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With the increasing influence of new energy power system, the prediction of Photovoltaic (PV) output power becomes more and more important In this paper, it is the first time to put forward a hybrid modeling method combining long–short term memory recurrent neural network (LSTM) and stochastic differential equation (SDE). This method realizes the prediction of PV output power in different seasons and overcomes the uncertainty of PV power generation. Wavelet analysis and automatic encoder are used to decompose data and extract important features. According to the detailed signal sequence and the approximate signal sequence, the LSTM prediction model is established. Meanwhile, the mathematical model of SDE is established according to the detailed signal sequence. Finally, the output sequences of the two models are reconstructed by wavelet transform. This hybrid model can not only realize the point prediction of PV output power according to the predicted mean value, but also achieve the interval prediction under different confidence levels according to the randomness. In this paper, the proposed method is applied to predict the PV output power of CHINT photovoltaic power generation system with installed capacity of 10MW in different seasons, and the weather forecast data with errors of ± 10%, ± 20% and ± 30% are used. Experimental results prove the effectiveness of the method. In the summer model considering forecast errors within ± 20% of weather forecast data, the RMSEs of BP neural network, LSTM and convolutional neural network (CNN) are 5.9468, 5.6762 and 5.8004 respectively. However, the RMSE of the mean prediction with the confidence level of 90% under the proposed method is 4.4647. With this method, the results of interval prediction and point prediction of PV output power can provide better decision support for the stable and safe operation of PV grid connection. They have higher reference value for energy dispatching departments. • Combining LSTM neural network with stochastic differential equation for the first time by wavelet analysis. • The features of weather data are strongly extracted by autoencoder. • Application of hybrid modeling method to photovoltaic power prediction. • Obtaining different confidence intervals by changing random factors. [ABSTRACT FROM AUTHOR]

Isogarcinol, a natural compound extracted from the fruits of Garcinia oblongifolia , has potential chemopreventive activity. This study aimed to elucidate the anti-tumor effects and mechanism of action of isogarcinol on nasopharyngeal carcinoma (NPC). Isogarcinol was isolated from Garcinia oblongifolia by using chromatographic separation. The anti-tumor effects of isogarcinol in NPC cells were tested by MTT assay, flow cytometry, wound healing assay, western blotting, transwell assay, colony formation assay, immunofluorescence, and transmission electron microscopy (TEM). The anti-tumor efficacy in vivo was evaluated in NPC cells xenograft models. Functional studies revealed that isogarcinol inhibited the proliferation, colony formation, migration and invasion abilities of NPC cells in vitro. Isogarcinol caused mitochondrial damage to overproduce reactive oxygen species through reducing the mitochondrial membrane potential and ΔΨm. Isogarcinol also substantially inhibited NPC cells growth in a xenograft tumor model without any obvious toxicity when compared with paclitaxel (PTX). Mechanistic studies have illustrated that isogarcinol increased the Bax/Bcl-2 ratio, cleaved caspase-3, and cytoplasmic cytochrome C levels to induce mitochondrial apoptosis. The ROS overproduction by isogarcinol could suppress EMT pathway via decreasing the levels of p-Akt and Snail. Furthermore, isogarcinol promoted the conversion of LC3-Ⅰ to LC3-Ⅱ, but increased p62 level to block autophagic flux, resulting in the accumulation of damaged mitochondria to promote autophagic cell death in NPC cells. This study provides a new theoretical foundation for the anti-tumor application of Garcinia oblongifolia and confirms that isogarcinol could be developed as a candidate drug for NPC treatment with low toxicity. [Display omitted] [ABSTRACT FROM AUTHOR]

Solid polymer electrolyte (SPE) has been considered as promising candidate electrolyte for solid-state lithium metal battery. However, the low ion conductivity and poor interface stability seriously hinder the development of SPE. Introducing the functional filler is a commonly used and effective approach to solving these issues. The poor compatibility and ambiguous mechanism of action are currently the main challenges. In this study, we design and synthesize carbon dots (NSFCDs) with quaternary functional groups, which are introduced into the SPE in the polymerization process of hybrid polymer electrolyte (HPE). The detailed effect law of polyfunctional groups on the polymer chain structure, interface structure of electrolyte/electrode and ion migration is systematically revealed. The dense polymer network endows HPE with enhanced mechanical properties. Through the regulation of polymer segments, the coordination environment of lithium ions is altered, promoting ion transport. The solid electrolyte interface (SEI) induced by NSFCDs and lithium salt anions effectively improves the morphology of lithium ion deposition and alleviates volume strain. As a result, the HPE based on polyethylene oxide (PEO) constructed by free radical polymerization of NSFCDs and polyethylene glycol diacrylate (PEGDA) exhibits excellent comprehensive performance, the assembled Li symmetric battery can cycle stably for 4000 h. [Display omitted] • Synthesis of high yield multifunctional group-doped carbon dots. • Carbon dots act as crosslinking centers to enhance mechanical strength and ionic conductivity. • Modulation of lithium-metal interfacial components to construct stable solid-state lithium-metal batteries. [ABSTRACT FROM AUTHOR]

