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This article considers the beampattern synthesis problem, and a single-point array response control (SPARC) algorithm is presented to adjust the array response at an arbitrary direction. Based on the theoretical analysis, it is found that the adaptive array theory-based optimal weight vector is a linear combination of the signal steering vector and the interference steering vector multiplied by a complex factor, and that the complex factor determines the array response at the interference direction. Inspired by this observation, the SPARC algorithm is presented to achieve quiescent pattern control. In contrast to other array response control-based pattern synthesis techniques, the SPARC algorithm obtains a deterministic expression of the complex factor after maximizing the magnitude response at the main-beam direction, and the closed-form expression of the designed weight vector is devised. Because of different pattern constraints in focused and shaped beampatterns, two low-complexity pattern synthesis schemes are presented employing the SPARC algorithm in an iterative manner. Moreover, the parameter selection principle of the SPARC and its comparison with other pattern synthesis methods are discussed. Simulation results show the effectiveness of the SPARC algorithm and the efficiency of the beampattern synthesis schemes.

High-purity single-photon sources (SPS) that can operate at room temperature are highly desirable for a myriad of applications, including quantum photonics and quantum key distribution. In this work, we realize an ultra-bright solid-state SPS based on an atomic defect in hexagonal boron nitride (hBN) integrated with a solid immersion lens (SIL). The SIL increases the source efficiency by a factor of six, and the integrated system is capable of producing over ten million single photons per second at room temperature. Our results are promising for practical applications of SPS in quantum communication protocols.

In practical Quantum Key Distribution (QKD) deployments we would like to design QKD solutions that provide for a target QKD key rate, in bits/pulse, at a specified upper-limit on the failure probability. However, in the finite-signalling setting, in which all real-world QKD systems exist, the common practice of achieving such a solution fails to deliver the maximum throughput rate of the classical decoder. This in turn means that the possibility that classical reconciliation becomes the bottleneck of the entire QKD protocol is not minimised. A design strategy that minimises this latter possibility, whilst achieving a target QKD rate with a target ceiling on the failure probability has not been developed – a situation we remedy here. Although our new design strategy detailed here is for LDPC codes and applied to two specific QKD protocols, the same strategy is generally applicable to all classical decoders and all QKD protocols. It is also deployable even in circumstances where the quantum bit error is variable, such as in satellite QKD systems.

The anti-tumor effect of selenium nanoparticles (SeNPs) has received more and more attention. However, the clinical application of SeNPs is not optimistic due to the poor stability. To improve the stability of SeNPs, many polymers are used to modify the SeNPs. However, most of the polymers are not approved by FDA. It is significant to develop a SeNPs product with good stability for clinic application. Dextran 70,000 (T70) and poloxamer 188 (P188) are FDA-approved pharmaceutical injection excipients. In this study, we decorate SeNPs with T70 and P188 and assess the physicochemical characterization, storage stability, and anti-tumor activities of T70-SeNPs and P188-SeNPs. Transmission electron microscopy (TEM) shows that T70-SeNPs and P188-SeNPs are spherical particles with particle sizes of 110 nm and 60 nm respectively. Fourier-Transform Infrared Spectra (FT-IR) show that T70 or P188 can interact with SeNPs through hydrogen bonding. Stability study shows that P188-SeNPs freeze-dried powder and T70-SeNPs freeze-dried powder remain stable at 4℃ for 6 months. T70-SeNPs and P188-SeNPs can aggregate in cell matrix and play an anti-tumor role to HepG2 by promoting apoptosis, increasing reactive oxygen species (ROS) content and reducing mitochondrial membrane potential (MMP). This study can provide reference for industrial production of SeNPs products.

This paper presents a beampattern synthesis scheme based on the single-point array response control with minimum pattern deviation (SPARC-MPD) method. The central concept of SPARC-MPD stems from adaptive array theory, and a closedform expression of the designed weight vector is devised. Comparing to the state-of-the-art methods like the accurate array response control (A2RC) approach, the SPARC-MPD method addresses the pattern distortion issue. Moreover, the SPARC-MPD method can realize accurate magnitude response control at one single direction and minimize the pattern deviation at any other direction simultaneously, leading to a faster convergence speed. Simulation results show the effectiveness of the SPARC-MPD method and the efficiency of the pattern synthesis scheme.

