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Efficient copper-catalyzed 1,2-difunctionalization of alkenes with commercially available BrCH2Cl as a chloromethylating source was carried out, in which mild conditions, high reactivity, excellent functional-group tolerance, and late-stage modification of a bioactive molecule are demonstrated. This strategy offers a solution for the diverse syntheses of nitrogen-containing terminal alkyl chlorides, a common synthetic handle that is promising for multiple derivatizations. Mechanistic studies indicate that a chloromethyl radical is involved in the catalytic cycle.

Uroplakin 1A (UPK1A) has recently been found dysregulation in many cancers. However, the functions of UPK1A and its underlying mechanisms in hepatocellular carcinoma (HCC) remain poorly understand. In the present study, we found that UPK1A was highly expressed in HCC tumor tissues compared with adjacent non-tumor tissues. Datasets from the Cancer Genome Atlas project (TCGA) and Gene expression Omnibus confirmed that UPK1A was highly expressed in HCC. High expression of UPK1A predicted poor overall survival (OS) in patients with HCC. Univariate and multivariate analysis showed that UPK1A was a significant and independent prognostic predictor for OS of patients with HCC. Functionally, silencing UPK1A suppressed HCC cell glycolysis and proliferation. Mechanistically, hypoxia-inducible factor 1α (HIF-1α) directly bound to the hypoxia response elements (HRE) of UPK1A promoter region, which led to the up-regulation of UPK1A under hypoxia. Furthermore, downregulation of UPK1A reduced key enzyme of glycolysis via regulating HIF-1α. Taken together, these data indicates the existence of a positive feedback loop between HIF-1α and UPK1A that modulates glycolysis and proliferation under hypoxia in HCC cells.

Background Gene therapy remains a significant challenge due to lots of barriers limiting the genetic manipulation technologies. As for non-viral delivery vectors, they often suffer insufficient performance due to inadequate cellular uptake and gene degradation in endosome or lysosome. The importance of overcoming these conserved intracellular barriers is increasing as the delivery of genetic cargo. Results A surface-functionalized non-viral vector involving the biomimetic mannitol moiety is initiated, which can control the cellular uptake and promote the caveolae-mediated pathway and intracellular trafficking, thus avoiding acidic and enzymatic lysosomal degradation of loaded gene internalized by clathrin-mediated pathway. Different degrees of mannitol moiety are anchored onto the surface of the nanoparticles to form bio-inspired non-viral vectors and CaP-MA-40 exhibits remarkably high stability, negligible toxicity, and significantly enhanced transgene expression both in vitro and in vivo. Conclusions This strategy highlights a paradigmatic approach to construct vectors that need precise intracellular delivery for innovative applications.

To study the effect, treatment course and adverse reactions of Ningmitai Capsules (NMT) in the treatment of chronic prostatitis (CP).We searched the CNKI, Wanfang, COMDD and VIP databases, Cochrane Library, PubMed, EMBASE and Chinese academic conference papers for related articles before October 2019 on the treatment of CP with NMT, evaluated the quality of the literature with the Jadad Scale, and conducted a meta-analysis using the Stata14 software.Totally, 20 articles were included in this study, involving 3558 cases of CP, 1807 in the observation group and 1751 as controls. In the treatment of CP, NMT combined with quinolone, tetracycline or macrolide exhibited remarkably better effect than any of the above antibiotics used alone (RR ［95% CI］: 1.270 ［1.215－1.328］, 1.232 ［1.132－1.340］ and 1.239 ［1.130－1.359］, respectively) and the combination therapy also showed a higher total efficacy after 2, 4 and 8 weeks of medication (RR ［95% CI］: 1.256 ［1.185－1.330］, 1.245 ［1.165－1.330］ and 1.244 ［1.131－1.369］, respectively), though a little lower at 4 and 8 than at 2 weeks. There was no statistically significant difference in the incidence rate of adverse reactions between the NMT combination and antibiotics alone groups (P = 0.441).NMT combined with antibiotics, particularly with quinolone, is superior to antibiotics alone in the treatment of CP, though with no statistically significant difference in the incidence rate of adverse reactions between the two options. The length of medication does not inference the therapeutic effect.

