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The reduction of selenite [Se(Ⅳ)] by microorganisms is a green and efficient detoxification strategy. We found that Se(Ⅳ) inhibited exopolysaccharide and protein secretion by Lactiplantibacillus plantarum BSe and compromised cell integrity. In this study, L. plantarum BSe reduced Se(Ⅳ) by increasing related enzyme activity and electron transfer. Genomic analysis demonstrated that L. plantarum BSe should be able to reduce Se(Ⅳ). Further transcriptome analysis showed that L. plantarum BSe enhanced its tolerance to Se(Ⅳ) by upregulating the expression of surface proteins and transporters, thus reducing the extracellular Se(Ⅳ) concentration through related enzymatic reactions and siderophore-mediated pathways. Lactiplantibacillus plantarum BSe was able to regulate the expression of related genes involved in quorum sensing and a two-component system and then select appropriate strategies for Se(Ⅳ) transformation in response to varying environmental Se(Ⅳ) concentrations. In addition, azo reductase was linked to the reduction of Se(Ⅳ) for the first time. The present study established a multipath model for the reduction of Se(Ⅳ) by L. plantarum , providing new insights into the biological reduction of Se(Ⅳ) and the biogeochemical cycle of selenium. [Display omitted] • Se(Ⅳ) compromised cell integrity of L. plantarum BSe and inhibited EPS secretion. • BSe reduces Se(Ⅳ) by improving enzyme activity and electron transfer. • BSe upregulated surface proteins and transporters to resist the Se(Ⅳ) stress. • Azo reductase was found to be related to the reduction of Se(Ⅳ) for the first time. [ABSTRACT FROM AUTHOR]

Highlights • HA hydrogel was prepared via hydrazone-/photo- dual crosslinking process. • HA hydrogel had topography and mechanical property similar to breast tumor tissue. • HA hydrogel promoted MCF-7 cells to cluster and secrete VEGF, bFGF and IL-8. • 3D culture enhanced cell migration and invasion potentials and in vivo tumorigenesis. Abstract In tumor biology, it is widely recognized that 3D rather than 2D cell culture can recapitulate key features of solid tumors, including cell-extracellular matrix (ECM) interactions. In this study, to mimick the ECM of breast cancer, hyaluronic acid (HA) hydrogels were synthesized from two polyvalent HA derivatives through a hydrazone and photo dual crosslinking process. HA hydrogels could be formed within 120 s. The hydrogels had similar topography and mechanical properties to breast tumor and displayed glutathione and hyaluronidase dual-responsive degradation behavior. Biological studies demonstrated that HA hydrogel could support the proliferation and clustering of breast cancer MCF-7 cells. The expression levels of VEGF, IL-8 and bFGF in hydrogel-cultured cells were significantly greater than those in 2D culture. Moreover, cells from hydrogel culture exhibited greater migration/invasion abilities and tumorigenicity than 2D-cultured cells. Therefore, the HA hydrogels are a promising ECM-mimicking matrix for in vitro construction of breast cancer. [ABSTRACT FROM AUTHOR]

Abstract The food sector produces large amounts of greenhouse gas (GHG) emissions, which has attracted attention of many researchers. Previous studies evaluated food carbon footprints (CFs) mainly based on food weight. Nutrient content of food could reflect food function better. However, different conclusions could be drawn based on different individual nutrients. The comprehensive trophic index has been used to evaluate food nutrition. In this study, CFs of nineteen carbohydrate-rich (CR) foods including grains, beans, root and tuber-food were investigated based on different functional units (weight, energy, protein, carbohydrate, and two comprehensive trophic indexes Nu 21 and Nu 11). The CF rankings of the foods varied when weight based-, energy based-, and individual nutrient based functional units were used. Potato, cereal foods, and beans showed the low-CF advantage when weight based-, carbohydrate based-, and protein based functional unit was used, respectively. Covering more nutrients in the functional unit is beneficial to get closer to the truth of environmental impact of different foods. The comprehensive trophic index based functional unit was more appropriate for illustrating food CFs. Nu 21 method was fairer to evaluate food CF from the viewpoint of individual food, while Nu 11 method was more appropriate from the viewpoint of balanced diet. The results also exhibited that consumption of more brown rice and standard grade flour could be a feasible plan to reduce carbon emissions in nowadays. Meanwhile, enhancing rotation of coarse cereals and increasing consumption of coarse foods could cut a considerable amount of carbon emissions further. Highlights • CFs of nineteen CR foods were investigated according to the LCA principle. • CFs of foods were evaluated based on different functional units. • Comprehensive evaluation of nutritional function was important to evaluate food CF. • Two nutrition profiling models were more appropriate to evaluate food CF. [ABSTRACT FROM AUTHOR]