Space-time steering vector mismatch of targets usually happens in the space-time adaptive processing (STAP) technique, causing space-time beam distortion. Due to the effects of clutter spectrum broadening and jamming, performance of the conventional STAP method deteriorates dramatically. This paper proposes a novel robust STAP method to improve the performance of clutter suppression and moving target detection. The proposed method employs the alternating projection and clutter cancellation method, to reconstruct the clutter plus jamming plus noise covariance matrix (CJNCM) and re-estimate the target steering vector. Firstly, reconstruction of CJNCM consists of summing the eigenvectors of the projection operator, combining the sample covariance matrix and the integral covariance matrix (ICM) of specific region. Secondly, the re-estimated target steering vector is obtained by estimating the dominant eigenvector of the ICM of the Region of Interest (ROI), which contains the target signal purely because CJNCM is cancelled before estimation. Finally, the robust space-time adaptive filtering weight vector is calculated through the MVDR method with the reconstructed CJNCM and the re-estimated target steering vector. Simulation results indicate that the proposed algorithm shows robust performance against space-time steering vector mismatch, better output signal-to-noise ratio performance and better moving target detection performance than the traditional robust STAP method.

Systemic transplantation of oxygen-glucose deprivation (OGD)-preconditioned primary microglia enhances neurological recovery in rodent stroke models, albeit the underlying mechanisms have not been sufficiently addressed. Herein, we analyzed whether or not extracellular vesicles (EVs) derived from such microglia are the biological mediators of these observations and which signaling pathways are involved in the process. Exposing bEnd.3 endothelial cells (ECs) and primary cortical neurons to OGD, the impact of EVs from OGD-preconditioned microglia on angiogenesis and neuronal apoptosis by the tube formation assay and TUNEL staining was assessed. Under these conditions, EV treatment stimulated both angiogenesis and tube formation in ECs and repressed neuronal cell injury. Characterizing microglia EVs by means of Western blot analysis and other techniques revealed these EVs to be rich in TGF-beta 1. The latter turned out to be a key compound for the therapeutic potential of microglia EVs, affecting the Smad2/3 pathway in both ECs and neurons. EV infusion in stroke mice confirmed the aforementioned in vitro results, demonstrating an activation of the TGF-beta/Smad2/3 signaling pathway within the ischemic brain. Furthermore, enriched TGF-beta 1 in EVs secreted from OGD-preconditioned microglia stimulated M2 polarization of residing microglia within the ischemic cerebral environment, which may contribute to a regulation of an early inflammatory response in postischemic hemispheres. These observations are not only interesting from the mechanistic point of view but have an immediate therapeutic implication as well, since stroke mice treated with such EVs displayed a better functional recovery in the behavioral test analyses. Hence, the present findings suggest a new way of action of EVs derived from OGD-preconditioned microglia by regulating the TGF-beta/Smad2/3 pathway in order to promote tissue regeneration and neurological recovery in stroke mice. China Scholarship Council ; German Research Foundation (DFG)

Designing a practical Continuous Variable (CV) Quantum Key Distribution (QKD) system requires an estimation of the quantum channel characteristics and the extraction of secure key bits based on a large number of distributed quantum signals. Meeting this requirement in short timescales is difficult. On standard processors, it can take several hours to reconcile the required number of quantum signals. This problem is exacerbated in the context of Low Earth Orbit (LEO) satellite CV-QKD, in which the satellite flyover time is constrained to be less than a few minutes. A potential solution to this problem is massive parallelisation of the classical reconciliation process in which a large-code block is subdivided into many shorter blocks for individual decoding. However, the penalty of this procedure on the important final secured key rate is non-trivial to determine and hitherto has not been formally analysed. Ideally, a determination of the optimal reduced block size, maximising the final key rate, would be forthcoming in such an analysis. In this work, we fill this important knowledge gap via detailed analyses and experimental verification of a CV-QKD sliced reconciliation protocol that uses large block-length low-density parity-check decoders. Our new solution results in a significant increase in the final key rate relative to non-optimised reconciliation. In addition, it allows for the acquisition of quantum secured messages between terrestrial stations and LEO satellites within a flyover timescale even using off-the-shelf processors. Our work points the way to optimised global quantum networks secured via fundamental physics., Comment: Updated References

