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The efficacy of intense pulsed light (IPL) in remodeling the extracellular matrix of aged skin had been proven by an increasing number of clinical trials. However, because of the lack of research about the underlying molecular and signaling mechanisms, its efficiency had not been accepted universally. A potential mechanism of IPL rejuvenation effects is due to its different effects on diverse cytokines, the impact of IPL on them may determine the phenotype and prognosis of the aged skin. We designed this study to evaluate the impact of IPL on the secretion of matrix metalloproteinase-1 (MMP-1), transforming growth factor-β1 (TGF-β1), and the mitogen-activated protein kinase (MAPK) signaling pathway in human skin fibroblasts, and tried to study the respective functions of MAPKs as mediators of the MMP-1, TGF-β1 secretion. Results showed that the MMP-1 secretion was only enhanced by IPL at 10 J/cm(2); while the TGF-β1 secretion was inhibited by IPL when the fluence was below 36 J/cm(2), but enhanced at 72 J/cm(2). Meanwhile, ERK inhibitor PD98059 decreased MMP-1 secretion, but did not show a significant influence on TGF-β1; JNK inhibitor SP600125 increased the secretion of MMP-1 and decreased the TGF-β1 secretion; P38 inhibitor SB203580 had no significant influence on MMP-1 but increased the secretion of TGF-β1. Our findings indicated that the bidirectional influence of IPL on the secretion of MMP-1 and TGF-β1 is a potential mechanism of its skin rejuvenation effect; and the secretion of these two cytokines can be mediated by MAPKs.

After loss of intestinal surface area, the remaining bowel undergoes a morphometric and functional adaptive response. Enterocytic expression of the transcriptional coregulator tetradecanoyl phorbol acetate induced sequence 7 (Tis7 )i s markedly increased in a murine model of intestinal adaptation. Mice overexpressing Tis7 in intestine have greater triglyceride absorption and weight gain when fed a high-fat diet (42% energy) than their wild-type (WT) littermates fed the same diet. These and other data suggest that Tis7 has a unique role in nutrient absorptive and metabolic adaptation. Herein, male Tis7 2/2 and WT mice were fed a high-fat diet (42% energy) for 8 wk. Weight was monitored and metabolic analyses and hepatic and intestinal lipid concentrations were compared after 8 wk. Intestinal lipid absorption and metabolism studies and intestinal resection surgeries were performed in separate groups of Tis7 2/2 and WT mice. At 8 wk, weight gain was less and jejunal mucosal and hepatic triglyceride and cholesterol concentrations were lower in Tis7 2/2 mice than in the WT controls. Following corn oil gavage, serum cholesterol, triglyceride, and FFA concentrations were lower in the Tis7 2/2 mice than in the WT mice. Incorporation of oral 3 [H] triolein into intestinal mucosal cholesterol ester and FFA was less in Tis7 2/2 compared with WT mice. Following resection, crypt cell proliferation rates and villus heights were lower in Tis7 2/2 than in WT mice, indicating a blunted adaptive response. Our results suggest a novel physiologic function for Tis7 in the gut as a global regulator of lipid absorption and metabolism and epithelial cell proliferation. J. Nutr. 140: 1907–1914, 2010.

Background: NOD2 single nucleotide polymorphisms have been associated with increased risk of ileal Crohn's disease (CD). This exploratory study was conducted to compare ileal mucosal gene expression in CD patients with and without NOD2 risk alleles. Methods: Ileal samples were prospectively collected from 18 nonsmoking CD patients not treated with anti-TNF-α biologics and 9 nonsmoking control patients without inflammatory bowel disease undergoing initial resection and genotyped for the 3 major NOD2 risk alleles (Arg702Trp, Gly908Arg, Leu1007fs). Microarray analysis was performed in samples from 4 NOD2R (at least 1 risk allele) CD patients, 4 NOD2NR (no risk alleles) CD patients, and 4 NOD2NR controls. Candidate genes selected by significance analysis of microarrays (SAM) were confirmed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assays of all the samples. Results: SAM detected upregulation of 18 genes in affected ileum in NOD2R compared to NOD2NR CD patients, including genes related to lymphocyte activation. SAM also detected altered ileal gene expression in unaffected NOD2NR ileal mucosal CD samples compared to NOD2NR control samples. qRT-PCR conducted on all the samples confirmed that increased CD3D expression in affected samples was associated with NOD2R status, and that increased MUC1, DUOX2, DMBT1 and decreased C4orf7 expression in unaffected samples was associated with CD, independent of NOD2 status. Conclusions: The results support the concept that NOD2 risk alleles contribute to impaired regulation of inflammation in the ileum. Furthermore, altered ileal gene expression, independent of NOD2 status, is detected in the unaffected proximal margin of resected ileum from CD patients. (Inflamm Bowel Dis 2010)