Geostatistical data plays a vibrant role for surface-based reservoir modeling through outcrop analogues, which is used to understand three-dimensional (3D) variability of petrophysical properties. The main purpose of this study is to improvise the surface-based 3D geo-modeling to demonstrate petrophysical characteristics and heterogeneities of Sandakan reservoirs, NW Borneo. We used point cloud data from Light Detection and Ranging (LiDAR) to build high-resolution virtual outcrop modeling (VOM) onto which we mapped 6 different lithofacies. Porosity and permeability of core plugs were measured to determine the average variance of petrophysical properties for each lithofacies. By utilizing the inte-gration of VOMs analogues and petrophysical properties in PetrelTM, we demonstrated the distribution and associations of all lithofacies in pseudo wells that have inherent thin beds heterogeneities in 3D geo-cellular model. The results concluded that the heterogeneity of thin beds in lithofacies is dependent on porosity and permeability with input dataset. According to the final model, cross-bedding sandstone (CBS), hummocky cross-stratified sandstone (HCSS) and trough cross-bedding sandstone (TCBS) show good reservoir quality due to high porosity ranging from: 25.6% to 20.4% and, 19.3%-14.5%, and permeability ranging from: 74.03 mD to 66.84 mD and, 64.86 mD to 21.01 mD. In contrast, massive to weak laminae sandstone (MWLS) and bioturbated sandstone (BS) show fair to poor reservoir quality, caused baffling of surrounding mud sediments in the reservoir lithofacies. Results also revealed that LiDAR based VOM with petrophysical properties can significantly reduce the risk and minimize the cost of reservoir modeling in petroleum industry. (c) 2021 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/ 4.0/).

Stimuli-responsive materials are promising paradigm applied to construct diagnostic and therapeutic intracellular controlled release vectors, while highlighting many challenges and opportunities. In this paper, six α-cyclodextrin-based supramolecular nanovectors were constructed and the efficacy of amine groups, stimuli-responsive profiles and endocytic mechanisms were investigated. The results indicated that the designed supermolecules can compact DNA to form stable complexes and display low cytotoxicity. Among them, PRPEI-2 with suitable PEI amine group exhibited enhanced transfecting performance, high dilution stability, nice serum compatibility, and good acid-responsive profiles to enable endosome escape, significantly higher than commercially available transfecting agent PEI25000, the most effective vector studied to date. The endocytic uptake mechanisms involved in the transfection was mainly through clathrin-mediated pathway, which is closely associated with and can be improved by endosome escape. Moreover, PRPEI-2/DNA polyplex can be effectively expressed in vivo even after 48 h via only single tail-vein injection, and the gene expression and main tissue distribution appeared in the testis, liver, brain and spleen. These excellent characteristics demonstrated that the supramolecular PRPEI-2 represents an excellent prospect as stimuli-responsive nanovectors for gene diagnosis and therapy.

With the purpose of improving solubility and permeability of acetazolamide (ACZ), two new solid forms including one salt with piperazine (PPZ), and one cocrystal with theophylline (THP), namely, ACZ-PPZ-H2O (1) and ACZ-THP (2), were synthesized and structurally characterized. The single-crystal X-ray diffraction analysis revealed that the three-dimensional structure of both 1 and 2 are maintained by abundant hydrogen bonding interaction. In molecular salt 1, PPZ2+ cations locate in and link to the cavities formed by ACZ− anions and solvent water molecules, while in cocrystal 2, the hydrogen bonding chains assembled by ACZ molecules weave the hydrogen bonding layer of THP molecules to a three-dimensional supramolecular structure. The powder dissolution and in vitro permeation experiments indicated that both solubility and permeability of ACZ were simultaneously improved after the formation of cocrystal and salt. Comparatively, the cocrystallization could remarkably enhance the permeability of ACZ, while the salt formation is more advantageous in increasing its solubility. The present study provides a new strategy of screening and prediction for simultaneously enhancing solubility and permeability of ACZ, which will be beneficial for the development of drugs with low solubility and poor permeability.

