Thyroid hormone-responsive protein mediates the response of chicken liver to fasting mainly through the cytokine-cytokine receptor interaction pathway.

1. The objective of this study was to explore the mediating role of thyroid hormone-responsive protein (THRSP) in the response of chicken liver to fasting.2. A batch of 7-d-old chicks with similar body weights were randomly divided into the control group and the fasting group (n = 10). The control group was fed ad libitum, while the test group fasted for 24 h. The liver and pectoral muscle tissues were collected. Chicken primary hepatocytes or myocytes were treated with different concentrations of thyroxine, glucose, insulin, oleic acid and palmitic acid, separately. Chicken primary hepatocytes were transfected with THRSP overexpression vector vs. empty vector, and the cells were used for transcriptome analysis. The mRNA expression of THRSP and other genes was determined by quantitative PCR.3. The expression of THRSP in chicken liver and pectoral muscle tissues was significantly inhibited by fasting (P < 0.05). In chicken primary hepatocytes, the expression of THRSP was significantly induced by thyroxine (0.25, 0.5, 1 mmol/l), glucose (50, 100 mmol/l), and insulin (20 nmol/l), and was significantly inhibited by palmitic acid (0.125, 0.25 mmol/l). In the myocytes, expression of THRSP was significantly induced by thyroxine (0.25, 0.5, 1 mmol/l), glucose (50 mmol/l) and oleic acid (0.125, 0.25 mmol/l), was significantly inhibited by insulin (5 nmol/l) and was not significantly affected by palmitic acid.4. Transcriptome analysis showed that overexpression of THRSP significantly affected the expression of 1411 DEGs, of which 1007 were up-regulated and 404 were down-regulated. The GO term and KEGG pathway enrichment analyses showed that these DEGs were mainly enriched in the interaction between cytokine and cytokine receptor and its regulation and signal transduction, cell growth and apoptosis and its regulation, immune response and retinol metabolism.5. In conclusion, the THRSP gene mediates biological effects of fasting by influencing the expressional regulation of the genes related to biological processes such as cytokine-cytokine receptor interaction, cell growth and apoptosis, immune response, retinol metabolism, including TGM2, HSD17B2, RUNX3, IRF1, ANKRD6, UPP2, IKBKE, and PYCR1 genes, in chicken liver.

Probing the effects of dietary selenised glucose on the selenium concentration, quality, and antioxidant activity of eggs and production performances of laying hens.

Selenised glucose (SeGlu) is a newly invented organic selenium compound being synthesised through the selenisation reaction of glucose with NaHSe. We hypothesised that glucose could be used as a carrier for the stable low-valent organoselenium to enhance the selenium concentrations of eggs. To probe the effects of SeGlu on production performances of laying hens, egg selenium concentration, egg quality, and antioxidant indexes, 360 Hy-Line Brown laying hens were randomly assigned to three treatment groups fed with a basal diet alone or the diet supplemented with 5 or 10 mg/kg of Se from SeGlu. The results showed that SeGlu treatment not only enhanced (P < 0.001) the Se concentration in albumen and yolks, glutathione peroxidase activity, and total antioxidant capacity of eggs but also increased (P = 0.032) the Haugh unit of eggs being stored for 2 weeks, while the production performances and egg qualities of fresh eggs were not affected. Moreover, SeGlu supplementation linearly (P < 0.001) increased the scavenging ability of superoxide radicals in eggs. Briefly, SeGlu can enhance the selenium deposition and antioxidant activity of eggs, thereby meeting the nutritional requirement for Se-deficient humans.

Thiamine modulates intestinal morphological structure and microbiota under subacute ruminal acidosis induced by a high-concentrate diet in Saanen goats.

