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An efficient iron-catalyzed asymmetric [4 + 2] cycloaddition of cyclopentadiene with α,β-unsaturated acyl imidazoles or 2-cinnamoylisoindoline-1,3-dione derivatives was developed to afford the addition products in high yield and selectivity. Interestingly, the absolute structures of the addition products were controlled by the auxiliaries via different coordination modes with the same type of catalyst.

A practical, highly efficient iron-catalyzed asymmetric Diels–Alder reaction of various alkylidene β-ketoesters with dienes was developed. Both cyclic and acyclic alkylidene β-ketoesters underwent the reaction well with the Fe-BPsalan complex as the catalyst to afford the addition products including estrone analogues in excellent yields, good to high diastereoselectivities and excellent enantioselectivities under mild reaction conditions. DFT calculations revealed the critical role of the steric effect in directing the reaction selectivity.

We have investigated the synergism between plant phenols and carotenoids in protecting the phosphatidylcholine (PC) membranes of giant unilamellar vesicles (GUVs) from oxidative destruction, for which chlorophyll-a (Chl-a) was used as a lipophilic photosensitizer. The effect was examined for seven different combinations of β-carotene (β-CAR) and plant phenols. The light-induced change in GUV morphology was monitored via conventional optical microscopy, and quantified by a dimensionless image-entropy parameter, ΔE. The ΔE-t time evolution profiles exhibiting successive lag phase, budding phase and ending phase could be accounted for by a Boltzmann model function. The length of the lag phase (LP in s) for the combination of syringic acid and β-CAR was more than seven fold longer than for β-CAR alone, and those for other different combinations followed the order: salicylic acid rutin > caffeic acid > quercetin > catechin, indicating that moderately reducing phenols appeared to be the most efficient membrane co-stabilizers. The same order held for the residual contents of β-CAR in membranes after light-induced oxidative degradation as determined by resonance Raman spectroscopy. The dependence of LP on the reducing power of phenols coincided with the Marcus theory plot for the rate of electron transfer from phenols to the radical cation β-CAR˙+ as a primary oxidative product, suggesting that the plant phenol regeneration of β-CAR plays an important role in stabilizing the GUV membranes, as further supported by the involvement of CAR˙+ and the distinct shortening of its lifetime as shown by transient absorption spectroscopy.

The present work is intended to investigate the morphological instability of lipid membrane induced by peroxyl radical (ROO

Phototherapy has drawn increasing attention including the use of nanocarriers with high drug loading capacity and delivery efficacy for target-specific therapy. We have made use of naturally-occurring halloysite nanotubes (HNTs) to build a biomimetic nanocarrier platform for target-specific delivery of phototherapeutic agents. The HNTs were decorated with poly(sodium- p -styrenesulfonate) (PSS) to enhance the biocompatibility, and were further functionalized by lumen loading the type-II photosensitizer indocyanine green (ICG). The HNT-PSS-ICG nanocarrier, without further tethering targeting groups, was shown to associate with the membrane of giant unilamellar vesicles (GUVs) via Pickering effects. Application of HNT-PSS-ICG nanocarrier to human breast cancer cells gave rise to a cell mortality as high as 95%. The HNT-PSS-ICG nanocarrier was further coated with MDA-MB-436 cell membranes to endow it with targeting therapy performance against breast cancer, which was confirmed by in vivo experiments using breast cancer tumors in mice. The membrane-coated and biocompatible nanocarrier preferentially concentrated in the tumor tissue, and efficiently decreased the tumor volume by a combination of photodynamic and photothermal effects upon near-infrared light exposure. Our results demonstrate that the HNT-based nanocarrier by virtue of facial preparation and high loading capacity can be a promising candidate for membrane-targeting nanocarriers.

