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In terms of treatment, a particularly targeted drug is needed to combat the COVID-19 pandemic. Although there are currently no specific drugs for COVID-19, traditional Chinese medicine(TCM) is clearly effective. It is recommended that through data analysis and mining of TCM cases (expert experience) and population evidence (RCT and cohort studies), core prescriptions for various efficacy can be obtained. Starting from a multidimensional model of regulating immunity, improving inflammation, and protecting multiple organs, this paper constructs a multidimensional model of targeted drug discovery, integrating molecular, cellular, and animal efficacy evaluation. Through functional activity testing, biophysical detection of compound binding to target proteins, multidimensional pharmacodynamic evaluation systems of cells (Vero E6, Vero, Vero81, Huh7, and caca2) and animals (mice infected with the new coronavirus, rhesus macaques, and hamsters), the effectiveness of effective preparations was evaluated, and various efficacy effects including lung moisturizing, dehumidification and detoxification were obtained. Using modern technology, it is now possible to understand how the immune system is controlled, how inflammation is reduced, and how various organs are protected. Complete early drug characterization and finally obtain effective targeted TCM. This article provides a demonstration resource for the development of new drugs specifically for TCM.

Treatment of late-stage lung cancer has witnessed limited advances. In contrast to the tremendous efforts toward improving adaptive immunity, approaches to modulating innate immunity are relatively immature. As important innate immune cells, tumor-associated macrophages (TAMs) account for a substantial fraction of tumor-infiltrating lymphocytes, which not only reverses the immune-suppressive tumor microenvironment but also facilitates an adaptive immune response. In this study, we developed a tumor-specific MMP-2-responsive CD47 blockage (TMCB) strategy to enable effective cancer immunotherapy. Briefly, the matrix metalloproteinase-2 (MMP-2)-responsive self-assembly peptide specifically recognizes CD47, which is highly expressed in lung tumor cells. Second, the MMP-2-responsive self-assembly peptide is efficiently cleaved by MMP-2, which is overexpressed in the tumor microenvironment. Finally, the generated residual peptide naturally self-assembles into peptide-based nanofibers. The in situ constructed nanofibers inhibit the canonical CD47 "Do not eat me" signal expressed on tumor cells to promote phagocytosis of tumor cells by macrophages, which further induces effective antigen presentation and initiates T cell-mediated adaptive immune responses to inhibit tumor growth. Thus, we described a peptide-based TMCB strategy that induces both innate and adaptive immune systems to inhibit tumor growth.

Graphical abstract Abbreviation: SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; COVID-19: Coronavirus Disease 2019., Highlights • TCM could reduce the all-cause mortality in COVID-19 patients. • TCM could inhibit virus replication and transcription of SARS-CoV-2. • TCM can attenuate the cytokine storm and immune deficiency caused by the SARS-CoV-2., Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the third coronavirus causing serious human disease to spread across the world in the past 20 years, after SARS and Middle East respiratory syndrome. As of mid-September 2020, more than 200 countries and territories have reported 30 million cases of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2, including 950,000 deaths. Supportive treatment remains the mainstay of therapy for COVID-19. The World Health Organization reported that four candidate drugs, including remdesivir, are ineffective or have little effect on COVID-19. According to China News, 90 % of Chinese patients with COVID-19 use traditional Chinese medicine (TCM), with an effectiveness rate of 80 %, and no deterioration in patient condition. We have compiled the direct evidence of TCM treatment for COVID-19 as of December 31, 2020. We describe the advantages of TCM in the treatment of COVID-19 based on clinical evidence and the required methods for its clinical use. TCM can inhibit virus replication and transcription, prevent the combination of SARS-CoV-2 and the host, and attenuate the cytokine storm and immune deficiency caused by the virus infection. The cooperation of many countries is required to establish international guidelines regarding the use of TCM in patients with severe COVID-19 from other regions and of different ethnicities. Studies on the psychological abnormalities in patients with COVID-19, and medical staff, is lacking; it is necessary to provide a complete chain of evidence to determine the efficacy of TCM in the related prevention, treatment, and recovery. This study aims to provide a reference for the rational use of TCM in the treatment of COVID-19.

