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Tao Liu,1,* Ronghua Zuo,2,* Jia Song,1,* Jia Wang,3 Zhijian Zhu,1 Lifang Sun,1 Shasha Wang,1 Baoyin Li,1 Yesheng Pan,1 Bing Wang1 1Department of Cardiology, Jinshan Branch of Shanghai Sixth People’s Hospital, Shanghai, 201500, People’s Republic of China; 2Department of Anesthesiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, People’s Republic of China; 3Department of Nephrology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bing Wang, Department of Cardiology, Jinshan Branch of Shanghai Sixth People’s Hospital, Shanghai, 201500, People’s Republic of China, Email wangbing860716@163.comObjective: The association between serum uric acid (sUA) and incident abdominal aortic calcification (AAC), and severe abdominal aortic calcification (SAAC) in the general population of the United States (US) is unclear. Therefore, this research aimed to investigate the association between sUA and the risk of AAC and SAAC.Methods: Individuals from National Health and Nutrition Examination Survey (NHANES) database were analyzed cross-sectionally between 2013 and 2014. The restricted cubic spline (RCS), multivariable logistic regression model and subgroup analysis were utilized to evaluate the correlation between sUA and incident AAC, and SAAC. In addition, generalized additive models with smooth functions were employed to survey the relationship between sUA and the degree of AAC.Results: This study included 3016 individuals from the NHANES database. According to the RCS plot, sUA levels were associated with the risk of AAC/SAAC in a U-shaped pattern in the US population. The degree of calcification decreased at first and then increased with the increase in the sUA level.Conclusion: Close monitoring and adequate control of sUA levels in the US general population may reduce the risk of AAC and SAAC.Keywords: abdominal aortic calcification, serum uric acid, cross-sectional study, China, United States

In the present study, we characterized a novel regulator MtTRC-1 in M. thermophila , which regulated cellulase production through direct transcriptional regulation of the Mthac-1 and Mtcbh-1 genes. Our data demonstrated that MtHAC-1 is a key factor for the cellulase secretion capacity of M. thermophila .

Association between neutrophil-to-lymphocyte ratio (NLR) on admission and poor prognosis in patients with acute heart failure (AHF) has been well established. However, the relationship between dynamic changes in NLR and in-hospital mortality in AHF patients has not been studied. Our purpose was to determine if an early change in NLR within the first week after AHF patients was admitted to intensive care unit (ICU) was associated with in-hospital mortality. Data from the medical information mart for intensive care IV (the MIMIC-IV) database was analyzed. The effect of baseline NLR on in-hospital mortality in critical patients with AHF was evaluated utilizing smooth curve fitting and multivariable logistic regression analysis. Moreover, comparison of the dynamic change in NLR among survivors and non-survivors was performed using the generalized additive mixed model (GAMM). There were 1169 participants who took part in the present study, 986 of whom were in-hospital survivors and 183 of whom were in-hospital non-survivors. The smooth curve fitting revealed a positive relationship between baseline NLR and in-hospital mortality, and multivariable logistic regression analysis indicated that baseline NLR was an independent risk factor for in-hospital mortality (OR 1.04, 95% CI 1.02,1.07, P-value = 0.001). After adjusting for confounders, GAMM showed that the difference in NLR between survivors and non-survivors grew gradually during the first week after ICU admission, and the difference grew by an average of 0.51 per day (β = 0.51, 95% CI 0.45–0.56, P-value

Interferons and chemokines-mediated immune responses are two general antiviral programs of the innate immune system in response to viral infections and have recently emerged as important players in systemic metabolism. In this study, we found that the chemokine CCL4 is negatively regulated by glucose metabolism and avian leukosis virus subgroup J (ALV-J) infection in chicken macrophages. This immune response is defined by low expression levels of CCL4 by high glucose treatment or ALV-J infection. Moreover, the ALV-J envelope protein is responsible for CCL4 inhibition. We further confirmed that CCL4 can inhibit glucose metabolism and ALV-J replication in chicken macrophages. The present study provides novel insights into the antiviral defence mechanism and metabolic regulation of the chemokine CCL4 in chicken macrophages.