Singlet oxygen (1O2) formed through photosensitization may initiate oxidative destruction of biomembranes, however, the influence from the spatial organization of photosensitizers (PS) relative to membranes remains unclear. To clarify this issue, we loaded riboflavin 5′-(dihydrogen phosphate) monosodium (FMN-Na) as a hydrophilic PS into the lumen of halloysite nanotubes (HNTs), and attached the nanoassemblies (FMN-Na@HNTs), via Pickering effects, to the outer surfaces of giant unilamellar vesicles (GUVs) of phospholipids. We also prepared GUVs dopped with lumiflavin (LF) as a lipophilic PS having a 1O2 quantum yield comparable to FMN-Na. FMN-Na capsulated in HNT was characterized by a longer triplet excited state lifetime (12.1 μs) compared to FMN-Na free in solution (7.5 μs), and FMN-Na in both forms efficiently generated 1O2 upon illumination. The spatio-effects of PS on the photosensitized morphological changes of membranes were studied using conventional optical microscopy by monitoring GUV morphological changes. Upon light exposure (400–440 nm), the GUVs attached with FMN-Na@HNT merely experienced membrane deformation starting from the original spherical shape, ascribed to Type II photosensitization with 1O2 as oxidant. In contrast, photooxidation of LF dopped GUVs mainly led to membrane coarsening and budding assigned to Type I photosensitization. The spatial effects of PS on photosensitized morphological changes were related to the different lipid oxidation products generated through Type I and Type II photosensitized lipid oxidation.

Developing novel microelectronic devices for electrochemical measurements and electrochemiluminescence (ECL) study is of great importance. Herein, we fabricated a submicrometer-sized dual carbon electrode (DCE) and investigated its annihilation ECL behavior under steady-state conditions for the first time. The oxidation and reduction of the model luminophore, [Ru(bpy)3]2+, occurred separately at the two sides of the DCE, and the electrogenerated ions then diffused to the gap between the two electrodes to generate the excited-state intermediate [Ru(bpy)3]2+* and ECL emission. Compared with other types of two-electrode systems, the prepared DCE possesses a smaller total size and an ultrasmall interelectrode distance of 60 nm or less, which could result in a shorter diffusion time and an amplified ECL signal without the purification of the solvent and supporting electrolytes. On the basis of the constructed ECL microscopic platform, we successfully obtained a stable and confined ECL signal in the vicinity of the electrode tip. Furthermore, a two-dimensional finite element method simulation of this model system was performed to quantitively analyze the concentration profiles of the electrogenerated species around the tip of the DCE and predict the concentrations of [Ru(bpy)3]2+* with various gap distances. The simulation results also proved that the higher concentrations of [Ru(bpy)3]2+* could be achieved with a smaller distance with a possible amplification factor of 6 (compared with the concentration when the gap distance is greater than 300 nm). This work provides an experimental model for further improvement of ECL efficiency and broadens the availability for annihilation ECL applications in small confined spaces.

β-Carotene degrades rapidly in a 2% oil-in-water emulsion, made from food-grade soy oil with 7.4 mg β-carotene/mL oil, during storage and when exposed to light. Added clove oil (2.0, 4.0, or 8.0 µL/mL of emulsion) protects against the photodegradation of β-carotene, regardless of the ratio between clove oil and β-carotene in the concentration range studied, suggesting that the regeneration of β-carotene is caused by eugenol, the principal plant phenol of clove oil to occur in the oil-water interface. Therefore, clove oil in low concentrations may find use as a natural protectant of provitamin A in enriched foods during retail display.