Ruminant animals are generally fed with starch-rich grain as the main energy source, and the incidence of metabolic diseases such as subacute ruminal acidosis (SARA) is high due to the intensive farming. Thiamin has been reported to alleviate SARA caused by high-concentrate diets, but the exact mechanism is not well understood. The goal of this study was to examine the role of thiamine in intestinal inflammation and microbiota caused by high-concentrate diets. The SARA model was induced by low neutral detergent fibre/starch ration to study the effects of thiamine on intestinal tissue structure and microbiota. 18 mid-lactation (148 ± 3 d in milk; milk yield = 0.71 ± 0.0300 kg/d) Saanen goats (BW = 36.5 ± 1.99 kg; body condition score = 2.73 ± 0.16, where 1 = emaciated and 6 = obese) in parities 1 or 2 were selected. The goats were randomly divided into three groups with six replicates: (1) control diet (C; concentrate:forage 30:70), (2) high-concentrate diet (H; concentrate:forage 70:30), and (3) high-concentrate diet with 200 mg of thiamine/kg of DM intake (H + T;concentrate:forage 70:30). The experimental period was lasted for 56 d. The small and large intestine, expression of inflammatory factor genes, tight junction protein genes, total antioxidant capacity, and intestinal microbiota were measured. The results showed that SARA was observed in treatment H, whereas rumen fluid pH was improved in treatment H + T. Treatment H + T also significantly repaired the intestinal tissue structure damaged by SARA, improved the total antioxidant capacity of the small intestinal mucosa, reduced mRNA expression of inflammatory factors in the small intestine tissue, and increased the mRNA expression of tight junction genes in small intestine tissue. The high-concentrate diet reduced the diversity of intestinal microbiota. When thiamine is added to the high-concentrate diet, the relative abundance of intestinal Firmicutes and beneficial bacteria represented by Lactobacilli were upregulated, and the relative abundance of Proteus, a marker of intestinal dysbacteriosis, returned to normal. In conclusion, thiamine supplementation could alleviate the damage to the intestinal tissue structure and microbial environment caused by SARA condition in dairy goats fed a high-concentrate diet.

Effects of feeding a Lactobacillus plantarum JL01 diet on caecal bacteria and metabolites of weaned piglets.

Currently, knowledge is limited concerning the impact of a Lactobacillus plantarum JL01 diet for weaned piglets on caecal bacteria and metabolite profiles. In our experiments, 24 weaned piglets were randomly divided into two groups; each piglet in the treatment groups (Cec-Lac) was fed a basic diet and administered 10 ml of L. plantarum JL01 (1·0 × 109  CFU per ml) every day. The control group (Cec-Con) was fed a basic diet. After feeding for 28 days, we analysed the parameters of the caecal digesta of weaned piglets. We used 16S rDNA gene sequencing and mass spectrometry (MS)-based metabolomics techniques to investigate the effect of a L. plantarum JL01 diet on intestinal microbial composition and its metabolite profiles in the caecum contents of weaned piglets. The results showed that the richness estimators (ACE and Chao indices) in the caecal bacteria increased in the Cec-Lac group. Prevotella_2 and Desulfovibrio decreased significantly, while Pantoea and Rectale_group increased in the caecum of weaned piglets in the Cec-Lac group. Furthermore, Pearson's correlation analysis revealed that the genus Rectale_group was positively correlated with indole-3-acetic acid (P < 0·05), and the genus Pantoea had the same correlation with 1-palmitoyl lysophosphatidic acid. The metabolomics analysis revealed that the L. plantarum JL01 diet supplementation had significant effects on tryptophan metabolism and fat digestion and absorption. The results indicated that the L. plantarum JL01 dietary supplementation not only altered the microbial composition but also mediated tryptophan metabolism and fat digestion and absorption in the caecum, factors that may further affect the health of the host.

Target antifungal peptides of immune signalling pathways in silkworm, Bombyx mori, against Beauveria bassiana.

Antifungal innate immunity is an important defence used by insects against entomogenous fungi. However, the downstream target antifungal peptides of different immune signalling pathways are unknown. We found that the Toll, Janus kinase/signal transducer and activator of transcription (Jak/STAT) and Immunodeficiency (IMD) signalling pathways in the silkworm, Bombyx mori, can be activated by Beauveria bassiana. Inhibition of the Toll, IMD and Jak/STAT signalling pathways reduced the antifungal activities of silkworm haemolymph. We verified the target antifungal peptides of different immune signalling pathways. The expression patterns of five anti-fungal peptide genes in silkworm larvae and BmN cells were detected after blocking or over-expressing the immune signalling pathways. The Toll signalling pathways mediated the expression of Bmcecropin A, Bmattacin 1 and Bmgloverin 2; IMD signalling pathways mediated Bmenbocin 1, Bmgloverin 2 and Bmattacin 1; Jak/STAT signalling pathways mediated Bmstorage protein 30K-19G1 (Bmsp 1), Bmattacin 1 and Bmcecropin A. These data indicated that anti-microbial peptide genes in B. mori evolved through expansion and selection of existing genes to adapt to the challenge of invasive microorganisms such as fungi. This information provides insight into the antifungal immune responses in B. mori and aids understanding of insect immune regulation mechanisms.