This paper presents a precise array response control with minimum pattern distortion (PARC-MPD) algorithm to synthesize beampatterns efficiently. Specifically, the magnitude and phase responses are considered to establish the minimum pattern distortion (MPD) criterion, and the geometric interpretation of response adjustment is given to understand the MPD criterion intuitively. The MPD solution is rigorously derived to realize precise magnitude response control at one intended direction and minimize the pattern distortion at any other direction simultaneously. Moreover, a novel pattern synthesis scheme based on the PARC-MPD algorithm is proposed to realize array response control in the mainlobe and sidelobe regions, and a brief comparison of the recently proposed array response control algorithms is provided to reveal their unified principle to beampattern synthesis. Simulation results under the linear and planar arrays are carried out to show the superiority of the PARC-MPD algorithm.

Grafted mesenchymal stem cells (MSCs) yield neuroprotection in preclinical stroke models by secreting extracellular vesicles (EVs). The neuroprotective cargo of EVs, however, has not yet been identified. To investigate such cargo and its underlying mechanism, primary neurons were exposed to oxygen‐glucose‐deprivation (OGD) and cocultured with adipose‐derived MSCs (ADMSCs) or ADMSC‐secreted EVs. Under such conditions, both ADMSCs and ADMSC‐secreted EVs significantly reduced neuronal death. Screening for signalling cascades being involved in the interaction between ADMSCs and neurons revealed a decreased autophagic flux as well as a declined p53‐BNIP3 activity in neurons receiving either treatment paradigm. However, the aforementioned effects were reversed when ADMSCs were pretreated with the inhibitor of exosomal secretion GW4869 or when Hrs was knocked down. In light of miR‐25‐3p being the most highly expressed miRNA in ADMSC‐EVs interacting with the p53 pathway, further in vitro work focused on this pathway. Indeed, a miR‐25‐3p oligonucleotide mimic reduced cell death, whereas the anti‐oligonucleotide increased autophagic flux and cell death by modulating p53‐BNIP3 signalling in primary neurons exposed to OGD. Likewise, native ADMSC‐EVs but not EVs obtained from ADMSCs pretreated with the anti‐miR‐25‐3p oligonucleotide (ADMSC‐EVsanti‐miR‐25‐3p) confirmed the aforementioned in vitro observations in C57BL/6 mice exposed to cerebral ischemia. The infarct size was reduced, and neurological recovery was increased in mice treated with native ADMSC‐EVs when compared to ADMSC‐EVsanti‐miR‐25‐3p. ADMSCs induce neuroprotection by improved autophagic flux through secreted EVs containing miR‐25‐3p. Hence, our work uncovers a novel key factor in naturally secreted ADMSC‐EVs for the regulation of autophagy and induction of neuroprotection in a preclinical stroke model.

This paper presents a multi-point array response control (MPARC) algorithm to realize fast beampattern synthesis. The MPARC algorithm stems from adaptive array theory, and it can adjust the array response at multiple angles, either simultaneously or individually. The designed weights are constructed as a linear combination of an initial weight vector and multiple steering vectors multiplied by different complex factors. Since the update of the designed weights would change the beampattern in the entire spatial domain, the minimum pattern distortion criterion is established to design the complex factors, and a closed-form weight vector is obtained. Moreover, a pattern synthesis scheme based on the MPARC algorithm is presented to synthesize focused and shaped beampatterns efficiently. The comparison with the existing oblique projection-based algorithms shows that the presented MPARC algorithm can achieve multi-point response adjustment with much lower computational complexity, and the angle omission problem is addressed in this paper. Numerical results are provided to demonstrate the performance of the MPARC algorithm in array response control and the efficiency in pattern synthesis.

In this work we review recent research in some select topics in quantum communications. In each of the topics chosen we highlight how the techniques presented are of direct interest to quantum protocols operating over macro-scales (inter-continental ranges) as well as to quantum protocols operating over nano-scales (inter-chip ranges).