Mutations in the plant homeodomain-like finger protein 6 (PHF6) gene are strongly associated with acute myeloid (AML) and T-cell acute lymphoblastic leukemia (T-ALL). In this study, we demonstrated that PHF6 can bind to H3K9me3 and H3K27me1 on the nucleolar chromatin and recruit histone methyltransferase SUV39H1 to the rDNA locus. The deletion of PHF6 caused a decrease in the recruitment of SUV39H1 to rDNA gene loci, resulting in a reduction in the level of H3K9me3 and the promotion of rDNA transcription. The knockdown of either SUV39H1 or PHF6 significantly attenuated the effects of increase in H3K9me3 and suppressed the transcription of rDNA induced by the overexpression of the other interacting partner, thereby establishing an interdependent relationship between PHF6 and SUV39H1 in their control of rRNA transcription. The PHF6 clinical mutants significantly impaired the ability to bind and recruit SUV39H1 to the rDNA loci, resulting in an increase in rDNA transcription activity, the proliferation of in vitro leukemia cells, and the growth of in vivo mouse xenografts. Importantly, significantly elevated levels of pre-rRNA were observed in clinical AML patients who possessed a mutated version of PHF6. The specific rDNA transcription inhibitor CX5461 significantly reduced the resistance of U937 AML cells deficient in PHF6 to cytarabine, the drug that is most commonly used to treat AML. Collectively, we revealed a novel molecular mechanism by which PHF6 recruits methyltransferase SUV39H1 to the nucleolar region in leukemia and provided a potential therapeutic target for PHF6 -mutant leukemia. Wild-type PHF6 is recognized as H3K9me3 and H3K27me1, and it recruits SUV39H1 to catalyze the methylation of H3K9 and H3K27 to inhibit the transcription of rDNA. When PHF6 is mutated, SUV39H1 cannot be recruited for rDNA methylation, resulting in uncontrolled rDNA transcription. [Display omitted] [ABSTRACT FROM AUTHOR]

Stabilizing zinc anode is a systematic project for aqueous zinc ion batteries (ZIBs), which needs to solve many problems such as dendrite growth, corrosion, hydrogen evolution, and other side reactions. It is urgent to develop a protective layer for zinc anode to solve these problems at one time. Based on the results of calculation, a hydrophobic multifunctional fluorinated carbon dots (F-CDs) protective layer with three kinds of zincophilic groups (-C O, -CHO and -F) was constructed on the Zn anode surface. As expected, these zincophilic groups on the F-CDs layer functioned as zincophilic sites to achieve uniform Zn deposition. Especially, the -F group could in-situ promote the formation of ZnF 2 under the F-CDs layer and the ZnF 2 layer is usually considered as a solid Zn2+ conductor layer to further even Zn deposition. Additionally, the experimental results also demonstrated that the F-CDs layer coupled with in-situ generated ZnF 2 interlayer can not only tackle above issues in an integrated way, but also induce the deposition of Zn on the preferred (002) plane. Therefore, the Zn@F-CDs anode exhibits an ultra-long cycling life over 3500 h at 1 mA cm–2, together with an excellent average coulombic efficiency (99.32% for over 1100 h) in half cells. [Display omitted] • The mutifunctional layer inhibit Zn dendrites and side reactions simultaneously. • F-CDs layers with three kinds of zincophilic groups achieve uniform Zn deposition. • the -F group on the F-CDs layer benefit to the in-situ formation of ZnF 2 interlayer. • Symmetric cells display low voltage hysteresis and excellent stability over 3500 h. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Various drugs have been designed in the past to act on intracellular targets. For the desired effects to be exerted, these drugs should reach and accumulate in specific subcellular organelles. CX-5461 represents a potent small-molecule inhibitor of rRNA synthesis that specifically inhibits the transcription driven by RNA polymerase (Pol) I and induces tumor cell death through triggering a pro-death autophagy. In the current study an innovative kind of CX-5461-loaded mesoporous silica nano-particles enveloped by polyethylene glycol (PEG), polydopamine (PDA) and AS-1411 aptamer (MSNs-CX-5461@PDA-PEG-APt) with the aim of treating cancer cells was constructed, in which the high-surface-area MSNs allowed for high drug loading, PDA acted as gatekeeper to prevent the leakage of CX-5461 from MSNs, PEG grafts on PDA surfaces increased the stable and biocompatible property in physiological condition, and AS-1411 aptamer promoted the nucleolar accumulation of CX-5461. MSNs-CX-5461@PDA-PEG-APt was characterized regarding releasing characteristics, steadiness, encapsulation of drugs, phase boundary potential as well as sizes of particles. Expectedly, In vitro assays showed that aptamer AS-1411 significantly increased the nucleolar accumulation of CX-5461. The aptamer-tagged CX-5461-loaded MSNs demonstrated to be more cytotoxic to cervical cancer cells compared to the control MSNs, due to relatively strong inhibition of rRNA transcription and induction of pro-death autophagy. The in vivo treatment with AS-1411-tagged CX-5461-loaded MSNs showed a stronger distribution in tumor tissues by animal imaging assay and a significantly higher inhibition effect on the growth of HeLa xenografts compared to AS-1411-untagged CX-5461-loaded MSNs. In addition, histology analysis indicated that MSNs-CX-5461@PDA-PEG-APt did not exhibit any significant toxicity on main organs. These results collectively suggested that MSNs-CX-5461@PDA-PEG-APt represents both a safe and potentially nucleolus-targeting anti-cancer drug. Statement of Significance Many drugs function in specific subcellular organelles. CX-5461 is a specific inhibitor of nucleolar rRNA synthesis. Here, we reported a novel aptamer-tagged nucleolus-targeting CX-5461-loaded nanoparticle, which specifically accumulated in nucleoli and significantly inhibited the tumor growth in vitro and in vivo through inhibiting rRNA transcription and triggering a pro-death autophagy. [ABSTRACT FROM AUTHOR]