Flavonoids are used as natural additives and antioxidants in foods, and after coordination to metal ions, as drug candidates, depending on the flavonoid structure. The rate of radical scavenging of the ubiquitous plant flavonoid kaempferol (3,5,7,4'-tetrahydroxyflavone, Kaem) was found to be significantly enhanced by coordination of Mg(II), Ca(II), Sr(II), and Ba(II) ions, whereas the radical scavenging rate of apigenin (5,7,4'-trihydroxyflavone, Api) was almost unaffected by alkaline earth metal (AEM) ions, as studied for short-lived b-carotene radical cations (beta-Car(center dot+)) formed by laser flash photolysis in chloroform/ethanol (7 : 3) and for the semi-stable 2,2-diphenyl-1-picrylhydrazyl radical, DPPH center dot, in ethanol at 25 degrees C. A 1 : 1 Mg(II)-Kaem complex was found to be in equilibrium with a 1 : 2 Mg(II)-Kaem(2) complex, while for Ca(II), Sr(II) and Ba(II), only 1 : 2 AEM(II)-Kaem complexes were detected, where all complexes showed 3hydroxyl and 4-carbonyl coordination and stability constants of higher than 10(9) L-2 mol(-2). The 1 : 2 Ca(II)-Kaem(2) complex had the highest second order rate constant for both beta-Car(center dot+) (5 x 10(8) L mol(-1) s(-1)) and DPPH center dot radical (3 x 10(5) L mol(-1) s(-1)) scavenging, which can be attributed to the optimal combination of the stronger electron withdrawing capability of the (n - 1)d orbital in the heavier AEM ions and their spatially asymmetrical structures in 1 : 2 AEM-Kaem complexes with metal ion coordination of the least steric hindrance of two perpendicular flavone backbones as ligands in the Ca(II) complex, as shown by density functional theory calculations.

Chlorophyll a (Chl a) as a lipophilic photosensitizer can induce biomembrane destruction via Type-II reaction involving singlet oxygen (1O2) as a primary initiator. Type-I oxidation by an excited-state photosensitizer reacting directly with lipid substrate also contributes but the primary intermediate remains to be verified experimentally. We have investigated the reaction dynamics initiated by Chl a-photosensitization involving oxygen and the -C=C- moieties of lipids in the membranes of small unilamellar vesicles (SUVs) prepared from phospholipids of different degree of unsaturation (0, 1 or 2). Under anaerobic condition, femtosecond time resolved absorption (fs-TA) combined with spectroelectrochemical spectroscopies validated the formation of Chl a − in subpicoseconds, and time resolved fluorescence spectroscopy revealed the rapid quenching of 1Chl a* with a rate constant of (28 ns)−1. These ultrafast processes, independent of oxygen, are ascribed to the electron transfer reaction from a -C=C- moiety to 1Chl a* as an initiation step of Type-I reaction. On longer timescales, ns-TA spectroscopy unraveled the drastic quenching of 3Chl a* by either -C=C- or O2, and the quenching by O2 was found to be 20 times more efficient. This together with the 1O2-luminesence analysis prove the involvement of both types of photosensitization. In addition, HPLC-MS spectroscopy confirmed the ketonic, the alcoholic and the core-aldehyde products of lipid oxidation. Moreover, the oxygen dependent partition between Type-I and Type-II reactions is discussed on a detailed kinetics basis, showing that the two mechanisms of lipid oxidation are equally important under an oxygen concentration of 1.3×10−5 M at room temperature.

To understand the contemporary and anticipated future (future 30–50 years) distribution of Chinese wild yellowhorn (Xanthoceras sorbifolium Bunge) and to improve the species’ in situ conservation strategy within the network of China’s National Nature Reserves (NNR), we used BiodiversityR to predict the species’ distribution utilizing the “always-suitable” map concept. We then delineated the always-suitable distributions with the existing NNRs to identify potential conservation areas using an approach that concurrently considered spatial distribution, gap analysis, the role of climate change, and economic analyses. Seven bioclimatic variable predictors and 12 environmental niche modelling submodels successfully contributed to the final model assembly (AUC = 0.916, κ = 0.398). The species range delineation indicated that 71 of the 427 NNRs were included in the always-suitable area, accounting for 26 007 km2 (1.58%) of the species total distribution. This mapping endeavour highlighted the negative impact of climate change with a projected 15%–20% habitat decline and expected species’ distribution centers shifting from the country’s northwest to the southeast. Our results predict the continuous deterioration of X. sorbifolium because of its existing utilization as an oil source and its increased bioenergy potential. The adoption of a flexible management strategy embracing acceptable trade-offs between conservation and utilization within China’s NNRs could effectively alleviate the expected species decline.

