Genomic analysis reveals a cryptic pangolin species.

Eight extant species of pangolins are currently recognized. Recent studies found that two mitochondrial haplotypes identified in confiscations in Hong Kong could not be assigned to any known pangolin species, implying the existence of a species. Here, we report that two additional mitochondrial haplotypes identified in independent confiscations from Yunnan align with the putative species haplotypes supporting the existence of this mysterious species/population. To verify the new species scenario we performed a comprehensive analysis of scale characteristics and 138 whole genomes representing all recognized pangolin species and the cryptic new species, 98 of which were generated here. Our morphometric results clearly attributed this cryptic species to Asian pangolins (Manis sp.) and the genomic data provide robust and compelling evidence that it is a pangolin species distinct from those recognized previously, which separated from the Philippine pangolin and Malayan pangolin over 5 Mya. Our study provides a solid genomic basis for its formal recognition as the ninth pangolin species or the fifth Asian one, supporting a new taxonomic classification of pangolins. The effects of glacial climate changes and recent anthropogenic activities driven by illegal trade are inferred to have caused its population decline with the genomic signatures showing low genetic diversity, a high level of inbreeding, and high genetic load. Our finding greatly expands current knowledge of pangolin diversity and evolution and has vital implications for conservation efforts to prevent the extinction of this enigmatic and endangered species from the wild.

Carbon Metabolism of a Soilborne Mn(II)-Oxidizing Escherichia coli Isolate Implicated as a Pronounced Modulator of Bacterial Mn Oxidation.

Mn(II)-oxidizing microorganisms are generally considered the primary driving forces in the biological formation of Mn oxides. However, the mechanistic elucidation of the actuation and regulation of Mn oxidation in soilborne bacteria remains elusive. Here, we performed joint multiple gene-knockout analyses and comparative morphological and physiological determinations to characterize the influence of carbon metabolism on the Mn oxide deposit amount (MnODA) and the Mn oxide formation of a soilborne bacterium, Escherichia coli MB266. Different carbon source substances exhibited significantly varied effects on the MnODA of MB266. A total of 16 carbon metabolism-related genes with significant variant expression levels under Mn supplementation conditions were knocked out in the MB266 genome accordingly, but only little effect on the MnODA of each mutant strain was accounted for. However, a simultaneous four-gene-knockout mutant (namely, MB801) showed an overall remarkable MnODA reduction and an initially delayed Mn oxide formation compared with the wild-type MB266. The assays using scanning/transmission electron microscopy verified that MB801 exhibited not only a delayed Mn-oxide aggregate processing, but also relatively smaller microspherical agglomerations, and presented flocculent deposit Mn oxides compared with normal fibrous and crystalline Mn oxides formed by MB266. Moreover, the Mn oxide aggregate formation was highly related to the intracellular ROS level. Thus, this study demonstrates that carbon metabolism acts as a pronounced modulator of MnODA in MB266, which will provide new insights into the occurrence of Mn oxidation and Mn oxide formation by soilborne bacteria in habitats where Mn(II) naturally occurs.

Identification of the Genes of the Plant Pathogen Pseudomonas syringae MB03 Required for the Nematicidal Activity Against Caenorhabditis elegans Through an Integrated Approach.

Nematicidal potential of the common plant pathogen Pseudomonas syringae has been recently identified against Caenorhabditis elegans. The current study was designed to investigate the detailed genetic mechanism of the bacterial pathogenicity by applying comparative genomics, transcriptomics, mutant library screening, and protein expression. Results showed that P. syringae strain MB03 could kill C. elegans in the liquid assay by gut colonization. The genome of P. syringae MB03 was sequenced and comparative analysis including multi locus sequence typing, and genome-to-genome distance placed MB03 in phylogroup II of P. syringae. Furthermore, comparative genomics of MB03 with nematicidal strains of Pseudomonas aeruginosa (PAO1 and PA14) predicted 115 potential virulence factors in MB03. However, genes for previously reported nematicidal metabolites, such as phenazine, pyochelin, and pyrrolnitrin, were found absent in the MB03 genome. Transcriptomics analysis showed that the growth phase of the pathogen considerably affected the expression of virulence factors, as genes for the flagellum, glutamate ABC transporter, phoP/phoQ, fleS/fleR, type VI secretion system, and serralysin were highly up-regulated when stationary phase MB03 cells interacted with C. elegans. Additionally, screening of a transposon insertion mutant library led to the identification of other nematicidal genes such as acnA, gltP, oprD, and zapE. Finally, the nematicidal activity of selected proteins was confirmed by heterologous expression in Escherichia coli.

