stress.

Chymosin (also known as rennin) plays an essential role in the coagulation of milk in the cheese industry. Chymosin is traditionally extracted from the rumen of calves and is of high cost. Here, we present an alternative method to producing bovine chymosin from transgenic tobacco plants. The CYM gene, which encodes a preprochymosin from bovine, was introduced into the tobacco nuclear genome under control of the viral 35S cauliflower mosaic promoter. The integration and transcription of the foreign gene were confirmed with Southern blotting and reverse transcription PCR (RT-PCR) analyses, respectively. Immunoblotting analyses were performed to demonstrate expression of chymosin, and the expression level was quantified by enzyme-linked immunosorbent assay (ELISA). The results indicated recombinant bovine chymosin was successfully expressed at an average level of 83.5 ng/g fresh weight, which is 0.52% of the total soluble protein. The tobacco-derived chymosin exhibited similar native milk coagulation bioactivity as the commercial product extracted from bovine rumen.

Objective: To investigate whether coronary artery revascularization therapies (CART), including percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG), can improve the in-hospital and long-term outcomes for acute myocardial infarction (AMI) patients with prior ischemic stroke (IS)., Methods: A total of 387 AMI patients with prior IS were enrolled consecutively from January 15, 2005 to December 24, 2011 in this cohort study. All patients were categorized into the CART group (n = 204) or the conservative medications (CM) group (n = 183). In-hospital cardiocerebral events and long-term mortality of the two groups after an average follow-up of 36 months were recorded by Kaplan-Meier survival curves and compared by Logistic regression and the Cox regression model., Results: The CART patients were younger (66.5 ± 9.7 years vs. 71.7 ± 9.7 years, P < 0.01), had less non-ST segment elevation myocardial infarction (11.8% vs. 20.8%, P = 0.016) and more multiple-vascular coronary lesions (50% vs. 69.4%, P = 0.031). The hospitalization incidence of cardiocerebral events in the CART group was 9.3% while 26.2% in the CM group (P < 0.01). CART significantly reduced the risk of in-hospital cardiocerebral events by 65% [adjusted odds ratio (OR) = 0.35, 95% CI: 0.13-0.92]. By the end of follow-up, 57 cases (41.6%) died in CM group (n = 137) and 24 cases (12.2%) died in CART group (n = 197). Cox regression indicated that CART decreased the long-term mortality by 72% [adjusted hazard ratio (HR) = 0.28, 95% CI: 0.06-0.46], while categorical analysis indicated no significant difference between PCI and CABG., Conclusions: CART has a significant effect on improving the in-hospital and long-term prognoses for AMI patients with prior IS.

Background: An alarming increment in pathogenic resistance to existing anti-microbial agents is a serious problem and the treatment of these bacterial infections is becoming increasingly challenging. Therefore, there is an urgent need to develop novel antimicrobial agents., Objective: As a part of our ongoing studies toward the development of novel antibacterial agents, the synthesis and antibacterial activity of a series of (Z)-5-((3-phenyl-1H-pyrazol-4-yl)methylene)-2-thioxothiazolidin-4-one derivatives will be discussed in this study., Method: (Z)-5-((3-phenyl-1H-pyrazol-4-yl)methylene)-2-thioxothiazolidin-4-one derivatives were designed, synthesized and evaluated for antibacterial activity. The structures were confirmed by IR, 1H NMR, 13C NMR and mass spectrometry. All of the synthesized compounds were evaluated in vitro using a 96-well microtiter plate and a serial dilution method to obtain their minimum inhibitory concentration (MIC) values against a variety of different strains, including multidrug-resistant clinical isolates., Results: The antibacterial test in-vitro showed that most compounds in series 7 and 9 exhibited significant inhibitory activities against anaerobic bacteria (Streptococcus mutans) strains with a MIC value of 1 µg/mL. Compounds 7c and 9c showed the most potent activity against MRSA (3167 and 3506) with a minimum inhibitory concentration (MIC) value of 1 µg/mL, which is equivalent to moxifloxacin and greater than gatifloxacin, oxacillin and norfloxacin. Additionally, compound 9c showed potent antibacterial activity against Bacillus subtilis (aerobic bacteria) with a MIC value of 2 µg/mL., Conclusion: The work suggests that these type of rhodanine compounds had a better potent activity against MRSA compared with other perviously reported rhodanine derivatives, which might provide a valuable information for the development of new antibacterial agents against multidrug-resistant clinical isolates MRSA.

Basic fibroblast growth factor (bFGF) is a multifunctional factor in acceleration of cell proliferation, differentiation and transference, and therefore widely used in clinical applications. In this study, expression vector pWX-Nt03 harboring a codon-optimized bFGF gene was constructed and introduced into the tobacco chloroplasts by particle bombardment. After four rounds of selection, bFGF was proved to integrate into the chloroplast genome of regenerated plants and two of four transgenic plants were confirmed to be homoplastomic by PCR and Southern hybridization. ELISA assay indicated that bFGF represented approximately 0.1% of total soluble protein in the leaves of transplastomic tobacco plants. This is the first report of bFGF expression via chloroplast transformation in model plant, providing an additional option for the production of chloroplast-produced therapeutic proteins.