• Sophflarine A, a novel matrine-derived alkaloid with significantly anti-NSCLC activity was isolated from sophora flavescens. • Sophflarine A could induce pyroptosis and activate autophagy to inhibit the proliferation in NSCLS cells. • Sophflarine A inhibited migration, invasion, colony formation and angiogenesis in NSCLC cells. • Sophflarine A treatment blocked tumor growth in an A549 cell-bearing orthotopic mouse model. Novel compounds and more efficient treatment options are urgently needed for the treatment of non-small cell lung cancer (NSCLC). The decoction of Sophora flavescens has been used to treat NSCLC in the clinic, and matrine-type alkaloids are generally considered to be the key pharmacodynamic material basis. But the previous study showed that common matrine-type alkaloids exhibit significant cytotoxicity only when at concentrations close to the millimolar (mM) level. The key antitumor alkaloids in S. flavescens seem to have not yet been revealed. The aim of this study was to screen water-soluble matrine alkaloid with novel skeleton and enhanced activity from S. flavescens , and to reveal the pharmacological mechanism of its therapeutic effect on NSCLC. Alkaloid was obtained from S. flavescens by chromatographic separation methods. The structure of alkaloid was determined by spectroscopic methods, and single-crystal X-ray diffraction. The mechanism of anti-NSCLC in vitro with cellular models was evaluated by MTT assay, western blotting, cell migration and invasion assay, plate colony-formation assay, tube formation assay, immunohistochemistry assay, hematoxylin and eosin staining. The antitumor efficacy in vivo was test in NSCLC xenograft models. A novel water-soluble matrine-derived alkaloid incorporating 6/8/6/6 tetracyclic ring system, named sophflarine A (SFA), was isolated from the roots of S. flavescens. SFA had significantly enhanced cytotoxicity compared with the common matrine-type alkaloids, having an IC 50 value of 11.3 μM in A549 and 11.5 μM in H820 cells at 48 h. Mechanistically, SFA promoted NSCLC cell death by inducing pyroptosis via activating the NLRP3/caspase-1/GSDMD signaling pathway, and inhibited cancer cell proliferation by increasing the ROS production to activate autophagy via blocking the PI3K/AKT/mTOR signaling pathway. Additionally, SFA also inhibited NSCLC cell migration and invasion by suppressing EMT pathway, and inhibited cancer cell colony formation and human umbilical vein endothelial cell angiogenesis. In concordance with the above results, SFA treatment blocked tumor growth in an A549 cell-bearing orthotopic mouse model. This study revealed a potential therapeutic mechanism of a novel matrine-derived alkaloid, which not only described a rational explanation for the clinical utilization of S. flavescens , but also provided a potential candidate compound for NSCLC treatment. [Display omitted] [ABSTRACT FROM AUTHOR]