Efficient copper-catalyzed 1,2-difunctionalization of alkenes with commercially available BrCH2Cl as a chloromethylating source was carried out, in which mild conditions, high reactivity, excellent functional-group tolerance, and late-stage modification of a bioactive molecule are demonstrated. This strategy offers a solution for the diverse syntheses of nitrogen-containing terminal alkyl chlorides, a common synthetic handle that is promising for multiple derivatizations. Mechanistic studies indicate that a chloromethyl radical is involved in the catalytic cycle.

Additional file 1: Figure S1. Characterization of the functionalized CaP-MA nanoparticles. Synthetic route (A) and 1H NMR (B) and FTIR (C) spectrum of the conjugated mannitol-alendronate (MA-AL); Size distribution and polydispersity index (PDI) of CaP (D), CaP-MA-5 (E), CaP-MA-20 (F) and CaP-MA-40 (G); Morphology of CaP and different CaP-MA nanoparticles (H); Evaluation the abilities of different nanoparticles to protect DNA (I), (+) represented incubation with DNase I and (-) represented incubation without DNase I, mean ± SD, n=3. ★The intensity was too low to be determined. Figure S2. The biocompatibility of CaP and CaP-MA-5/20/40 nanoparticles. Cell viability of CaP nanoparticles, CaP-MA nanoparticles (A), and MA-AL (B) measured by the MTT assay. The mixture of fresh blood and nanoparticles after 1 hour incubation (C), Lip-2000 (a), CaP-MA-40 (b), CaP-MA-20 (c), CaP-MA-5 (d), CaP (e), saline (f), Triton-X (g). Hemolytic rates of Lip-2000, CaP and CaP-MA-5/20/40 nanoparticles (D). Data are shown as mean ± SD (n=3). * P

A copper-catalyzed dichloromethylazidation of alkenes using commercially available BrCCl2H as a stoichiometric dichloromethylating reagent has been reported. Mechanistic studies indicated that a dichloromethyl radical was involved in the catalytic cycle. This transformation has demonstrated mild conditions, high reactivity, excellent functional-group tolerance, and a broad substrate scope, and thus it has offered a new solution for difunctionalization of alkenes to make diverse transformable dichloromethylated molecules.

Background: In the present study, we investigated the role of ornithine decarboxylase (ODC) in the methyl jasmonate (MeJA)-regulated postharvest quality maintenance of Agaricus bisporus (J. E. Kange) Imbach button mushrooms by pretreating mushrooms with a specific irreversible inhibitor called α-difluoromethylornithine (DFMO) before exposure to MeJA vapor.; Results: Mushrooms were treated with 0 or 100 µmol L-1 MeJA or a combination of 120 µmol L-1 DFMO and 100 µmol L-1 MeJA, respectively, before storage at 4 °C for 21 days. Treatment with MeJA alone induced the increase in ODC activity whereas this effect was greatly suppressed by pretreatment with DFMO. α-Difluoromethylornithine strongly attenuated the effect of MeJA on decreasing cap opening, slowing the decline rate of soluble protein and total sugar, and accumulating total phenolics and flavonoids. α-Difluoromethylornithine pretreatment also counteracted the ability of MeJA to inhibit polyphenol oxidase and lipoxygenase activities, and malondialdehyde production, and to stimulate superoxide dismutase and catalase activities. It also largely downregulated MeJA-induced accumulation of free putrescine (Put).; Conclusion: These results reveal that ODC is involved in MeJA-regulated postharvest quality retention of button mushrooms, and this involvement is likely to be associated with Put levels. © 2018 Society of Chemical Industry.; © 2018 Society of Chemical Industry.

A novel palladium-catalyzed C-H formylation of electron-rich N-, O-, and S-containing heteroarenes has been developed. The key to success is that the commercially available BrCHCl2 was used as a stoichiometric carbonyl source. Mechanistic investigations indicated that different from the known Reimer-Tiemann reaction, this net C-H formylation proceeded through an electrophilc radical-type path.

The first example of copper-catalyzed direct formylation of alkenyl C–H bonds for the facile synthesis of α,β-unsaturated aldehydes has been developed. This transformation has demonstrated high reactivity, mild reaction conditions and a broad substrate scope. BrCHCl2 is expected to be developed as an efficient stoichiometric C1 building block in organic synthesis.