Load carrying capacity is of importance in the evaluation of the stability of submarine pressure shell structure. During the buckling process of cylindrical shell under hydrostatic pressure, the total potential energy of ring-stiffened cylindrical shell can be divided into constant component, linear component and square nonlinear component. Based on the derivations of buckling loads of smooth cylindrical shell and ring-stiffened cylindrical shell, the reduced stiffness method (RSM) is applied to assess the role of different stiffness reductions in the evaluation of stable load carrying capacity of cylindrical shell. This study shows: (1) the circumferential membrane stiffness is influence the stability of cylindrical shell largest; (2) the ring ribs have a significant effect on the overall stability of ring-stiffened cylindrical shells under hydrostatic pressure; (3) the circumferential buckling wave number of ring-stiffened cylindrical shell may not depend on the membrane stiffness reduction of shell, but it increases with the bending stiffness reduction of ring ribs. [ABSTRACT FROM AUTHOR]

This work includes the design of fully flexible wearable data glove to ensure that strain sensors are accurately connected to the hand joints to accurately measure the joints motions of the finger joints. A real-time flexible wearable gesture-to-alphabets translation system was reported of integrating visual data with somatosensory data from ten flexible stretchable sensors-based data glove and a camera, assisted by machine learning. The device recognized the 26 letters with a recognition rate of up to 99.63% and a recognition time of less than 1 s, which helps to understand observations of sign as words and texts. [Display omitted] • The design of fully flexible wearable data glove. • A system of sign annotation generation to words via integrating visual data with somatosensory data from flexible strain sensor-based data glove is constructed, and the effectiveness of the proposed system is demonstrated through experiments for quantitative evaluations. • A real-time flexible wearable gesture-to-alphabets translation system was reported. • The device recognized the 26 letters with a recognition rate of up to 99.63% and a recognition time of <1 s. Sign language forms a significant way of communication for deaf-mute people. There are different types of sign languages of different countries in different regions. The sign language recognition system translates the gestures into the alphabet, which solves a barrier in comprehension of conversation. Visual techniques and somatosensory strain sensors are both useful modalities to detect sign gesture. In order to improve the recognition accuracy and wear resistance, this paper proposes a real-time alphabets conversion system, which combines the visual data with the data glove based on flexible strain sensor and the somatosensory data of the camera, supplemented by deep learning. In this learning structure, convolutional neural network is used to process the visual data, and then the sparse neural network for sensor data fusion and recognition is realized in the feature layer. A module is proposed to train the linking of hand motions primitives to alphabets (A–Z). The proposed framework is tested on a dataset of sign and descriptive alphabets. The proposed system would recognize the 26 letters with a recognition rate of up to 99.50% and a recognition time of less than 1 s, which helps to understand observations of sign as words and texts. [ABSTRACT FROM AUTHOR]

Prostate cancer gene expression marker 1 (PCGEM1) has been identified as an oncogenic long non-coding RNA (lncRNA) in diverse cancers, but it has never been linked with colorectal cancer (CRC). Former studies have shown the mutual regulation between lncRNAs and transcription factors (TFs) in cancer. CCCTC binding factor (CTCF) has been reported to transcriptionally activate lncRNAs in cancers. We predicted the binding of CTCF on PCGEM1 promoter through UCSC (https://genome.ucsc.edu/), but their relation has not been studied. We aimed to investigate whether and how PCGEM1 functioned in CRC cells and the interaction between PCGEM1 and CTCF. The impacts of PCGEM1 and CTCF inhibition on CRC cells were verified through loss-of-function experiments. Mechanism experiments were used to prove the binding between CTCF and PCGEM1 in CRC progression. PCGEM1 possessed a high expression level in CRC cells as well as tumors. CTCF transcriptionally activated PCGEM1 expression. Knockdown of PCGEM1 or CTCF impeded proliferation and migration and drove apoptosis of CRC cells. Moreover, PCGEM1 bound miR-433–3p to prevent miR-433–3p from targeting CTCF. We first revealed PCGEM1/miR-433–3p/CTCF positive feedback loop as an oncogenic axis in CRC cells, which potentially provides new clues for the advancement of CRC treatment. [ABSTRACT FROM AUTHOR]