Extreme weather like typhoon leaves significantly terrible influence on the stability of power grid in the coastal area. A high-voltage transmission line includes hundreds of towers and usually stretches hundreds of kilometers. It is not economical to install typhoon monitoring system throughout the transmission line. This paper proposes a typhoon inversion method (TIM) for transmission line which utilizes engineering wind field model and only requires monitoring data from a few towers. The developed method is called YanMeng wind field (YM) with directional mutation genetic algorithm (DMGA) for transmission lines, or YM-DMGA method. DMGA utilizes real-time monitoring data, and improves simulation accuracy of average wind speed by dynamically optimizing two critical parameters $B$ and $z_{0}$ in wind field model, which is a great improvement over the traditional YM model relying on historical data. The TIM is mainly composed of three parts, the meteorological monitoring system (MMS), the YM-DMGA model, and the software system. The TIM collects real-time measured wind data of particular monitoring stations through the MMS. Meanwhile, wind data of the whole transmission line is simulated using the YM-DMGA and displayed by the software system. Then the method proposed is verified to be effective in three aspects. First of all, the YM-DMGA method has great enhancement in accuracy, for the coefficient of determination $R_{square}$ increases from 0.811 to 0.986. Secondly, DMGA in the method has quicker convergent speed than typical GA, with fitness converged in the 269th epoch, earlier than that for typical GA, 656th epoch. Lastly, DMGA has better optimal fitness value of 0.6239, bigger than that of typical GA, 0.5891. At the end of the paper, an application of the method to an 110kV double-circuit transmission line is presented to reveal the risk under the impact of the super typhoon Rammasun.

Objective: Myocardial ischemia is the stoppage or insufficiency of blood flow to the myocardium, depriving cells of oxygen supply which leads to their apoptosis or death. Currently, the management of patients has improved, making it possible to reduce myocardial infarction injury with new strategies of reperfusion and pharmacologic treatment. Methods: A rat model of myocardial ischemia and reperfusion injury (MIRI) was created and subjected to cryptotanshinone (CRY) with or without JAK1 inhibitor filgotinib (FILGO) treatment. H&E staining was used for histopathologic evaluation of heart injury, and TTC staining was employed for evaluation of the infarct size. Western blotting and immunofluorescence were used to measure the protein expression and qRT-PCR for determining mRNA expression. Results: CRY significantly reduced the area of the infarct, the number of apoptotic cells, and the concentrations of lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) induced by ischemia/reperfusion (I/R). Subsequent analysis showed that CRY repressed the expression of caspase-12, CHOP, and GRP78, but enhanced the phosphorylation of JAK and STAT3. However, FILGO treatment markedly abolished the beneficial effect of CRY pretreatment on cardiomyocyte damage, apoptosis, cardiac function, and inhibition of endoplasmic reticulum stress (ERS)-dependent apoptosis marker proteins. Conclusion: CRY may alleviate MIRI by inhibiting ERS-dependent apoptosis by activating the JAK1/STAT3 signaling pathway.

Foot-and-mouth disease virus (FMDV) is a highly contagious virus that causes severe vesicular disease of cloven-hoofed animals. Various endocytosis mechanisms are involved in the entry of FMDV after binding to the integrin and heparan sulfate (HS) receptors. However, the mechanism of FMDV using other unknown receptors to enter the cells remains unclear. Here, we reported that the endocytosis and endosomal pathways are employed by FMDV to invade the Chinese hamster ovary cell line (CHO-677) without the integrin and HS receptors. We demonstrated that the internalization of FMDV into CHO-677 cells was abrogated by chlorpromazine, an inhibitor of clathrin-mediated endocytosis. Knockdown of the clathrin heavy chain decreased the viral protein abundance. Incubation of the CHO-677 cells with the inhibitors of caveolae-mediated endocytosis or transfection by caveolin-1 siRNA also limited FMDV replication. In addition, we determined that the acidic environment and the existence of dynamin were essential for FMDV infection in CHO-677 cells. The endosomal proteins Rab5 (early endosome) and Rab7 (late endosome), but not Rab11 (recycling endosome), were utilized by FMDV during infection. These data provide a new entry model of FMDV by unknown receptors which will help to better understand the pathogenesis mediated by FMDV.

