Intermedin1-53 Inhibits NLRP3 Inflammasome Activation by Targeting IRE1α in Cardiac Fibrosis.

Intermedin (IMD), a paracrine/autocrine peptide, protects against cardiac fibrosis. However, the underlying mechanism remains poorly understood. Previous study reports that activation of nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammasome contributes to cardiac fibrosis. In this study, we aimed to investigate whether IMD mitigated cardiac fibrosis by inhibiting NLRP3. Cardiac fibrosis was induced by angiotensin II (Ang II) infusion for 2 weeks in rats. Western blot, real-time PCR, histological staining, immunofluorescence assay, RNA sequencing, echocardiography, and hemodynamics were used to detect the role and the mechanism of IMD in cardiac fibrosis. Ang II infusion resulted in rat cardiac fibrosis, shown as over-deposition of myocardial interstitial collagen and cardiac dysfunction. Importantly, NLRP3 activation and endoplasmic reticulum stress (ERS) were found in Ang II-treated rat myocardium. Ang II infusion decreased the expression of IMD and increased the expression of the receptor system of IMD in the fibrotic rat myocardium. IMD treatment attenuated the cardiac fibrosis and improved cardiac function. In addition, IMD inhibited the upregulation of NLRP3 markers and ERS markers induced by Ang II. In vitro, IMD knockdown by small interfering RNA significantly promoted the Ang II-induced cardiac fibroblast and NLRP3 activation. Moreover, silencing of inositol requiring enzyme 1 α (IRE1α) blocked the effects of IMD inhibiting fibroblast and NLRP3 activation. Pre-incubation with PKA pathway inhibitor H89 blocked the effects of IMD on the anti-ERS, anti-NLRP3, and anti-fibrotic response. In conclusion, IMD alleviated cardiac fibrosis by inhibiting NLRP3 inflammasome activation through suppressing IRE1α via the cAMP/PKA pathway.

A hierarchical emulsion system stabilized by soyasaponin emulsion droplets.

Oil/water (O/W) emulsion droplets coated with soyasaponin (Ssa) were used as emulsifiers to prepare emulsions with hierarchical configurations (2.82 µm). Ssa is a natural triterpenoid with amphiphilic properties and an excellent emulsifying activity. Stable O/W emulsions were prepared and characterized using an ultrasonic method at a Ssa concentration of 2.5 wt%. The resultant hierarchical emulsions were further prepared using O/W droplets as emulsifiers. It was observed that the stability of the hierarchical emulsions changed with alterations to the ratio of O/W droplets to the oil phase. As the number of droplets increased, the more the surface area of the hierarchical emulsion was covered. Additional observations included a decreased particle size, increased negative charge and viscoelastic behavior, and enhanced emulsion stability. The emulsion was most stable when the O/W droplet addition was 29%. The addition of O/W droplets continued to increase, and there was an imbalance in the ratio of O/W droplets to the oil phase; the excess O/W droplets induced instability in the emulsion, resulting in a degradation of the emulsion quality. We monitored hierarchical emulsions with different concentrations of emulsifiers for 30 days, and the results indicated that hierarchical emulsions could meet the demand for long-term storage. This provides a new theoretical basis for the construction and application of complex emulsion systems.

Prevalence of celiac disease in China: Meta-analysis and serological survey in high-risk populations.

OBJECTIVE: To summarize data from a serological survey of high-risk populations in Guangdong Province, China, and to perform a meta-analysis to investigate the prevalence and seroprevalence of celiac disease (CD) in the Chinese general and high-risk populations. METHODS: We collected data from the serological survey of high-risk population of CD in Guangdong Province, China (N = 1390) by testing their serum tissue transglutaminase immunoglobulin A (tTG-IgA), deamidated gliadin peptides immunoglobulin A (DGP-IgA) and deamidated gliadin peptides immunoglobulin G (DGP-IgG). Additionally, a literature search was performed on PubMed, EMBASE, Cochrane Library and three Chinese databases for articles published up to 20 December 2020 to estimate the pooled prevalence and seroprevalence of CD in China. RESULTS: In the serological survey, 0.94% (13/1390) of individuals were positive for CD antibodies. In a meta-analysis of 18 studies, the seroprevalence of CD in the general Chinese population was 0.27% (95% confidence interval [CI] 0.02%-0.71%). While that in the high-risk population was 8.34% (95% CI 4.90%-12.54%) (odds ratio 7.27, 95% CI 4.06-13.04). The prevalence of biopsy-confirmed CD in high-risk Chinese populations was 4.44% (95% CI 1.53%-8.58%). The seroprevalence of CD varied with patients' geographical origin, being higher in northern China than in southern China. CONCLUSIONS: Early diagnosis of CD by serological screening in high-risk population and generous serological testing in those with vague symptoms, especially in northern China, are recommended.