Recently, the bulk-heterojunction (BHJ) organic photovoltaic cells (OPVs) have attracted more attention owing to their potentials in low-weight, cost-effective, semi-transparent, colorful, and flexible. As one of the most promising candidates non-fullerene small molecule acceptors (SMA) in BHJ OPVs, fluoranthene-fused imide (FFI) derivatives can effectively regulate energy level and absorption by functional modification of active sites on its backbone. Nevertheless, it is still a challenge to design molecules based on FFI materials to achieve significant improvements in optoelectronic performance. Therefore, the key to this work is to explore the influence of introducing functional substituents at different active sites of FFIs on the photoelectric properties. By introducing different number of substituent groups with different electron-withdrawing and electron-donating capacities at FFI backbones active sites, could lead to construct “D-A-D” structures. By density functional theory (DFT) and time-dependent density functional theory (TD-DFT) calculations, we demonstrated that constructing “D-A-D” structure in FFI derivatives wouldn’t impact apparently on charge transfer process, because the nearly vertical dihedral angles exhibit in these geometrical configurations between between “D units” and “A units”. This has become a main factor limiting the performance improvement of FFI-based SMAs with “D-A-D” structures. On the contrary, it would be an effective approach to control the number of electron-withdrawing groups reasonably at FFI backbone in order to design more excellent performance for FFIs.

Background: An outbreak of 2019 novel coronavirus (COVID-19) started in December 2019 in Wuhan, China and spread rapidly across the globe In light of most COVI

As an important means of regulating ligands, steric hindrance effect is always the first choice to construct structures. It is rare to assemble complexes with different topological and structural types by increasing or decreasing the steric hindrance of ligands and to regulate their properties. Here, we successfully obtained two types of lanthanide structures [Ln(H2L1)(NO3)3]n (1: Dy; 2: Gd, H2L1 ​= ​6,6'-((1E,1′E)-((2,2-dimethylpropane-1,3-diyl)bis(azanylylidene))bis(methanylylidene))bis(2-methoxyphenol)) and [Ln2(H2L2)3(NO3)6]·(CH3CN)x·(CH3OH)y (3: Dy, x ​= ​3, y ​= ​0; 4: Gd, x ​= ​y ​= ​2, H2L2 ​= ​6,6'-((1E,1′E)-((2,2-dimethylpropane-1,3-diyl)bis(azanylylidene))bis(methanylylidene))bis(2-ethoxyphenol)), which are controlled by ligands with the steric hindrance effect. For the all structures, the ligands are distorted when they coordinate with lanthanide ions, which make the ligands form helical structures around Ln(III) ions. For chains 1 and 2, there is a single twisted ligand bridging to form a one-dimensional spiral chain between the Ln(III) ion and the Ln(III) ion. But for complexes 3 and 4, there is a helical dinuclear structure formed by the cross-bridging of a double twisted ligand between the Ln(III) ion and the Ln(III) ion. AC magnetic susceptibilities show that chain 1 is a single-molecule magnet (SMM), which exhibits obviously frequency dependent behavior with the energy barriers of 39.6 (3) K and 44.6 (5) K, but complex 3 shows field-induced single-molecule magnetic behavior. The magnetocaloric effects (MCEs) show that chain 2 has bigger value of S than that of complex 4.