• A pioneering "grafting from" drug coordination polymerization strategy was proposed. • A fully-coordinated and full-active Cu 2 O/drug core/shell nanoplatform was prepared. • Obtained nanoplatform-mediated ROS storm could induce immunogenic cell death. • Nanoplatform/αPD-1 combination could induce robust systemic antitumor immunity. Precise manipulation of reactive oxygen species (ROS) breakthrough threshold exhibits great potential in destroying solid tumors, reprogramming "immune-cold" tumor and potentiating immunotherapy. However, it is still challenging to develop efficient ROS initiation devices. Herein, we propose a pioneering "grafting from" drug coordination polymerization strategy and develop a fully-coordinated and full-active Cu 2 O/drug core/shell nanoparticles for multimodal cancer therapy. Chemotherapeutic drug cisplatin (CDDP) and photosensitizer indocyanine green (ICG) were loaded onto the surface of hydrazided hyaluronic acid-decorated Cu 2 O (HA-Cu 2 O) nanoparticles through an infinite hydrazide-cisplatin-sulfonic acid coordination mechanism, obtaining CDDP/ICG-coloaded HA-Cu 2 O (HCCI) nanoplatform. The HCCI nanoplatform exhibited a rapid acid-responsive dissociation behavior and released ICG, Cu+ and CDDP to achieve efficient triple combined photodynamic therapy/chemodynamic therapy/chemotherapy. Importantly, such a combination induced efficient immunogenic cell death cascade mediated by powerful ROS storm to reprogram "immune-cold" tumors and potentiate immunotherapy. The combination of HCCI nanoplatform and αPD-1 not only eradicated primary tumors but effectively inhibited distal tumor growth, lung metastasis and tumor recurrence through reprogramming tumor microenvironment and activating CD8+ T cell antitumor immunity. Collectively, we have presented a drug coordination polymerization loading strategy to develop a robust multimodal antitumor nanoplatform, and this study provides a new direction for the design of nanodrug delivery systems. [ABSTRACT FROM AUTHOR]

The aim of this paper is to quantitatively evaluate the extent of collapse of a bulk carrier when the ship is subjected to extreme wave loads. A hydro-elastoplasticity theory, which was proposed by the present authors and takes into account the interaction between the large elasto-plastic deformation and the wave load evaluation, is applied to the ship’s structure with the assumption that a plastic hinge is formed in the midship region when the hull girder collapses in extreme wave conditions. The dynamic response of the hinge can be expressed by the relationship between the vertical bending moment and the curvature, which are obtained using nonlinear Finite Element Analysis (FEA). A comparative correct moment–curvature curve and a reasonable load evaluation are necessary for prediction of the severity of the collapse for the actual ship. A bulk carrier hull model with one frame space is constructed and analysed using an arc-length control method (Riks method). The geometric nonlinearity resulting from large deformations and the material nonlinearity are taken into account. The presence of an initial imperfection is considered using the consistent imperfection mode method in the FEA. A prediction of the extent of collapse for a bulk carrier subjected to an extreme wave load is carried out using the hydro-elastoplasticity approach. This analysis clarifies the extent to which the hull girder may collapse in extreme wave conditions at an exceedance probability of 1/1000 in several short-term sea states. [ABSTRACT FROM AUTHOR]