Retinoid X receptors (RXRs) are nuclear receptors that can activate transcription as homodimers or as obligate heterodimeric partners of other nuclear receptors. While the crystal structures of the RXR ligand-binding domains (LBD) have been previously determined, the dynamics of activation is less well characterized at an atomic level. To probe the effect of ligand binding on RXR LBD dynamics, we initiated nuclear magnetic resonance studies of recombinant human RXRalpha LBD (T223-T462) with and without bound 9-cis-retinoic acid (9cRA). The 1HN, 15N, 13C(alpha), 13CO, and 13C(beta) resonance assignments were established for 164 of 240 residues in apo-RXRalpha LBD. Resonances corresponding to an additional 47 residues emerged upon 9cRA binding. These additional residues included those located in the vicinity of the ligand-binding pocket (helices H3, H5, and strands S1, S2), as well as residues located at the dimerization interface (helices H9 and H10). Thus 9cRA binding stabilized the ligand-binding pocket and had allosteric effects on the dimerization interface. Ligand-induced chemical shift perturbations outside the binding cavity were mapped to helix H3 and the AF-2 helix H12, indicating conformational changes in these regions. However, helix H11, a component of the tetramerization interface, and a large part of helix H10, a component of the dimerization interface, remained undetectable even after 9cRA binding. Although apo- and holo-hRXRalpha LBD existed predominantly as homodimers in solution, exchange between monomeric, dimeric, and tetrameric forms of the protein could have contributed to line broadening of cross-peaks corresponding to helices H10 and H11. 15N T1, T2, and steady-state {1H}-15N NOE data collected at 500 and 700 MHz static magnetic fields showed that the internal motions for the residues in the H1-H3 loop (K245-D263) were much less restricted than those in the protein core for both apo- and holo-forms. Significant exchange R(ex) contributions to the transverse relaxation rate were detected for most of the residues measured in both apo- and holo-RXRalpha LBDs by transverse relaxation optimized spectroscopy-Carr-Purcell-Meiboom-Gill (CPMG) experiments at two B1 field strengths. Taken together these results suggest that the RXRalpha LBD exists as a dynamic ensemble of conformations, even after binding its cognate ligand. Such dynamic characteristics may allow RXRalpha to partner with multiple nuclear receptors.

Cellular retinol-binding protein I (CRBP I) and cellular retinol-binding protein II (CRBP II) are closely homologous proteins that play distinct roles in the maintenance of vitamin A homeostasis. The solution structure and dynamics of CRBP I and CRBP II were compared by multidimensional NMR techniques. These studies indicated that differences in the mean backbone structures of CRBP I and CRBP II were localized primarily to the alphaII helix. Intraligand NOE cross-peaks were detected for the hydroxyl proton in the NOESY spectrum of CRBP I-bound retinol, but not for CRBP II-bound retinol, indicating that the conformational dynamics of retinol binding are different for these two proteins. As determined by Lipari-Szabo formalism, both the apo and holo forms of CRBP I and CRBP II are conformationally rigid on the pico- to nanosecond timescale. transverse relaxation optimized spectroscopy-Carr-Purcell-Meiboom-Gill -based 15N relaxation dispersion experiments at both 500 MHz and 600 MHz magnetic fields revealed that 84 and 62 residues for apo-CRBP I and II, respectively, showed detectable conformational exchange on a micro- to millisecond timescale, in contrast to three and seven residues for holo-CRBP I and II, respectively. Thus binding of retinol markedly reduced conformational flexibility in both CRBP I and CRBP II on the micro- to millisecond timescale. The 15N relaxation dispersion curves of apo-CRBP I and II were fit to a two-state conformational exchange model by a global iterative fitting process and by an individual (residue) fitting process. In the process of carrying out the global fit, more than half of the residue sites were eliminated. The individual chemical exchange rates k(ex), and chemical shift differences, Deltadelta, were increased in the putative portal region (alphaII helix and betaC-betaD turn) of apo-CRBP II compared to apo-CRBP I. These differences in conformational flexibility likely contribute to differences in how CRBP I and CRBP II interact with ligands, membranes and retinoid metabolizing enzymes.