Ponkan is one of the two easy-peeling mandarins grown in China, and ‘Xinnu’ Ponkan ( Citrus reticulata Blanco) is a major cultivar in the industry. We selected a spontaneous mutant of ‘Xinnu’ named ‘Zaomi’ Ponkan. Compared to the wild type, ‘Zaomi’ Ponkan exhibited alternating agronomic traits comprising earlier colouring, thinner peel, fewer seeds and higher sugar content. Pollen analysis showed that ‘Zaomi’ produced a greater number of deformed, nonviable pollen grains. Experiments in self- and cross-pollination suggested that self-incompatibility of ‘Zaomi’ contributes to the seedlessness of ‘Zaomi’ × ‘Zaomi’. Fruit quality analysis demonstrated that ‘Zaomi’ was a high-sugar mutant that was not affected by pollinating combination. This study on the fruit characteristics of ‘Zaomi’ indicates that partial male sterility and self-incompatibility contributes to fewer or no seeds; natural pollination promotes the overall fruit quality of ‘Zaomi’ Ponkan. These results provide an explanation of the seed formation of ‘Zaomi’ Ponkan and supply information relevant to its commercial planting.

Aim Early interventions in prediabetes can prevent or delay the incidence of type 2 diabetes mellitus (T2DM). The aim of this review was to assess the efficacy and safety of traditional Chinese patent medicine (TCPM) on the prevention of T2DM. Methods Seven electronic databases were searched to identify eligible trials published until June 1, 2016. Randomized controlled trials (RCTs) that compared TCPM plus lifestyle modification (LM) versus LM alone were included for in the. RCTs that used TCPM plus LM compared with placebo plus LM were also included. Methodological quality was assessed using the Cochrane Collaboration Risk of Bias tool. A random- or fixed-effect model was used to analyze outcomes that were expressed as risk ratios (RRs) or mean differences (MD), and the I2 statistic was used to assess heterogeneity. Results Twenty-six trials with a total of 4169 participants met the inclusion criteria. Subgroup analysis confirmed that, compared with LM alone, TCPM and LM together were significantly better at reducing diabetes (RR, 0.47; 95% CI, 0.38–0.59) and normalizing blood glucose (RR, 0.76; 95% CI, 0.69–0.85). They also caused a greater reduction in fasting plasma glucose (FBG) (MD, −0.37; 95% CI, −0.62 to −0.13), 2-h plasma glucose (2 h PG) (MD, −0.91; 95% CI, −1.35 to −0.47) and body mass index (BMI) (MD, −0.45; 95% CI, −0.76 to −0.14). Compared with placebo plus LM, TCPM plus LM was superior at reducing diabetes (RR, 0.55; 95% CI, 0.45–0.68) and normalizing blood glucose (RR, 0.62; 95% CI, 0.50–0.76). The interventions were also associated with a decline in FBG levels (MD, −0.68; 95% CI, −1.25 to −0.11) and 2 h PG levels (MD, −1.07; 95% CI, −1.85 to −0.29). There were no significant differences in adverse events in either group. Subgroup and sensitivity analyses found no significant difference in overall effects among all study characteristics, indicating that the overall effects were stable. Generally, the quality of evidence was low for the effect of TCPM on the incidence of diabetes and normalization of blood glucose, and was very low for the effects of TCPM on FBG, 2 h PG, and BMI. Conclusions Based on this systematic review, TCPM may reduce the risk of progression to T2DM and increase the possibility of regression toward normoglycemia. As a result of the methodological drawbacks of the included studies, more rigorously designed RCTs are required to more reliably assess the efficacy of TCPM and long-term follow-up is needed before TCPM can be recommended for prediabetic patients.

The impact of thienopyridine reloading on clinical outcomes, and residual high platelet reactivity (HPR) is unclear. We sought to compare the HRP-related effect of prasugrel and clopidogrel reloading in the already clopidogrel-loaded patients undergoing percutaneous coronary intervention (PCI).In this prospective, two-center, randomized, open-label study, patients with HPR who had undergone PCI after a clopidogrel (300-600mg) loading dose (LD) were enrolled. Among screened (n=153), HPR was determined in seventy-six patients, who were randomized to either repeated clopidogrel (300mg LD, followed by 75mg MD daily) or prasugrel (20mg LD, followed by 5mg MD daily). The primary endpoint was HPR at 24h after PCI, as determined by the VerifyNow assay. The rates of sustained high and low platelet reactivity, periprocedural myocardial injury (PMI) and 30-day clinical outcomes were also assessed.Higher inhibition of platelet reactive units (PRU) was observed in the prasugrel group than after clopidogrel reloading (Pre-PCI: 284.4±32.0 vs 279.5±32.5, p=0.504; Post-PCI: 100.0±67.0 vs 202.9±65.8, p0.001; 30days: 170.8±69.8 vs 215.1±62.4, p=0.007). There were less HRP post-PCI after prasugrel compared with the clopidogrel group (2.7 vs 36.1%, p0.001). However, reloading with prasugrel did not reduce PMI compared to clopidogrel (36.8% vs 39.5%, p=0.813).Prasugrel reloading led to a greater reduction in HPR, but similar with clopidogrel PMI in post-PCI patients. Larger randomized evidence is needed for optimization of loading strategies with thienopyridines.NCT01609647.