The Association Between Sarcopenic Obesity and Hypertension, Diabetes, and Abnormal Lipid Metabolism in Chinese Adults.

OBJECTIVE: Sarcopenic obesity is associated with several negative health outcomes. However, there are only a few studies on the relationship between SO and metabolic diseases such as diabetes, hypertension, and abnormal lipid metabolism in Chinese adults. The aim of this work was to evaluate the association between SO and hypertension, diabetes, and abnormal lipid metabolism in Chinese adults, and explore the prediction of SO using relevant anthropometric indicators. MATERIALS AND METHODS: All participants underwent a questionnaire interview for the collection of demographic data. Thereafter, they underwent physical examination for the measurement of anthropometric variables, which was performed using bioelectrical impedance analysis. Biochemical measurements were determined according to standard laboratory procedures used for the evaluation of blood parameters. RESULTS: We included 14,926 patients aged 35-74 years old. The mean age of the participants was 56.75 ± 9.76 years old, and 39.80% of them were male. The mean body mass index (BMI) was 24.94 ± 3.40 kg/m2, and the overall prevalence of SO was 65.1%. The results showed that shorter people; people with faster heart rate; heavier weight; lower waist circumference (WC), BMI, triglyceride level, total cholesterol, and low-density lipoprotein cholesterol levels; and higher high-density lipoprotein cholesterol level are at risk for SO. CONCLUSION: The prevalence of SO is high (65.1%) in Chinese adults aged 35-74 years old. The occurrence of SO is related to hypertension, diabetes, and abnormal lipid metabolism. BMI, WC, and waist-hip ratio may be predictive indicators of SO. The incidence of SO may be reduced by timely intervention and health education for persons at risk of the condition.

Perivascular adipose tissue-derived stromal cells contribute to vascular remodeling during aging.

Aging is an independent risk factor for vascular diseases. Perivascular adipose tissue (PVAT), an active component of the vasculature, contributes to vascular dysfunction during aging. Identification of underlying cell types and their changes during aging may provide meaningful insights regarding the clinical relevance of aging-related vascular diseases. Here, we take advantage of single-cell RNA sequence to characterize the resident stromal cells in the PVAT (PVASCs) and identified different clusters between young and aged PVASCs. Bioinformatics analysis revealed decreased endothelial and brown adipogenic differentiation capacities of PVASCs during aging, which contributed to neointimal hyperplasia after perivascular delivery to ligated carotid arteries. Mechanistically, in vitro and in vivo studies both suggested that aging-induced loss of peroxisome proliferator-activated receptor-γ coactivator-1 α (PGC1α) was a key regulator of decreased brown adipogenic differentiation in senescent PVASCs. We further demonstrated the existence of human PVASCs (hPVASCs) and overexpression of PGC1α improved hPVASC delivery-induced vascular remodeling. Our finding emphasizes that differentiation capacities of PVASCs alter during aging and loss of PGC1α in aged PVASCs contributes to vascular remodeling via decreased brown adipogenic differentiation.

Inhibition of endoplasmic reticulum stress by intermedin1-53 attenuates angiotensin II-induced abdominal aortic aneurysm in ApoE KO Mice.