The objective of the study is to evaluate the efficacy and safety of oral inosine pranobex as compared with acyclovir in the treatment of recurrent herpes labialis (RHL) and recurrent herpes genitalis (RHG). A multicenter double-blind, double-dummy, randomized, controlled, parallel group trial was conducted in 144 patients with RHL and 144 RHG. Patients were assigned to treatment in one of two groups: (i) inosine pranobex group (active inosine pranobex, 1 g four times daily, and acyclovir placebo); or (ii) acyclovir group (active acyclovir, 200 mg five times daily, and inosine pranobex placebo). The total symptom score (TSS) of patients with RHL did not differ in the inosine pranobex and acyclovir group on the 3rd or 7th day of treatment. There was also no difference in the efficacy rates between the two groups. No difference of TSS was observed between patients with RHG taking inosine pranobex and acyclovir on days 3 or 5 of the treatment, respectively. The short-term clinical recurrence rate of RHG at 3-month follow-up was much lower in the inosine pranobex group than acyclovir group. The incidence of hyperuricemia was higher in the inosine pranobex group than acyclovir group. In conclusion, inosine pranobex was as effective as acyclovir in treating RHL and RHG with significantly greater reduction of the short-term recurrence rate of herpes genitalis at 3-month follow up. Long-term recurrence rates at 6 months or longer remain to be determined. Hyperuricemia should be monitored during the treatment.

To analyze the results of nine-round environmental specimen surveillance programs in five live poultry markets pre-, during and post the 'closing days' and to evaluate the effects of 'closing days' on live poultry markets regarding the control against avian influenza pollution.In January 2014, control measures including culling poultry, completely cleaning and disinfecting and a 'three-day-closing' measure were conducted in five live poultry markets which were found positive for H7N9 nucleic acid in the 1(st) round environmental specimen surveillance program. Second surveillance program was conducted after a thorough disinfection campaign was launched. Several times surveillance were conducted in one week, after the markets were reopened. RT-PCR was used to test the nucleic acid of HA, H5, H7 and H9 viruses.654 specimens from the environment were collected and tested. During the first round surveillance program, positive rates for influenza A and H5/H7/H9 nucleic acid of poultry stalls appeared to be 94.44% and 61.11% respectively. The positive rates of poultry stalls reduced to 0 after the disinfection campaign but increased again after the markets reopened. The positive rate for influenza A of poultry stalls slightly increased from 50.00% in the third surveillance to 72.22% in the ninth surveillance (P0.05). The positive rate for H5/H7/H9 of poultry stalls showed a significantly increasing trend, from 0 in the third surveillance to 44.44% in the ninth surveillance (P0.01). The positive rates for influenza A and H5/H7/H9 nucleic acid of specimens were 28.89% and 17.78% respectively. The positive rate of specimens reduced to 0 after disinfection while increased again after reopening of the markets. The positive rate for influenza A of specimens slightly increased from 19.67% in the third surveillance to 27.54% in the ninth surveillance programs (P0.05). The positive rate for H5/H7/H9 of specimen showed a significant increasing trend, from 0 in the third surveillance to 8.70% in the ninth-round surveillance programs (P0.01). The positive rate for influenza A was the highest for slaughter- related specimens of 22.4% (35/156). The positive rates for influenza A from sewage and drinking water being collected on the later stage after the markets reopened (25.9%, 12.4%)were higher than those on the early stage (8.3%, 8.6%) (P0.05). The positive rate for influenza A of poultry stalls with overnight poultry storage (91.7%) was significant higher than that of poultry stalls without the overnight storage (33.3%). The positive rate for influenza A of poultry stalls in which simultaneously selling different kinds of poultry (85.7%) was significant higher than that of poultry stalls in which selling only one kind of poultry at one time (25.0%) (P0.05).Slaughter in live poultry markets posed a large risk of pollution diffusion. Sewage and drinking water showed an accumulation effect for avian influenza virus. Overnight poultry storage and selling different kinds of poultry at one time at the poultry stalls seemed the risk factors for avian influenza virus transmission. Complete cleaning, disinfecting and several 'closing days' for live poultry markets seemed effective in eliminating avian influenza virus. Once the markets were reopened, they seemed to be soon polluted again.

Effective therapies are limited for patients with parenteral nutrition-dependent short bowel syndrome. We previously showed that intestinal expression of the transcriptional coregulator tetradecanoyl phorbol acetate-induced sequence 7 ( tis7) is markedly increased during the adaptive response following massive small bowel resection and tis7 plays a role in normal gut lipid metabolism. Here, we further explore the functional implications of tis7 deletion in intestinal lipid metabolism and the adaptive response following small bowel resection. Intestinal tis7 transgenic ( tis7tg), tis7−/−, and wild-type (WT) littermates were subjected to 50% small bowel resection. Mice were fed a control or a high-saturated-fat (42% energy) diet for 21 days. Survival, body weight recovery, lipid absorption, mucosal lipid analysis, and the morphometric adaptive response were analyzed. Quantitative real-time PCR was performed to identify tis7 downstream gene targets. Postresection survival was markedly reduced in high-fat, but not control, diet-fed tis7−/− mice. Decreased survival was associated with anastomotic inflammation and intestinal obstruction postresection. High-fat, but not control, diet-fed tis7−/− mice had increased intestinal IL-6 expression. Intestinal lipid trafficking was altered in tis7−/− compared with WT mice postresection. In contrast, high-fat diet-fed tis7tg mice had improved survival postresection compared with WT littermates. High-fat diet feeding in the setting of tis7 deletion resulted in postresection anastomotic inflammation and small bowel obstruction. Tolerance of a calorie-rich, high-fat diet postresection may require tis7 and its target genes. The presence of luminal fat in the setting of tis7 deletion promotes an intestinal inflammatory response postresection.