The coordinate reference misalignment caused by ship angular deformation is an important factor affecting the operational performance of shipborne weapons and equipment. Based on the local inertial measurement units (IMUs) distributed on the ship and the deformation law of ship mechanics, the whole ship deformation prediction can be realized. The influence of local reference number and installation location on the accuracy of deformation prediction is studied in this paper. The simulation results show that when the installation position of the ship local IMU can better reflect the ship vibration model characteristics, four sets of local inertial reference can be used to predict the angular deformation at any point of the whole ship by the least square estimation method. The interpolation prediction error is less than 2.5″ (1σ), and the extension prediction error is less than 5″ (1σ).

PM

Real-time aerosol extinction retrieved by Micro-pulse LIDAR and concentrations of PM

To understand the process of passenger transportation on the urban and rural roads accurately, objectively and reasonably, this article in six aspects of the station yard layout, line network, operation management, service level, fiscal policy and technical equipment, constructing a multi-level evaluation index system of complete.

Discovery of 5-hydroxymethylcytosine (5hmC) in mammalian genomes has excited the field of epigenetics, but information on the genome-wide distribution of 5hmC is limited. Globozoospermia is a rare but severe cause of male infertility. To date, the epigenetic mechanism, especially 5hmC profiles involved in globozoospermia progression, remains largely unknown. Here, utilizing the chemical labeling and biotin-enrichment approach followed by Illumina HiSeq sequencing, we showed that (i) 6664, 9029 and 6318 genes contain 5hmC in normal, abnormal, and globozoospermia sperm, respectively; (ii) some 5hmC-containing genes significantly involves in spermatogenesis, sperm motility and morphology, and gamete generation; (iii) 5hmC is exclusively localized in sperm intron; (iv) approximately 40% imprinted genes have 5hmC modification in sperm genomes, but globozoospermia sperm exhibiting a large portion of imprinted genes lose the 5hmC modification; (v) six imprinted genes showed different 5hmC patterns in abnormal sperm (GDAP1L1, GNAS, KCNK9, LIN28B, RB1, RTL1), and five imprinted genes showed different 5hmC patterns in globozoospermia sperm (KCNK9, LIN28B, RB1, SLC22A18, ZDBF2). These results suggested that differences in genome-wide 5hmC patterns may in part be responsible for the sperm phenotype. All of this may improve our understanding of the basic molecular mechanism underlying sperm biology and the etiology of male infertility.

This study was designed to evaluate the antioxidant activity of samples extracted from Jinhua ham. The activities of SOD and contents of MDA and NO were measured after mice were kept on feeding the four peaks separated by using chromatographic column. Peak-3 obviously enhanced the activity of SOD and MDA. Peak-1 and peak-2 had little influence on the activity of SOD and MDA. Peak-4 decreased their activities. All peaks obviously decreased content of NO. Results showed that these four peaks had excellent antioxidant activity. Finally, influences of sample extracted from ham on SOD activity, MDA content and GSH-PX activity in vitro of mouse liver and heart were also studied. Certain dose of samples would lead the decrease of SOD activity, MDA content and GSH-PX activity. This results showed that the sample have certain oxidant capacity.

This study was designed to evaluate the antioxidant activity of samples extracted from Jinhua ham by using such chemical assays as DPPH, scavenging hydroxyl free radical and ABTS. The results demonstrate that antioxidant capacity of the extracted sample is lower than oxidation capacity of Vc. The IC50 spot of samples ranges between 0.6 % and 2.5 % (mass fraction of solute).