Endoplasmic reticulum stress (ERS) is involved in the development of abdominal aortic aneurysm (AAA). Since bioactive peptide intermedin (IMD)1-53 protects against AAA formation, here we investigated whether IMD1-53 attenuates AAA by inhibiting ERS. AAA model was induced by angiotensin II (AngII) in ApoE KO mouse background. AngII-treated mouse aortas showed increased ERS gene transcription of caspase12, eukaryotic translation initiation factor 2a (eIf2a) and activating transcription factor 4(ATF4).The protein level of ERS marker glucose regulated protein 94(GRP94), ATF4 and C/EBP homologous protein 10(CHOP) was also up-regulated by AngII. Increased ERS levels were accompanied by severe VSMC apoptosis in human AAA aorta. In vivo administration of IMD1-53 greatly reduced AngII-induced AAA and abrogated the activation of ERS. To determine whether IMD inhibited AAA by ameliorating ERS, we used 2 non-selective ERS inhibitors phenyl butyrate (4-PBA) and taurine (TAU). Similar to IMD, PBA, and TAU significantly reduced the incidence of AAA and AAA-related pathological disorders. In vitro, AngII infusion up-regulated CHOP, caspase12 expression and led to VSMC apoptosis. IMD siRNA aggravated the CHOP, caspase12-mediated VSMC apoptosis, which was abolished by ATF4 silencing. IMD infusion promoted the phosphorylation of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) in aortas in ApoE KO mice, and the AMPK inhibitor compound C abolished the protective effect of IMD on VSMC ERS and apoptosis induced by AngII. In conclusion, IMD may protect against AAA formation by inhibiting ERS via activating AMPK phosphorylation.

Dicyanamide Bridged Cu(II)36-Metallacrown-6 Complex with 1,4,7-Triisopropyl-1,4,7-Triazacyclononane and Binding Properties with DNA.

A novel 36-metallacrown-6 complex [CuL(N(CN)2)(PF6)]6∙0.5H2O 1 was achieved using a tridendate ligand, 1,4,7-triisopropyl-1,4,7-triazacyclononane (L), and a flexible ligand, dicyanamide in MeOH. The µ1,5 bridging models of the dicyanamide ligand linked the macrocycle to form in a specific size with the chair conformation. The anion was important to form this 36-metallacrown-6 complex, as change was obtained with the larger anion BPh4-, binuclear copper compound 2. The magnetic property indicates that slightly ferromagnetic interactions resulted from a superexchange mechanism. DNA binding properties were also studied. UV and fluorescence spectra showed that complex 1 could bind with DNA.

LRWD1 Regulates Microtubule Nucleation and Proper Cell Cycle Progression in the Human Testicular Embryonic Carcinoma Cells.

Leucine-rich repeats and WD repeat domain containing protein 1 (LRWD1) is a testis-specific protein that mainly expressed in the sperm neck where centrosome is located. By using microarray analysis, LRWD1 is identified as a putative gene that involved in spermatogenesis. However, its role in human male germ cell development has not been extensively studied. When checking in the semen of patients with asthenozoospermia, teratozoospermia, and asthenoteratozoospermia, the level of LRWD1 in the sperm neck was significantly reduced with a defective neck or tail. When checking the sub-cellular localization of LRWD1 in the cells, we found that LRWD1 resided in the centrosome and its centrosomal residency was independent of microtubule transportation in NT2/D1, the human testicular embryonic carcinoma, cell line. Depletion of LRWD1 did not induce centrosome re-duplication but inhibited microtubule nucleation. In addition, the G1 arrest were observed in LRWD1 deficient NT2/D1 cells. Upon LRWD1 depletion, the levels of cyclin E, A, and phosphorylated CDK2, were reduced. Overexpression of LRWD1 promoted cell proliferation in NT2/D1, HeLa, and 239T cell lines. In addition, we also observed that autophagy was activated in LRWD1 deficient cells and inhibition of autophagy by chloroquine or bafilomycin A1 promoted cell death when LRWD1 was depleted. Thus, we found a novel function of LRWD1 in controlling microtubule nucleation and cell cycle progression in the human testicular embryonic carcinoma cells. J. Cell. Biochem. 119: 314-326, 2018. © 2017 Wiley Periodicals, Inc.

Intermedin1-53 attenuates vascular calcification in rats with chronic kidney disease by upregulation of α-Klotho.

Deficiency in α-Klotho is involved in the pathogenesis of vascular calcification. Since intermedin (IMD)1-53 (a calcitonin/calcitonin gene-related peptide) protects against vascular calcification, we studied whether IMD1-53 inhibits vascular calcification by upregulating α-Klotho. A rat model of chronic kidney disease (CKD) with vascular calcification induced by the 5/6 nephrectomy plus vitamin D3 was used for study. The aortas of rats with CKD showed reduced IMD content but an increase of its receptor, calcitonin receptor-like receptor, and its receptor modifier, receptor activity-modifying protein 3. IMD1-53 treatment reduced vascular calcification. The expression of α-Klotho was greatly decreased in the aortas of rats with CKD but increased in the aortas of IMD1-53-treated rats with CKD. In vitro, IMD1-53 increased α-Klotho protein level in calcified vascular smooth muscle cells. α-Klotho knockdown blocked the inhibitory effect of IMD1-53 on vascular smooth muscle cell calcification and their transformation into osteoblast-like cells. The effect of IMD1-53 to upregulate α-Klotho and inhibit vascular smooth muscle cell calcification was abolished by knockdown of its receptor or its modifier protein, or treatment with the protein kinase A inhibitor H89. Thus, IMD1-53 may attenuate vascular calcification by upregulating α-Klotho via the calcitonin receptor/modifying protein complex and protein kinase A signaling.