There is a strong desire to develop docetaxel (DTX) formulation with good therapeutic effectiveness in view of serious adverse reactions of the commercial formulation of DTX (Taxotere®). In this study, a redox-responsive DTX-vitamin E prodrug was successfully formulated into liposomes with the drug loading of 4.14% ± 0.10%. Compared with DTX liposomes, the DTX prodrug liposomes (DPLs) showed good stability for 30-d shelf life and during dilution with different media. In vitro antitumor activity of DPLs on human prostatic carcinoma PC-3 cells and human lung cancer A549 cells was evaluated using cytotoxicity and apoptosis assays. In spite of a decrease in in vitro antitumor activity, the in vivo pharmacokinetic study reveals that DPLs exhibit significantly longer DTX plasma half-life (t1/2, 1.38-fold) and higher bioavailability (AUC0−t, 14.49-fold) compared with DTX liposomes. The antitumor activity of DPLs to the A549 tumor xenograft model showed selective accumulation in tumor tissue, significant inhibition the growth of the tumors and a much lower toxicity as seen in body weight loss, compared with DTX-Solution. Taken together, the results showed that DPLs is a promising strategy for DTX antitumor delivery.

Quantum key distribution (QKD) provides the opportunity to deliver unconditional communication security. The most robust version of QKD relies on quantum entanglement. Very recently, ubiquitous deployment of such entanglement-based QKD over large distances has moved closer to reality, as verified by quantum entanglement distribution from a low Earth orbit satellite. We will demonstrate that this robust form of QKD via space will require a renewed focus on short-block length error-correcting codes in order to facilitate the reconciliation phase of the key distribution. Focusing on discrete variable QKD and adopting the low data rates consistent with measured entanglement distribution from space, we quantify the benefits of state-of-the-art short- block length codes in the context of device- independent QKD. Our results highlight the trade- off between the attainable key throughput vs the communication latency encountered in space-based implementations of this ultra-secure technology.

The aim of the present study is to investigate whether the use of the biorelevant concentration of conventional surfactants as an alternative medium to simulated fasted state intestinal fluid (FaSSIF) for drugs with different acid–base properties is feasible. First, the equilibrium solubility of seven drugs representing diverse acid–base properties was determined. The solubility of those drugs was studied in pH 6.5 blank FaSSIF, FaSSIF containing physiological levels of sodium taurocholate and lecithin, and blank FaSSIF containing a series of concentrations of Tween 80 or sodium dodecyl sulfate (SDS) at 37 °C using the shake-flask method. The results demonstrated that the solubility of the seven drugs in 0.07% and 0.10% Tween 80 solutions matched better with the biorelevant media FaSSIF than SDS solutions (0.05% to 0.10%). Then the dissolution behavior of the BCS class II drug lacidipine was determined in SDS solutions, Tween 80 solutions and FaSSIF. Compared with FaSSIF, 0.07% Tween 80 was proved to be the best biorelevant-mimetic medium for lacidipine oral solid formulations. Then the dissolution tests of micronized lacidipine, carbamazepine, glimepiride and carvedilol tablets were conducted as internal and external validations, respectively. The results all demonstrated that the biorelevant concentration of Tween 80 could be set as 0.07% and such a cost-effective medium will hold a great potential in drug development and quality control of oral solid dosage forms.

A novel X-shaped four-armed gemini-like peglyated distearylglycerol (Gemini-PEG2K-GCDS), with two hydrophilic PEG heads and two hydrophobic stearic acid tails, was successfully synthesized and used as a nanomicellar carrier for delivery of doxorubicin. The critical micelle concentration of the amphiphilic copolymer was higher than 10(-6). Mean particle size and zeta potential of DOX-encapsulated Gemini-PEG2K-GCDS nanomicelles (DOX-GNMs) was 20.4nm and+3.91mv, respectively. Encapsulation efficiency of DOX-GNMs was as high as 94.6 and DOX release was pH-dependent from DOX-GNMs, ensuring the stability of nanomicelles in blood circulation and rapid release of DOX in tumor cells. Pharmacokinetic studies in rats following i.v. administration, DOX-GNMs demonstrated longer retention in blood and larger AUC (19.1-fold of t1/2 and 12.9-fold of AUC) compared with DOX solutions (DOX-Sol). Tissue distribution studies indicate that DOX-GNMs had higher tumor accumulation (4.6-fold) and lower heart toxicity in H22 tumor-bearing mice (17.4-fold) at 48h after administration in comparison with DOX-Sol. Moreover, IC50 of DOX-GNMs increased by 3.3-fold, 2.0-fold and 2.3-fold compared with DOX-Sol in P-gp over-expressing MCF-7/Adr cells after 24h, 48h and 72h, internalized via macropinocytosis-mediated and clathrin-mediated endocytosis. This study suggests that Gemini-PEG2K-GCDS nanomicelle is a promising long circulating delivery system for anti-tumor drugs via extended blood circulation and improved tumor distribution.