To predict the passenger travel sharing rate in the inter-city comprehensive passenger traffic channels, the passenger transport properties of the inter-city comprehensive passenger transport channels were combined, variables with different characteristics were introduced into utility function, the application of Logit model was improved, the comprehensive passenger transport channels of Guangzhou-Huizhou, Shenzhen-Huizhou, Dongguan-Huizhou were taken as examples to conduct the prediction applications of the passenger travel sharing in the railway passenger transportation, highway passenger transportation and non-commercial transportation. The results showed that the improved model could effectively carry out the passenger travel share prediction in inter-city comprehensive passenger transport channels.

The beef flavor was selected to carry out toxicological analysis regarding food intake, body weight, organs weight and blood biochemical indexes in mice. The results show that beef flavor could suppress food intake but promote mice weight compared with the control group. Flavor intake has significant effect on the ratio of liver and lung weight to the whole body weight, but it has no difference in the ratio of heart, spleen and kidney weight. Some biochemical indexes about fat metabolism in blood such as the total protein, total bile acid and alkaline phosphatase are respectively 4 g/L, 0.7μmol/L and 23 IU/L more than the control group. These factors and cholesterol, triglyceride, low density lipoprotein, high-density lipoprotein cholesterol in the mice blood all have extremely significant differences (P

In China, many kinds of natural products extracted from plant and animal were used to treat cancer. Flavonoids extracted from tartary buckwheat and skin peptide purified from rufous-spotted torrent frog had respectively been proved to have anti-tumor activity. In present study, both tartary buckwheat flavonoids and amphibian frog peptides were applied for cell proliferation inhibitory activity against human gastric cancer MGC 80-3 cells using MTT assay. According to the data, the buckwheat flavonoids exhibited much stronger anti-tumor activity than amphibian peptides, and the complex mixture of this two kinds of bioactive compounds still possess anti-tumor activity.

A novel probe based on ferrocenyl-1,3,4-thiadiazol-containing Schiff base was synthesized by the reaction of 5-ferrocenyl-1,3,4-thiadiazol-2-amine and 4-(diethylamino)salicylaldehyde, and characterized by IR, NMR, HRMS and X-ray analysis. UV-vis spectral and fluorescence property of the probe were investigated. The probe can be used to colorimetric sensitive and selective fluorescent recognition of Cu(2+) in buffer solution. Moreover, the probe can detect Cu(2+) by electrochemical method. Additionally, the Schiff base was successfully used as a selective and sensitive fluorescent probe for monitoring Cu(2+) ions in living cells.

We aimed to assess the feasibility, safety, and efficacy of radiofrequency (RF) ablation for the treatment of large (≥5 cm in greatest diameter) hepatic hemangiomas.Thirty-six patients (15 male, 21 female; mean age 50 years) with 41 hepatic hemangiomas ≥5 cm in diameter were enrolled and treated with RF ablation attributable to the presence of enlargement tendency and/or persistent hemangioma-associated symptoms. Twenty patients had 24 hemangiomas10 cm, and 16 patients had 17 hemangiomas ≥10 cm. Technical success, complications related to RF ablation, completed ablation, symptom relief, change in size of ablation zone, and recurrence of the residual tumor were analyzed.Of the 41 hemangiomas with a mean diameter 10 ± 4 cm (range, 5-22 cm), 26 subcapsular lesions were treated with a laparoscopic approach, and 15 lesions located in liver parenchyma underwent a computed tomography-guided percutaneous approach. RF ablation was performed successfully in all patients. There were 62 complications related to the ablation in 22 patients, including 6 of 20 patients with hemangiomas10 cm and all the 16 patients with hemangiomas ≥10 cm. According to the Dindo-Clavien classification, 2 complications (lower esophageal fistula and acute respiratory distress syndrome, Grade III and Grade IV, respectively) were major in 2 patients with hemangiomas ≥10 cm; all the other were minor in 20 patients (Grade I). All the complications were recovered by conservative treatment. Thirty-eight (93%) of 41 hepatic hemangiomas were ablated completely, including all the 24 lesions10 cm and 14 of 17 lesions ≥10 cm. All the symptoms related to hemangiomas disappeared (n = 22) or were ameliorated (n = 4) after ablation. The mean diameter of ablation zone was decreased to 6 ± 3 cm (2-12 cm) in a mean follow-up period (X ± SD) of 15 ± 6 months (range, 6-24 months), without recurrence or enlargement of the 3 residual tumors.The present study supports RF ablation as an alternative treatment for hepatic hemangiomas ≥5 cm (but smaller than 10 cm) for the low risk of complications and likelihood of complete ablation, but, in contrast, RF ablation appears to be an inappropriate method for hepatic hemangiomas ≥10 cm because of the high occurrence rate of complications.