[Prediction of total nitrogen and alkali hydrolysable nitrogen content in loess using hyperspectral data based on correlation analysis and partial least squares regression].

Wuqi County of Shaanxi Province, where the vegetation recovering measures have been carried out for years, was taken as the study area. A total of 100 loess samples from 24 different profiles were collected. Total nitrogen (TN) and alkali hydrolysable nitrogen (AHN) contents of the soil samples were analyzed, and the soil samples were scanned in the visible/near-infrared (VNIR) region of 350-2500 nm in the laboratory. The calibration models were developed between TN and AHN contents and VNIR values based on correlation analysis (CA) and partial least squares regression (PLS). Independent samples validated the calibration models. The results indicated that the optimum model for predicting TN of loess was established by using first derivative of reflectance. The best model for predicting AHN of loess was established by using normal derivative spectra. The optimum TN model could effectively predict TN in loess from 0 to 40 cm, but the optimum AHN model could only roughly predict AHN at the same depth. This study provided a good method for rapidly predicting TN of loess where vegetation recovering measures have been adopted, but prediction of AHN needs to be further studied.

Targeted inhibition of prostate cancer metastases with an RNA aptamer to prostate-specific membrane antigen.

Cell-targeted therapies (smart drugs), which selectively control cancer cell progression with limited toxicity to normal cells, have been developed to effectively treat some cancers. However, many cancers such as metastatic prostate cancer (PC) have yet to be treated with current smart drug technology. Here, we describe the thorough preclinical characterization of an RNA aptamer (A9g) that functions as a smart drug for PC by inhibiting the enzymatic activity of prostate-specific membrane antigen (PSMA). Treatment of PC cells with A9g results in reduced cell migration/invasion in culture and metastatic disease in vivo. Importantly, A9g is safe in vivo and is not immunogenic in human cells. Pharmacokinetic and biodistribution studies in mice confirm target specificity and absence of non-specific on/off-target effects. In conclusion, these studies provide new and important insights into the role of PSMA in driving carcinogenesis and demonstrate critical endpoints for the translation of a novel RNA smart drug for advanced stage PC.

[Survey on seroepidemiological status and vaccine coverage of hepatitis B among children in Chaoyang district of Beijing in 2010].

OBJECTIVE: To explore seroepidemiological status and vaccine coverage of hepatitis B in children aging under 15 years old in Chaoyang district of Beijing. METHODS: A total of 1602 children aging under 15 years old, residents or floating population who had lived here more than six months, were randomly selected by multistage cluster sampling, from Chaoyang district of Beijing in year 2010. The demographic information and vaccine coverage of hepatitis B vaccine (HepB) were collected by self-designed questionnaire.5 ml blood was collected from each subject and the serum HBsAg, anti-HBs and anti-HBc were detected by Abbott microparticle enzyme-linked immunoassay. Those whose HBsAg was positive were then tested HBeAg and anti-HBe. The positive rate of hepatitis B indicators and coverage rate of HepB in different population were compared. RESULTS: The positive rate of HBsAg, anti-HBs and anti-HBc were 0.56% (9/1602), 64.17% (1028/1602) and 2.12% (34/1602), respectively; while the age standardized rates were separately 0.57%, 66.36% and 1.98%; and the gender-adjusted rates were 0.56%, 64.23% and 2.12% respectively. The positive rate of anti-HBs was statistically significant (χ(2) = 165.445, P = 0.000). The positive rate of anti-HBs was up to 90.73% (235/259) among 1-2 years old children, followed by 76.22% (141/185) among 13 - 15 years old children, 67.21% (166/247) among 3 - 4 years old children, 61.22% (150/245) among 9 - 10 years old children, 60.68% (142/234) among 11 - 12 years old children, 49.05% (103/210) among 5 - 6 years old children and 40.99% (91/222) among 7 - 8 years old children. The average coverage rate of HepB was 90.44% (1371/1516), separately 93.76% (661/705) in residents and 87.55% (719/811) in floating population. The difference was statistically significant (χ(2) = 16.829, P = 0.000). CONCLUSION: HBsAg positive rate in children under 15 years old in Chaoyang district of Beijing dropped to less than 1% and the coverage rate of HepB had reached over 90%. It is suggested that we should pay more attention to increase the coverage rate of HepB among floating children under 15 years old.