Objective: To investigate the effects of intrauterine infection in different periods on the placenta and endometrial blood vessel formation of pregnant rats and the growth and development of fetal rats.Methods: According to the random number table method, 32 pregnant rats were divided into the early infection group, the mid-term infection group, the late infection group and the control group, with 8 rats in each group. On the 3rd, 9th and 15th day of pregnancy, lipopolysaccharide was injected intraperitoneally to construct intrauterine infection models. The pregnant rats in the control group were intraperitoneally injected with the same dose of 0.9% sodium chloride solution. On the 18th day of pregnancy, the inflammatory factors [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α)], the blood vessel density of placenta and endometrium in the placental tissues of pregnant rats, dead fetus + absorbed fetus, the inflammatory factors IL-6, TNF-α and oxidation reaction indicators [malondialdehyde (MDA) and myeloperoxidase (MPO)] in the fetal rat lung and brain tissues were detected.Results: The changing trend of IL-6 and TNF-α levels in the placental tissues of pregnant rats with intrauterine infection in different periods was: the control group < the late infection group < the mid-term infection group < the early infection group, the differences were statistically significant (p the late infection group > the mid-term infection group > the early infection group, the differences were statistically significant (p < .05). The blood vessel density of placenta and endometrium, the mean number of fetuses, brain coefficient and lung coefficient in the late infection group were significantly increased in comparison with the early infection group and the mid-term infection group. The total number and the ratio of dead fetus + absorbed fetus, the levels of IL-6, TNF-α, MDA and MPO in brain and lung tissues were significantly reduced, and the differences were statistically significant (p < .05). The blood vessel density of placenta and endometrium, brain coefficient and lung coefficient of pregnant rats in the mid-term infection group were significantly increased in comparison with the early infection group, and the differences were statistically significant (p < .05). There was no statistically significant difference in the other indicators between the two groups (p > .05).Conclusions: Intrauterine infection in different periods can inhibit placental and endometrial angiogenesis, and affect the survival rate of fetal rats and the growth and development of brain and lung. The reason may be related to the aggravation of fetal inflammatory responses and oxidative stress. The earlier the intrauterine infection occurs, the severer the adverse effects on the fetal rats will be.

It has been demonstrated that Agaricus bisporus (J.E. Kange) Imbach fruit body exerts enhanced postharvest quality retention when treated with 100 μmol L −1 exogenous methyl jasmonate (MeJA) vapor. In this study, fruit bodies of A. bisporus were treated with 100 μmol L −1 MeJA vapor or the combination of 100 μmol L −1 MeJA and 20 μmol L −1 N ω -hydroxy-nor- l -arginine (nor-NOHA, an inhibitor of arginase), respectively, before they were stored for 21 d at 4 °C. Our data showed that treatment with MeJA alone indeed induced the increased transcription and activity of arginase whereas this effect was largely inhibited by pretreatment with nor-NOHA. In correspondence to this observation, nor-NOHA suppressed the ability of MeJA to decrease open caps and to down-regulate malondialdehyde (MDA) production and polyphenol oxidase (PPO) and lipoxygenase (LOX) activities. Biochemical analysis further demonstrated that nor-NOHA counteracted the MeJA in stimulating antioxidant enzyme activities of catalase (CAT) and superoxide dismutase (SOD) and accumulating total phenolics and flavonoids. In addition, the effect of MeJA in slowing the decline rate of soluble protein and total sugar contents was also partially impaired by nor-NOHA. Taken together, our findings firmly showed that arginase acts as an important regulatory factor in maintaining the MeJA-induced mushroom quality retention during postharvest storage.