Background Hepatocellular carcinoma (HCC) with high heterogeneity is one of the most frequent malignant tumors throughout the world. However, there is no research to establish a ferroptosis-related lncRNAs (FRlncRNAs) signature for the patients with HCC. Therefore, this study was designed to establish a novel FRlncRNAs signature to predict the survival of patients with HCC. Method The expression profiles of lncRNAs were acquired from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. FRlncRNAs co-expressed with ferroptosis-related genes were utilized to establish a signature. Cox regression was used to construct a novel three FRlncRNAs signature in the TCGA cohort, which was verified in the GEO validation cohort. Results Three differently expressed FRlncRNAs significantly associated with prognosis of HCC were identified, which composed a novel FRlncRNAs signature. According to the FRlncRNAs signature, the patients with HCC could be divided into low- and high-risk groups. Patients with HCC in the high-risk group displayed shorter overall survival (OS) contrasted with those in the low-risk group (P P = 0.045 in GEO cohort). This signature could serve as a significantly independent predictor in Cox regression (multivariate HR > 1, P 1, P Conclusion The three FRlncRNAs might be potential therapeutic targets for patients, and their signature could be utilized for prognostic prediction in HCC.

Steel lattice towers are commonly used as supporting structures for overhead transmission lines. Extreme wind conditions like typhoons can cause significant damage on those steel towers and consequently jeopardize the safe operation of transmission lines. In the line sections where a river crossing is unavoidable, the steel lattice towers are designed to be much taller and stronger than regular towers owing to safety and operation considerations. In previous typhoon events in Hainan Province of China, none of the installed river-crossing towers have collapsed or experienced significant damages, except in the aftermath of super typhoon Rammasun in 2014, when two 95-m tall river-crossing suspension towers collapsed. This paper presents the structural failure analysis of these two collapsed lattice steel transmission towers: The improved genetic algorithm (IGA) was applied to solve the typhoon wind field model for improved resolution of wind records measured during the Rammasun event and based on of 10-min average wind speeds. The IGA used the field measurement data to generate time-varying typhoon key parameters that lead to a more accurate prediction of the wind field than the conventional method. Then a systematic procedure was developed to investigate the failure mechanism of steel lattice towers under fluctuating wind loads combined with rain loads with consideration of the aerodynamic characteristics of the transmission tower-line system. The results show that the root-cause of the structural failure of the two transmission towers was overstressing of the tower main leg members in the second panel above the ground. Based on the numerical simulation of typhoon wind loads and the structural failure analysis procedure applied in this study, a general reinforcement method of river-crossing towers is proposed and the implementation of a typhoon warning method is recommended to identify the potential risks in transmission lines and formulate corresponding typhoon emergency plans to reduce the losses caused by typhoons.

The S-doped MoO2/C nanofibers (S-doped carbon and MoO2) are prepared through a sulfuration reaction. For one thing, the introduction of sulfur into the carbon structure can significantly enhance charge transportation velocity and provide more additional activity sites to accommodate Na+. For another, it is able for molybdenum disulfide with higher theoretical capacity to promote the Na+ storage. So we investigate the S-doped MoO2/C nanofibers as for SIBs, the electrode yields a high reversible capacity at 0.1 A g−1 after 50 cycles (269 mA h g−1). Even at 5 A g−1, it maintains superior long-term cycling stability and holds 86 mA h g−1 over 1200th cycle. The whole synthetic process is high yielding, eco-friendly, making it suitable for large-scale production applications.

Process research, development, and manufacture of TP-808 (1), a key intermediate for the discovery and manufacture of tetracycline analogues, is described. The process used for the preparation of 1 avoids chromatographic purifications and has been substantially improved over the previously reported preparation. The robustness of the process was demonstrated in a 76.1 kg manufacturing campaign with 56% overall yield.