The microbial resistance has become a global hazard with the irrational use of antibiotics. Infection of drug-resistant bacteria seriously threatens human health. Currently, there is an urgent need for the development of novel antimicrobial agents with new mechanisms and lower levels of toxicity. In this paper, a series of (S ,Z)-4-methyl-2-(4-oxo-5-((5-substitutedphenylfuran-2-yl) methylene)-2-thioxothiazolidin-3-yl)pentanoic acids via a Knoevenagel condensation were synthesized and evaluated for their antibacterial activity in - vitro. The synthesized compounds were characterized by IR, (1)H NMR and MS. The antibacterial test in - vitro showed that all of the synthesized compounds had good antibacterial activity against several Gram-positive bacteria (including multidrug-resistant clinical isolates) with minimum inhibitory concentration (MIC) values in the range of 2-4 µg/mL. Especially compounds 4c, 4d, 4e and 4f were the most potent, with MIC values of 2 µg/mL against four multidrug-resistant Gram-positive bacterial strains.

Aim: Apolipoprotein E (ApoE) plays an important role in the transport and metabolism of lipids. Recent studies show that bone mass is increased in young apoE(-/-) mice. In this study we investigated the bone phenotype and metabolism in aged apoE(-/-) mice., Methods: Femurs and tibias were collected from 18- and 72-week-old apoE(-/-) mice and their age-matched wild-type (WT) littermates, and examined using micro-CT and histological analysis. Serum levels of total cholesterol, oxidized low-density lipoprotein (ox-LDL) and bone turnover markers were measured. Cultured bone mesenchymal stem cells (BMSCs) from tibias and femurs of 18-week-old apoE(-/-) mice were used in experiments in vitro. The expression levels of Sirt1 and Runx2 in bone tissue and BMSCs were measured using RT-PCR and Western blot analysis., Results: Compared with age-matched WT littermates, young apoE(-/-) mice exhibited high bone mass with increased bone formation, accompanied by higher serum levels of bone turnover markers OCN and TRAP5b, and higher expression levels of Sirt1, Runx2, ALP and OCN in bone tissue. In contrast, aged apoE(-/-) mice showed reduced bone formation and lower bone mass relative to age-matched WT mice, accompanied by lower serum OCN levels, and markedly reduced expression levels of Sirt1, Runx2, ALP and OCN in bone tissue. After BMSCs were exposed to ox-LDL (20 μg/mL), the expression of Sirt1 and Runx2 proteins was significantly increased at 12 h, and then decreased at 72 h. Treatment with the Sirt1 inhibitor EX527 (10 μmol/L) suppressed the expression of Runx2, ALP and OCN in BMSCs., Conclusion: In contrast to young apoE(-/-) mice, aged apoE(-/-) mice showe lower bone mass than age-matched WT mice. Long-lasting exposure to ox-LDL decreases the expression of Sirt1 and Runx2 in BMSCs, which may explain the decreased bone formation in aged apoE(-/-) mice.

A long air plasma channel can be formed by filamentation of intense femtosecond laser pulses. However, the lifetime of the plasma channel produced by a single femtosecond laser pulse is too short (only a few nanoseconds) for many potential applications based on the conductivity of the plasma channel. Therefore, prolonging the lifetime of the plasma channel is one of the key challenges in the research of femtosecond laser filamentation. In this study, a unique femtosecond laser source was developed to produce a high-quality femtosecond laser pulse sequence with an interval of 2.9 ns and a uniformly distributed single-pulse energy. The metre scale quasi-steady-state plasma channel with a 60-80 ns lifetime was formed by such pulse sequences in air. The simulation study for filamentation of dual femtosecond pulses indicated that the plasma channel left by the previous pulse was weakly affected the filamentation of the next pulse in sequence under our experimental conditions.