To evaluate the technical and clinical outcomes of early laparoscopic radiofrequency (RF) ablation for spontaneously ruptured hepatocellular carcinoma (HCC).From April 2005 to July 2015, ten patients with spontaneously ruptured HCC treated by laparoscopic RF ablation in our hospital were included in the study. The post treatment outcomes were recorded and analyzed.The mean size of the 10 HCCs was 6.6 ± 2.2 cm (4.0-10.1 cm) in the maximal dimension. Procedures of laparoscopic RF ablation were performed successfully for all patients. Complete ablation was achieved in 60.0% patients (6/10). Four patients with incompletely ablated tumors received repeated RF ablation to achieve complete ablation. During clinical follow-up, 3 (30.0%) patients developed minor complications and no patient had peritoneal recurrence. As of March 2016 (with a mean follow-up of 32.9 months), 3 patients (30.0%) were alive and 7 (70.0%) died. Of the 10 patients, the 1- and 3-year survival rates were 90.0% and 70.0%, respectively.Early laparoscopic RF ablation therapy is an effective treatment measure for spontaneously ruptured HCC in selected patients, which presents an advantage of achieving simultaneous hemostasis, tumor elimination, and rinsing of peritoneal cavity to minimize the risk of peritoneal metastasis.

Reversible lysine acetylation is one of the most important protein posttranslational modifications that plays essential roles in both prokaryotes and eukaryotes. However, only a few lysine deacetylases (KDACs) have been identified in prokaryotes, perhaps in part due to their limited sequence homology. Herein, we developed a ‘clip-chip’ strategy to enable unbiased, activity-based discovery of novel KDACs in the Escherichia coli proteome. In-depth biochemical characterization confirmed that YcgC is a serine hydrolase involving Ser200 as the catalytic nucleophile for lysine deacetylation and does not use NAD+ or Zn2+ like other established KDACs. Further, in vivo characterization demonstrated that YcgC regulates transcription by catalyzing deacetylation of Lys52 and Lys62 of a transcriptional repressor RutR. Importantly, YcgC targets a distinct set of substrates from the only known E. coli KDAC CobB. Analysis of YcgC’s bacterial homologs confirmed that they also exhibit KDAC activity. YcgC thus represents a novel family of prokaryotic KDACs. DOI: http://dx.doi.org/10.7554/eLife.05322.001, eLife digest After proteins have been made, they can be modified in several ways. For example, chemical tags called acetyl groups may be added to (and later removed from) the protein to regulate cell activities such as aging and metabolism. Enzymes are proteins that help catalyze the reactions that add or remove the acetyl tags on certain “substrate” proteins. In the bacteria species Escherichia coli, many enzymes that help to add acetyl groups to proteins have been discovered. However, only a single E. coli “deacetylase” enzyme that removes the acetyl group has been identified. Now, Tu, Guo, Chen et al. have devised a technique to identify new deacetylases, called the “clip-chip” approach. In this method, thousands of proteins that are potential deacetylases are arrayed on a glass slide, and substrate proteins are immobilized on another slide. The two slides are then clipped together face-to-face, allowing the potential enzymes to transfer to the substrate slide and interact with the substrates. Using this approach, Tu, Guo, Chen et al. identified a protein called YcgC as a deacetylase in bacteria. Further characterization experiments revealed that YcgC works in a different way to other known deacetylases, and that it targets different substrates to the previously known E. coli deacetylase. Tu, Guo, Chen et al. found that the equivalents of YcgC in other bacteria species are also deacetylases; these enzymes therefore represent a new deacetylase family. In the future, the clip-chip approach could be used to discover new members of other enzyme families. DOI: http://dx.doi.org/10.7554/eLife.05322.002