Garnet-based Li 6.5 La 3 Zr 1.5 Ta 0.5 O 12 (LLZTO) is a prospective solid-state electrolyte with fast ionic mobility and distinguished chemical/electrochemical stabilities toward Li metal. However, Li dendrite propagated within LLZTO bulk is one of the main obstacles to the practical application of solid-state batteries. Herein, we propose to inhibit Li dendrite growth through in-situ construction of a multifunctional interlayer of Li 2 S/LiSn alloy achieved via a conversion reaction of SnS layer coated on the surface of the LLZTO pellet. DFT calculation reveals that the interfacial contact of LLZTO and Li is considerably improved via Li 2 S/LiSn interlayer, consequently contributing to a low interfacial impendence (5.1 Ω cm2). Furthermore, the electronic insulativity of LLZTO is also meliorated to suppress electron tunneling. As a result, with effectively restraining the Li dendrite, the Li|LLZTO@Li 2 S/LiSn|Li symmetrical battery exhibits a superb long-term Li plating/stripping performance over 1500 h and 700 h under 0.2 and 0.4 mA cm−2, respectively. Furthermore, the LFP|LLZTO@Li 2 S/LiSn|Li full battery displays notable cycling performance (99.8% capacity retention after 100 cycles at 1 C) and rate properties (160.6 mAh g−1 at 0.1 C and 116.3 mAh g−1 at 1 C). This facile and effective method may provide a feasible strategy for eliminating the interfacial issue and achieving dendrite-free solid-state Li metal batteries. [Display omitted] • A dense and continuous multifunctional conductive interlayer of Li 2 S and LiSn alloy is successfully constructed on the surface of the Li 6.5 La 3 Zr 1.5 Ta 0.5 O 12 (LLZTO) pellet. • The CCD of Li|LLZTO@Li 2 S/LiSn|Li symmetrical cell reaches 0.9−2. • Symmetrical cell can cycle steadily at a high current density of 0.4 mA cm−1 for over 700 h. • Full battery with LiFePO 4 as a cathode displays distinguished cycle performance. [ABSTRACT FROM AUTHOR]

[Display omitted] A new hydrocyanine probe containing a ROS-responsive element and a mitochondrial-targeting moiety, as well as a thiol-reactive chloromethyl group, has been designed for imaging reactive oxygen species (ROS) in the mitochondria of live cells. This hydrocyanine probe is cell-permeable, selectively targets mitochondria and responds to superoxide and hydroxyl radical, and can be used for detection of ROS production in the mitochondria of live cells caused by an oxidative stress. [ABSTRACT FROM AUTHOR]

We developed a system of biodegradable nanoparticles (NPs) of 5,10,15,20-tetrakis(4-aminophenyl)-21H,23H-porphine (TAPP) centered, 4 arm star-shaped copolymers based on poly(ε-caprolactone) (PCL) and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) for combinatory chemophotodynamic therapy by using docetaxel (DTX) as a model anticancer drug and TAPP as photodynamic sensitizer. TPGS component in the copolymer plays an important role in enhancing the drug encapsulation efficiency, drug release kinetics and cellular uptake of the NPs, as well as in overcoming the multidrug resistance due to inhibition of P-glycoproteins (P-gp) of the cancer cells. We demonstrated in vitro by using the MCF7/ADR breast cancer cells of P-gp overexpression and the HeLa cervical cancer cells that the proposed chemophotodynamic therapy by the DTX-loaded TAPP-PCL- b -TPGS NPs could have much higher therapeutic effect than the original drug Taxotere®. IC 50 data showed that the DTX-loaded TAPP-PCL- b -TPGS NPs chemophotodynamic therapy could be 9.36 and 56.5-fold efficient after 24 and 48 h treatment, respectively in comparison with the Taxotere® chemotherapy. The in vivo investigation by employing a cervical cancer xenograft model further confirmed the advantages of the proposed chemophotodynamic therapy by the DTX-loaded TAPP-PCL- b -TPGS NPs versus the Taxotere® chemotherapy. [ABSTRACT FROM AUTHOR]