We investigated a possible person-to-person transmission within a family cluster of two confirmed influenza A(H7N9) patients in Guangzhou, China. The index case, a man in his late twenties, worked in a wet market that was confirmed to be contaminated by the influenza A(H7N9) virus. He developed a consistent fever and severe pneumonia after 4 January 2014. In contrast, the second case, his five-year-old child, who only developed a mild disease 10 days after disease onset of the index case, did not have any contact with poultry and birds but had unprotected and very close contact with the index case. The sequences of the haemagglutinin (HA) genes of the virus stains isolated from the two cases were 100% identical. These findings strongly suggest that the second case might have acquired the infection via transmission of the virus from the sick father. Fortunately, all 40 close contacts, including the other four family members who also had unprotected and very close contact with the cases, did not acquire influenza A(H7N9) virus infection, indicating that the person-to-person transmissibility of the virus remained limited. Our finding underlines the importance of carefully, thoroughly and punctually following-up close contacts of influenza A(H7N9) cases to allow detection of any secondary cases, as these may constitute an early warning signal of the virus's increasing ability to transmit from person-to-person. .

Purpose A virologic surveillance program for A(H7N9) virus was conducted from April 15, 2013 to February 14, 2014 in Guangzhou, aiming to clarify the geographical distribution of A(H7N9) viruses among live poultry markets (LPMs) and poultry farms in Guangzhou. Virological and serological surveys of poultry workers were also conducted to evaluate the risk of poultry-to-human transmission of the A(H7N9) virus. Methods 36 retail LPMs, 6 wholesale LPMs and 8 poultry farms were involved in our surveillance program. About 20 live poultry and environmental samples were obtained from each surveillance site at every sampling time. Different environmental samples were collected to represent different poultry-related work activities. RT-PCR and virus culture were performed to identify the A(H7N9) virus. Hemagglutinin inhibition assay and RT-PCR were conducted to detect possible A(H7N9) infection among poultry workers. Results A total of 8900 live poultry and environmental samples were collected, of which 131(1.5%) were tested positive for A(H7N9) virus. 44.4% (16/36) of retail LPMs and 50.0% (3/6) of wholesale LPMs were confirmed to be contaminated. No positive samples was detected from poultry farms. A significant higher positive sample rate was found in environmental samples related to poultry selling (2.6%) and slaughtering (2.4%), compared to poultry holding (0.9%). Correspondingly, A(H7N9) viruses were isolated most frequently from slaughter zone. In addition, 316 poultry workers associated with the 19 contaminated-LPMs were recruited and a low seroprevalence (1.6%) of antibody against A(H7N9) virus was detected. An asymptomatic A(H7N9) infection was also identified by RT-PCR. Conclusions Our study highlights the importance of conducting effective surveillance for A(H7N9) virus and provides evidence to support the assumption that slaughtering is the key process for the propagation of A(H7N9) virus in retail LPMs. Moreover, the ability of A(H7N9) virus to cross species barrier is proved to be still limited.

Targeted surveillance for influenza A(H7N9) identified 21 cases of infection with this virus in Guangzhou, China, during April 1, 2013–March 7, 2014. The spectrum of illness ranged from severe pneumonia to asymptomatic infection. Epidemiologic findings for a family cluster of 1 severe and 1 mild case suggested limited person-to-person transmission of this virus.

The structure and backbone dynamics of rat holo cellular retinol-binding protein II (holo-CRBP II) in solution has been determined by multidimensional NMR. The final structure ensemble was based on 3980 distance and 30 dihedral angle restraints, and was calculated using metric matrix distance geometry with pairwise Gaussian metrization followed by simulated annealing. The average RMS deviation of the backbone atoms for the final 25 structures relative to their mean coordinates is 0.85(±0.09) A. Comparison of the solution structure of holo-CRBP II with apo-CRBP II indicates that the protein undergoes conformational changes not previously observed in crystalline CRBP II, affecting residues 28-35 of the helix-turn-helix, residues 37-38 of the subsequent linker, as well as the β-hairpin C-D, E-F and G-H loops. The bound retinol is completely buried inside the binding cavity and oriented as in the crystal structure. The order parameters derived from the 15 N T 1 , T 2 and steady-state NOE parameters show that the backbone dynamics of holo-CRBP II is restricted throughout the polypeptide. The T 2 derived apparent backbone exchange rate and amide 1 H exchange rate both indicate that the microsecond to second timescale conformational exchange occurring in the portal region of the apo form has been suppressed in the holo form.