Identification of a small molecule 1,4-bis-[4-(3-phenoxy-propoxy)-but-2-ynyl]-piperazine as a novel inhibitor of the transcription factor p53.

AIM: To identify novel small compound inhibitor of p53 protein. METHODS: Mouse embryonic fibroblasts (MEF) and mouse embryonic stem (ES) cells were tested. Cell proliferation rate was determined using a Cell Proliferation Kit. The mRNA and protein levels of p53-related genes were measured using real-time PCR and Western blotting, respectively. Global response in the p53 signaling network was analyzed using Illumina whole-genome expression BeadChips. RESULTS: Treatment of MEF cells with a small molecule 1,4-bis-[4-(3-phenoxy-propoxy)-but-2-ynyl]-piperazine (G5) at 10 µmol/L for 24 h markedly reduced the mRNA and protein levels of the p53 downstream genes MDM2 and p21. In G5-treated ES cells, a total of 372 differentially expressed genes were identified, and 18 among them were direct downstream genes of p53; 6 out of 9 p53-repressed genes were upregulated, and 5 out of 9 p53-activated genes were downregulated. In both MEF cells and ES cells, treatment of with G5 (10 µmol/L) up to 48 h neither affected the proliferation rate nor caused morphological alterations. CONCLUSION: G5 inhibits p53 activity and simultaneously preserves the normal growth and proliferation of cells, therefore is a new compound for studies of p53-mediated cell manipulation.

A comparative study of the hyobranchial apparatus in Hynobiidae (Amphibia: Urodela).

The morphology of the adult hyobranchial apparatus has played an important role in understanding the systematics and evolution of urodeles, but the hyobranchial apparatus of hynobiid salamanders has received little attention so far. In this study, the hyobranchial apparatus of eight hynobiid salamanders (Hynobius leechii, Onychodactylus zhangyapingi, Ranodon sibiricus, Batrachuperus pinchonii, Salamandrella keyserlingii, Liua shihi, Pachyhynobius shangchengensis and Pseudohynobius flavomaculatus) is described and compared based on the clearing and double-staining method. The basic elements of the hyobranchial apparatus of the eight species are similar, including one basibranchial, cornua, one pair of radial loops, one pair of ceratohyals, one pair of hypobranchials II, one pair of ceratobranchials II, one urohyal (absent in O. zhangyapingi), one pair of the complex of hypobranchial I and ceratobranchial I (separated in certain species). Although the hyobranchial apparatus is similar among hynobiid salamanders and shows a unique morphological pattern, there are also certain species-specific distinctions that may be used for specific or generic diagnosis. The results of an ancestral state reconstruction of five traits showed that the ossified basibranchial, the presence of a separated hypobranchial I and ceratobranchial I, the absence of a urohyal, the ossified hypobranchial I and the partially ossified ceratohyal are derived traits. The state shown by the traits of each species is consistent with the phylogenetic position of each species. Compared with other Urodela, the hyobranchial apparatus of this group shows certain distinctive features that may represent the diagnostic characters of the family Hynobiidae. The partially ossified ceratohyal is correlated with the habitat and represents an ecological adaptation.

Characterization of 3-hydroxyisobutyrate dehydrogenase, HIBADH, as a sperm-motility marker.