Metallic Na with high specific capacity is considered as one of the most desirable alternatives for both stationary and portable electrical energy storage. However, uncontrollable dendrite generated from sluggish electrochemical kinetics and chemical instability of the solid-electrolyte interphase (SEI) layer seriously hampers the practical application of Na metal anode. Herein, interface-rich artificial interlayer composed of NaBr/Na 3 P nano-crystallines (NaBrP) is constructed on Na metal surface to manipulate the Na diffusion behaviors. As assisted theoretically, Na 3 P phase with rich ionic conductive channels greatly eliminates the diffusion barriers for Na+ permeation, while NaBr phase with low surface diffusion barrier and large band gap ensures fast spread of Na+ along the interface with promoted ionic distribution and interfacial stability. Furthermore, undesirable Na dendrites and electrolyte decomposition are significantly suppressed from the interlayer with high mechanical and chemical stability. In virtue of this robust interlayer, columnar and uniform Na is herein plated beneath NaBrP-protected electrode with a dendrite-free morphology, which achieves a prolonged lifespan of symmetrical cells over 700 h with minor polarization fluctuation and promotes the Na 3 V 2 (PO 4) 3 based full cells with a long-term stability of 500 cycles at 5 C as well as a high rates capacity of 38.4 mAh g−1 at 30 C (13.5 mA cm−2). This work systemically discovers the internal mechanism of Na+ transport within the SEI component, and provides an efficient strategy to realize high-performance sodium metal anode. A rationally designed interlayer is efficiently constructed on Na metal surface by immersing Na foil into an DME solvent contained PBr 3 at room temperature followed by a rolling pressing process, which allows a columnar sodium metal anode with a long-term stability and achieves high performance sodium metal battery. [Display omitted] • A robust artificial interlayer composed of Na 3 P and NaBr is efficiently constructed on Na metal anode. • Enhanced electrochemical Kinetics has been demonstrated by DFT calculations and symmetric cell. • Columnar sodium deposition is observed with this interlayer. • Na 3 P/NaBr modified Na metal exhibited enhanced electrochemical performance over 700 h. [ABSTRACT FROM AUTHOR]

Abstract: A star-shaped biodegradable polymer, mannitol-core poly(d,l-lactide-co-glycolide)-d-α-tocopheryl polyethylene glycol 1000 succinate (M-PLGA-TPGS), was synthesized in order to provide a novel nanoformulation for breast cancer chemotherapy. This novel copolymer was prepared by a core-first approach via three stages of chemical reaction, and was characterized by nuclear magnetic resonance, gel permeation chromatography and thermogravimetric analysis. The docetaxel-loaded M-PLGA-TPGS nanoparticles (NPs), prepared by a modified nanoprecipitation method, were observed to be near-spherical shape with narrow size distribution. Confocal laser scanning microscopy showed that the uptake level of M-PLGA-TPGS NPs was higher than that of PLGA NPs and PLGA-TPGS NPs in MCF-7 cells. A significantly higher level of cytotoxicity was achieved with docetaxel-loaded M-PLGA-TPGS NPs than with commercial Taxotere®, docetaxel-loaded PLGA-TPGS and PLGA NPs. Examination of the drug loading and encapsulation efficiency proved that star-shaped M-PLGA-TPGS could carry higher levels of drug than linear polymer. The in vivo experiment showed docetaxel-loaded M-PLGA-TPGS NPs to have the highest anti-tumor efficacy. In conclusion, the star-like M-PLGA-TPGS copolymer shows potential as a promising drug-loaded biomaterial that can be applied in developing novel nanoformulations for breast cancer therapy. [Copyright &y& Elsevier]

Proper regulation of plasma membrane protein endocytosis by external stimuli is required for cell growth and survival. In yeast, excess levels of certain nutrients induce endocytosis of the cognate permeases to prevent toxic accumulation of metabolites. The α-arrestins, a family of trafficking adaptors, stimulate ubiquitin-dependent and clathrin-mediated endocytosis by interacting with both a client permease and the ubiquitin ligase Rsp5. However, the molecular mechanisms that control α-arrestin function are not well understood. Here, we show that α-arrestin Aly1/Art6 is a phosphoprotein that specifically interacts with and is dephosphorylated by the Ca2+- and calmodulin-dependent phosphoprotein phosphatase calcineurin/PP2B. Dephosphorylation of Aly1 by calcineurin at a subset of phospho-sites is required for Aly1-mediated trafficking of the aspartic acid and glutamic acid transporter Dip5 to the vacuole, but it does not alter Rsp5 binding, ubiquitinylation, or stability of Aly1. In addition, dephosphorylation of Aly1 by calcineurin does not regulate the ability of Aly1 to promote the intracellular sorting of the general amino acid permease Gap1. These results suggest that phosphorylation of Aly1 inhibits its vacuolar trafficking function and, conversely, that dephosphorylation of Aly1 by calcineurin serves as a regulatory switch to promote Aly1-mediated trafficking to the vacuole. [ABSTRACT FROM AUTHOR]