The structure and dynamics of rat apo-cellular retinol binding protein II (apo-CRBP II) in solution has been determined by multidimensional NMR analysis of uniformly enriched recombinant rat 13 C, 15 N-apo-CRBP II and 15 N-apo-CRBP II. The final ensemble of 24 NMR structures has been calculated from 3274 conformational restraints or 24.4 restraints/ residue. The average root-mean-square deviation of the backbone atoms for the final 24 structures relative to their mean structure is 1.06 A ˚ . Although the average solution structure is very similar to the crystal structure, it differs at the putative entrance to the binding cavity, which is formed by the helix-turn-helix motif, the bC-bD turn and the bE-bF turn. The mean coordinates of the main-chain atoms of amino acid residues 28-38 are displaced in the solution structure relative to the crystal structure. The side-chain of F58, located on the bC-bD turn, is reoriented such that it interacts with L37 and no longer blocks entry into the ligandbinding pocket. Residues 28-35, which form the second helix of the helixturn-helix motif in the crystal structure, do not exhibit a helical conformation in the solution structure. The solution structure of apo-CRBP II exhibits discrete regions of backbone disorder which are most pronounced at residues 28-32, 37-38 and 73-76 in the bE-bF turn as evaluated by the consensus chemical shift index, the root-mean-square deviation, amide 1 H exchange rates and 15 N relaxation studies. These studies indicate that fluctuations in protein conformation occur on the ms to ms timescale in these regions of the protein. Some of these exchange processes can be directly observed in the three-dimensional 15 N-resolved NOESY spectrum. These results suggest that in solution, apo-CRBP II undergoes conformational changes on the ms to ms time-scale which result in increased access to the binding cavity. # 1999 Academic Press

Interactions between the epithelium and surrounding mesenchyme/stroma play an important role in normal gut morphogenesis, the epithelial response to injury, and epithelial carcinogenesis. The tumor microenvironment, composed of stromal cells including myofibroblasts and immune cells, regulates tumor growth and the cancer stem cell niche. Deletion of epimorphin (Epim), a syntaxin family member expressed in myofibroblasts and macrophages, results in partial protection from colitis and from inflammation-induced colon cancer in mice. We sought to determine whether epimorphin deletion protects from polyposis in the Apcmin/+mouse model of intestinal carcinogenesis. Epim− /−mice were crossed to Apcmin/+mice; Apcmin/+and Apcmin/+/Epim− /−mice were killed at 3 mo of age. Polyp numbers and sizes were quantified in small intestine and colon, and gene expression analyses for pathways relevant to epithelial carcinogenesis were performed. Primary myofibroblast cultures were isolated, and expression and secretion of selected growth factors from Apcmin/+and Apcmin/+/Epim− /−myofibroblasts were examined by ELISA. Small bowel polyposis was significantly inhibited in Apcmin/+/Epim− /−compared with Apcmin/+mice. Apcmin/+/Epim− /−compared with Apcmin/+polyps and adjacent uninvolved intestinal mucosa had increased transforming growth factor-β (TGF-β) expression and signaling with increased P-Smad2/3 expression. Myofibroblasts isolated from Apcmin/+/Epim− /−vs. Apcmin/+mice had markedly decreased hepatocyte growth factor (HGF) expression and secretion. We concluded that Epim deletion inhibits polyposis in Apcmin/+mice, associated with increased mucosal TGF-β signaling and decreased myofibroblast HGF expression and secretion. Our data suggest that Epim deletion reduces tumorigenicity of the stromal microenvironment.