Time-dependent Microhardness Gradients of Self-adhesive Resin Cements Under Dual- and Self-curing Modes.

CLINICAL RELEVANCE: Acid-functional monomers in self-adhesive resin cements may decrease their self-curing polymerization ability. Light irradiation optimizes polymerization performance. SUMMARY: Purpose: The aim of this study was to investigate Knoop microhardness of self-adhesive resin cements under dual- and self-curing modes in simulated canals for describing the polymerization behavior.Methods and Materials: Slots in lightproof silicone cylinders with one open end were filled with the following eight materials: a traditional resin cement (Duolink), a core build-up resin material (MultiCore Flow), and six self-adhesive resin cements (RelyX Unicem 2, G-Cem Automix, Maxcem, Biscem, Multilink Speed, and PermaCem 2.0). The resins were exposed to light through the open end and then stored in a lightproof box. The Knoop hardness gradient for each resin was measured after 1 hour and 120 hours. Surface readings were obtained at 1-mm intervals from 1 mm to 10 mm away from the open ends. The data were analyzed by two-way analysis of variance and the Student-Newman-Keuls test (α=0.05).Results: All the resin materials had stable Knoop hardness numbers (KHNs) at a certain depth; their KHNs in the self-curing mode did not change (p>0.05). The region above this certain depth was regarded as having undergone the dual-curing mode, and the KHN decreased gradually with depth (p<0.05). Between 1 and 120 hours postexposure, the ratio of the KHN at a 5-mm depth (self-cured) to that at a 1-mm depth (dual-cured) increased in Duolink and MultiCore Flow. However, the ratios of the six adhesive resin cements varied.Conclusion: Without light, most self-adhesive resin cements differed from traditional dual-cured resin materials in terms of Knoop micro-hardness, and they had a lesser capacity for chemical-induced curing.

Association between caveolin-1 and stroke: a systematic review and meta-analysis.

OBJECTIVE: Caveolin-1 plays critical roles in regulating signal transduction and cholesterol trafficking in cells. However, the relationship between caveolin-1 and stroke remains less reported. MATERIALS AND METHODS: In this study, we reviewed information from seventeen studies to get the qualitative evidence of the influence of the caveolin-1 on stroke and collected data from three of the seventeen studies to conduct meta-analysis. The original studies classified participants into two groups with stroke group and control group, respectively. The random-effect model was used in the meta-analysis with the standardized mean difference (SMD) as the measure indicator. RESULTS: Our data showed that the SMD (95% confidence intervals, CIs) between the control group and the stroke group was -0.5449 [-2.3344, 1.0000]. For the subgroup analysis, The SMD (95% confidence intervals, CIs) between the control group and the ischemic stroke group was -1.4589 [-5.0129, 2.0951], and between the control group and the hemorrhagic stroke group was 0.3438 [-0.4140, 1.1017]. CONCLUSIONS: Although the differences are not statistically significant between the two groups, the high level of caveolin-1 are associated with the stroke, which may remedy the stroke. Besides, an opposite result was observed for the association of the caveolin-1 on the ischemic stroke and hemorrhagic stroke. To confirm this association, further studies are necessary.

[CD137 signaling promotes angiogenesis through regulating macrophage M1/M2 polarization].