Stimuli-responsive materials are promising paradigm applied to construct diagnostic and therapeutic intracellular controlled release vectors, while highlighting many challenges and opportunities. In this paper, six

// Ya-Xuan Zhang 1, * , Wei Zhao 1, * , Ya-Jie Tang 1 1 Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei Key Laboratory of Industrial Microbiology, Hubei Provincial Cooperative Innovation Center of Industrial Fermentation, Hubei University of Technology, Wuhan 430068, China * These authors have contributed equally to this work Correspondence to: Ya-Jie Tang, e-mail: yajietang@QQ.com Keywords: podophyllum derivatives, carbon-sulfur and carbon-amine bonds, mitochondrial depolarization, antitumor mechanism Received: December 06, 2015 Accepted: February 28, 2016 Published: March 17, 2016 ABSTRACT Herein is a first effort to study effect of carbon-sulfur (C-S) and carbon-nitrogen (C-N) bonds modification on the antitumor activity of the podophyllum derivatives in HeLa cells. Compared with the derivative modified by the C-N bond, the C-S bond modification exhibited superior antitumor activity by further causing significant mitochondria depolarization from three signaling pathway. First, a large number of microtubules were depolymerized by 4β-S-heterocyclic substituted podophyllum derivatives. The increasing free tubulin bond with voltage-dependent anion-selective channel (VDAC). Second, cAMP-dependent protein kinase A (PKA) was activated by 4β-S-heterocyclic substituted podophyllum derivatives. And then the activated PKA further caused significantly mitochondria depolarization. Third, the activated PKA also activated c-Jun N-terminal kinase (JNK) and further deceased MMP by improving the level of reactive oxygen species. Understanding the molecular events that contribute to drug-induced tumors apoptosis should provide a paradigm for a more rational approach to antitumor drug design.

Reservoir studies in the Sandakan sub-basin NW Borneo are challenging and inexplicable due to complex diagenetic effects such as compaction, cementation, dissolution and depositional means including grain size, sorting and packing with reference to clay texture. These diagenetic effects together impart significant amounts of uncertainty on reservoir quality assessment. In this regard, we documented the mineralogical, diagenetic and reservoir properties of sandstones from the Sandakan Formation, NW Borneo through thin sections, SEM, XRD, XRF, He-porosimeter and poroperm. In order to analyze the influential parameters, we used matrix, grain rearrangement and clay coating around detrital grains for the reservoir quality. Our results show that the sub-litharenites to quartz arenite that dominate in the sandstones are drawn from recycled orogenic sand. Furthermore, reservoir properties of the sandstones were ascertained to be controlled by diagenesis, micro quartz with clay coatings and pressure dissolution of feldspar with the alteration of lithic fragments. The result shows that the physical compaction, rearrangements and ductility of grains were the reasons that reduced porosity and permeability. The main reason for porosity reduction in the present study is pressure dissolution that resulted in the form of chemical compaction induced by micas with grain contacts. Nonetheless, through SEM and petrography, clay coatings around the grains and dissolution of feldspar were found to optimally contribute to the preservation of reservoir properties. Dissolution of feldspar and kaolinization resulted in the formation of secondary porosity that allows meteoric water to percolate through the open and detachment spaces of quartz or other grains. This percolation is also responsible in enhancing the pore throat radii in the reservoir media of the analyzed sandstones. These traits are obliging to diagenetic effects on porosity and permeability, which are linked with the physical compaction and clays coating to reduce and preserve the reservoir properties respectively of same type of reservoirs globally.

This study investigated changes in endogenous polyamine (PA) content, PA-related amino acid content, and the expression of PA-related genes in different tissues (cap, gill, and stipe) of the edible mushroom (Agaricus bisporus J.E. Lange Imbach) during postharvest storage. The results showed that the putrescine (Put) content increased substantially and continuously in all tissues, and was highest in stipe during storage. Strong positive correlations were observed between Put content and the extent of cap opening. Minor changes in spermidine (Spd) and spermine (Spm) contents were observed during storage, both of which were highest in gills during spore production. PA-related amino acid content and PA-related gene expression were also developmentally and tissue-specifically regulated. The expression levels of AbASS, AbASL, AbARG, and AbOAT increased in gills and reached the highest level when the pileus started cap opening; however, at the same time, in the stipe these expression levels decreased rapidly to the lowest level. The expression levelsof AbODC and AbSAMDC increased in gills with storage duration, which possibly contributed to the highest Spd level. Furthermore, proline and glutamate contents presented an opposite changing trend during storage, indicating that they are likely generated in a coordinated way in different tissues. In addition, Put biosynthetic pathways are likely differently regulated in gill and stipe: Put production in gills mainly happened via ornithine decarboxylase, while Put in stipes may be synthesized via an alternative pathway. These results indicate that PA biosynthesis and its distribution correlate positively with the continuing development of A. bisporus postharvest.