The present study was to examine the distribution of lymphatic vessels in the penis of normal adult males, which could provide an anatomical basis for improvement of incisions in penile lengthening surgery, and may also help to prevent postoperative refractory edema. Thirteen normal adult male volunteers were recruited for this study. Contrast agent was injected subcutaneously in the foreskin of the penis, and after two minutes magnetic resonance lymphangiography (MRL) was performed. The acquired magnetic resonance images were analyzed to determine the changes in the number and diameter of lymphatic vessels in different parts of the penis. Maximum intensity projections (MIP) and materializes interactive medical image control system (MIMICS) were applied to analyze the overall distribution of lymphatic vessels in the penis. Magnetic resonance imaging (MRI) showed that the lymphatic vessels were in conspicuous contrast with surrounding tissues and could be clearly identified. Penile lymphatic vessels were clearly visible in the root of the penis. At the junction of the penis and the abdominal wall, all lymphatic vessels were found to be concentrated in the dorsal part of the penis. MIP two-dimensional reconstruction showed that the overall distribution of relatively large lymphatic vessels in the dorsal and ventral parts of the penis could be seen clearly on bilateral 45° position, but not inside the abdominal wall because some of lymphatic vessels were overlapped by other tissues in the abdomen. MIMICS three-dimensional reconstruction was able to reveal the overall spatial distribution of lymphatic vessels in the penis from any angle. The reconstruction results showed that there were 1-2 main lymphatic vessels on the root of dorsal penis, which coursed along the cavernous to the first physiological curvature of the penis. Lymphatic vessels merged on both sides of the ventral penis. At the root of the penis, lymphatic vessels gradually coursed to the dorsal surface of the penis and folded at the abdominal wall to the outside, and finally merged into the inguinal lymph nodes. The changes in distribution, number and diameter of the lymphatic vessels in the penis were observed by MRI. MIP and MIMICS reconstructions directly revealed the anatomical features of penile lymphatic vessels such as spatial distribution, overall alignment, and the relations to adjacent structures, drainage and reflux. The study will provide the anatomical basis for penile surgery, penile lymphatic reflux disorders caused by trauma or lymphatic vessels obstruction, and lymph node metastasis in penile cancer., (© 2014 Wiley Periodicals, Inc.)

Background: We aimed to evaluate serum levels of S-100 beta (S-100β) and neuron specific enolase (NSE) in patients with coronary heart disease (CHD) after off-pump versus on-pump coronary artery bypass graft (CABG) surgery., Methods: The PubMed (~2013) and the Chinese Biomedical Database (CBM) (1982 ~ 2013) were searched without language restrictions. After extraction of relevant data from selected studies, meta-analyses were conducted using STATA software (Version 12.0, Stata Corporation, College Station, Texas USA). Possible sources of heterogeneity were examined through univariate and multivariate meta-regression analyses and verified by Monte Carlo Simulation., Results: Eleven studies with a total of 411 CHD patients met the inclusion criteria. Our meta-analysis showed no significant difference in serum S-100β and NSE levels between the on-pump group and the off-pump group before surgery. In the on-pump group, there was a significant difference in serum S-100β levels of CHD patients between before and after surgery, especially within the first 24 h after surgery. Furthermore, in the on-pump group, there was a significant difference in serum NSE levels of CHD patients between before and after surgery, particularly at 0 h after surgery. In the off-pump group, there was an obvious difference in serum S-100β levels between before and after surgery, especially within 24 h after surgery. Our results also demonstrated that serum S-100β and NSE levels of CHD patients in the on-pump group were significantly higher than those of patients in the off-pump group, especially within 24 h after surgery., Conclusions: Our findings provide empirical evidence that off-pump and on-pump CABG surgeries may increase serum S-100β and NSE levels in CHD patients, which was most prominent within 24 h after on-pump CABG surgery.

Background: The current reports on the association of claudin-4 expression with gastric cancer outcome were inconsistent. Thus, we conducted a meta-analysis to assess the association of claudin-4 expression with the prognosis and clinical parameters more precisely., Methods: Systematic searches on PubMed, Embase, and Cochrane Library prior to December 2014 were performed. The pooled hazard ratio (HR) with its 95 % confidence interval (95 %CI) was used to assess the prognostic value of claudin-4 expression with gastric cancer patients, and the pooled odds ratio (OR) with its 95 %CI was used to assess the association with clinical parameters., Results: Nine studies with a total of 1265 gastric cancer patients were included. Overall, the pooled results showed that over-expression of claudin-4 was associated with a poor survival in gastric cancer patients (HR: 2.01, 95 % CI: 1.62-2.50). Over-expression of claudin-4 was also associated with advanced stage (OR: 1.96, 95 % CI: 1.08-3.56) and lymphoid node metastasis (OR: 1.72, 95 % CI: 1.05-2.81) of gastric cancer patients. No significant publication bias was found among the studies (P > 0.05)., Conclusions: This meta-analysis shows that over-expression of claudin-4 is associated with progress of gastric cancer and poor prognosis of gastric cancer patients.

Many remarkable properties of graphene are derived from its large energy window for Dirac-like electronic states and have been explored for applications in electronics and photonics. In addition, strong electron-phonon interaction in graphene has led to efficient photo-thermo energy conversions, which has been harnessed for energy applications. By combining the wavelength independent absorption property and the efficient photo-thermo energy conversion, here we report a new type of applications in sound wave generation underlined by a photo-thermo-acoustic energy conversion mechanism. Most significantly, by utilizing ultrafast optical pulses, we demonstrate the ability to control the phase of sound waves generated by the photo-thermal-acoustic process. Our finding paves the way for new types of applications for graphene, such as remote non-contact speakers, optical-switching acoustic devices, etc.