Summary The dynamic economic emission dispatch (DEED) of power system occupies a decisive position in the process of energy conservation and emissions reduction. DEED incorporating valve point effect of generator units is a dynamic multi-objective non-convex optimization problem with the characteristic of nonlinearity, strong-constraint, and multi-peak. This paper proposed a new modified non-dominated sorting genetic Algorithm-II with selection based on dynamic crowding distance and new controlled elitism to solve DEED, which can guarantee the diversity of population under the premise of elitism of population. A deep analysis about blocked evolution produced by heuristic operation which is used to handle the complicate constraints is executed, and a modified heuristic operation based on forward search operator has been firstly implemented to solve the problem. A new membership function has been defined to describe the superiority–inferiority of the individuals in the Pareto set, from which the best compromise solution is selected. Finally, case studies were carried out with the classic 10-units test system. The simulation results demonstrate the better global search and better results acquirement capability of the proposed modified non-dominated sorting genetic Algorithm-II comparing with existing non-dominated sorting genetic Algorithm-II. Copyright © 2016 John Wiley & Sons, Ltd.

Process research and development of the fully synthetic broad spectrum tetracycline TP-2758, with a chiral pyrrolidine side chain at the C-8 position, is described. The process utilizes two key intermediates, 7 and 10, in a convergent approach that allows for manufacturing of sufficient quantities of API to supply preclinical and early clinical development. The pyrrolidine moiety was introduced into the left-hand piece (LHP) 10 with high enantioselectivity using Ellman’s sulfinamide chemistry, and the absolute configuration was confirmed by X-ray crystal structure analysis.

Glucose-6-phosphate dehydrogenase (G6PD) is a rate-limiting enzyme of the pentose phosphate pathway. Multiple studies have previously revealed that elevated G6PD levels promote cancer progression in numerous tumor types; however, the underlying mechanism remains unclear. In the present study, it was demonstrated that high G6PD expression is a poor prognostic factor in bladder cancer, and the levels of G6PD expression increase with increasing tumor stage. Patients with bladder cancer with high G6PD expression had worse survival rates compared with those with lower G6PD expression in resected tumors. In vitro experiments revealed that knockdown of G6PD suppressed cell viability and growth in Cell Counting Kit-8 and colony formation assays, and increased apoptosis in bladder cancer cell lines compared with normal cells. Further experiments indicated that the weakening of the survival ability in G6PD-knockdown bladder cancer cells may be explained by intracellular reactive oxygen species accumulation and protein kinase B pathway suppression. Furthermore, it was additionally revealed that 6-aminonicotinamide (6-AN), a competitive G6PD inhibitor, may be a potential therapy for bladder cancer, particularly in cases with high G6PD expression, and that the combination of cisplatin and 6-AN may optimize the clinical dose or minimize the side effects of cisplatin.

This report shows evidence for nosocomial transmission of H7N9 influenza from a patient to two physicians who provided care.

The C-8 position of the tetracyclines has been largely underexplored because of limitations in traditional semisynthetic techniques. Employing a total synthetic approach allowed for modifications at the C-7 and C-8 positions, enabling the generation of structure-activity relationships for overcoming the two most common tetracycline bacterial-resistance mechanisms: ribosomal protection (tet(M)) and efflux (tet(A)). Ultimately, several compounds were identified with balanced activity against both Gram-positive and Gram-negative bacteria, including pathogens bearing both types of tetracycline-resistance mechanisms. Compounds were screened in a murine systemic infection model to rapidly identify compounds with oral bioavailability, leading to the discovery of several compounds that exhibited efficacy when administered orally in murine pyelonephritis and pneumonia models.

Process research and development of the first fully synthetic broad spectrum 7-fluorotetracycline in clinical development is described. The process utilizes two key intermediates in a convergent approach. The key transformation is a Michael–Dieckmann reaction between a suitable substituted aromatic moiety and a key cyclohexenone derivative. Subsequent deprotection and acylation provide the desired active pharmaceutical ingredient in good overall yield.