Cisplatin is one of the most widely used platinum-based anticancer chemotherapeutic drugs. However, its low solubility, serious side effects and the development of cisplatin resistance limit its further use in the clinic. Controlling the delivery and release of cisplatin at the targeted site efficiently is a meaningful way to overcome these undesirable side effects of cisplatin. Herein, a tumor targeted and stimuli responsive nano-delivery system for cisplatin was constructed using branched polyethyleneimine (BPEI) as the backbone, disulfide bond as the redox-responsive covalent linker and hyaluronic acid (HA) as targeting recognition unit which can bind selectively to the receptor of CD44, which is highly expressed on the A549 tumor cells. The cisplatin-polyethyleneimine conjugate BPEI-SS-Pt was prepared and the drug loading of cisplatin was up to 32.66 ± 0.06%. After optimized the coating weight ratio of HA and BPEI-SS-Pt, the nanoparticle delivery system HA-(BPEI-SS-Pt)-1/4 outperformed with smaller particle size of 159.0 ± 21.0 nm, narrow polydispersity index (PDI) of 0.069 ± 0.022 and higher cisplatin loading of 29.23 ± 0.18%, showing specific tumor-targeting ability and redox-responsive drug release manner. Moreover, for the treatment of cancer in vivo, it achieved more effective antitumor performance along with minor side effects and systemic toxicity compared with cisplatin which is of great significance for the chemotherapeutic drug in the clinic.

Non-viral nanovectors have attracted much attention owing to their ability to condense genetic materials and their ease of modification. However, their poor stability, low biocompatibility and gene degradation in endosomes or lysosomes has significantly hampered their application in vivo and in the clinic. In an attempt to overcome these difficulties a series of bovine serum albumin (BSA)-calcium phosphate (CaP) nanoparticles were constructed. The CaP condenses with DNA to form nanocomplexes coated with a biomimetic corona of BSA. Such complexes may retain the inherent endocytosis profile of BSA, with improved biocompatibility. In particular the transgene performance may be enhanced by stimulating the cellular uptake pathway via caveolae-mediated endocytosis. Two methods were employed to construct and optimize the formulation of BSA-CaP nanomaterials. The optimized BSA-CaP-50-M2 nanoparticles prepared by our second method exhibited good stability, negligible cytotoxicity and enhanced transgene performance with long-term expression for 72 h in vivo even with a single dose. Determination of the cellular uptake pathway and Western blot revealed that cellular uptake of the designed BSA-CaP-50-M2 nanoparticles was mainly via caveolae-mediated endocytosis in a non-degradative pathway in which the biomimetic uptake profile of BSA was retained.

In the present study, we investigated the role of ornithine decarboxylase (ODC) in the methyl jasmonate (MeJA)-regulated postharvest quality maintenance of Agaricus bisporus (J. E. Kange) Imbach button mushrooms by pretreating mushrooms with a specific irreversible inhibitor called α-difluoromethylornithine (DFMO) before exposure to MeJA vapor.Mushrooms were treated with 0 or 100 µmol LThese results reveal that ODC is involved in MeJA-regulated postharvest quality retention of button mushrooms, and this involvement is likely to be associated with Put levels. © 2018 Society of Chemical Industry.

In sky-wave over-the-horizon radar system, it is difficult to detect ship because the Doppler shift of the ship is very close to the strong ocean clutter. Traditional clutter cancellation algorithms suppress ocean clutter by estimating clutter parameters and removing the clutter signal in time domain. However, they estimate the clutter parameters by the maximum value of the post DFT spectrum and thus lead to the low accuracy. In this paper, a modified clutter cancellation algorithm is proposed, which corrects estimated frequency by utilizing the three maximum spectrum values and overcomes the poor cancellation performance caused by inaccurate estimation of clutter parameters. Compared with traditional clutter cancellation algorithm, the proposed algorithm can get more accurate clutter parameters and reduce the energy and expansion of the remaining clutter. Simulation demonstrated that the proposed algorithm had a better clutter cancellation performance compared to the traditional ones.