LPCAT1 reprogramming cholesterol metabolism promotes the progression of esophageal squamous cell carcinoma.

Tumor cells require high levels of cholesterol for membrane biogenesis for rapid proliferation during development. Beyond the acquired cholesterol from low-density lipoprotein (LDL) taken up from circulation, tumor cells can also biosynthesize cholesterol. The molecular mechanism underlying cholesterol anabolism in esophageal squamous cell carcinoma (ESCC) and its effect on patient prognosis are unclear. Dysregulation of lipid metabolism is common in cancer. Lysophosphatidylcholine acyltransferase 1 (LPCAT1) has been implicated in various cancer types; however, its role in esophageal squamous cell carcinoma (ESCC) remains unclear. In this study, we identified that LPCAT1 is highly expressed in ESCC and that LPCAT1 reprograms cholesterol metabolism in ESCC. LPCAT1 expression was negatively correlated with patient prognosis. Cholesterol synthesis in ESCC cells was significantly inhibited following LPCAT1 knockdown; cell proliferation, invasion, and migration were significantly reduced, along with the growth of xenograft subcutaneous tumors. LPCAT1 could regulate the expression of the cholesterol synthesis enzyme, SQLE, by promoting the activation of PI3K, thereby regulating the entry of SP1/SREBPF2 into the nucleus. LPCAT1 also activates EGFR leading to the downregulation of INSIG-1 expression, facilitating the entry of SREBP-1 into the nucleus to promote cholesterol synthesis. Taken together, LPCAT1 reprograms tumor cell cholesterol metabolism in ESCC and can be used as a potential treatment target against ESCC.

Synthesis of MnO/C/Co3O4 nanocomposites by a Mn2+-oxidizing bacterium as a biotemplate for lithium-ion batteries.

The biotemplate and bioconversion strategy represents a sustainable and environmentally friendly approach to material manufacturing. In the current study, biogenic manganese oxide aggregates of the Mn2+-oxidizing bacterium Pseudomonas sp. T34 were used as a precursor to synthesize a biocomposite that incorporated Co (CMC-Co) under mild shake-flask conditions based on the biomineralization process of biogenic Mn oxides and the characteristics of metal ion subsidies. X-ray photoelectron spectroscopy, phase composition and fine structure analyses demonstrated that hollow MnO/C/Co3O4 multiphase composites were fabricated after high-temperature annealing of the biocomposites at 800°C. The cycling and rate performance of the prepared anode materials for lithium-ion batteries were compared. Due to the unique hollow structure and multiphasic state, the reversible discharge capacity of CMC-Co remained at 650 mAh g-1 after 50 cycles at a current density of 0.1 Ag-1, and the coulombic efficiency remained above 99% after the second cycle, indicating a good application potential as an anode material for lithium-ion batteries.

Synthesis of MnO/C/NiO-Doped Porous Multiphasic Composites for Lithium-Ion Batteries by Biomineralized Mn Oxides from Engineered Pseudomonas putida Cells.