In this paper we describe how the capacitated user equilibrium can be approximated by sequential uncapacitated models by the use of a penalty function. The efficiency of the method is governed by the algorithmic performance of the uncapacitated model. A skew gradient-based Newton method is used to solve the capacitated user equilibrium within the feasible region of path flows. In the path-flow region, the straight gradient is defined as the derivative of the objective function with respect to the flow of the corresponding path, while the skew gradient is defined for each particular origin destination pair and is characterized by the average cost of all the paths for that pair. Instead of movement of flow toward the shortest path, in the equilibration procedure path flows below the average decrease and path flows above the average increase. The characteristics of the Newton method with the column generation procedure are combined to achieve the efficient determination of the equilibrium point. Numerical experiments demonstrate the excellent performance of the proposed method and highlight its potential applications.

Selected polycyclic aromatic hydrocarbons (PAHs) in surface sediments of the Yalujiang Estuary, North China, have been investigated by gas chromatography-mass spectrometry (GC-MS) for flood season (August, 1994) and dry season (May, 1996), respectively. PAHs concentrations from sediments range from 68 to 1500 ngg(-1) depending upon the sample locations. The most contaminated sediment samples are found in the turbidity maximum area for both dry and flood seasons. The source of PAHs is most likely pyrolytic, with minor contributions from petrogenic and diagenetic PAHs for some samples. Perylene is mainly derived from biogenic inputs, and occurs at almost stations. In the Yalujiang Estuary, both biogenic and anthropogenic hydrocarbons are primarily derived form riverine discharges and are accumulated in the mixing zone. The overall levels of PAHs in this study are low compared to other regions and reveal moderate PAHs pollution in the Yalujiang Estuary.

In the preparation of phosphate prodrugs of PD154075, several strategies of linking a phosphate group to the indole moiety were studied. A novel linker, p-hydroxymethylbenzoyloxymethoxycarbonyl, was discovered to provide the phosphate prodrug of PD154075 (compound 9) with significantly increased aqueous solubility, sufficient stability in aqueous solution and good bio-reconversion in vivo.

The polyhalogenated benzimidazole nucleosides 2,5,6-trichloro-1-(β-d-ribofuranosyl)benzimidazole (TCRB) and the 2-bromo analogue (BDCRB) were synthesized in our laboratory and established as potent and selective antiviral agents against human cytomegalovirus (HCMV) with a novel mode of action. In an effort to study the behavior of the key substructure of these analogues in a dimensionally stretched-out manner and probe the spatial limitation of the target enzyme(s), a series of N1- and N3-ribonucleosides of imidazo[4,5-b]quinolines were designed as linear dimensional analogues. The nucleosides 6,7-dichloro-1-(β-d-ribofuranosyl)imidazo[4,5-b]quinolin-2-one and 6,7-dichloro-3-(β-d-ribofuranosyl)imidazo[4,5-b]quinolin-2-one were selected and prepared as the key intermediates in this study. During this study, a novel photoassisted annulation was developed for the synthesis of 6,7-dichloroimidazo[4,5-b]quinolin-2-one, which overcame several problems that were encountered with the literature annulation method. ...

Convergent synthesis of 8-fluoronaphthalen-1-ylamine (6) was achieved through the reaction of 1H-naphtho[1,8-de][1,2,3]triazine (15) with HF-pyridine under mild conditions. This new synthesis for the preparation of 6 overcame many scale-up challenges that exist in the methods reported in the literature and provided a practical alternative synthesis of 1-(8-fluoronaphthalen-1-yl)piperazine (1).

Human cytomegalovirus (HCMV) remains a significant clinical problem in neonates and immunocompromised individuals such as those undergoing transplantation as well as individuals with acquired immune deficiency syndrome (AIDS). Recently in our laboratory, 2,5,6-trichloro-1-(β-d-ribofuranosyl)benzimidazole (TCRB, 1a) and 2-bromo-5,6-dichloro-1-(β-d-ribofuranosyl)benzimidazole (BDCRB, 1b) were found to have better activities in cell culture studies against HCMV than the clinically used agents ganciclovir and foscarnet. These benzimidazole compounds appear to act by a unique mechanism. However, as the biological target of TCRB and BDCRB has not been completely identified, 2,6,7-trichloro-1-(β-d-ribofuranosyl)naphtho[2,3-d]imidazole (2) was designed as a linear dimensional analogue of TCRB for a study on the spatial limitation of the binding site in the target enzyme. In the synthesis, a convenient route was developed for the synthesis of 2-substituted 6,7-dichloronaphtho[2,3-d]imidazoles involving a Diels−Ald...