Objective: To investigate whether CD137 signaling can promote angiogenesis via regulating macrophage M1/M2 polarization. Methods: (1) The primary peritoneal macrophages in mice induced by 3% thiglycollate broth were divided into three groups: control group, CD137 signaling activated group and CD137 signaling inhibited group. Various specific markers of M1 and M2 macrophages were detected to observe the phenotype change of macrophages, and the macrophages protein expression of CD137, CD86 and CD206 was detected by flow cytometry (FCM). The protein and mRNA expression of induced nitric oxide synthase (iNOS), arginase Ⅰ(Arg-1) was determined by Western blot and RT-PCR, respectively. The secretion levels of IL-12 and IL-10 in culture supernatant of macrophages were detected by ELISA. (2) Macrophages were co-cultured with the endothelial cells (bEnd.3), and macrophages were implanted in the upper chamber, endothelial cells were implanted in stromal glue of the lower chamber. The experiment was divided into three groups: the control group, CD137 signaling activated group and peroxisome proliferator-activated receptor-γ (PPAR-γ) inhibited group, and tube formation ability of endothelial cells in each group was determined. Results: (1) The purity of primary peritoneal macrophages in mice was (97.93±1.31)%. The expression of CD137 on the surface of macrophages was (97.40±2.70)%. (2) Compared with control group, the mRNA and protein expression levels of Arg-1 were significantly increased and the mRNA and protein expression of iNOS were significantly decreased in CD137 signaling activated group (all P<0.05). Compared with CD137 signaling activated group, the mRNA and protein expression of Arg-1 were significantly lower and the mRNA and protein expression levels of iNOS were significantly higher in CD137 signaling inhibited group (all P<0.05). FCM results showed that the average fluorescence intensity of CD206 was higher, while the average fluorescence intensity of CD86 was lower in CD137 signaling activated group than in control group (P<0.05, P<0.01, respectively); the expression of CD206 was significantly lower, while the expression of CD86 was higher, in the CD137 signaling inhibited group than in CD137 signaling activated group (P<0.05, P<0.01, respectively). ELISA results showed that the secretion of IL-10 was higher, and the secretion level of IL-12 was significantly lower in CD137 signaling activated group than in control group (both P<0.01); the secretion of IL-10 was significantly lower and the secretion of IL-12 was significantly higher in CD137 signaling inhibited group than in CD137 signaling activated group (both P<0.05). (3) Values of the formation of tube length and branch number were both longer in CD137 signaling activated group than control group (P<0.05). The formation of the tube length and branch number were less in PPAR-γ inhibited group than in CD137 signaling activated group (P<0.05). Conclusion: CD137 signaling can promote angiogenesis by regulating macrophage M1/M2 polarization.

[Characteristics and prognostic value of peripheral blood T lymphocyte subsets in patients with severe influenza].

Objective: To investigate the characteristics and prognostic value of peripheral blood T lymphocyte subsets in patients with severe influenza. Methods: This was a single-center cross-sectional study in influenza patients admitted to Peking Union Medical College Hospital from August 2017 to April 2018. Peripheral blood lymphocyte subsets were detected by flow cytometry in both patients and 108 healthy controls. Influenza patients were divided into mild group and severe group. Severe patients were further classified into alive and fatal subgroups. Results: A total of 42 influenza patients were recruited in this study, including 24 severe cases (6 deaths). The remaining 18 cases were mild. The peripheral blood lymphocyte counts and lymphocyte subset counts (B, NK, CD4(+)T, CD8(+)T) in either mild patients[795 (571,1 007), 43 (23,144), 70 (47,135), 330 (256,457), 226 (148,366) cells/µl respectively] or severe patients[661 (474,1 151),92 (52,139), 54 (34,134), 373 (235,555), 180 (105,310) cells/µl respectively] were both significantly lower than those of healthy controls [1 963 (1 603,2 394),179 (119,239), 356 (231,496), 663 (531,824), 481 (341,693) cells/µl respectively]. Meanwhile, the T cells and CD8(+)T counts in fatal patients [370 (260,537) cells/µl and 87 (74,105) cells/µl] were significantly lower than those in severe and alive patients [722 (390,990) cells/µl and 222 (154,404) cells/µl]. CD8(+)HLA-DR/CD8(+)and CD8(+)CD38(+)/CD8(+)T cell activating subgroups in mild cases[(53.7±19.2)% and 74.8% (64.1%,83.7%) respectively] were significantly higher than those in severe cases[(38.5±21.7)% and 53.3% (45.3%,67.2%) respectively].Moreover,CD8(+)HLA-DR/CD8(+)count in severe and alive group was higher than that in fatal group [(46.1±19.1)% vs. (18.2±14.6)%, P<0.01]. Logistic regression analysis showed that CD8(+)T cell count (OR=0.952, 95%CI 0.910-0.997, P=0.035) and CD8(+)HLA-DR/CD8(+)T (OR=0.916, 95%CI 0.850-0.987, P=0.022) were both negatively correlated with mortality.Peripheral blood lymphocyte counts in mild cases rapidly decreased within 1 day after diagnosis, and returned to the basic level one week later. Conclusions: All peripheral blood lymphocyte subsets (T,B,NK) in patients with influenza are significantly reduced. These findings are consistent with the immunological characteristics of respiratory viral infections, in which peripheral lymphocytes (especially T cells) migrate to respiratory tract in the early stage and circulate to the peripheral blood after recovery. The activated CD8(+)T cell counts in peripheral blood are negatively correlated with the severity of disease, which could be considered as a prognostic indicator of severe influenza.