To explore the clinical application and significance of the technique of orthotopic liver resection.From January 2004 to December 2011, five patients with huge hepatocellular carcinoma with invasion or severe adhesion of diaphragm were undergone right semi-liver resection using the technique of orthotopic liver resection. The right hemi-liver was isolated from the first liver portal, second liver portal and third liver portal, then isolated from the normal liver, finally the tumor and the invaded diaphragm were resected or removed from the severe adhesion. The approach to hepatic resection involved routine use of Peng's multifunctional operative dissector, selective control of in and out-flow of liver, control of inferior vena cava (IVC) and liver hanging maneuver, anterior approach, etc.The operations were successfully performed in 5 patients. Operative time was 120, 180, 150, 150 and 160 min, respectively. The amount of blood loss were 350, 350, 400, 450, 600 ml, respectively. Postoperative complications were pleural effusion in 3 cases, and other 2 cases recovered without complications.Although the technique of orthotopic liver resection has a high technical requirement for surgeons, it provides a surgical method and operative opportunity for the patients whose tumor has invaded diaphragm or has been severe adhesion with diaphragm and conventional liver resection cannot be performed.

Emerging evidence has led to considerable interest in the role of Traf2- and Nck-interacting kinase (TNIK) in polycystic ovary syndrome (PCOS) development. However, the epigenetic mechanism regulating TNIK transcription remains largely unknown. Here, we show that (i) TNIK mRNA expression is significantly increased in PCOS ovarian tissues, compared to normal ovarian tissues; (ii) PCOS ovarian tissues exhibit a hypermethylation pattern at the cg10180092 site, (iii) and cg10180092 is the critical site for the transcriptional regulation of TNIK. Mechanistically, hypermethylated cg10180092 site-mediated loss of holocarboxylase synthetase (HLCS)-related H3K9me enrichment activated TNIK transcription in PCOS ovarian tissues. Notably, a substantial body of evidence indicates that DNA hypermethylation is an alternative mechanism for gene inactivation, and a new role for DNA hypermethylationmediated TNIK activating was observed in this study. This may improve our understanding of divergent transcriptional regulation in the initiation and progression of TNIK-related PCOS.

Nicotinamide adenine dinucleotide (NAD) is a crucial molecule of energy production and signal transduction processes that have been linked to ovarian cancer development. Notably, emerging evidence has led to considerable interest in the role of DNA methyltransferase 1 (DNMT1) in the initiation and progression of ovarian cancer. However, dynamic crosstalk between NAD and DNMT1 is poorly understood. Here, we show that DNMT1 levels are upregulated, along with increased NAD levels in non-BRCA1-mutated ovarian cancer cells. In contrast, DNMT1 levels are not affected by increasing NAD levels in BRCA1-mutated ovarian cancer cells. Mechanistically, BRCA1 inactivity-mediated loss of H3K9ac enrichment around the core promoter inhibits DNMT1 transcription. Consistent with this, BRCA1 levels correlate with DNMT1 levels (R = 0.534, R < 0.001) in human ovarian cancer specimens. Therefore, these results highlight a novel regulatory effect of NAD on DNMT1, and further correlate the physiological properties of NAD metabolism with DNMT1-mediated biological processes. All of this may improve our understanding of the basic molecular mechanism underlying NAD- and DNMT1-related ovarian cancer progression.