A major drawback of traditional photocatalysts like TiO2 is that they can only work under illumination, and the light has to be UV. As a solution for this limitation, visible-light-driven energy storage photocatalysts have been developed in recent years. However, energy storage photocatalysts that are full-sunlight-driven (UV-visible-NIR) and possess long-lasting energy storage ability are lacking. Here we report, a Pt-loaded and hydrogen-treated WO3 that exhibits a strong absorption at full-sunlight spectrum (300–1,000 nm), and with a super-long energy storage time of more than 300 h to have formaldehyde degraded in dark. In this new material system, the hydrogen treated WO3 functions as the light harvesting material and energy storage material simultaneously, while Pt mainly acts as the cocatalyst to have the energy storage effect displayed. The extraordinary full-spectrum absorption effect and long persistent energy storage ability make the material a potential solar-energy storage and an effective photocatalyst in practice.

This paper presents a predicate-driven document filing system for organizing and automatically filing documents. A document model consists of two basic elements: frame templates representing document classes, and folders which are repositories of frame instances. The frame templates can be organized to form a document type hierarchy, which helps classify and file documents. Frame instances are grouped into a folder on the basis of user-defined criteria, specified as predicates which determine whether a frame instance belongs to a folder. Folders can naturally organized into a folder organization which represents the user's real world document filing system. The predicate consistency problem is discussed to eliminate two abnormalities from a folder organization: inapplicable edges (filing paths) and redundant folders. An evaluating net (including an association dictionary, an instantiation component and a production system) is then proposed for evaluating whether a frame instance satisfies the predicate of a folder during document filing. And the concept of consistency a rule base is also discussed.

Regioselective ribosylation conditions were established which gave both 6,7-dichloro-1-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)imidazo[4,5-b]quinolin-2-one (4) and 6,7-dichloro-3-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)imidazo [4,5-b]quinolin-2-one (5), respectively, in high yield from 6,7-dichloroimidazo[4,5-b]quinolin-2-one (6). The distributions of the sites of ribosylation under a variety of conditions are discussed.

A novel photo-assisted annulation was developed for the synthesis of 6,7-dichloroimidazo[4,5-b]quinolin-2-one. This mild ring closure method has circumvented problems associated with the previous methods and should tolerate a variety of functional groups.

This paper formally specifies a document model for office information systems, including formal definitions of document types (frame templates), a document type hierarchy, folders, and folder organizations. Folder Organizations are defined using predicates and directed graphs. AReconstruction Problem for folder organizations is then formulated; viz., under what circumstances it is possible to reconstruct a folder organization from its folder level predicates. The Reconstruction Problem is solved in terms of such graph-theoretic concepts as Associated Digraphs, transitive closure, and redundant/nonredundant filing paths. A Transitive Closure Inversion algorithm is then presented which efficiently recovers a Folder Organization digraph from its Associated Digraph.

Utilizing a fully synthetic route to tetracycline analogues, the C-9 side-chain of the fluorocyclines was optimized for both antibacterial activity and oral efficacy. Compounds were identified that overcome both efflux (tet(K), tet(A)) and ribosomal protection (tet(M)) tetracycline-resistance mechanisms and are active against Gram-positive and Gram-negative organisms. A murine systemic infection model was used as an oral efficacy screen to rapidly identify compounds with oral bioavailability. Two compounds were identified that exhibit both oral bioavailability in rat and clinically relevant bacterial susceptibility profiles against major respiratory pathogens. One compound demonstrated oral efficacy in rodent lung infection models that was comparable to marketed antibacterial agents.