The matched filter of chaotic radar system proposed by Ned J. Corron can be implemented through low-cost analog devices. But the spectrum of transmitted signal of this system is dispersion, causing signal in the process of propagation prone to spectrum leaked. To solve the problem, this paper proposes a low-cost signal design method. In transmitter, making chaotic signal become a band-limited signal by filtering to shape the spectrum; in receiver, using synchronization and filtering to recover the chaotic signal. The proposed method is implemented with low-cost analog devices; in addition, the method is still valid when the SNR is as low as-20dB.

The parameter estimation of the Polynomial Phase Signals (PPS) is one of the core issues. In this paper, UKF-based algorithm is proposed to estimate the parameter of PPS embedded in Gaussian noise. The algorithm constructs an adequate state-space model to represent the PPS and the model can also be implied in real radar signal. Unscented Kalman filtering is applied to estimate the signal parameters. The method achieves the lower SNR threshold, the faster convergence speed, the higher accuracy and more stable estimation performance compared with the existing methods. Simulation also verifies the efficiency of the proposed method.

The echo signals of sky-wave over-the-horizon radar involve ionospheric phase contamination with spectrum expansion. The bragg peaks expand and cover the frequency spectrum of low speed target. So ionospheric phase decontamination is necessary before coherent integration. The traditional Hankel Rank Reduction (HRR) phase decontamination method constructs the Hankel matrix by folding the echo signal, estimating instantaneous frequency through singular value decomposition. But HRR method requires the prior information of signal components. The estimation is invalid without priori information. The algorithm presented in this paper does not require the priori information. The algorithm based on matched fourier transform can accurately estimate the phase contamination function for the clutter noise ratio is high. Simulation shows that the proposed algorithm has better performance in phase decontamination.

We introduce a new approach to investigate the stability of controlled tree-shaped wave networks and subtrees of complex wave networks. It is motivated by regarding the network as branching out from a single edge. We present the recursive relations of the Laplacian transforms of adjacent edges of the system in its branching order, which form the characteristic equation. In the stability analysis, we estimate the infimums of the recursive expressions in the inverse order based on the spectral analysis. It is a feasible way to check whether the system is exponentially stable under any control strategy or parameter choice. As an application we design the control law and study the stability of a 12-edge tree-shaped wave network.

In this paper, the solution expansion for an inverted pendulum system with time delay is studied. The linearized model of this nonlinear system near its equilibrium is derived on the assumption that a unique equilibrium exists in it. Then the asymptotic expressions of its eigenvalues and the eigenvalues’ corresponding eigenvectors are obtained. Moreover, although the set of these eigenvectors does not form a Schauder basis for the state space, the solution of this model still can be expressed by these eigenvectors in the form of infinite series under certain conditions. Finally, a simulation is provided to support these results.

Cerebral dopamine neurotrophic factor (CDNF), previously known as the conserved dopamine neurotrophic factor, belongs to the evolutionarily conserved CDNF/mesencephalic astrocyte-derived neurotrophic factor MANF family of neurotrophic factors that demonstrate neurotrophic activities in dopaminergic neurons. The function of CDNF during brain ischemia is still not known. MANF is identified as an endoplasmic reticulum (ER) stress protein, however, the role of CDNF in ER stress remains to be fully elucidated. Here, we test the neuroprotective effect of CDNF on middle cerebral artery occlusion (MCAO) rats and neurons and astrocytes treated with oxygen&ndash, glucose depletion (OGD). We also investigate the expression of CDNF in cerebral ischemia and in primary neurons treated with ER stress-inducing agents. Our results show that CDNF can significantly reduce infarct volume, reduce apoptotic cells and improve motor function in MCAO rats, while CDNF can increase the cell viability of neurons and astrocytes treated by OGD. The expression of CDNF was upregulated in the peri-infarct tissue at 2 h of ischemia/24 h reperfusion. ER stress inducer can induce CDNF expression in primary cultured neurons. Our data indicate that CDNF has neuroprotective effects on cerebral ischemia and the OGD cell model and the protective mechanism of CDNF may occur through ER stress pathways.