A biotemplated cation-incoporating method based on bacterial cell-surface display technology and biogenic Mn oxide mineralization process was developed to fabricate Mn-based multiphasic composites as anodes for Li-ion batteries. The engineered Pseudomonas putida MB285 cells with surface-immobilized multicopper oxidase serve as nucleation centers in the Mn oxide biomineralization process, and the Mn oxides act as a settler for incorporating Ni ions to form aggregates in this process. The assays using X-ray photoelectron spectroscopy, phase compositions, and fine structures verified that the resulting material MnO/C/NiO (CMB-Ni) was porous multiphasic composites with spherical and porous nanostructures. The electrochemical properties of materials were improved in the presence of NiO. The reversible discharge capacity of CMB-Ni remained at 352.92 mAh g-1 after 200 cycles at 0.1 A g-1 current density. In particular, the coulombic efficiency was approximately 100% after the second cycle for CMB-Ni.

Vicagrel enhances aspirin-induced inhibition of both platelet aggregation and thrombus formation in rodents due to its decreased metabolic inactivation.

Both aspirin and vicagrel are effective antiplatelet drugs, with the potential for concomitant use as another dual-antiplatelet therapy for the prevention of recurrent thrombotic or ischemic events. Because they both are the substrates of carboxylesterase 2 (CES2), aspirin attenuated the metabolic activation of and platelet response to vicagrel in mice treated with the two drugs concomitantly. In this study, we sought to clarify whether vicagrel could affect platelet responses to aspirin and their underlying mechanisms. Plasma levels of aspirin and salicylic acid were determined by liquid chromatography-tandem mass spectrometry, inhibition of arachidonic acid (AA)-induced whole-blood platelet aggregation by aspirin was assessed with an aggregometer, and their antithrombotic effects were evaluated by arteriovenous shunt thrombosis model. The results showed that concomitant use of vicagrel (5, 10, or 20 mg/kg) led to an average of 55% and 77% increases in systemic exposure of aspirin (Cmax and AUC0-t) and 2.8-fold increase in suppression of AA-induced platelet aggregation in mice when compared with use of aspirin alone. In the rat thrombus formation model, vicagrel (1 mg/kg) enhanced inhibition of thrombosis formation by aspirin (5 mg/kg), but not vice versa. We conclude that vicagrel increases platelet responses to aspirin and also enhances inhibition of thrombus formation of aspirin due to decreased CES2-catalyzed aspirin inactivation in rodents, and that an integrated net effect on thrombus formation in vivo is superior to inhibition of AA- or ADP-induced platelet aggregation ex vivo by either of the two drugs if taken concomitantly.

Invasive-noninvasive Sequential Ventilation for the Treatment of Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

BACKGROUND: The study aimed to evaluate the efficacy and safety of invasivenoninvasive sequential ventilation versus invasive ventilation in the treatment of Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD). METHODS: PubMed, Cochrane, Embase, Wanfang, CNKI, VIP database were searched by the index words to identify the qualified RCTs, and relevant literature sources were also searched. The latest research was conducted in June 2017. Relative Risks (RR), and Mean Difference (MD) along with 95% confidence interval (95% CI) were used to analyze the main outcomes. RESULTS: Twenty-nine RCTs were involved in this analysis of 1061 patients in the invasivenoninvasive sequential ventilation group (In-non group) and 1074 patients in the invasive ventilation group (In group). The results indicated that compared with the invasive ventilation, invasive-noninvasive sequential ventilation would significantly decrease the incidence of VAP (RR:0.20, 95%CI: 0.16-0.26), mortality (RR:0.38, 95%CI: 0.26-0.55), reintubation (RR:0.39, 95%CI: 0.27-0.55); and statistically reduced the duration of invasive ventilation (MD:-9.23, 95%CI: -10.65, -7.82), the total duration of mechanical ventilation (MD:-4.91, 95%CI: -5.99, -3.83), and the length of stay in the ICU (MD:-5.10, 95%CI: -5.43, -4.76). CONCLUSION: The results demonstrated that the application of noninvasive sequential ventilation after invasive ventilation at the pulmonary infection control window has a significant influence on VAP incidence, mortality, and the length of stay in the ICU, but further well-designed, adequately powered RCTs are required to validate the conclusion.