Background The annual differences in the seasonal influenza vaccine and the circulating strains make it necessary to assess influenza vaccine effectiveness (VE) yearly. We assessed the effectiveness of the trivalent inactivated influenza vaccine for the 2010–2011 and 2011–2012 influenza seasons among children in Guangzhou, China. Methods We conducted a 1:2 matched case–control study based on date of birth (±7 days), gender, and area of residence. The influenza cases from surveillance sites in Guangzhou were laboratory-confirmed during the 2010–2012 seasons. The controls were randomly selected from children aged 6–59 months in the Children's Expanded Programmed Immunization Administrative Computerized System. The influenza vaccination information for both cases and controls was retrieved from this system. Results We analyzed the vaccination information for 1255 influenza cases and 2510 matched controls in 2 influenza seasons in Guangzhou, China. We found that the VE for vaccination during the 2010–2011 and 2011–2012 seasons of virus circulation was 73·2% (95% confidence interval (CI), 52·2–85·0%) and 52·9% (95% CI, 42·1–61·7%), respectively. The VE decreased from 68·9% (95% CI, 57·5–77·2%) in the period between January and March to 48·4% (95% CI, 33·8–59·7%) in the period between April and June. Conclusions This post-licensing study of VE found moderate protection against influenza for vaccinated children aged 6–59 months. Although the influenza vaccine strains for the 2010–2011 and the 2011–2012 seasons were the same, our study indicated that annual vaccination is recommended even for those who received the vaccine during the previous season.

Influenza vaccine has to be reformulated each year due to the ever-changing antigenicity of the influenza virus. However, few post-licensure studies of influenza vaccine are available in China. We aimed to measure the effectiveness of seasonal influenza vaccine during 2 consecutive seasons. Among children in Guangzhou aged 6 to 59 mo in 2010-2012, we matched each child with clinically diagnosed influenza to 3 healthy children. Cases with clinically diagnosed influenza were identified from surveillance system. Healthy controls were randomly sampled from the Children's Expanded Programmed Immunization Administrative Computerized System. Conditional logistic regression was used to calculate vaccine effectiveness (VE). A total of 275 matched sets of subjects were included. VE levels against clinically diagnosed influenza for both seasons combined was 47.4% [95% confidence interval (CI), 8.5-69.8%] for full vaccination for children aged 6-35 mo, 33.6% (95% CI, 5.4-53.5%) for any vaccination for children aged 6-59 mo, respectively. VE by time since vaccination for any vaccination was 34.6% (95% CI, 4.7-55.2%) in 0-5 mo, and no protection was observed in 6-11 mo. Annual, full and timely vaccination should be encouraged for children.

A 21-amino acid glycopeptide (Gp21) was isolated and purified in multi-milligram yields from commercially available human serum transferrin (HSTF) by a combination of tryptic digestion, Con A affinity chromatography, and reverse phase HPLC. The peptide chain of Gp21 contains a single N-glycosylation site to which a diantennary oligosaccharide is attached. The amino acid sequence and the glycan primary structure of Gp21 have been verified by peptide sequencing, electrospray mass spectrometry, and one-dimensional 1H NMR spectroscopy. Different glycoforms were found for the glycan of Gp21 derived from two different batches of commercial HSTF. These glycoforms differ from one another in the number of NeuAc residues (ranging from 0 to 2) and/or the number of Gal residues (ranging from 1 to 2). As for the monogalacto species, in the two-dimensional nuclear Overhauser effect (NOE) spectrum of Gp21, interglycosidic NOEs were observed between Man4 in the alpha (1-->3) branch and the terminal GlcNAc beta (1-->2) residue. No interglycosidic NOE was observed between Man4' in the alpha (1-->6) branch and the terminal GlcNAc residue. These observations indicate that the terminal GlcNAc residue in the minor glycoforms of Gp21 is exclusively located in the alpha (1-->3) branch of the Gp21 glycan. The occurrence of such a carbohydrate structure in HSTF has not been reported before. The 1H and 13C NMR spectra of Gp21 have been completely assigned by two-dimensional homonuclear and heteronuclear spectroscopy. The close similarity of the 1H and 13C chemical shift values for the Gp21 glycan with the respective values for the peptide-free diantennary oligosaccharide (Wieruszeski et al., Glycoconjugate J., 6 (1989) 183-194) indicates that the 1H and 13C chemical shifts of the diantennary oligosaccharide are not perturbed by the presence of the Gp21 peptide fragment. The complete 1H and 13C resonance assignments and the full characterization of the primary structure of Gp21 will permit us to study the conformation and dynamics of the N-linked diantennary oligosaccharides while covalently attached to a polypeptide fragment.

To evaluate the short-term efficacy and safety of propranolol for problematic infantile hemangiomas.Oral propranolol was administered to 68 infants with heamngiomas diagnosed by clinical evaluation and adjuvant examination at 1.0~2.0 mg per kilogram of body weight per day, divided to 2 or 3 times. The patients revisited once a month. The changes of the tumor size, texture, and color were monitored and recorded at a regular interval.The adverse effects after medication were observed and managed accordingly.The short-term results were evaluated using a 4-grade system.All the 68 infants were followed up for 3-13 months, except that 1 infants combined with other diseases and 4 withdrew.The overall response was Scale 1 in 8 infants, Scale II in 13, Scale III in 29, and Scale IV in 13. No serious adverse effects were seen, but none cured entirely as well.Oral propranolol is safe and effective for infantile heamngioma with good short-term result. It could be used as the primary drug for problematic infantile hemangiomas at the rapid growth stage of hemangiomas.

