The enhancement of cellular internalization and subsequent achievement of a nuclear targeting of nanocarriers play an important role in maximizing the therapeutic potency and minimizing the side effects of encapsulated drugs. Herein, a multifunctional micellar nanoplatform simultaneously with high cell penetration and nuclear targeting through pH-triggered surface charge reversal is presented. The miscellar system is constructed from poly(ethylene glycol)-poly(ε-caprolactone) with 2,3-dimethylmaleic anhydride-Tat decoration (PECL/DA-Tat). DA groups are used to mask the positive charge of Tat to prolong blood circulation of the nanocarriers. In the mildly acidic environment of tumor tissue, the system exhibits ultrasensitive negative to positive charge reversal, facilitating the cell internalization and subsequent nuclear targeting. The chemotherapeutic 10-hydroxycamptothecin conjugated to methoxy polyethylene glycol, which is loaded in this micelle, obviously enhances cytotoxicity against tumor cells. The in vivo therapy in mice bearing 4T1 breast tumor reveals that the system has a significant enhancement of both the endocytosis and nuclear enrichment, showing a highly effective antitumor efficacy and inhibition to lung metastasis.
To observe the histological changes in human skin within 32 days after death to explore its potential significance in forensic practice. The intact full-thickness skin and subcutaneous tissue from the sternum of eight corpses were placed in an environment of 4–6 °C for 4 h, 6 h, 12 h, 18 h, 24 h, 36 h, 48 h, 60 h, 72 h, 84 h, 96 h, 6 d, 8 d, 10 d, 12 d, 16 d, 20 d, 24 d, 28 d, and 32 d. Then, the whole layer of the skin was stained with haematoxylin & eosin. The histological morphology of the epidermis, dermis and appendages (sweat glands, hair follicles, and sebaceous glands) was observed under an light microscope. The epithelial nucleus condensed at 24 h after death, and cell lysis was exhausted after 20 days. The post-mortem changes in the dermis occurred later than that of the epidermis (72 h), but after epidermal changes started, the change was more rapid. At 16 d, the layers had become homogenized. The epidermis and dermis had completely separated 24 d after death. The changes in the sweat glands appeared earlier (24 h) and disappeared later (32 days); the sebaceous glands and hair follicles began to undergo degenerative changes at 96 h after death, and at approximately 20 d, only their contour remained. There were individual and structural differences in the post-mortem histological changes in the skin. At 4–6 °C ambient temperature, some structures of the human skin still exist for a long time after death, and these structures can be used to identify the source of the tissue; post-mortem histological changes in the skin occur at specific times, which can be used to help infer the time of death. A comprehensive observation of changes in the skin composition/structure is required to comprehensively analyse possible death times.
Considerable efforts have been devoted to enhancing the cell penetration of nanoparticles by coating cell‐penetrating peptides (CPPs) on the surface. However, the internalization mechanism for a CPP at different concentrations varies a lot. It is acknowledged that the mechanism is restricted to endocytic pathway at relatively low concentrations; however, direct translocation becomes dominant at high concentrations. This raises an interesting question on how the surface Tat coating density of the nanoparticles would influence their cell–membrane interaction and the consequent internalization behavior. This study systematically investigates the effect of Tat peptides on the internalization behavior of polymeric micelles by tuning surface Tat coating density, incubation concentrations, incubation time, and other factors using poly(ethylene glycol)–poly(ε‐caprolactone) copolymer (PEG‐PCL) micelles. It is found that both energy‐dependent and energy‐independent pathways are involved in the cellular uptake process, and the Tat‐conjugated polymeric micelles strongly accumulated on the cell surface at initial stage. The membrane‐anchoring and internalization rate increase with the increasing Tat coating density. Furthermore, the increasing of Tat coating density accelerates the energy‐independent pathway. It is envisioned that this finding will further shed light on the surface modification of nanoparticles for enhanced cell penetration and direct translocation into cell cytoplasm.
The service life prediction of reinforced concrete (RC) structures in marine environment is essential in structural repair and health monitoring. In this paper, a numerical model for predicting the service life of reinforced concrete is first developed which considering the time-varying boundary of chloride concentration, critical chloride concentration and density of corrosion current. Based on the model, the effects of water–cement ratio, reinforcement diameter, concrete cover thickness and critical chloride ion concentration on the service life and deterioration duration of RC structures are investigated. The key factors affecting the service life of reinforced concrete structures are determined. More importantly, based on regression analysis, a new simplified empirical model for predicting the service life of RC structures is also developed. It provides a fast assessment tool for practical engineers. Both the numerical model and empirical model validated are suitable for practical engineering applications. The results show that with the increase of water–cement ratio, the service life of reinforced concrete structure decreases exponentially. And with the increase of the thickness of the concrete cover, the service life, deterioration duration, and safety reserve increase linearly. However, the influence of the diameter of the reinforcing bar on the service life can be ignored.
A method is introduced to realize spatiotemporal chaos projective synchronization for a weighted network. The coupling function between connected nodes of the weighted network is derived and the range of the linear coefficient matrix of separated configuration in state equation of the node is obtained through constructing an appropriate Lyapunov function. Each node of the weight network is a laser spatiotemporal chaos model in which Bragg acousto-optical bistable system and unilateral coupled map lattices are taken as the local function and the spatial extended system, respectively. The projective synchronization effect of the weighted network is checked by numerical emulation. The results show that projective synchronization can be realized even if the coupling strength between the nodes are given arbitrary weight values.
Firstly, importance of severe accident provision is highlighted in view of Fukushima Daiichi accident. Then, extensive review of the past researches on severe accident phenomena in LWR is presented within this study. Various complexes, physicochemical and radiological phenomena take place during various stages of the severe accidents of Light Water Reactor (LWR) plants. The review deals with progression of the severe accidents phenomena by dividing into core degradation phenomena in reactor vessel and post core melt phenomena in the containment. The development of various computer codes to analyze these severe accidents phenomena is also summarized in the review. Lastly, the need of international activity is stressed to assemble various severe accidents related knowledge systematically from research organs and compile them on the open knowledge base via the internet to be available worldwide.
Energy dissipation mechanism is very important for the structural collapse-resistant performance under strong earthquakes. Two reinforced concrete (RC) frame-shear-wall structures with different span-depth ratios in coupling beams were designed according to current Chinese seismic design code and then analyzed by nonlinear time-history analysis method under a serial of strong earthquake records. Based on the analysis results, energy dissipation mechanism and collapse-resistant performance of the two structures under strong earthquakes are studied. And the “strong wall limb-weak coupling beam” mechanism, which is achieved in the structure with larger span-depth ratio in coupling beams, is proposed to serve as the reasonable energy dissipation mechanism for RC frame-shear-wall structure. The damage of wall limb is controlled effectively under this energy dissipation mechanism, which leads to good collapse-resistant performance.
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