Enhanced responsiveness of platelets to vicagrel in IL-10-deficient mice through STAT3-dependent up-regulation of the hydrolase arylacetamide deacetylase in the intestine.

BACKGROUND AND PURPOSE: Vicagrel is a novel promising antiplatelet drug designed for overcoming clopidogrel resistance. There is limited evidence indicating that exogenous IL-10 suppresses CYP3A4 activity in healthy subjects and that IL-10 knockout (KO) mice exhibit increased clopidogrel bioactivation compared with wild-type (WT) mice. In this study, we sought to determine whether IL-10 could play an important role in the metabolism of and platelet response to vicagrel in mice. EXPERIMENTAL APPROACH: IL-10 KO and WT mice were administered vicagrel, then their plasma H4 (active metabolite of vicagrel) concentrations were determined by LC-MS/MS, and inhibition of ADP-induced whole-blood platelet aggregation by vicagrel was assessed with an aggregometer. The mRNA and protein levels of several relevant genes between IL-10 KO and WT mice were measured by qRT-PCR and Western blots, respectively. Intestinal Aadac protein levels were measured in IL-10 WT mice injected i.p. with vehicle control, Stattic, or BAY 11-7082. KEY RESULTS: Compared with WT mice, IL-10 KO mice exhibited significantly increased plasma levels of H4 and enhanced platelet responses to vicagrel, as well as significantly higher mRNA and protein levels of arylacetamide deacetylase (Aadac) in the intestine. In WT mice, STAT3, not NF-κB, mediated Aadac expression in the intestine. CONCLUSIONS AND IMPLICATIONS: IL-10 suppresses metabolic activation of vicagrel through down-regulation of Aadac in mouse intestine in a STAT3-dependent manner and, consequently, attenuates platelet responses to vicagrel, suggesting that the antiplatelet effect of vicagrel may be modulated by changes in plasma IL-10 levels in relevant clinical settings.

Aspirin Attenuates the Bioactivation of and Platelet Response to Vicagrel in Mice.

Vicagrel, a novel acetate analogue of clopidogrel, exerts more potent antiplatelet effect than clopidogrel in rodents. Relevant evidence indicated that aspirin and vicagrel are the drug substrate for carboxylesterase 2. Accordingly, it is deduced that concomitant use of aspirin could attenuate the bioactivation of and platelet response to vicagrel. To clarify whether there could be such an important drug-drug interaction, the differences in both the formation of vicagrel active metabolite H4 and the inhibition of adenosine diphosphate-induced platelet aggregation by vicagrel were measured and compared between mice treated with vicagrel alone or in combination with aspirin. The plasma H4 concentration was determined by liquid chromatography-tandem mass spectrometry, and the inhibition of platelet aggregation by vicagrel was assessed by whole-blood platelet aggregation. Compared with vicagrel (2.5 mg·kg) alone, concurrent use of aspirin (5, 10, or 20 mg·kg) significantly decreased systemic exposure of H4, an average of 38% and 41% decrease in Cmax and AUC0-∞ in mice when in combination with aspirin at 10 mg·kg, respectively. Furthermore, concomitant use of aspirin (10 mg·kg) and vicagrel (2.5 mg·kg) resulted in an average of 66% reduction in the inhibition of adenosine diphosphate-induced platelet aggregation by vicagrel. We conclude that aspirin significantly attenuates the formation of vicagrel active metabolite H4 and platelet response to vicagrel in mice, and that such an important drug-drug interaction would appear in clinical settings if vicagrel is taken with aspirin concomitantly when marketed in the future.

Human UGT2B7 is the major isoform responsible for the glucuronidation of clopidogrel carboxylate.