Abstract: Cervical cancer remains a critical problem that is second only to breast cancer affecting women worldwide. The objective of this study was to develop formulation of docetaxel-loaded biodegradable poly(ɛ-caprolactone-co-lactide)-d-α-tocopheryl polyethylene glycol 1000 succinate (PCL-PLA-TPGS) nanoparticles for cervical cancer chemotherapy. A novel random copolymer, PCL-PLA-TPGS, was synthesized from ɛ-caprolactone, lactide and d-a-tocopheryl polyethylene glycol 1000 succinate (TPGS) by ring-opening polymerization. The obtained polymers were characterized by 1H NMR, FTIR, GPC and TGA. The docetaxel-loaded PCL-PLA-TPGS nanoparticles were prepared by a modified solvent extraction/evaporation technique and characterized in terms of size and size distribution, morphology, surface charge and physical state of encapsulated docetaxel. Cellular uptake and in vitro cytotoxicity of nanoparticle formulations were done in comparison with commercial formulation Taxotere® to investigate the efficacy of PCL-PLA-TPGS nanoparticles. In vitro cellular uptakes of such nanoparticles were investigated with CLSM, demonstrating the coumarin 6-loaded PCL-PLA-TPGS nanoparticles could be internalized by Hela cells. In vitro cancer cell viability experiment showed that judged by IC50, the PCL-PLA-TPGS nanoparticle formulation was found to be more effective in cell number reduction than the Taxotere® after 48 h (p < 0.05), 72 h (p < 0.05) treatment. In conclusion, the PCL-PLA-TPGS copolymer could be acted as a novel and promising biologically active polymeric matrix material for nanoparticle formulation in cervical cancer treatment. [ABSTRACT FROM AUTHOR]

Abstract: Multidrug resistance (MDR) of tumor cells is a major obstacle to the success of cancer chemotherapy. Poloxamers have been used in cancer therapy to overcome MDR. The objective of this research is to test the feasibility of paclitaxel-loaded poly(ε-caprolactone)/Poloxamer 188 (PCL/Poloxamer 188) nanoparticles to overcome MDR in a paclitaxel-resistant human breast cancer cell line. Paclitaxel-loaded nanoparticles were prepared by a water–acetone solvent displacement method using commercial PCL and self-synthesized PCL/Poloxamer 188 compound, respectively. PCL/Poloxamer 188 nanoparticles were found to be of spherical shape and tended to have a rough and porous surface. The nanoparticles had an average size of around 220nm, with a narrow size distribution. The in vitro drug release profile of both nanoparticle formulations showed a clear biphasic release pattern. There was an increased level of uptake of PCL/Poloxamer 188 nanoparticles (PPNP) in the paclitaxel-resistant human breast cancer cell line MCF-7/TAX, in comparison with PCL nanoparticles. The cytotoxicity of PCL nanoparticles was higher than commercial Taxol® in the MCF-7/TAX cell culture, but the differences were not significant. However, the PCL/Poloxamer 188 nanoparticles achieved a significantly higher level of cytotoxicity than both of PCL nanoparticle formulation and Taxol®, indicating that paclitaxel-loaded PCL/Poloxamer 188 nanoparticles could overcome MDR in human breast cancer cells and therefore could have considerable therapeutic potential for breast cancer. [Copyright &y& Elsevier]

The synthesis of 10 N-(fluoren-9-ylmethoxycarbonyl)glycopyranosylamine uronic acids that are amenable to solid-phase synthesis is described. The general synthetic strategy involves initial incorporation of the protected amine, followed by selective TEMPO oxidation of C-6 hydroxyl groups to give the corresponding Fmoc-protected sugar amino acids. Amine incorporation may be accomplished from aminolysis of the free sugar or from glycosyl azide reduction. The reactions can be carried out on multigram scale, providing access to unique monomer units for future incorporation into combinatorial library syntheses. [Copyright &y& Elsevier]

Per-O-acetylated d-glycopyranoses derived from both mono- and disaccharides were first converted to glycosyl iodides and subsequently reacted with an azide source to achieve the stereoselective synthesis of β-d-glycosyl azides after deacetylation. Low-temperature (4 °C) TEMPO oxidation of the monosaccharides provided the corresponding uronic acids, which were purified as the free acids. Oxidation of the lactosyl- and cellobiosyl azides resulted in diacid formation. However, 4′,6′-O-benzylidene protection enabled selective oxidation of the C-6 hydroxyl. 2-Acetamido-2-deoxy-d-glycopyranosyl azides were also prepared and converted to uronic acids completing the library synthesis. [Copyright &y& Elsevier]