As a result of the rapid development and diffusion of information and communication technologies, enterprises are consistently improving their ability to respond to environmental changes. With regard to green entrepreneurship, an increasing number of green-tech ventures have been launched in response to various environmental challenges such as carbon emissions, environmental pollution, and climate change. This study examined the relationship among strategic orientations (i.e., technological orientation and marketing orientation), network positions (i.e., network centrality and bridging position), and innovation performance of green-tech ventures. With original data from 116 green-tech ventures of the Yixing Environmental and Cleaner Technology Park, the results identified both technological orientation and marketing orientation as important antecedents of innovation performance. However, unlike previous literature, this study did not find direct effects of network centrality and bridging position on innovation performance. Identified as a moderating effect, bridging position might enhance the innovation performance of strategic orientations, but no significant moderating role of network centrality was found. Overall, these findings enable a better understanding of the network positions of green-tech ventures that represent an asset for the creation of superior innovation performance.

In the following paper, a Re(I) complex with electron-withdrawing oxadiazole group in its diamine ligand (denoted as N-N) was synthesized. Its single crystal structure analysis confirmed the successful synthesis of both ligand and complex. The central Re(I) ion localized in a traditional octahedral coordination environment. The diamine ligand 2-(pyridin-2-yl)-5-(p-tolyl)-1,3,4-oxadiazole (denoted as PPOZ) took a coplanar structure and the corresponding face-to-face π-π attraction between PPOZ ligands made the Re(I) complex molecules adjust a highly ordered arrangement which was positive to improve emissive performance. In order to repress the excited state geometric relaxation and further improve the emissive performance, the Re(I) complex was doped into a polymer host poly(vinylpyrrolidone) via electrospinning, resulting in composite fibers. The morphology of those composite fibers was analyzed by electron microscopy. The photophysical comparison between bulk sample and composite fibers indicated that the composite fibers showed emission blue shift, longer excited state lifetime and improved photostability. Further analysis suggested that the excited state geometric relaxation could be effectively repressed when the Re(I) complex molecules were immobilized in the polymer matrix, leading to above variations.

A graphical tuning method for fractional-order PID ( PI λ D μ ) controllers is proposed based on the sensitivity function constraint of the closed-loop, which provides the information on robustness to plant uncertainties. The stabilizing regions in integral-derivative plane of the controller are first identified using a graphical stability criterion applicable to fractional-delay systems. Then, via Leibniz Sector Formula, the stabilizing region is optimized with respect to the two fractional orders of the controller to expect bigger stabilizing regions. Finally, the sensitivity function constraint of the closed-loop is mapped into stabilizing region by means of the explicit algebraic equations which can be solved efficiently. Numerical examples of a second-order integrating delay process are followed in each design procedure to show the effectiveness of the method.