Recently, Local Binary Pattern (LBP) operator has been applied into face recognition successfully. Center-symmetric Local Binary Pattern is a variation operator of LBP, which can not only reduce the dimensionality of LBP features, but also capture the gradient information better than basic LBP. In this paper, an algorithm is proposed for face recognition based on center-symmetric LBP. The main idea of the algorithm is using the center-symmetric LBP operator three times for extracting three-level face features with the assumption that a gray face image encoded by center-symmetric LBP operator is still a gray image. Since different level face features make different contributions to face recognition, we put appropriate weighting on each level face feature. The experimental results show that the proposed algorithm performances superiority over the comparative algorithms on ORL and the subset of FERET face databases.

To determine the influence of intense pulsed light (IPL) on the secretion of TGF-beta1 in cultured human fibroblasts and the intervention of JNK inhibitor.The callan foreskin fibroblasts were cultured and divided into 2 groups. In the IPL treatment group, cells were irradiated with IPL with fluences of 0 (negative control), 10, 18, 27, 36, and 36 J/cm2*2 (irradiated with IPL with fluences of 36 J/cm2 twice). In the IPL+inhibitor group, cells were irradiated with IPL with fluences of 36 J/cm2 after incubation with the inhibitor SP600125 for 2 h. TGF-beta1 in the culture supernatant was evaluated 48 h after the irradiation using enzyme-linked immunosorbent assay.Compared with the negative control, TGF-beta1 in the culture supernatant decreased at the IPL irradiation of 10, 18, 27, and 36 J/cm2, whereas TGF-beta1 increased at the IPL irradiation of 36 J/cm2*2. In the IPL+inhibitor group, the concentration of TGF-beta1 in the culture supernatant decreased compared with the controls (P0.05).IPL can suppress the secretion of TGF-beta1 at the lower fluence and promote the secretion at a higher fluence. JNK inhibitor may play an inhibitive role when IPL regulates the TGF-beta1 secretion in cultured human fibroblasts. IPL may stimulate TGF-beta1 secretion of the fibroblast cells in human skin via JNK signal pathway.

The effect of retinoid X receptor (RXR) antagonists on the conformational exchange of the RXR ligand-binding domain (LBD) remains poorly characterized. To address this question, we used nuclear magnetic resonance spectroscopy to compare the chemical shift perturbations induced by RXR antagonists and agonists on the RXRalpha LBD when partnered with itself as a homodimer and as the heterodimeric partner with the peroxisome proliferator-activated receptor gamma (PPARgamma) LBD. Chemical shift mapping on the crystal structure showed that agonist binding abolished a line-broadening effect caused by a conformational exchange on backbone amide signals for residues in helix H3 and other regions of either the homo- or hetero-dimer, whereas binding of antagonists with similar binding affinities failed to do so. A lineshape analysis of a glucocorticoid receptor-interacting protein 1 NR box 2 coactivator peptide showed that the antagonists enhanced peptide binding to the RXRalpha LBD homodimer, but to a lesser extent than that enhanced by the agonists. This was further supported by a lineshape analysis of the RXR C-terminal residue, threonine 462 (T462) in the homodimer but not in the heterodimer. Contrary to the agonists, the antagonists failed to abolish a line-broadening effect caused by a conformational exchange on the T462 signal corresponding to the RXRalpha LBD-antagonist-peptide ternary complex. These results suggest that the antagonists lack the ability of the agonists to shift the equilibrium of multiple RXRalpha LBD conformations in favor of a compact state, and that a PPARgamma LBD-agonist complex can prevent the antagonist from enhancing the RXRalpha LBD-coactivator binding interaction.

To explore the effect of intense pulsed laser (IPL) on anti-aging and its mechanism.Rat skin was continuously irradiated ex vivo by IPL at certain wavelengths with different energy densities. The rats were irradiated twice with an interval of 2 weeks. We measured superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, hydroproline (Hyp) content, and the level of apoptosis-related gene B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax) in the IPL treatment groups, and then compared with those in the model groups and the control group.SOD activity and Hyp content in the IPL treatment groups were higher than those in the model groups, and MDA content in the IPL treatment group was lower than that in the model group (P0.05). IPL irradiation increased Bcl-2 protein content in rat skin cells, but had no effect on Bax protein expression.IPL is effective to improve the appearance of aging skin. Its mechanism may relate to maintaining the balance of oxidation and anti-oxidation, restoring oxidase activity, and regulating the death of skin cells by increasing Bcl-2 expression.