A novel and all-active aMOF, DOX@FeTH, is developed via a one-step self-assembly strategy. The aMOF can effectively suppress tumor growth via a ferroptosis-apoptosis synergetic therapeutic modality. Moreover, the aMOF has excellent photothermal performance and the hyperthermia can enhance tumor penetration and further improve antitumor effect. Owing to simple ingredients, facile preparation process, and integrated multifunctionalities, DOX@FeTH aMOF holds great potential for clinical translation. [Display omitted] • A novel aMOF with triple-stimuli responsiveness was prepared via one-pot method. • The aMOF with favorable photothermal effect could penetrate deeply into tumor. • Self-supplied Fe2+, inactivated GPX4 and elevated H 2 O 2 co-induced ferroptosis. • The aMOF killed tumor cells via a ferroptosis-apoptosis synergistic modality. The combination of ferroptosis and apoptosis that act with different mechanisms holds enormous potential in cancer treatment. However, how to simply but effectively integrate the two modalities into a single platform is an enormous challenge. Herein, based on our newly discovered Fe(II)-hydrazide coordination self-assembly strategy, we design and develop an all-active amorphous metal organic framework (aMOF) for photothermally boosted ferroptosis-apoptosis synergistic anti-tumor therapy. The aMOF is prepared via one-pot co-assembly of doxorubicin (DOX), Fe2+ ions and 3,3′-dithiobis(propionohydrazide) (TPH) and subsequent decoration with TPH-functionalized hyaluronic acid. The obtained DOX@FeTH is amorphous in structure, and it exhibits favorable photothermal performance and displays pH/GSH/laser triple-responsive degradation behavior. The aMOF can be specifically internalized by CD44-overexpressed 4T1 cells and efficiently inhibit GPX4 activity via disulfide bond-mediated glutathione depletion, elevate intracellular H 2 O 2 level by DOX-induced NOX4 activation, and consequently amplify lipid peroxidation with the assistance of self-supplied Fe2+, resulting in remarkable ferroptotic cell death. Meanwhile, the released DOX causes apoptotic cell death. Moreover, the aMOF-mediated hyperthermia can promote tumor penetration and augment the synergistic efficacy. Hence, the tumors are effectively suppressed by the synergistic treatment of DOX@FeTH with laser. This work provides a new strategy for fabricating aMOFs and opens a new horizon for tumor treatment. [ABSTRACT FROM AUTHOR]

Accurately predicting relative binding affinities and biological potencies for ligands that interact with proteins remains a significant challenge for computational chemists. Most evaluations of docking and scoring algorithms have focused on enhancing ligand affinity for a protein by optimizing docking poses and enrichment factors during virtual screening. However, there is still relatively limited information on the accuracy of commercially available docking and scoring software programs for correctly predicting binding affinities and biological activities of structurally related inhibitors of different enzyme classes. Presented here is a comparative evaluation of eight molecular docking programs (Autodock Vina, Fitted, FlexX, Fred, Glide, GOLD, LibDock, MolDock) using sixteen docking and scoring functions to predict the rank-order activity of different ligand series for six pharmacologically important protein and enzyme targets (Factor Xa, Cdk2 kinase, Aurora A kinase, COX-2, pla2g2a, β Estrogen receptor). Use of Fitted gave an excellent correlation (Pearson 0.86, Spearman 0.91) between predicted and experimental binding only for Cdk2 kinase inhibitors. FlexX and GOLDScore produced good correlations (Pearson > 0.6) for hydrophilic targets such as Factor Xa, Cdk2 kinase and Aurora A kinase. By contrast, pla2g2a and COX-2 emerged as difficult targets for scoring functions to predict ligand activities. Although possessing a high hydrophobicity in its binding site, β Estrogen receptor produced reasonable correlations using LibDock (Pearson 0.75, Spearman 0.68). These findings can assist medicinal chemists to better match scoring functions with ligand-target systems for hit-to-lead optimization using computer-aided drug design approaches. [ABSTRACT FROM AUTHOR]

A modified internal circulation (MIC) reactor with an external circulation system was proposed and the performance of treating dyeing wastewater using both MIC and typical IC reactor were compared. Utilization of the external circulation system in the MIC reactor could dramatically improve the mixing intensity of the biomass with the wastewater and resulted in better performance. The COD removal efficiency, biogas production, volatile fatty acids and effluent color were approximately 87%, 98 L d −1 , 180 mg L −1 and 100 times, respectively, in the MIC reactor with a hydraulic retention time of 5 h and organic loading rate of 15 kg COD m −3 d −1 . The hydrodynamics of the MIC reactor under different flows rate of external circulation were also analyzed using computational fluid dynamics (CFD) method. The optimal flow rate of external circulation was 12 L min −1 , which resulted in a corresponding up-flow velocity of 40 m h −1 . The consistency of the result between experiment and simulation validated the scientificity of CFD technique applied to numerical simulation of the MIC reactor. [ABSTRACT FROM AUTHOR]