Characterizing complex dynamic behaviors arising from various inclined oil–water two-phase flow patterns is a challenging problem in the fields of nonlinear dynamics and fluid mechanics. We systematically carried out inclined oil–water two-phase flow experiments for measuring the time series conductance fluctuating signals of different flow patterns. We using the dynamic segmentation algorithm incorporating with phase space reconstruction analyze the measured experimental signals to uncover the dynamic behaviors underlying different flow patterns. Specifically, given a time series from a two-phase flow, we move a sliding pointer over the time series and for each position of the pointer we calculate the dynamic difference measure of the phase space orbits generated from the segment to the left and to the right of the pointer. A number of experimental signals under different flow conditions are investigated in order to reveal the dynamical characteristics of inclined oil–water flows. The results indicate that the heterogeneity of dynamic difference measure series is sensitive to the transition among different flow patterns and the standard deviation of dynamic difference measure series can yield quantitative insights into the nonlinear dynamics of the two-phase flow. These properties render the dynamic segmentation algorithm-based approach particularly useful for uncovering the dynamic behaviors of inclined oil–water two-phase flows.

The stabilizing parameter sets and the guaranteed gain-margin (GM) and phase-margin (PM) regions of proportional-integral-derivative (PID) controllers for a class of processes with time-delay are discussed in the paper. The admissible range of stabilizing proportional-gain is first derived by a version of Hermite–Biehler Theorem and the evaluation of some properties of the functions involved in the closed-loop characteristic equation. Then, the stabilizing region in integral-derivative plane, for a fixed proportional-gain, is drawn and identified directly in terms of a graphical stability criterion applicable to time-delay systems. Further, in the stabilizing region, the gain-margin and phase-margin specifications are considered using the same strategy as drawing the stability boundary lines, based on the technique of gain-phase margin tester (GPMT). Illustrating examples are followed in each design step to show the effectiveness of the method.

Understanding the nonlinear and complex dynamics underlying the gas–liquid slug flow is a significant but challenging problem. We systematically carried out gas–liquid two-phase flow experiments for measuring the time series of flow signals, which is studied in terms of the mapping from time series to complex networks. In particular, we construct directed weighted complex networks (DWCN) from time series and then associate different aspects of chaotic dynamics with the topological indices of the DWCN and further demonstrate that the DWCN can be exploited to detect unstable periodic orbits of low periods. Examples using time series from classical chaotic systems are provided to demonstrate the effectiveness of our approach. We construct and analyze numbers of DWCNs for different gas–liquid flow patterns and find that our approach can quantitatively distinguish different experimental gas–liquid flow patterns. Furthermore, the DWCN analysis indicates that slug flow shows obvious chaotic behavior and its unstable periodic orbits reflect the intermittent quasi-periodic oscillation behavior between liquid slug and large gas slug. These interesting and significant findings suggest that the directed weighted complex network can potentially be a powerful tool for uncovering the underlying dynamics leading to the formation of the gas–liquid slug flow.

This article focuses on H"~ performance design for fractional-order systems with time-delay, using fractional-order proportional-derivative (PD^@m) controllers. First, the stabilizing parameters region in proportional-derivative plane of PD^@m controller, for a fixed derivative-order, is determined in terms of a graphical stability criterion applicable to fractional-order time-delay systems. Then, in the stabilizing region, the pairs of proportional and derivative gains of PD^@m controller are calculated for a range of frequencies, which satisfy the H"~-norm constraint of complementary sensitivity function and define the H"~ boundary curve. Finally, by changing the derivative-order of PD^@m controller, we observe the relationship between the H"~ curve and the derivative-order. Examples are followed to illustrate the design procedure.

The characterization of complex patterns arising from three-phase (e.g., oil–gas–water) flows is an important problem with significant engineering and industrial applications. Based solely on measured conductance fluctuation signals from experimental three-phase flows, we propose a method to characterize and distinguish three commonly observed flow patterns. Using the phase characterization method, we first calculate the instantaneous phase from the signals. Then, through performing a scaling analysis, detrended fluctuation analysis (DFA), we extract scaling behaviors associated with the phase fluctuations and find that the DFA scaling exponent is sensitive to the transition among different flow patterns, which can be used to characterize nonlinear dynamics of the three-phase flow. From a novel perspective, we investigate the three-phase flow in terms of phase characterization and scaling analysis. The results indicate that our method can provide new insights into the exploration of complex mechanism in flow pattern transition. The effectiveness of the method is demonstrated and its broader applicability is articulated.