A novel redox-responsive PEG-sheddable copolymer of disulfide-linked polyethylene glycol 5000-lysine-di-tocopherol succinate (P 5k SSLV) was designed and synthesized. Thin-film hydration method was used to prepare DOX-loaded P 5k SSLV nanomicelle. To optimize the preparation technology, we investigate the effects of dosage, type of organic solvent, hydration temperature and time, and cryoprotectant on drug-loading content, encapsulation efficiency, particle size, and zeta potential. The mean particle size and zeta potential were determined by Zetasizer. The morphology of the P 5k SSLV-DOX nanomicelles was visualized by transmission electron microscopy. The drug-loading content and encapsulation efficiency of P 5k SSLV-DOX nanomicelle were investigated by UV. The drug-loading content, encapsulation efficiency, particle size, and zeta potential of the final optimized nanomicelles were 4.58%, 97.20%, 30.21 nm and −0.84 mV, respectively. In addition, the stability of nanomicelles was investigated, which included dilution stability and storage stability. The results showed that P 5k SSLV-DOX nanomicelle had good dilution stability and storage stability at 4 °C. The preparation method of P 5k SSLV-DOX nanomicelle with thin-film hydration method was practical and simple, which was valuable to be further studied.

A redox-responsive poly(ethylene glycol) (PEG)-sheddable copolymer of disulfide-linked PEG 5000-lysine-di-tocopherol succinate (P(5k)SSLV) is developed which can self-assemble into nanomicelles in aqueous condition and trigger the rapid release of encapsulated drugs within tumor cells. The reduction-insensitive doxorubicin (DOX)-loaded P(5k)LV (P(5k)LV-DOX) nanomicelles are further prepared. Then head-to-head comparison of P(5k)SSLV-DOX, P(5k)LV-DOX and DOX-Sol is performed concerning in vitro release, cytotoxicity, cellular uptake and apoptosis. Results show that P(5k)SSLV-DOX nanomicelles have a faster DOX release, a higher anti-tumor activity and more DOX concentrating in the nucleus than P(5k)LV-DOX nanomicelles. In conclusion, the redox-responsive P(5k)SSLV nanomicelles might hold a great potential to improve chemotherapy by tumor-triggering intracellular rapid release. The outcomes of this study also address the significance of such head-to-head comparison studies in translational research of nanomedicine.

Spherical nanoparticles as a classic delivery vehicle for anticancer drugs have been extensively investigated, but study on the shape of nanoparticles has received little attention until now. Here, a nonspherical poly(ethylene glycol) (PEG)-stabilized bilayer nanodisk consisting of 1,2-distearyl-sn-glycero-3-phosphocholine (DSPC) and PEG5000-glyceryl distearate (PEG5K-GCDS) was prepared for doxorubicin delivery, called DOX-Disks. The prepared disks were open bilayer structures, with a hydrophobic discoid center built by DSPC and a hydrophilic PEG edge. Mean particle diameter of the disk was 80.14 nm, and the disk height was about 6 nm with aspect ratio about 12. Encapsulation efficiency of DOX-Disks was as high as 96.1%, and DOX release from DOX-Disks was pH-dependent (25.6% of total DOX released at 24 h in pH 7.4). The pharmacokinetic performances showed that DOX-Disks demonstrated long circulation time in blood and larger AUC (11.7-fold of t1/2 and 31.7-fold of AUC) in rats compared with DOX solutions (DOX-Sol). Tissue distribution in H22 tumor bearing mice demonstrated higher tumor accumulation (9.7-fold) and lower heart toxicities (25.7-fold) at 48 h after iv administration, in comparison with DOX-Sol. In addition, DOX-Disks exhibited much effectiveness in inhibiting tumor cell growth, and the IC50 values were 2.03, 0.85, and 0.86 μg/mL for DOX-Sol and 0.23, 0.24, and 0.20 μg/mL for DOX-Disks after treatment for 48, 72, and 96 h against MCF-7/Adr cells, respectively. DOX-Disks were taken up into MCF-7/Adr cells via energy-dependent endocytosis processes, involved in clathrin-mediated, macropinocytosis-mediated, and non-clathrin- and non-caveolae-mediated endocytosis pathways. In summary, such PEG-stabilized bilayer nanodisks could be one of the promising carriers for antitumor drugs via extended blood circulation and improved tumor distribution.