Abstract: In this study, poly(l-lactide-co-β-malic acid) (PLMA) copolymer was synthesized via ring-opening polymerization of l-lactide and β-benzyloxycarbonyl-β-propiolactone, followed by removal of benzyl protective groups through hydrogenolysis. Novel biomorphic PLMA scaffolds with a honeycomb-like structure were prepared using cane as template. We investigated the chemical structure and physicochemical properties of PLMA copolymer and the morphology and biocompatibility of biomorphic PLMA scaffolds. The results confirmed the chemical structure of PLMA copolymer. The amorphous copolymer had a glass transition temperature of 49°C. The PLMA scaffolds well retained the morphology of cane, and had a porosity of 85.5% and a compressive modulus of 766.2±36.1kPa. in vitro biocompatibility evaluation with MC3T3-E1 cells demonstrated the potential of the biomorphic PLMA scaffolds for bone tissue engineering. [Copyright &y& Elsevier]

In this study, biomorphic poly(dl-lactic-co-glycolic acid)/nano-hydroxyapatite (PLGA/nHA) composite scaffolds were successfully prepared using cane as a template. The porous morphology, phase, compression characteristics and in vitro biocompatibility of the PLGA/nHA composite scaffolds and biomorphic PLGA scaffolds as control were investigated. The results showed that the biomorphic scaffolds preserved the original honeycomb-like architecture of cane and exhibited a bimodal porous structure. The average channel diameter and micropore size of the PLGA/nHA composite scaffolds were 164±52μm and 13±8μm, respectively, with a porosity of 89.3±1.4%. The incorporation of nHA into PLGA decreased the degree of crystallinity of PLGA, and significantly improved the compressive modulus of biomorphic scaffolds. The in vitro biocompatibility evaluation with MC3T3-E1 cells demonstrated that the biomorphic PLGA/nHA composite scaffolds could better support cell attachment, proliferation and differentiation than the biomorphic PLGA scaffolds. The localization depth of MC3T3-E1 cells within the channels of the biomorphic PLGA/nHA composite scaffolds could reach approximately 400μm. The results suggested that the biomorphic PLGA/nHA composite scaffolds were promising candidates for bone tissue engineering. [ABSTRACT FROM AUTHOR]

Abstract: It is well known that for two p-rough paths, if their first levels of iterated integrals are close in p-variation sense, then all levels of their iterated integrals are close. In this paper, we prove that a similar result holds for the paths provided the first terms are close in a ‘uniform’ sense. The estimate is explicit, dimension free, and only involves the p-variation of two paths and the ‘uniform’ distance between the first terms. Applications include estimation of the difference of the signatures of two uniformly close paths (Lyons and Xu, 2011 [6]), and convergence rates for Gaussian rough paths (Riedel and Xu, 2012 [7]). [Copyright &y& Elsevier]

2D cell culture is widely utilized to develop anti-cancer drugs and to explore the mechanisms of cancer tumorigenesis and development. However, the findings obtained from 2D culture often fail to provide guidance for clinical tumor treatments since it cannot precisely replicate the features of real tumors. 3D tumor models capable of recapitulating native tumor microenvironments have been proved to be a promising alternative technique. Herein, we constructed a breast tumor model from novel hyaluronic acid (HA) hydrogel which was prepared through photocrosslinking of methacrylated HA. The hydrogel was used as a biomimetic extracellular matrix to incubate MCF-7 cells. It was found that methacrylation degree had great effects on hydrogel's microstructure, mechanical performances, and liquid-absorbing and degradation abilities. Optimized hydrogel exhibited highly porous morphology, high equilibrium swelling ratio, suitable mechanical properties, and hyaluronidase-responsive degradation behavior. The results demonstrated that the HA hydrogel facilitated MCF-7 cell proliferation and growth in an aggregation manner. Furthermore, 3D-cultured MCF-7 cells not only up-regulated the expression of VEGF, bFGF and interleukin-8 but exhibited greater invasion and tumorigenesis capabilities compared with 2D-cultured cells. Therefore, the HA hydrogel is a reliable substitute for tumor model construction. [Display omitted] • The hyaluronic acid hydrogel was synthesized by a facile photo-crosslinking approach. • 3D breast tumor models were successfully constructed from hyaluronic acid hydrogels. • 3D-cultured MCF-7 cells efficiently replicated key cellular features of tumor in vivo. • 3D-cultured MCF-7 cells exhibited enhanced tumorigenicity than 2D-cultured ones. [ABSTRACT FROM AUTHOR]