Clopidogrel is predominantly hydrolyzed to clopidogrel carboxylic acid (CCA) by carboxylesterase 1, and subsequently CCA is glucuronidated to clopidogrel acyl glucuronide (CAG) by uridine diphosphate-glucuronosyltransferases (UGTs); however, the UGT isoenzymes glucuronidating CCA remain unidentified to date. In this study, the glucuronidation of CCA was screened with pooled human liver microsomes (HLMs) and 7 human recombinant UGT (rUGT) isoforms. Results indicated that rUGT2B7 exhibited the highest catalytical activity for the CCA glucuronidation as measured with a mean Vmax value of 120.9 pmol/min/mg protein, 3- to 12-fold higher than that of the other rUGT isoforms tested. According to relative activity factor approach, the relative contribution of rUGT2B7 to CCA glucuronidation was estimated to be 58.6%, with the minor contributions (3%) from rUGT1A9. Moreover, the glucuronidation of CCA followed Michaelis-Menten kinetics with a mean Km value of 372.9 µM and 296.4 µM for pooled HLMs and rUGT2B7, respectively, showing similar affinity for both. The formation of CAG was significantly inhibited by azidothymidine and gemfibrozil (well-characterized UGT2B7 substrates) in a concentration-dependent manner, or by fluconazole (a typical UGT2B7-selective inhibitor) in a time-dependent manner, for both HLMs and rUGT2B7, respectively. In addition, CCA inhibited azidothymidine glucuronidation (catalyzed almost exclusively by UGT2B7) by HLMs and rUGT2B7 in a concentration-dependent manner, indicating that CCA is a substrate of UGT2B7. These results reveal that UGT2B7 is the major enzyme catalyzing clopidogrel glucuronidation in the human liver, and that there is the potential for drug-drug interactions between clopidogrel and the other substrate drugs of UGT2B7.

Mrp3 Transports Clopidogrel Acyl Glucuronide from the Hepatocytes into Blood.

Clopidogrel acyl glucuronide (CLP-G) is a major phase II metabolite of clopidogrel generated in the liver for further excretion into urine; however, it is unclear whether CLP-G transports from hepatocytes into blood. Because multidrug resistance-associated protein 3 (MRP3) is predominantly expressed in the sinusoidal side of hepatocytes and preferentially transports glucuronide conjugates of drug metabolites from hepatocytes into bloodstream, we hypothesized that MRP3 could be such an efflux transporter for CLP-G. In this study, we compared the liver-to-plasma ratios of clopidogrel and its metabolites (including CLP-G) between Abcc3 (ATP-binding cassette, subfamily C, member 3) knockout (KO) and wild-type (WT) mice. We also evaluated the ATP-dependent uptake of clopidogrel and CLP-G as well as estradiol-17ß-d-glucuronide into human recombinant MRP3 inside-out membrane vesicles in the presence or absence of ATP. The results indicated that the liver-to-plasma ratio of CLP-G was 11-fold higher in KO mice than in WT mice, and that uptake of CLP-G (1 or 10 µM each) into the membrane vesicles was 11.8- and 3.8-fold higher in the presence of ATP than in the presence of AMP, respectively. We conclude that Mrp3 transports CLP-G from the hepatocytes into blood in an ATP-dependent manner.

Annexin-A1 enhances breast cancer growth and migration by promoting alternative macrophage polarization in the tumour microenvironment.

Macrophages are potent immune cells with well-established roles in the response to stress, injury, infection and inflammation. The classically activated macrophages (M1) are induced by lipopolysaccharide (LPS) and express a wide range of pro-inflammatory genes. M2 macrophages are induced by T helper type 2 cytokines such as interleukin-4 (IL4) and express high levels of anti-inflammatory and tissue repair genes. The strong association between macrophages and tumour cells as well as the high incidences of leukocyte infiltration in solid tumours have contributed to the discovery that tumour-associated macrophages (TAMs) are key to tumour progression. Here, we investigated the role of Annexin A1 (ANXA1), a well characterized immunomodulatory protein on macrophage polarization and the interaction between macrophages and breast cancer cells. Our results demonstrate that ANXA1 regulates macrophage polarization and activation. ANXA1 can act dually as an endogenous signalling molecule or as a secreted mediator which acts via its receptor, FPR2, to promote macrophage polarization. Furthermore, ANXA1 deficient mice exhibit reduced tumour growth and enhanced survival in vivo, possibly due to increased M1 macrophages within the tumor microenvironment. These results provide new insights into the molecular mechanisms of macrophage polarization with therapeutic potential to suppress breast cancer growth and metastasis.