In addition to being a physiological protective barrier, the gastrointestinal mucosal membrane is also a primary obstacle that hinders the oral absorption of many therapeutic compounds, especially drugs with a poor permeability. In order to resolve this impasse, we have designed multifunctional nanomicelles based on the acetylcysteine functionalized chitosan-vitamin E succinate copolymer (CS-VES-NAC, CVN), which exhibit marked bioadhesion, possess the ability to penetrate mucus, and enhance the oral absorption of a hydrophobic drug with a poor penetrative profile, paclitaxel. The intestinal absorption (Ka = 0.38 ± 0.04 min(-1), Papp = 0.059 cm · min(-1)) of CVN nanomicelles was greatly improved (4.5-fold) in comparison with paclitaxel solution, and CLSM (confocal laser scanning microscope) pictures also showed not only enhanced adhesion to the intestinal surface but improved accumulation within intestinal villi. The in vivo pharmacokinetics indicated that the AUC0-t (586.37 ng/mL · h) of CVN nanomicelles was markedly enhanced compared with PTX solution. In summary, the novel multifunctional CVN nanomicelles appear to be a promising nanocarrier for insoluble and poorly permeable drugs due to their high bioadhesion and permeation-enhancing capability.

Purpose We had conducted a comprehensive study on preparation, characterization and pharmacokinetics of nimodipine nanocrystals for oral administration previously, and nimodipine nanocrystals displayed lower dissolution profiles but higher bioavailability than Nimotop®. In this study, we aimed at elucidating the reasons of unfavorable in vitro in vivo correlation for NMD nanocrystals and Nimotop® with a hypothesis that special oral absorption mechanism was involved in the absorption of nimodipine nanocrystals. Methods Investigations of oral absorption mechanism of the nanocrystals were performed on everted gut sac models, lymphatically (mesenteric lymph duct) cannulated SD rats, Caco-2 cell monolayers and chylomicron flow blocking rats, respectively. Results The permeability of nanocrystals in duodenum, ileum and colon was not superior to that of Nimotop®, suggestive of special absorption mechanisms involved. Exudates of nanocrystals from enterocytes were detected in mesenteric lymphatic fluids using a transmission electron microscope, and the bioavailability was only about half of the control after the mesenteric lymph was blocked. The nanocrystals were taken up by enterocytes via macropinocytosis and caveolin-mediated endocytosis pathways. Conclusions It was impossible to establish a favorable in vitro in vivo correlation for NMD nanocrystals and Nimotop®, because portions of the nanocrystals underwent macropinocytosis and caveolin-mediated endocytosis by enterocytes as intact nanocrystal forms, then bypassed the liver first-pass metabolism.