Herein is a first effort to systematically study the significance of carbon-sulfur (C-S) and carbon-amine (C-NH) bonds on the antitumor proliferation activity of podophyllum derivatives and their precise mechanism of apoptosis. Compared with the derivative modified by a C-NH bond, the derivative modified by a C-S bond exhibited superior antitumor activity, the inhibition activity of target proteins tubulin or Topo II, cell cycle arrest and apoptosis induction. Antitumor mechanistic studies showed that the death receptor and the mitochondrial apoptotic pathways were simultaneously activated by the C-S bond modified aromatic heterocyclic podophyllum derivatives with a higher cellular uptake percentage of 60–90% and induction of a higher level of reactive oxygen species (ROS). Only the mitochondrial apoptotic pathway was activated by the C-NH bond modified aromatic heterocyclic podophyllum derivatives, with a lower cellular uptake percentage of 40–50%. This study provided insight into effects of the C-S and C-NH bond modification on the improvement of the antitumor activity of Podophyllum derivatives.

This work aims to provide sampling of halogen-containing aniline podophyllum derivatives and their mode of action with an in-depth comparison among fluorine, chloride and bromide for clarifying the important role and impact of fluorine substitution on enhancing antitumor activity, with an emphasis on the development of drug rational design for antitumor drug. The tumor cytotoxicity of fluoride-containing aniline podophyllum derivatives were in general improved by 10–100 times than those of the chloride and bromide-containing aniline podophyllum derivatives since fluoride could not only strongly solvated in protic solvents but also forms tight ion pairs in most aprotic solvents. When compared with chloride and bromide, the higher electronegativity fluoride substituted derivatives significantly enhanced mitochondrial apoptosis pathway by remarkably increasing the expression of caspase-9 in HeLa cells. The current findings would stimulate an enormous amount of research directed toward exploiting novel leading compounds based on podophyllum derivatives, especially for the fluoride-substituted structures with promising antitumor activity.

The nano self-assembly profiles of amphiphilic gene delivery vectors could improve the density of local cationic head groups to promote their DNA condensation capability and enhance the interaction between cell membrane and hydrophobic tails, thus increasing cellular uptake and gene transfection. In this paper, two series of cationic amphiphilic β-cyclodextrin (β-CD) derivatives were designed and synthesized by using 6-mono-OTs-β-CD (1) as the precursor to construct amphiphilic gene vectors with different building blocks in a selective and controlled manner. The effect of different type and degree of cationic head groups on transfection and the endocytic mechanism of β-CD derivatives/DNA nanocomplexes were also investigated. The results demonstrated that the designed β-cyclodextrin derivatives were able to compact DNA to form stable nanocomplexes and exhibited low cytotoxicity. Among them, PEI-1 with PEI head group showed enhanced transfection activity, significantly higher than commercially available agent PEI25000 especially in the presence of serum, showing potential application prospects in clinical trials. Moreover, the endocytic uptake mechanism involved in the gene transfection of PEI-1 was mainly through caveolae-mediated endocytosis, which could avoid the lysosomal degradation of loaded gene, and had great importance for improving gene transfection activity.

In this note, we firstly recall the main results in [1] and their brief proofs. As applications of the results, we study the control problem of the general networks of strings. Some new examples of networks of strings with circuits are given.

In this paper, we explore an approach to check the exponential stability of the distributed parameter system with non-collocated feedback. We regard the characteristic determinant as an entire function with parameters that usually are the feedback gains. By checking that there is no zero of this entire function on the imaginary axis for some parameters, we assert that there is no spectrum of the system in the closed right half-plane. Further, we check the Riesz basis property of the eigenvectors of the system, and hence get the exponential stability of the system. As an example, we study a hybrid system consisting of onedimensional wave equation with tip mass and non-collocated feedback. By finding out the condition of no spectrum on the imaginary axis, we determine the exponential stability region of the parameters of the hybrid system.