The C-terminal activation function-2 (AF-2) helix plays a crucial role in retinoid X receptor alpha (RXRalpha)-mediated gene expression. Here, we report a nuclear magnetic resonance (NMR) study of the RXRalpha ligand-binding domain complexed with 9-cis-retinoic acid and a glucocorticoid receptor-interacting protein 1 peptide. The AF-2 helix and most of the C-terminal residues were undetectable due to a severe line-broadening effect. Due to its outstanding signal-to-noise ratio, the C-terminus residue, threonine 462 (T462) exhibited two distinct crosspeaks during peptide titration, suggesting that peptide binding was in a slow exchange regime on the chemical shift timescale. Consistently, the K(d) derived from T462 intensity decay agreed with that derived from isothermal titration calorimetry. Furthermore, the exchange contribution to the (15)N transverse relaxation rate was measurable in either T462 or the bound peptide. These results suggest that T462 is a sensor for coactivator binding and is a potential probe for AF-2 helix mobility.

The structural mechanism of allosteric communication between retinoid X receptor (RXR) and its heterodimer partners remains controversial. As a first step towards addressing this question, we report a nuclear magnetic resonance (NMR) study on the GW1929-bound peroxisome proliferator-activated receptor gamma (PPARgamma) ligand-binding domain (LBD) with and without the 9-cis-retinoic acid (9cRA)-bound RXRalpha LBD. Sequence-specific 13C(alpha), 13C(beta), and 13CO resonance assignments have been established for over 95% of the 275 residues in the PPARgamma LBD monomer. The 1HN, 15N, and 13CO chemical shift perturbations induced by the RXRalpha LBD binding are located at not only the heterodimer interface that includes the C-terminal residue Y477 but also residues Y473 and K474 in the activation function-2 (AF-2) helix. This result suggests that 9cRA-bound RXRalpha can affect the PPARgamma AF-2 helix in solution and demonstrates that NMR is a powerful new tool for studying the mechanism of allosteric ligand activation in RXR heterodimers.

Dyschromatosis symmetrica hereditaria (DSH) is a hereditary skin disease characterized by the presence of hyperpigmented and hypopigmented macules on face and dorsal aspects of the extremities that appear in infancy or early childhood. Genetic studies have identified mutations in the double-stranded RNA-specific adenosine deaminase (DSRAD) gene, encoding double-stranded RNA-specific adenosine deaminase, to be responsible for this disorder. Here, we report two novel mutations c.2116 G > A (E706K) and c.2848 C > T (Q950X) in the DSRAD gene identified in two Chinese pedigrees with DSH. This study should be useful for genetic counseling and prenatal diagnosis for affected families and in expanding the database on DSRAD gene mutations in DSH.

Cellular retinol-binding protein II (CRBP II) is a member of the cellular retinol-binding protein family, which is expressed primarily in the small intestine. To investigate the physiological role of CRBP II, the gene encoding CRBP II was inactivated. The saturable component of intestinal retinol uptake is impaired in CRBP II(-/-) mice. The knockout mice, while maintained on a vitamin A-enriched diet, have reduced (40%) hepatic vitamin A stores but grow and reproduce normally. However, reducing maternal dietary vitamin A to marginal levels during the latter half of gestation results in 100% mortality/litter within 24 h after birth in the CRBP II(-/-) line but no mortality in the wild type line. The neonatal mortality in heterozygote offspring of CRBP II(-/-) dams (79 +/- 21% deaths/litter) was increased as compared with the neonatal mortality in heterozygote offspring of wild type dams (29 +/- 25% deaths per litter, p0.05). Maternal CRBP II was localized by immunostaining in the placenta at 18 days postcoitum as well as in the small intestine. These studies suggest that both fetal as well as maternal CRBP II are required to ensure adequate delivery of vitamin A to the developing fetus when dietary vitamin A is limiting.

In this two-years surveillance of 2009 pandemic influenza A (H1N1) (pH1N1) in Guangzhou, China, we reported here that the scale and duration of pH1N1 outbreaks, severe disease and fatality rates of pH1N1 patients were significantly lower or shorter in the second epidemic year (May 2010-April 2011) than those in the first epidemic year (May 2009-April 2010) (P0.05). Similar to seasonal influenza, pre-existing chronic pulmonary diseases was a risk factor associated with fatal cases of pH1N1 influenza. Different from seasonal influenza, which occurred in spring/summer seasons annually, pH1N1 influenza mainly occurred in autumn/winter seasons in the first epidemic year, but prolonged to winter/spring season in the second epidemic year. The information suggests a tendency that the epidemics of pH1N1 influenza may probably further shift to spring/summer seasons and become a predominant subtype of seasonal influenza in coming years in Guangzhou, China., published_or_final_version