PURPOSE: Asthenozoospermia is a major cause of male infertility. However, the molecular mechanisms underlying sperm-motility defects remain largely unknown in the majority of cases. In our previous study, we applied a proteomic approach to identify unknown proteins that were downregulated in spermatozoa with low motility compared to spermatozoa with good motility. Several sperm motility- related proteins have been identified. In this study, 3-hydroxyisobutyrate dehydrogenase (HIBADH), one of the proteins identified using the proteomic tools, is further characterized. METHODS: Reverse-transcription polymerase chain reactions (RT-PCR), western blotting, and immunofluorescence assays (IFA) were preformed to investigate the expression pattern. The enzymatic activity of HIBADH was evaluated in sperm with good (>50 %), moderate (< 50 %) and lower motility (< 20 %). RESULTS: Using RT-PCR, we found that transcripts of HIBADH are enriched in the cerebellum, heart, skeletal muscle, uterus, placenta, and testes of male humans. In western blotting, it is expressed in the placenta, testes, and spermatozoa. During spermiogenesis, HIBADH is located at the mid-piece (a specialized development from the mitochondria) of elongating, elongated, and mature sperm. The enzymatic activity of HIBADH in sperm with moderate and lower motility were significantly reduced compared with good motility (P<0.0001 and P<0.05, respectively). CONCLUSIONS: Our study indicated that HIBADH is involved in the mitochondrial function of spermatozoa, and maintains sperm motility. It may serve as a sperm-motility marker.

[Study on family aggregation and risk factors of hepatitis B virus transmission in Chaoyang district, Beijing].

OBJECTIVE: To explore the family aggregation and risk factors of hepatitis B virus (HBV) transmission in Chaoyang district of Beijing. METHODS: A total of 5266 families were randomly selected for the multi-stage cluster sampling study in Chaoyang district of Beijing in 2010. The family members who aged between 1 and 70 years old and lived constantly in Beijing for over half a year, were recruited as subjects. There were 14 491 subjects in total, including temporary residents who did not have Beijing household account, except foreigners. 5 ml venous blood was drawn from every subject. A self-designed questionnaire was used to collect the basic information of the population and the risk factors of the hepatitis B transmission. Microparticle enzyme-linked immunoassay was applied to test five indicators of hepatitis B. Negative binomial distribution test was used among the HBsAg positive families to calculate the family aggregation rate of hepatitis B. Single factor analysis and multi-factor logistic regression model were used to analyze the risk factors of HBV transmission. RESULTS: In all, 308 out of 5266 families had HBsAg positive members, accounting for 5.85%.383 out of 14 410 subjects were HBsAg positive, rating at 2.66%. The HBsAg positive rate among subjects under 14 years old was the lowest, at 0.56% (9/1603); and the positive rate among subjects aging between 35 and 44 years old was the highest, at 4.27% (47/1029). Negative binomial distribution test showed that the family aggregation rate of HBV infection was 7.66% (χ² = 15.10, P < 0.05). The analysis of family aggregation of HBsAg positive showed that 17.39% (8/46) of the transmission was from father to child, 13.04% (6/46) was from mother to child, 30.44% (14/46) was between couples, and another 39.13% (18/46) was between siblings or other relatives. Both single factor analysis and multi-factor logistic regression analysis showed that hepatitis B positive family members (OR = 5.40, 95%CI: 5.24 - 5.55), hepatitis B positive friends and colleagues (OR = 1.55, 95%CI: 1.11 - 1.99) and blood donation and transfusion history (OR = 1.96, 95%CI: 1.76 - 2.15) were the risk factors of HBV infection. CONCLUSION: HBV transmission showed family aggregation in Beijing, however, the risk factors needed further studies.

Rational truncation of an RNA aptamer to prostate-specific membrane antigen using computational structural modeling.

RNA aptamers represent an emerging class of pharmaceuticals with great potential for targeted cancer diagnostics and therapy. Several RNA aptamers that bind cancer cell-surface antigens with high affinity and specificity have been described. However, their clinical potential has yet to be realized. A significant obstacle to the clinical adoption of RNA aptamers is the high cost of manufacturing long RNA sequences through chemical synthesis. Therapeutic aptamers are often truncated postselection by using a trial-and-error process, which is time consuming and inefficient. Here, we used a "rational truncation" approach guided by RNA structural prediction and protein/RNA docking algorithms that enabled us to substantially truncateA9, an RNA aptamer to prostate-specific membrane antigen (PSMA),with great potential for targeted therapeutics. This truncated PSMA aptamer (A9L; 41mer) retains binding activity, functionality, and is amenable to large-scale chemical synthesis for future clinical applications. In addition, the modeled RNA tertiary structure and protein/RNA docking predictions revealed key nucleotides within the aptamer critical for binding to PSMA and inhibiting its enzymatic activity. Finally, this work highlights the utility of existing RNA structural prediction and protein docking techniques that may be generally applicable to developing RNA aptamers optimized for therapeutic use.