In the previous study, we have synthesized an amphiphilic copolymer of nanostructure-forming material and P-glycoprotein (P-gp) inhibitor, lysine-linked ditocopherol polyethylene glycol 2000 succinate (PLV2K). The cytotoxicty in vitro and anticancer efficacy in vivo after intravenous administration of DOX-loaded PLV2K micelles (PLV2K-DOX) was found more effective than DOX solution (DOX-Sol). However, its performance and mechanism on oral absorption of doxorubicin are not well understood yet. PLV2K-DOX are spherical micelles with a narrow size distribution of 20.53 ± 2.44 nm. With an in situ intestinal perfusion model, the intestinal absorption potential of PLV2K-DOX was evaluated in comparison with DOX-Sol. PLV2K-DOX was specifically absorbed in duodenum and ileum sites of rats after oral administration. The intestinal absorption rate (Ka) of PLV2K-DOX is 3.19-, 1.61-, and 1.80-fold higher than that of DOX-Sol in duodenum, jejunum, and ileum, respectively. In Caco-2 uptake studies, PLV2K-DOX micelles significantly improve the internalized amount of DOX by P-gp inhibition of free PLV2K copolymer and endocytosis of DOX-loaded nanoparticles. Moreover, PLV2K-DOX micelles improve the membrane permeability of DOX by multiple transcytosis mechanisms, including caveolin-, clathrin-dependent, and caveolin-/clathrin-independent transcytosis in Caco-2 transport studies. However, the transepithelia electrical resistance (TEER) of Caco-2 cellular monolayer is not changed, suggesting no involvement of paracellular transport of PLV2K-DOX. In vivo pharmacokinetics in rats following oral administration demonstrated that PLV2K-DOX demonstrates higher AUC (5.6-fold) and longer t1/2 (1.2-fold) than DOX-Sol. The findings suggest the new PLV2K micelles might provide an effective nanoplatform for oral delivery of anticancer drugs with poor membrane permeability and low oral bioavailability.

Stealth active targeting nanoparticles (NPs) usually include two types of ligand sites: ligand anchored on distal ends of the polyethylene glycol (PEG) and ligand buried under pegylated layer. The latter typical case is hyaluronic acid (HA)-based NPs; however, there is little information available for the latter NPs about effect of the optimal density of surface PEG coating on the blood circulation time, cellular uptake and in vivo anticancer activity. Thus, in this study, in order to optimize the anticancer effects of HA-based NPs, we focus on how uncovalent pegylation degree modulates blood circulation time and cellular uptake of HA-based NPs. We firstly designed a new double-hydrophilic copolymer by conjugating HP-β-cyclodextrin with HA, and this carrier was further pegylated with adamantyl-peg (ADA-PEG) to form inclusion complex HA-HPCD/ADA-PEG, termed as HCPs. The supramolecular nanoassemblies were fabricated by host-guest and polar interactions between HCPs and doxorubicin (Dox), with vitamin E succinate (VES) being a nanobridge. Despite the active recognition between HA and CD44 receptor, the cellular uptake and targeting efficiency of HA-NPs decreased with the increasing peg density, demonstrating HA was partly buried by high density peg coating. However, the high density of peg coating was beneficial to long circulation time, tumor biodistribution and anticancer activity in vivo. NPs with 5% peg coating had the optimal cellular targeting efficiency in vitro and anticancer effects in vivo. The findings suggest that balancing long circulation property and cellular uptake is important to achieve the optimal antitumor efficacy for pegylated HA-based NPs, and that PEG coating densities cannot be extended beyond a certain density for shielding effect without compromising the efficacy of hyaluronic acid targeted delivery.

A redox-responsive poly(ethylene glycol) (PEG)-sheddable copolymer of disulfide-linked PEG 5000-lysine-di-tocopherol succinate (P(5k)SSLV) is developed which can self-assemble into nanomicelles in aqueous condition and trigger the rapid release of encapsulated drugs within tumor cells. The reduction-insensitive doxorubicin (DOX)-loaded P(5k)LV (P(5k)LV-DOX) nanomicelles are further prepared. Then head-to-head comparison of P(5k)SSLV-DOX, P(5k)LV-DOX and DOX-Sol is performed concerning in vitro release, cytotoxicity, cellular uptake and apoptosis. Results show that P(5k)SSLV-DOX nanomicelles have a faster DOX release, a higher anti-tumor activity and more DOX concentrating in the nucleus than P(5k)LV-DOX nanomicelles. In conclusion, the redox-responsive P(5k)SSLV nanomicelles might hold a great potential to improve chemotherapy by tumor-triggering intracellular rapid release. The outcomes of this study also address the significance of such head-to-head comparison studies in translational research of nanomedicine.