Li metal is the ultimate anode material for Li based battery with high energy density. However, inhomogeneous charge distribution from the unbalanced ion/electron transport is usually generated at the electrode surface, leading to the uncontrollable dendrites with poor reversibility. Herein, interconnected Li 3 P@Cu ion/electron conductive interlayer activated from interfacial reaction between Cu 3 P arrays and metallic Li is efficiently constructed on Li foil surface through room-temperature mechanical rolling process for charge redistribution. Demonstrated by theoretic calculation, the diffusion barrier of Li+ is remarkably reduced from Li 3 P interphase with high ionic conductivity, while the electron-conductive Cu domains ensures well-dispersed current density, facilitating the uniform distribution of interfacial Li+ flux. Furthermore, the interconnected skeletons with extensive active channels significantly enhances the electrochemical kinetics and promotes the reversibility of Li plating/stripping processes. As expected, a prolonged lifespan of symmetrical cells over 1500 h with lower polarization is successfully achieved at 1 mA cm−2, further improving the rates and cycling performances of LiFePO 4 based full cells in mass loading of 8.5 mg cm−2 with a capacity retention up to 91.7% after 300 cycles. This work proposed a rational interlayer design for interfacial charge redistribution and presents an efficient strategy to realize dendrite-free Li metal anode. The practical application of Li metal battery is predominately retarded by the uncontrollable dendrite growth from unbalanced ion/electron transport. In this work, a room-temperature interfacial reaction was applied to construct Li 3 P/Cu mixed conductive layer for interfacial charge redistribution via a facial mechanical rolling press method. Interestingly, the derived coating layer with mixed ion/electron conductive feature significantly enhances the electrochemical kinetics and promotes the interfacial charge redistribution with a dendrite-free deposition morphology. Greatly, Li@MCI based symmetric cells achieves a prolonged lifespan over 1500 h at 1 mA cm−2 with lower polarization than that of Li based cells, which further promotes the rate performance and stability of the Li@MCI based full batteries with a high-loading LiFePO 4 cathode (8.5 mg cm−2). [Display omitted] • Interconnected Li 3 P@Cu MCI was efficiently constructed on Li foil surface for interfacial charge redistribution. • Enhanced electrochemical Kinetics has been demonstrated by DFT calculations and symmetric cell. • Epitaxially growth of lithium was achieved within Li 3 P@Cu interlayer. • Li 3 P@Cu modified Li metal exhibited robust electrochemical performance over 1500 h. [ABSTRACT FROM AUTHOR]

[Display omitted] • Self-assembly characteristics of nanoparticle, polymer and surfactant are studied. • Molecular dynamics mechanism of Coulomb, vdW and hydration effects is analyzed. • An electric triple layer structure for self-assembly aggregate is established. • The attraction layer in Gouy-Chapman-Stern + ion-attraction model is explained. Research on dispersion and stability of nanoparticles in liquid media is one of the key subjects for nanomaterial utilization. Coarse-grained molecular dynamics simulations are carried out to research the self-assembly behaviors of the nanoparticles, PEO (polyethylene oxide) and OTAC (octadecyltrimethylammonium chloride) compound solution system, so as to explore the mechanism of nanoparticle dispersion stability with PEO and OTAC additives. It shows that nanoparticles influence and participate the self-assembly process of PEO and OTAC molecules mainly by electrostatic interactions. In the formation of nanoparticle-PEO-OTAC aggregate, the electrostatic potential plays a controlling role, while the van der Waals potential and hydration effect mainly stabilize and regulate the local connections between different individuals so as to balance the electrostatic potential. An electric triple layer (inner layer-coordinating adsorption layer-diffusion layer) structure is formed in the nanoparticle-PEO-OTAC aggregate, wherein the coordinating adsorption layer is essentially the secondary coordinating adsorption of individuals to the inner layer. [ABSTRACT FROM AUTHOR]

To improve the load capacity and reduce the influence of misalignment, the mathematical model and computerized analysis of spiral bevel gears based on geometric elements have been developed, which are point contact with normal cross-sectional circular arc tooth profiles and established on spherical involute spiral bevel drives, leading to the separability of shaft angle. The meshing theory and numerical model of the meshing pairs are put forward. The contact and meshing performance are discussed in detail, which include the point-contact meshing characteristics, the separability of shaft angle, the sliding characteristics and the contact ratio of the meshing pairs. The formation of contact and bending stress during the cycle of meshing is presented. The influence of misalignment on the contact pattern and transmission errors is analyzed. The proposed ideas have been demonstrated by fabrication and rolling tests of the prototypes to ensure the validity of the meshing theory and manufacturing feasibility of the new design. [ABSTRACT FROM AUTHOR]