[Impact of CD137-CD137L signaling on secretion of mouse vascular smooth muscle cells-derived exosomes: role of Rab7 pathway].

Objective: To investigate whether CD137-CD137L signaling could affect the secretion of mouse vascular smooth muscle cells (VSMCs) -derived exosomes through autophagy mediated Rab7 pathway. Methods: Primary thoracic aorta VSMCs from C57BL/6J mouse were obtained by tissue block adherence method. VSMCs between the third to fifth passages were used and VSMCs were divided into 4 groups: control group, CD137 agonist group, lentivirus control group, Rab7 lentiviral interference group. VSMCs in CD137 agonist group were treated with recombinant protein of CD137L (10 µg/ml), VSMCs in lentivirus control group were treated with lentiviral followed by recombinant protein of CD137L (10 µg/ml), VSMCs in Rab7 lentiviral interference group were treated with Rab7 lentiviral intervention followed by recombinant protein of CD137L (10 µg/ml). Western blot was used to detect the protein expression of LC3Ⅱ, p62, Rab7, CD9, CD81 and Hsc70. Fluorescence microscopy was used to track the changes of autophagy in cells infected with mRFP-GFP-LC3. Transmission electron microscope was used to observe the morphology and size of VSMCs-derived exosomes. The nanoparticle tracking analysis(NTA) was used to detect the concentration and size of exosomes in each group. Results: (1) The expressions of Rab7, LC3Ⅱ and p62 protein in VSMCs of CD137 activation group were significantly higher than those in control group (all P<0.05). The expressions of Rab7, LC3Ⅱ and p62 protein in Rab7 lentivirus interference group was lower than in CD137 activation group (all P<0.05), while the expressions were similar between the lentivirus control group and the CD137 activation group (all P>0.05). (2) The total number of fluorescent spots and yellow fluorescent spots in the VSMCs of the CD137 activation group were higher than those in the control group (all P<0.05), and the number of yellow fluorescent spots was higher than that of the red fluorescent spots in the VSMCs of the CD137 activation group ((50.3±0.9) vs. (10.3±1.5)/cell). The total numbers of fluorescent spots and yellow fluorescent spots in VSMCs of Rab7 lentivirus interference group were lower than those of CD137 activation group (both P<0.05), and the number of red fluorescent spots in VSMCs was higher than that of yellow fluorescent spots ((40.7±4.0) and (10.7±1.2)/cell) in the Rab7 lentiviral interference group. The total numbers of fluorescent spots and yellow fluorescent spots in the VSMCs were similar between the lentivirus control group and the CD137 activation group (all P>0.05). (3) Under transmission electron microscopy, the size of the VSMCs-derived exosomes was about 30-150 nm. The exosome markers (CD9, CD81) could be detected in vesicles by Western blot. NTA results showed that the concentration of VSMCs-derived exosomes was significantly higher in the CD137-activated group than in the control group (P<0.05), which was significantly lower in the Rab7 lentiviral interference group than in the CD137-activation group (P<0.05) and was similar between the lentivirus control group and the CD137 activation group (P>0.05). The expression of Hsc70 protein in exosomes secreted by CD137 activation group was higher than that in the control group (P<0.05). The expression of Hsc70 protein in exosomes was lower in Rab7 lentivirus interference group than in the CD137 activation group (P<0.05), which was similar between the lentivirus control group and the CD137 activation group (P>0.05). The expression of LC3Ⅱ protein in exosome was higher in CD137 activation group than in control group (P<0.05), which was lower in Rab7 lentivirus interference group than in CD137 activation group (P<0.05), which was similar between the lentivirus control group and the CD137 activation group (P>0.05). Conclusion: The CD137-CD137L signaling may affect the secretion of mouse VSMCs-derived exosomes through modulating the Rab7 pathway mediated autophagy.