The aim of the present study was to correlate in vitro properties of drug formulation to its in vivo performance, and to elucidate the deciding properties of oral absorption. Gastrointestinal simulation technology (GST) was used to simulate the in vivo plasma concentration-time curve and was implemented by GastroPlus™ software. Lansoprazole, a typical BCS class II drug, was chosen as a model drug. Firstly, physicochemical and pharmacokinetic parameters of lansoprazole were determined or collected from literature to construct the model. Validation of the developed model was performed by comparison of the predicted and the experimental plasma concentration data. We found that the predicted curve was in a good agreement with the experimental data. Then, parameter sensitivity analysis (PSA) was performed to find the key parameters of oral absorption. The absorption was particularly sensitive to dose, solubility and particle size for lansoprazole enteric-coated tablets. With a single dose of 30 mg and the solubility of 0.04 mg/ml, the absorption was complete. A good absorption could be achieved with lansoprazole particle radius down to about 25 μm. In summary, GST is a useful tool for profiling biopharmaceutical deciding properties of absorption of lansoprazole enteric-coated tablets and guiding the formulation optimization.

Cylinder head with good concept design provides possibility for excellent NVH performance of engine. In order to achieve this, NVH function of cylinder head should be taken into account at concept stage to make sure a good foundation for late stage of engineering. In this chapter, at concept stage of engine development, designs of three different cylinder heads such as global architecture, water jacket, bolt number, bolt position and ribs in different sections are evaluated and compared. In this way, good designs and weaknesses are separated and sorted out in views of NVH. Along with these good designs, one head design of these three is rebuild and recalculated by means of simulation. Results show good NVH improvement of modes and responses and eventually proved the validity of designs. By the research in this chapter, firstly, the NVH performance of production has been improved. Secondly, reasonable structure characteristics of cylinder head are obtained which could be a part of cylinder head design database in view of NVH. And one creditable simulation working flow, by use of mode analysis method and structural attenuation method, for improving cylinder head NVH performance in engine concept development stage is established as well.

To improve the water quality of Wangyu River, which is the important diversion channel for Water Transfer from Yangtze River to Lake Taihu, a ecological spur-dike was constructed in Wangyu River, This project combined the traditional water conservancy engineering with the biofilm technology, which can not only slow velocity and settle down sediment but also degrade organic pollutants and absorption nutrients in river water by organisms in biofilm. After 39 days of the construction, biofilm characters on the surface of globular biofilter were performed five times to analyze the changing process of microbial community. In addition, 3 sites of water samples were also observed before and behind the spur-dike, and in the background of Wangyu River. it was found that spur-dike has good effect on water purification. Results show that 70 taxa of attaching organism were identified on the biofilter, and major divisions were Bacillariopyta 37, Chlorophyta 20 and Cyanophyta 7. Compared with the background values, the purification efficiency of SS, TP, TN and COD Mn were at the range of 5.1%–61.2%, 16.4%–57.2%, 8.2%–17.7%, 1.6%–34.5%, respectively. This study provided support for the development of river ecosystem restoration projects of in the future.

Pollutants resuspension in sediments affected by wind-wave could influence on the water quality in shallow lakes. The resuspension of surface sediments from Zhushan Bay, Taihu Lake was simulated by using a pneumatic annular flume in this study. There were 6 kinds of wind speeds in this experiment, including 1.60m/s, 3.62m/s, 6.36m/s, 8.04m/s, 10.38m/s and 14.10m/s. The velocity of water column was measured by Acoustic Doppler Velocimeter (ADV) in each wind forcing. The characteristics on release of suspended solid (SS) and total Hg in the processes of sediment resuspension were studied by layered sampling technology. The experimental results show that 6m/s was a critical wind speed which could change the hydrodynamic conditions significantly. The total resuspended amount of sediments was increased with the enhancement of hydrodynamic disturbances, and during the resuspension event, the total resuspended amount changed slightly after 5 hours except the latter two wind forcing conditions. There was no significant correlation between the release amount of Hg and hydrodynamic disturbance intensity. According to the relativity analysis between total Hg and SS in the overlying water, it could be known that particulate Hg is not the main existence of total Hg in the water column. Based on the analysis of wind speed (V), mean flow velocity (ū) and total resuspended amount of sediment particulates (W), quantitative relationships were achieved among these three variables, and they could be expressed by ū =0.2939V1.7683, W=1.9638V2.1609, and W=11.639exp(0.1669 ū). These three formulas could provide calculated methods of total resuspended amount of sediment particulates in shallow lakes.