Circulating 25-hydroxyvitamin D level and prognosis of lung cancer patients: A systematic review and meta-analysis.

BACKGROUND: Previous studies suggested a possible influence of circulating 25-hydroxyvitamin D [25(OH)D] level on the prognosis of lung cancer patients, but conflicting findings were reported. A systematic review and meta-analysis was thus conducted to comprehensively assess the influence of circulating 25(OH)D level on the prognosis of lung cancer patients. METHODS: Prospective or retrospective cohort studies assessing the influence of circulating 25(OH)D level on the prognosis of lung cancer patients were considered eligible. Hazard Ratios (HR) were pooled using meta-analysis. RESULTS: Eight studies with 2166 lung cancer patients were included. Meta-analysis of unadjusted HRs from four studies showed low circulating 25(OH)D level was significantly correlated with poor overall survival in lung cancer (HR=1.30, 95%CI 1.08-1.55, P=0.004). Meta-analysis of adjusted HRs from eight studies suggested that low circulating 25(OH)D level was not significantly correlated with poor overall survival (HR=1.25; P=0.13). However, sensitivity analysis suggested an obvious change in the pooled HRs when excluding single study by turns. When the study by Liu et al. was omitted, low circulating 25(OH)D level was significantly correlated with poor overall survival (HR=1.34; P=0.04). CONCLUSION: The present systematic review and meta-analysis suggested a correlation between low circulating 25(OH)D level and poor overall survival in lung cancer. More studies are needed to further validate the finding above.

Effect of salvianolic acid A and C compatibility on inflammatory cytokines in rats with unilateral ureteral obstruction.

OBJECTIVE: To investigate the effect of salvianolic acid A and C component molecules, which are involved in drug compatibility, on inflammatory cytokine expression that affects human chemokine ligand 5 (CCL5) and chemokine ligand 10 (CXCL10) levels in rats with unilateral ureteral obstruction (UUO). METHODS: Fifty Sprague Dawley rats were randomly divided into five groups: normal, model, salvianolic acid A, salvianolic acid C and salvianolic acid A and C groups. The normal group was used as the control, and the other groups of rats had a UUO model established. The control group had free access to food and water, and the other groups received the corresponding drugs for 2 weeks. After the last administration, urine ß2-microglobulin (ß 2-MG) and N-acetyl-ß-D-glucosaminidase (NAG) levels were analyzed. After 24 h, all rats were sacrificed and the serum was analyzed for creatinine (Cr) and blood urea nitrogen (BUN) levels. Rat kidneys were removed, and CCL5 and CXCL10 inflammatory cytokine mRNA expression was measured using real-time fluorescent quantitative reverse transcription-polymerase chain reaction (RT-PCR). Kidney fibrosis was observed using hematoxylin-eosin (HE) staining and Masson trichrome staining. RESULTS: In the salvianolic acid A and salvianolic acid C treatment groups, serum Cr and urine NAG levels were significantly lower than in the model group (both P < 0.05). In all treatment groups, urine ß2-MG levels were significantly lower than in the model group (all P < 0.05). Compared with model group, the pathological changes and collagen deposition improved to varying degrees (both P < 0.05). CCL5 and CXCL10 mRNA expression decreased to different degrees compared with the model group (both P < 0.05). CONCLUSION: Salvianolic acid A and C are component molecules of drug compatibility, and they may protect renal function and improve tubular function and renal pathology to a certain degree in UUO. This improvement may be related to a reduction in inflammatory cytokines CCL5 and CXCL10 secretion in the UUO rat kidney.

Alu-directed transcriptional regulation of some novel miRNAs.