Rational design of peptides with anti-HCV/HIV activities and enhanced specificity.

Lack of vaccines for HCV and HIV makes the antiviral drug development urgently needed. The recently identified HCV NS5A-derived virucidal peptide (C5A) demonstrated a wide spectrum of activities against viruses. In this study, the C5A sequence SWLRDIWDWICEVLSDFK was utilized as the framework to study the effect of the modulation of peptide helicity and hydrophobicity on its anti-HCV and anti-HIV activities. Peptide helicity and hydrophobicity were altered by substitutions of varying amino acids on the non-polar face of C5A. Peptide hydrophobicity has been proved to play a crucial role in peptide anti-HCV or anti-HIV activities. Peptide helicity was relatively independent with antiviral activity. However, peptide analogs with dimerized structure in an aqueous medium while maintaining the ability to be induced into a more helical structure in a hydrophobic environment may tend to show comparable or improved antiviral activity and specificity to C5A. By modulating peptide helicity and hydrophobicity, we improved the specificity of C5A against HCV and HIV by 23- and 69-fold, respectively, in terms of the ratio of hemolytic activity to antiviral activity. We demonstrated that obtained by de novo design approach, peptide I6L/I10L/V13L may be a promising candidate as a new anti-HCV and anti-HIV therapeutic.

Improvement of acetic acid tolerance and fermentation performance of Saccharomyces cerevisiae by disruption of the FPS1 aquaglyceroporin gene.

The FPS1 gene coding for the Fps1p aquaglyceroporin protein of an industrial strain of Saccharomyces cerevisiae was disrupted by inserting CUP1 gene. Wild-type strain, CE25, could only grow on YPD medium containing less than 0.45% (v/v) acetic acid, while recombinant strain T12 with FPS1 disruption could grow on YPD medium with 0.6% (v/v) acetic acid. Under 0.4% (v/v) acetic acid stress (pH 4.26), ethanol production and cell growth rates of T12 were 1.7 ± 0.1 and 0.061 ± 0.003 g/l h, while those of CE25 were 1.2 ± 0.1 and 0.048 ± 0.003 g/l h, respectively. FPS1 gene disruption in an industrial ethanologenic yeast thus increases cell growth and ethanol yield under acetic acid stress, which suggests the potential utility of FPS1 gene disruption for bioethanol production from renewable resources such as lignocelluloses.

[Prevalence of metabolic syndrome among rural adult residents in Ningxia.].

OBJECTIVE: To describe the prevalence of metabolic syndrome (MS) among rural adult residents in Ningxia, under IDF2005 ATP III 2005 AHA and CDs2004 definition. METHODS: Stratified cluster sampling methods was used and the participants were interviewed by trained health workers under a structured questionnaire. The number of research subjects was 1612. Fasting plasma glucose (FPG), blood lipids, body mass index (BMI) and blood pressure (BP) of all samples (1612 subjects) were measured. and related data was analysed by IDF2005, ATP III 2005 AHA, as well as CDs2004 definition of MS. RESULTS: The age-standardized prevalence of MS was 15.00% by ATP III 2005 AHA definition and 11.80% by IDF 2005 definition and 6.71% by CDs 2004 definition, respectively. Based on IDF 2005 and ATP III 2005 AHA definition, women had higher prevalence than men (16.3% vs. 5.4%, 18.9% vs. 8.9%, P < 0.01), but there was no significant difference (P > 0.05) between them according to the CDs definition. MS prevalence among Hui (Muslim) ethnic group was higher than Han ethnic group (P < 0.05). The prevalence of MS increased with age in all samples and the prevalence of MS started at age of 35 in Hui ethnic group, higher than in Han ethnic group. There was no significant difference in the prevalence rates of MS between male Hui ethnic group and male Han ethnic group (P > 0.05). The prevalence of MS in female Hui ethnic group was higher than Han ethnic group females (P < 0.05). CONCLUSION: The prevalence of MS was high in the rural adult residents, in Ningxia. Clusters of MS components were commonly seen, and the main disorder appeared in lipid abnormalities and abnormal glucose metabolism. It is necessary to discuss that the cut off point of central obesity for the waist circumference diagnostic criteria of MS in different ethnic groups in China. Big differences on the components of MS were seen in different ethnic groups. It is important to choose suitable MS definition for prevention of MS and to reduce the incidence of cardiovascular disease.