Fatty acids modulate the expression of pyruvate kinase and arachidonate-lipoxygenase through PPARγ/CYP2C45 pathway: a link to goose fatty liver.

Cytochrome P-450 2C45 (CYP2C45) is the most highly expressed cytochrome P-450 isoform in chicken liver, and may play an important role in avian liver biology. However, information regarding the function of CYP2C45 in fatty liver is generally limited. The aim of this study was to investigate the role of CYP2C45 during the development of goose fatty liver. Our result indicated that the transcription of CYP2C45, together with PK and ALOX5, was increased in goose liver upon overfeeding for 19 D (P < 0.05). In goose primary hepatocytes, CYP2C45 RNA expression was also upgraded by the treatment with various chemicals like insulin, the fatty acids, and PPAR agonists (P < 0.05). We also found that both CYP2C45 overexpression and troglitazone treatment could increase the expression of pyruvate kinase (PK) and arachidonate 5-lipoxygenase (ALOX5), and furthermore, showed that the up-regulation of PK and ALOX5 induced by troglitazone could be suppressed by small interfering RNAs targeting CYP2C45 (P < 0.05). These findings suggest that fatty acids treatment and the overfeeding can induce the up-regulation of CYP2C45 expression possibly via PPARγ and that the induction of PK and ALOX5 in goose fatty liver is at least partially attributed to fatty acid-induced expression of CYP2C45. Thus, our data provides an insight into the mechanism by which glycolysis and arachidonic acid metabolism are modulated in goose fatty liver.

[Magnetic resonance imaging and diffusion weighted imaging features of focal peliosis hepatis].

Objective: To investigate the MRI and diffusion weighted imaging (DWI) features of focal peliosis hepatis. Methods: The clinical data and MRI of 19 cases with focal peliosis hepatis confirmed by pathology from January 2012 to March 2018 in Zhongshan Hospital of Fudan University were retrospectively analyzed. The number, location, size, shape, signal intensity of plain scan of lesions, enhancement pattern of lesions, vessels within lesions, and perfusion disorders of hepatic parenchyma were analyzed. The apparent diffusion coefficient (ADC) values of the lesions and adjacent hepatic parenchyma were measured, then the differences between them were explored statistically. All 24 lesions were categorized into group A with tumor-related chemotherapy and group B without tumor-related chemotherapy. The differences of MR features between the two groups were explored statistically. Results: In all 24 lesions, 22 lesions were located in the right lobe, 2 lesions in the left lobe. The median size was 7.5-72.0 (24.4±17.2) mm.On T(1)WI,21 lesions showed slightly hypointensity, 1 lesion showed slightly hyperintensity and 2 lesions were isointensity; all 24 lesions showed slightly hyperintensity on T(2)WI, and isointensity or slightly hyperintensity on DWI. The mean ADC value was (1.511±0.415)×10(-3) mm(2)/s in the lesions and (1.769±0.690)×10(-3) mm(2)/s in the adjacent hepatic parenchyma, which showed no difference between the two groups (P>0.05). On dynamic MR images, 20 lesions showed gradually filling enhancement, 4 lesions showed markedly and persistent enhancement. Punctiform or filiform vessels were found in 9 lesions. Adjacent hepatic perfusion disorders showed in 8 lesions. The median lesion size was 7.5-38.5(17.6±9.8) mm in the tumor-related-chemotherapy group and 9.0-72.0(33.8±21.2) mm in the no chemotherapy group.There was significant difference between the two groups (P<0.05). Conclusions: The MRI performance of focal peliosis hepatis had a certain characteristic. MRI combined with diffusion weighted imaging could help to make diagnoses.

Time-Resolved Photoelectron Studies of Thiophene and 2,5-Dimethylthiophene.