Understanding the dynamics of oil–gas–water three-phase flow has been a challenge in the fields of nonlinear dynamics and fluid mechanics. We systematically carried out oil–gas–water three-phase flow experiments for measuring the time series of flow signals, which is studied in terms of the mapping from time series to complex networks. Two network mapping methods are proposed for the analysis and identification of flow pattern dynamics, i.e. Flow Pattern Complex Network (FPCN) and Fluid Dynamic Complex Network (FDCN). Through detecting the community structure of FPCN based on K-means clustering, distinct flow patterns can be successfully distinguished and identified. A number of FDCN's under different flow conditions are constructed in order to reveal the dynamical characteristics of three-phase flows. The network information entropy of FDCN is sensitive to the transition among different flow patterns, which can be used to characterize nonlinear dynamics of the three-phase flow. These interesting and significant findings suggest that complex networks can be a potentially powerful tool for uncovering the nonlinear dynamics of oil–gas–water three-phase flows.

We propose a method to characterize and distinguish flow patterns in experimental two-phase (e.g., gas–liquid) flows. The basic idea is to calculate the instantaneous phase from the signal and to extract scaling behaviors associated with the phase fluctuations. The effectiveness of the method is demonstrated and its applicability is articulated.

This note deals with the problem of the stabilizing parameter set of PID controllers for high-order all pole plants with time-delay. The time constants of the plants are assumed to be arbitrary, either positive or negative. First of all, the stabilizing range of the proportional gain is given in terms of a version of the Hermite–Beihler Theorem and the properties of the imaginary part of the closed-loop characteristic quasi-polynomial. Then, based on a graphical stability criterion for time-delay systems, the stabilizing region in integral-derivative space is drawn and identified for a fixed admissible proportional gain. An algorithm for determining the stabilizing parameter set of PID controllers is also proposed. Finally, case studies are provided to illustrate the shapes of the stabilizing regions.

This work provides a new approach for phase-lead/lag compensators to achieve the desired specifications of gain and phase margins for all-pole stable plants with time-delay. The stabilizing regions of lead/lag compensators are first determined in terms of a graphical stability criterion. These regions are drawn graphically, not to be calculated mathematically. Then, by defining appropriate functions relative to the requirements of gain and phase margins, the curves in the stabilizing regions satisfying the pre-specified gain and phase margins can be drawn, which gives the complete information on gain and phase margins. Illustrative examples are given to show the design procedure and to compare our method with other existing tuning rules.

Ferromagnetic resonance for magnetic thin films is found to be coexisted with the trans- mission resonance of a T-type microwave microstrip at certain applied magnetic fields. The frequency dependence of conductivity, the magnetization, and the magnetic anisot- ropy of magnetic films can be eventually solved from the measured resonance frequency and quality Q factors of the resonance spectra. Equivalent resistances (R), inductances (L), and capacitances (C) corresponding to the displayed transmission S21 spectra are sim- ulated to comply with proper values. With this equivalent circuit, an accurate determina- tion of the magnetic properties can be closely scrutinized.

This work focuses on deriving the necessary and sufficient stability condition of transmission control protocol (TCP) network with a proportional-integral (PI) active queue management (AQM) scheme via a parameter space approach. First, a fluid-flow TCP s nonlinear model is converted into a linear time-delay system of neutral type. Second, the stability of the closed-loop system is characterized in terms of the network's and the controller s parameters. By simulation studies we investigate the boundary s relations of these two kinds of parameters in the parameter space and illustrate how PI controller s parameters affect the stability. Finally, different stability conditions are compared to show the less conservatism of our necessary- and sufficient-condition-based method, and simulation experiments by both Matlab and NS-2 are conducted to prove our claim.