Regioselective ribosylation conditions were established which gave both 6,7-dichloro-1-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)imidazo[4,5-b]quinolin-2-one (4) and 6,7-dichloro-3-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)imidazo [4,5-b]quinolin-2-one (5), respectively, in high yield from 6,7-dichloroimidazo[4,5-b]quinolin-2-one (6). The distributions of the sites of ribosylation under a variety of conditions are discussed.

The polyhalogenated benzimidazole nucleosides 2,5,6-trichloro-1-(β-d-ribofuranosyl)benzimidazole (TCRB) and the 2-bromo analogue (BDCRB) were synthesized in our laboratory and established as potent and selective antiviral agents against human cytomegalovirus (HCMV) with a novel mode of action. In an effort to study the behavior of the key substructure of these analogues in a dimensionally stretched-out manner and probe the spatial limitation of the target enzyme(s), a series of N1- and N3-ribonucleosides of imidazo[4,5-b]quinolines were designed as linear dimensional analogues. The nucleosides 6,7-dichloro-1-(β-d-ribofuranosyl)imidazo[4,5-b]quinolin-2-one and 6,7-dichloro-3-(β-d-ribofuranosyl)imidazo[4,5-b]quinolin-2-one were selected and prepared as the key intermediates in this study. During this study, a novel photoassisted annulation was developed for the synthesis of 6,7-dichloroimidazo[4,5-b]quinolin-2-one, which overcame several problems that were encountered with the literature annulation method. ...

Integrin αvβ3 plays a major role in various signaling pathways, cell apoptosis, and tumor angiogenesis. To examine the functions and roles of αvβ3 integrin, a stable CHO-677 cell line expressing the murine αvβ3 heterodimer (designated as "CHO-677-mαvβ3" cells) was established using a highly efficient lentiviral-mediated gene transfer technique. Integrin subunits αv and β3 were detected at the gene and protein levels by polymerase chain reaction (PCR) and indirect immunofluorescent assay (IFA), respectively, in the CHO-677-mαvβ3 cell line at the 20th passage, implying that these genes were successfully introduced into the CHO-677 cells and expressed stably. A plaque-forming assay, 50% tissue culture infective dose (TCID50), real-time quantitative reverse transcription-PCR, and IFA were used to detect the replication levels of Foot-and-mouth disease virus (FMDV) in the CHO-677-mαvβ3 cell line. After infection with FMDV/O/ZK/93, the cell line showed a significant increase in viral RNA and protein compared with CHO-677 cells. These findings suggest that we successfully established a stable αvβ3-receptor-expressing cell line with increased susceptibility to FMDV. This cell line will be very useful for further investigation of αvβ3 integrin, and as a cell model for FMDV research.

The polyhalogenated benzimidazole nucleosides 2,5, 6-trichloro-1-(beta-D-ribofuranosyl)benzimidazole (TCRB) and the 2-bromo analogue (BDCRB) were synthesized in our laboratory and established as potent and selective inhibitors of human cytomegalovirus (HCMV) with a novel mode of action. In an effort to study the behavior of the key substructure in a dimensionally extended manner and probe the spatial limitation of the target enzyme(s), a series of 2-substituted 6, 7-dichloro-1-(beta-D-ribofuranosyl)naphtho¿2,3-dĭmidazoles and the N1- and N3-ribonucleosides of 2-substituted 6,7-dichloroimidazo¿4, 5-bquinolines were prepared. The nucleosides 6, 7-dichloro-1-(beta-D-ribofuranosyl)imidazo¿4,5-bquinolin-2-one and 6,7-dichloro-3-(beta-D-ribofuranosyl)imidazo¿4,5-bquinolin-2-one were selected and used as the key synthetic intermediates in the imidazo¿4,5-bquinoline series. Evaluation of the compounds for activity against HCMV and herpes simplex virus type 1 revealed that the trichloro analogues of TCRB (2a, 3a) were nearly as active against HCMV as TCRB but were more cytotoxic. The results suggest that extending the heterocycle of TCRB affected the affinity for the HCMV target only slightly but increased the affinity for cellular enzymes.