The photoinduced dynamics of thiophene and 2,5-dimethylthiophene (2,5-DMT) were investigated upon excitation at 200 and 255 nm (2,5-DMT only) using time-resolved photoelectron spectroscopy and compared with results from ab initio coupled cluster calculations. For thiophene, depopulation of the initially excited B2(π3π4*) state to the lower-lying A1(π2π4*) state occurs within 25 ± 20 fs, with a subsequent bifurcation into a ring-puckering channel and a ring-opening channel with lifetimes of 80 ± 20 and 450 ± 50 fs, respectively. For 2,5-DMT, the dynamics following excitation at 200 nm is described by a monoexponential decay with a time constant of 120 ± 20 fs, while that following excitation at 255 nm is best fit by a biexponential decay with time constants of 115 ± 20 fs and 15 ± 3 ps, respectively. The fast signal observed after excitation of 2,5-DMT is assigned to the ring-opening channel, which is favored with respect to thiophene due to a lower excited-state barrier along the ring-opening coordinate and an increased inertia toward the ring-puckering channel. Coupled cluster calculations have been undertaken to compare the relaxation dynamics of thiophene to thiazole and isothiazole. For the latter two molecules, we find a strong gradient along the ring-opening coordinate in the Franck-Condon region of the initially populated ππ* state and predict that ring-opening is the dominating relaxation channel after photoexcitation. We use the extracted information for a comparison of the thiophene dynamics with the light-induced processes observed in other five-membered heterocyclic molecules.

The ring-opening channel and the influence of Rydberg states on the excited state dynamics of furan and its derivatives.

One important relaxation pathway for photo-excited five-membered heterocyclic organic molecules is ring-opening via a dissociative πσ* state. In this study, we investigate the influence of this pathway in furan and several hydrogenated and methylated derivatives by combining time-resolved photoelectron spectroscopy with time-dependent density functional theory and coupled cluster calculations. We find strong experimental evidence that the ring-opening channel is the major relaxation channel in furan, 2,3-dihydrofuran, and 2-methylfuran (2-MF). In 2,5-dimethylfuran (25-DMF), however, we observe that the molecules relax either via a π3s Rydberg state or through a direct return to the ground state by undergoing ring-puckering motions. From the supporting calculations, for 2-MF and 25-DMF, we predict that there is strong mixing between the πσ* state and the π3s Rydberg state along the ring opening pathway. However, in 25-DMF, no crossing between the πσ*/π3s state and the initially excited ππ* state can be found along the ring opening coordinate, effectively blocking this channel.

[Opportunistic infection in systemic lupus erythematosus patients: the disease spectrum and the characteristics of peripheral lymphocyte subsets].

Objective: To investigate the common opportunistic infections and the characteristics of peripheral lymphocyte subsets in patients with systemic lupus erythematosus (SLE). Methods: From December 2013 to December 2016, peripheral lymphocyte subsets were consecutively detected by flow cytometry in treated SLE patients with or without opportunistic infections (OIs) . The lymphocyte subsets in healthy donors were used as normal control group. Results: A total of 145 treated SLE patients were enrolled including 108 with OIs and 37 without OIs. The common OIs were cytomegalovirus (CMV) diseases (66/108), Pneumocystis jirovecii pneumonia (PJP, 16/108), other fungal infections (16/108), Epstein-Barr virus (EBV, 15/108) and tuberculosis (14/108). Compared with treated SLE without OIs, total lymphocyte, CD(4+) T, and CD(8+) T lymphocyte counts were significantly reduced in SLE with OIs [1 260 (780, 1 810) cells/µl vs. 565 (399, 1 043) cells/µl, P<0.001; 485 (280, 811) cells/µl vs. 173 (95, 327) cells/µl, P<0.001; 464 (339, 764) cells/µl vs. 265 (158, 424) cells/µl, P=0.003, respectively]. Conclusions: The common OIs in treated SLE patients were CMV diseases, PJP, other fungi, EBV and tuberculosis. OIs are prone to develop in SLE patients with severe lymphocytopenia, especially CD(4+) T cell depletion.

Metformin alters DNA methylation genome-wide via the H19/SAHH axis.