The implant containing Nestorone is a promising long-acting contraceptive especially suitable for lactating women. In this study, two experiments were designed to observe the effect of Nestorone on the gonadotropic cells in pituitary of rats for analyzing its antiovulation mechanism. In the first experiment, the ED 50 of Nestorone on inhibiting ovulation was found to be 1.32 mg/kg. The serum luteinizing hormone (LH) levels were significantly lower 60 h after being treated with Nestorone at 8:30–9:00 a.m. on Day 2 (D2) of estrus. Image analysis showed that the average size of the LH cells in groups treated with Nestorone at 2 or 4 mg/kg was larger than that of the control. In the group treated with 4 mg/kg, most of gonadotropic cells were regular round in shape. And, abundant granules in cytoplasm were found in those cells, which indicated that the LH stored in cells was not released. In the second experiment, the rats were treated with Nestorone at 5 mg/kg at 11:30–12:00 a.m. on D2 of estrus. The normal or higher expression of LHβ mRNA in pituitary suggested that the synthesis of LH was not inhibited by the treatment with Nestorone. The expression of PR mRNA in pituitary was significantly lower than that of the control at 33 h after treatment. This might be a direct effect of Nestorone, since there were no differences in the serum E 2 and P 4 levels between the treated and the control group. It is concluded that Nestorone prevents ovulation through inhibition of LH secretion and it has no effect on synthesis of LH. Progesterone receptors in pituitary might be involved in this process, but further study is needed to gain more evidence.

Multiple epidemiologic studies show that adeno-associated virus (AAV) is negatively associated with cervical cancer (CX CA), a cancer which is positively associated with human papillomavirus (HPV) infection. Mechanisms for this correlation may be by Rep78's (AAV's major regulatory protein) ability to bind the HPV-16 p97 promoter DNA and inhibit transcription, to bind and interfere with the functions of the E7 oncoprotein of HPV-16, and to bind a variety of HPV-important cellular transcription factors such as Sp1 and TBP. c-Jun is another important cellular factor intimately linked to the HPV life cycle, as well as keratinocyte differentiation and skin development. Skin is the natural host tissue for both HPV and AAV. In this article it is demonstrated that Rep78 directly interacts with c-Jun, both in vitro and in vivo, as analyzed by Western blot, yeast two-hybrid cDNA, and electrophoretic mobility shift-supershift assay (EMSA supershift). Addition of anti-Rep78 antibodies inhibited the EMSA supershift. Investigating the biological implications of this interaction, Rep78 inhibited the c-Jun-dependent c-jun promoter in transient and stable chloramphenicol acetyl-transferase (CAT) assays. Rep78 also inhibited c-Jun-augmented c-jun promoter as well as the HPV-16 p97 promoter activity (also c-Jun regulated) in in vitro transcription assays in T47D nuclear extracts. Finally, the Rep78–c-Jun interaction mapped to the amino-half of Rep78. The ability of Rep78 to interact with c-Jun and down-regulate AP-1-dependent transcription suggests one more mechanism by which AAV may modulate the HPV life cycle and the carcinogenesis process.

We report a facile and efficient strategy for the preparation of graphene-Ag2Se nanocomposites. The reduction of graphene oxide (GO) to graphene was accompanied by the formation of Ag2Se particles on the surface of graphene nanosheets. The results of X-ray diffraction (XRD) and Fourier transform infrared (FTIR) confirmed the efficient reduction of GO. Transmission electron microscopy (TEM) images of the sample revealed the morphology of the architecture of graphene-Ag2Se hybrid. Photoluminescence (PL) measurement was further employed to study the optical properties of the nanocomposites. The results show that the graphene-Ag2Se nanocomposites can be prepared by a simple hydrothermal method, and Ag2Se particles are well distributed on the graphene nanosheets.

Optical second harmonic generation (SHG) has been used to analyze the ULSI process, including low energy ion-implantation and rapid thermal annealing (RTA). The projected range of the low energy ion-implantation is approximately 20 nm, which results in a region that is transformed into an amorphous state by high dose ion-implantation, and the surface layer region is recrystallized during RTA process. The symmetrical point group of the Si (1 1 1) surface layer is 3 mm, which differs from that of centrosymmetric bulk Si which has no dipole contribution. The reflected SHG (RSHG) of the Si (1 1 1) is contributed mainly from the surface dipole and surface quadrupole. A plot of RSHG versus azimuthal angle reveals information on the recrystallization of amorphous silicon during RTA. The optimization of RTA step is determined by RSHG, which is shown to be suitable for analyzing the ULSI process.