BACKGROUND: Despite many studies on the biogenesis, molecular structure and biological functions of microRNAs, little is known about the transcriptional regulatory mechanisms controlling the spatiotemporal expression pattern of human miRNA gene loci. Several lines of experimental results have indicated that both polymerase II (Pol-II) and polymerase III (Pol-III) may be involved in transcribing miRNAs. Here, we assessed the genomic evidence for Alu-directed transcriptional regulation of some novel miRNA genes in humans. Our data demonstrate that the expression of these Alu-related miRNAs may be modulated by Pol-III. RESULTS: We present a comprehensive exploration of the Alu-directed transcriptional regulation of some new miRNAs. Using a new computational approach, a variety of Alu-related sequences from multiple sources were pooled and filtered to obtain a subset containing Alu elements and characterized miRNA genes for which there is clear evidence of full-length transcription (embedded in EST). We systematically demonstrated that 73 miRNAs including five known ones may be transcribed by Pol-III through Alu or MIR. Among the new miRNAs, 33 were determined by high-throughput Solexa sequencing. Real-time TaqMan PCR and Northern blotting verified that three newly identified miRNAs could be induced to co-express with their upstream Alu transcripts by heat shock or cycloheximide. CONCLUSION: Through genomic analysis, Solexa sequencing and experimental validation, we have identified candidate sequences for Alu-related miRNAs, and have found that the transcription of these miRNAs could be governed by Pol-III. Thus, this study may elucidate the mechanisms by which the expression of a class of small RNAs may be regulated by their upstream repeat elements.

[Effects of delayed opening of infarct-related artery on late left ventricular remodeling in patients with acute anterior myocardial infarction].

OBJECTIVE: To assess the effect of delayed opening of the infarct-related artery (IRA) by percutaneous coronary intervention (PCI) on the late left ventricular remodeling after acute anterior myocardial infarction (AAMI). METHODS: Sixty four patients with initial Q-wave AAMI and with the total occluded IRA conformed by angiogram at 9.1 +/- 2.3 (2 - 14) days after the onset were divided into successful PCI group and control group (not receiving PCI or the IRA not re-opened). Two-D echocardiogram was performed at acute phase (about 3 weeks), 2 and 6 months after onset of AAMI respectively to detect the left ventricular function and left ventricular wall motion abnormality (VWMA). The total congestive heart failure events were recorded during 6 months follow-up. RESULTS: VWMA scores, left ventricular ejection fraction (LVEF), left ventricular end-diastolic and end-systolic volume indexes (LVEDVI and LVESVI) were similar in 2 groups at acute phase and 2 months after the onset of AAMI. There were no differences between the parameters above at acute phase and 2 months in each group too. VWMA scores and LVEF did not changed significantly at 6 months in each group compared with those at acute phase and 2 months (P > 0.05). But LVEDVI and LVESVI were significantly smaller in the successful PCI group than those in the control group (P < 0.01, P < 0.05). The rate of congestive heart failure events was 19% in control group and 2.0% in successful PCI group (P > 0.05) respectively. CONCLUSIONS: Delayed opening of IRA in AAMI could prevent the late phase but not the early phase of left ventricular remodeling after AMI.

A QSAR model of PAHs carcinogenesis based on thermodynamic stabilities of biactive sites.

Polycyclic aromatic hydrocarbons (PAHs) have been adopted to study the carcinogenesis of chemicals experimentally and theoretically. A model of carcinogenic activity of 48 PAHs was obtained based on the calculated relative thermodynamic stabilities of epoxide and carbonium intermediates of the PAHs. Using both epoxyl-energy and cationized-energy of two active sites, the model reasonably predicts the carcinogenic activity of these PAHs and shows a good ability to distinguish between carcinogenic and noncarcinogenic PAHs. Furthermore, the model suggests that double active sites and their distance characteristics are important factors in the chemical carcinogenesis of PAHs. The physical meaning of the energies corresponding addition reactions with DNA is also discussed.