Abstract: The aim of this work was to investigate the effect of triblock copolymer poloxamer 188 on nanoparticle morphology, size, cancer cell uptake, and cytotoxicity. Docetaxel-loaded nanoparticles were prepared by oil-in-water emulsion/solvent evaporation technique using biodegradable poly(lactic-co-glycolic acid) (PLGA) with or without addition of poloxamer 188, respectively. The resulting nanoparticles were found to be spherical with a rough and porous surface. The nanoparticles had an average size of around 200 nm with a narrow size distribution. The in vitro drug-release profile of both nanoparticle formulations showed a biphasic release pattern. An increased level of uptake of PLGA/poloxamer 188 nanoparticles in the docetaxel-resistant MCF-7 TAX30 human breast cancer cell line could be found in comparison with that of PLGA nanoparticles. In addition, the docetaxel-loaded PLGA/poloxamer 188 nanoparticles achieved a significantly higher level of cytotoxicity than that of docetaxel-loaded PLGA nanoparticles and Taxotere (P < .05). In conclusion, the results showed advantages of docetaxel-loaded PLGA nanoparticles incorporated with poloxamer 188 compared with the nanoparticles without incorporation of poloxamer 188 in terms of sustainable release and efficacy in breast cancer chemotherapy. From the Clinical Editor: The effects of poloxamer 188, a triblock copolymer were studied on nanoparticle morphology, size, cancer cell uptake and cytotoxicity. An increased level of uptake of PLGA/poloxamer 188 nanoparticles in resistant human breast cancer cell line was demonstrated, resulting in a significantly higher level of cytotoxicity. [Copyright &y& Elsevier]

• Bi/GO composites with different Bi content were synthesized by a novel and efficient electrochemical method. • Bi 2 O 2 2+and reduced graphene oxide, which make Bi/GO composites possess high ionic and electrical conductivity, were generated during the reaction. • The small volume expansion of Bi/GO composite during sodiation is attributed to the existence of GO. • The Bi/GO composite anode displays superior rate performance and excellent cycling stability. Bismuth, a promising attribute for sodium-ion batteries, which have been attracting significant attention owing to their advantages of high volumetric capacity and suitable operating potential. However, most traditional Bi-based materials are suffered from pulverization and fracture of the electrodes caused by dramatic volume variation, consequently diminishing the cycle stability. Herein, in this work, bismuth embedded within graphene oxide matrices have been obtained by utilizing a novel and efficient electrochemical method. Through the strong reducing properties of Zintl clusters Bi 2 2−, GO is partially reduced to generate reduced graphene oxide with better electrical conductivity. Simultaneously, Bi is strongly loaded on the GO through Bi-O-C bonding, which can form Bi 2 O 2 2+ with excellent ionic conductivity. Moreover, the volume expansion of Bi during sodiation can be effectively buffered in the GO matrices. As a result, this Bi/GO composite exhibits excellent electrochemical performances in sodium-ion batteries (SIBs), including a high specific capacity of 258 mAh g−1 at 10 A g−1 and an excellent cycle stability with high retained capacity of 315 mAh g−1 after 500 cycles at 2 A g−1. This work paves the way to prepare designated promising electrode materials for high-performance SIBs, and thoroughly understands mechanism of electrochemical methods for preparing materials. [Display omitted] [ABSTRACT FROM AUTHOR]

TAR binding protein 43 (TDP-43) is normally present in the nucleus but mislocalized in the cytoplasm in a number of neurodegenerative diseases including Huntington's disease (HD). The nuclear loss of TDP-43 impairs gene transcription and regulation. However, it remains to be investigated whether loss of TDP-43 influences trinucleotide CAG repeat expansion in the HD gene, a genetic cause for HD. Here we report that CRISPR/Cas9 mediated-knock down of endogenous TDP-43 in the striatum of HD knock-in mice promoted CAG repeat expansion, accompanied by the increased expression of the DNA mismatch repair genes, Msh3 and Mlh1 , which have been reported to increase trinucleotide repeat instability. Furthermore, suppressing Msh3 and Mlh1 by CRISPR/Cas9 targeting diminished the CAG repeat expansion. These findings suggest that nuclear TDP-43 deficiency may dysregulate the expression of DNA mismatch repair genes, leading to CAG repeat expansion and contributing to the pathogenesis of CAG repeat diseases. • Knockdown of endogenous TDP-43 in HD knock-in mice promoted CAG repeat expansion. • Knockdown of TDP-43 increased the DNA mismatch repair genes such as MSH3 and MLH1. • Inhibition of MSH3 and MLH1 reduced the expansion of CAG repeats in HD knock-in mice. [ABSTRACT FROM AUTHOR]