Human papillomavirus type 16 (HPV-16) infection is positively associated with cervical cancer, whereas adeno-associated virus (AAV) infection is negatively associated with this same cancer. In earlier studies these two virus types have been shown to directly interact, with AAV inhibiting or enhancing papillomavirus functions depending upon the specific circumstances. One defined interaction between these two viruses is the ability of the AAV Rep78 major regulatory protein to inhibit gene expression of the E6 promoter of BPV-1 (bovine papillomavirus type 1) and HPV types 16 and 18. As Rep78 is a DNA binding transcription factor, we considered whether Rep78 might bind HPV-16 DNA. Here, Rep78 is demonstrated to bind a 44-base pair region (nucleotides 14-56) within the HPV-16 p97 promoter using the electrophoretic mobility shift assay. This region is important for HPV-16 because it includes functional Sp1 and E2 protein binding motifs as well as part of the origin of replication. Furthermore, two Rep78 amino acid substitution mutants, at positions 77 or 64-65, were identified that did not recognize p97 DNA. Both of these Rep78 mutants were found to be defective for inhibition of p97 promoter activity in HeLa and T-47D nuclear extracts in vitro, in a transient chloramphenicol acetyltransferase assay, as well as defective for full inhibition of HPV-16-directed focus formation. These data, taken together, strongly suggest that the Rep78-p97 promoter interaction is at least partially responsible for Rep78-mediated inhibition of HPV-16. Finally, the finding that Rep78 specifically recognizes p97 DNA is surprising because the p97 promoter region contains no GAGC motifs, the core motif for Rep78 recognition. These data suggest that the p97 promoter may represent a new prototypical DNA target type for Rep78.

The tumorigenicity of 7-chlorobenz[α]anthracene (7-C1-BA), an environmental contaminant, and 7-bromobenz[α]anthracene (7-Br-BA) was determined in the male B6C3F 1 newborn mouse. Mice receiving 7-C1-BA and 7-Br-BA by i.p. injections at a dose of 1600 nmol per mouse on 1, 8, and 15 days after birth developed 92 and 96% hepatocellular adenomas, and 100 and 83% hepatocellular carcinoma, respectively. Metabolism by liver microsomes of 15-day-old mice each produced the corresponding trans -3,4-dihydrodiol. Analysis by 32 P-postlabeling/HPLC indicated the presence of DNA adducts derived from 7-C1-BA trans -3,4-dihydrodiol and 7-Br-BA trans -3,4-dihydrodiol. Our results indicate that both 7-C1-BA and 7-Br-BA are potent carcinogens and that bay-region diol epoxides are the ultimate metabolites that lead to DNA adduct formation and tumor initiation.

32 P-Postlabeling-HPLC is a highly sensitive analytical method for identification of chemical-modified DNA adducts isolated from samples obtained from experimental animals or humans exposed to carcinogenic chemicals. To determine optimal 32 P-postlabeling-HPLC conditions for efficient separation, we report here the use of ten diol-epoxide-modified 3′,5′-bisphosphate deoxynucleotides derived from benzo[ a ]pyrene (BaP), nitrated BaP, and related compounds. After testing ODS-modified, C 4 -modified, phenyl-modified, diphenyl-modified, and cyclodextrin-bonded reversed-phase HPLC columns, we found that the Vydac diphenyl-modified column can efficiently separate these 3′,5′-bisphosphate deoxynucleotides. The results suggest that 32 P-postlabeling-HPLC is a potentially useful methodology for detecting environmental carcinogens that can be metabolized to diol-epoxides. The relationships between the structures of anti -diol-epoxides and HPLC retention order are also discussed.