Efficiencies of mismatch discrimination using size-varied capture probes were examined at various hybridization temperatures. The probes were 17, 15, 13, 11, 9, and 7 nucleotides long and contained single-base mismatches at their 3′ ends. The optimal signal intensity and efficiency of base stacking hybridization on mismatch discrimination were observed for capture probes with a melting temperature (Tm) value of 36°C, in the detection of DNA sequence variations at 40°C. We employed asymmetric PCR to prepare single-stranded target DNA labeled with a fluorescent dye, and the PCR product was hybridized on the DNA microarray with no further purification. Our efforts have enhanced the sensitivity and simplified the procedures of base stacking hybridization on mismatch discrimination. As a model experiment, this improved technology was used to identify plasmid templates of human leukocyte antigen (HLA)-A alleles 2601, 2902, and 0206 on oligonucleotide microarrays. It is now possible to apply this simple, rapid, sensitive, and reliable base stacking hybridization technology to detect DNA sequence variations on microarrays in clinical diagnosis and other applications.

Shenqi is a traditional Chinese polyherbal medicine has been widely used for the treatment of allergic rhinitis (AR). The aim of this study was to investigate the anti-allergic rhinitis activity of Shenqi and explore its underlying molecular mechanism. Ovalbumin (OVA)-induced allergic rhinitis rat model was used to evaluate the anti-allergic rhinitis effect of Shenqi. The effect of Shenqi on IgE-mediated degranulation was measured using rat basophilic leukemia (RBL-2H3) cells. Primary spleen lymphocytes were isolated to investigate the anti-allergic mechanism of Shenqi by detecting the expression of transcription factors via Western blot and the level of cytokines (IL-4 and IFN-γ) via ELISA. In OVA-induced AR rat models, Shenqi relieved the allergic rhinitis symptoms, inhibited the histopathological changes of nasal mucosa, and reduced the levels of IL-4 and IgE. The results from the in vitro study certified that Shenqi inhibited mast cell degranulation. Furthermore, the results of GATA3, T-bet, p-STAT6, and SOCS1 expression and production of IFN-γ and IL-4 demonstrated that Shenqi balanced the ratio of Th1/Th2 (IFN-γ/IL-4) in OVA-stimulated spleen lymphocytes. In conclusion, these results suggest that Shenqi exhibits an obvious anti-allergic effect by suppressing the mast cell-mediated allergic response and by improving the imbalance of Th1/Th2 ratio in allergic rhinitis.

Asymmetric dimethylarginine (ADMA) induces vascular smooth muscle cells (VSMCs) migration. VSMC phenotype change is a prerequisite of migration. RhoA and Rho-kinase (ROCK) mediate migration of VSMCs. We hypothesize that ADMA induces VSMC migration via the activation of Rho/ROCK signal pathway and due to VSMCs phenotype change. ADMA activates Rho/ROCK signal pathway that interpreted by the elevation of RhoA activity and phosphorylation level of a ROCK substrate. Pretreatment with ROCK inhibitor, Y27632 completely reverses the induction of ADMA on ROCK and in turn inhibits ADMA-induced VSMCs migration. When the Rho/ROCK signal pathway has been blocked by pretreatment with Y27632, the induction of ERK signal pathway by ADMA is completely abrogated. Elimination of ADMA via overexpression of dimethylarginine dimethylaminohydrolase 2 (DDAH2) and L-arginine both blocks the effects of ADMA on the activation of Rho/ROCK and extra cellular signal-regulated kinase (ERK) in VSMCs. The expression of differentiated phenotype relative proteins was reduced and the actin cytoskeleton was disassembled by ADMA, which were blocked by Y27632, further interpreting that ADMA inducing VSMCs migration via Rho/ROCK signal pathway is due to its effect on the VSMCs phenotype change. Our present study may help to provide novel insights into the therapy and prevention of atherosclerosis.

A simple and efficient method for the preparation of benzils through the solid state oxidation reaction of benzoins by FeCl3 · 6H2O at low-heating temperatures(80 ~ 90°C) is described. The oxidation conditions are mild. The products are easily separated with no pollutions produced.