The molecular mechanisms underlying the antineoplastic properties of metformin, a first-line drug for type 2 diabetes, remain elusive. Here we report that metformin induces genome-wide alterations in DNA methylation by modulating the activity of S-adenosylhomocysteine hydrolase (SAHH). Exposing cancer cells to metformin leads to hypermethylation of tumor-promoting pathway genes and concomitant inhibition of cell proliferation. Metformin acts by upregulating microRNA let-7 through AMPK activation, leading to degradation of H19 long noncoding RNA, which normally binds to and inactivates SAHH. H19 knockdown activates SAHH, enabling DNA methyltransferase 3B to methylate a subset of genes. This metformin-induced H19 repression and alteration of gene methylation are recapitulated in endometrial cancer tissue samples obtained from patients treated with antidiabetic doses of metformin. Our findings unveil a novel mechanism of action for the drug metformin with implications for the molecular basis of epigenetic dysregulation in cancer. This novel mechanism of action also may be occurring in normal cells.

Bioavailability of aspirin in rats comparing the drug's uptake into gastrointestinal tissue and vascular and lymphatic systems: implications on aspirin's chemopreventive action.

Aspirin is an effective analgesic and antiplatelet drug that in addition to its ability to reduce pain, inflammation and fever, appears to have efficacy in the prevention/treatment of a range of diseases including heart disease, numerous cancers and Alzheimer's. It is important to understand the bioavailability of aspirin and its major metabolite, salicylic acid, since dosage and route of administration can vary for treating differing diseases, and the major side-effects of aspirin, upper gastrointestinal ulceration and bleeding, are dose-dependent. We examined the time course for gastroduodenal uptake of aspirin and the appearance of its major metabolite salicylic acid in blood and lymph after intragastric (to simulate oral) and intraduodenal (to simulate enteric-coating) dosing in rats. Results show that after intragastric dosing, intact aspirin is absorbed primarily by the gastric mucosa and to a lesser extent by the duodenal mucosa. When aspirin is dosed intragastrically or intraduodenally, a much greater concentration of aspirin enters the lymph than the blood. In contrast, the concentration of salicylic acid was higher in blood than in lymph. Lymph levels of both aspirin and salicylic acid were sufficiently high so as to perform a pharmacologic function there, possibly as a chemopreventive agent against colon cancer and potentially the metastatic spread of non-gastrointestinal cancers.

Harm and Benefits of Salvage Transplantation for Hepatocellular Carcinoma: An Updated Meta-analysis.

OBJECTIVE: The aim of this work was to compare salvage liver transplantation (SLT) and primary liver transplantation (PLT) in terms of the harm and benefits. METHODS: The authors searched Pubmed, Embase, and the Cochrane Library from their dates of establishment to December 2015. Based on selection and exclusion criteria, 2 researchers screened the literature independently. The meta-analysis was performed with the use of the Review Manager software. Meta-analysis of the pooled standard mean difference (SMD) and odds ratio (OR) with 95% confidence interval (CI) were calculated based on either a fixed-effects or a random-effects model. In addition, risk of bias was assessed with the use of the Newcastle-Ottawa scale. RESULTS: Sixteen studies were selected, involving almost 8,707 patients. According to the pooled estimates, compared with PLT, SLT was associated with a longer operative time (SMD, 0.28; 95% CI, 0.11-0.46;), higher intraoperative blood loss (SMD, 0.41; 95% CI, 0.08-0.75;), more postoperative bleeding (OR, 1.95; 95% CI, 1.10-3.45), an increased risk of recurrence (OR, 2.08; 95% CI, 1.24-3.50), and poorer 3-year (OR, 0.86; 95% CI, 0.76-0.98) and 5-year (OR, 0.86; 95% CI, 0.76-0.98) overall survival rates. However, no difference was detected between case and control groups in either rates of postoperative complications or such aspects as perioperative mortality, length of intensive care unit stay, length of hospital stay, and 1-year overall survival rate. CONCLUSIONS: The 3-year and 5-year overall survival rates were inferior in SLT, which shows that PLT is a better treatment strategy for transplantable hepatocellular carcinoma (HCC). However, considering the severe organ limitation and the feasibility and safety of SLT, it provides a better option for patients with HCC recurrence after curative resection.