Abstract: A similarity search on the structural analogs of an inhibitor of BACE-1 with IC50 2.8μM, which contained a P1 benzothiazole group together with a triazine ring linked by a secondary amine group, was described in this Letter and some more potent inhibitors against BACE-1 were identified. The most potent compound 5 (IC50 =0.12μM) increases the inhibitory potency by 24 folds. Our results suggest that a pyrrolidinyl side group at the P3′ and P4′ of the inhibitors are favored for strong inhibition and a small aromatic group at the P4 position is also essential to the potency. [ABSTRACT FROM AUTHOR]

Abstract: Nowadays identification of novel non-peptide β-secretase (BACE-1, hereinafter) inhibitors with low cytotoxicity and good blood–brain barrier (BBB) property holds common interest of drug discovery for Alzheimer’s disease. Twenty SPECS compounds were tested in BACE-1 FRET assays and methylthiazoletetrazolium (MTT) cytotoxicity experiment. Two compounds: 2 and 15 demonstrated IC50 values of 0.53 and 9.4μM. In addition, 2 showed least toxic effect to the neuroblastoma cells. The results from both in silico and in vitro studies provided new pharmacophoric entities for chemical synthesis and optimization on the current discovered BACE-1 small molecule inhibitors. [Copyright &y& Elsevier]

Abstract: Owing to the fluctuations in the financial markets from time to time, some input variables, in particular the interest rate, spot exchange rate and volatility, in the Garman–Kohlhagen model [M.B. Garman, S.W. Kohlhagen, Foreign currency option values, Journal of International Money and Finance 2 (1983) 231–237] cannot be expected in a precise sense. Therefore, the fuzzy set theory introduced by Zadeh [L.A. Zadeh, Fuzzy sets, Information and Control 8 (1965) 338–353] can provide a useful tool to deal with this kind of impreciseness. In this paper, three different versions of the G–K model, the put-call parity relationship and the calculation formulas of the Greek letters according to these three different G–K models are then proposed based on fuzzy set theory. Under the considerations of fuzzy foreign and domestic interest rates, fuzzy spot exchange rate and fuzzy volatility, the European currency option prices and the Greek letters turn into fuzzy numbers or closed intervals. This means that the investors can pick any European currency option price and Greek letters with an acceptable belief degree or belief degree weighting parameter for his later use. The empirical results indicate that the Greeks calculated under fuzzy environment can be considered as a useful tool for managing option risk for an option writer. [Copyright &y& Elsevier]

Abstract: This Letter describes an efficient approach by integrating virtual screening with bioassay technology for finding small organic inhibitors targeting β-secretase (BACE-1). Fifteen hits with inhibitory potencies ranging from 2.8 to 118μM (IC50) against β-secretase were successfully identified. Compound 12 with IC50 of 2.8μM is the most potent hit against BACE-1. Docking simulation from gold 3.0 suggests putative binding mode of 12 in BACE-1 and potential key pharmacophore groups for further designing of non-peptide compounds as more powerful inhibitors against BACE-1. [Copyright &y& Elsevier]

Temporal dependency and mutual impact are two major aspects of the qualitative analysis of stock prices. Modeling the dynamic and complex nature of both the timeline and the mutual impact network is a challenging task for stock price prediction. Furthermore, if we want to capture the high-frequency changes of stock price, the time series will become extremely long, leading to a practical challenge in terms of modeling. To address these challenges, this paper proposes a novel memory-based hierarchical recurrent neural encoder (MHieR-encoder) to embed the time series of stock price into a new representation that preserves (i) the sequential dependency of the time series and (ii) the proximity relationships across stocks in the impact network. The hierarchical structure of the proposed model can easily capture the long-range dependence from an extremely long time series, including in terms of high-frequency prices. Moreover, to capture the dynamic mutual impact across stocks, the intermediate results of the impact network will be stored in the memory module to support further exploration at the training stage. The method is validated using an extremely long time series composed of the one-minute prices derived from the all the Chinese stocks. The results show that MHieR-encoder outperforms all the 8 baselines in the bull market, bear market, calm bull market and calm bear market, and significantly improves the accuracy to 52.2% in a three-class prediction: rising, falling and flat. [ABSTRACT FROM AUTHOR]

Combination of different therapy modalities with multiple tumoricidal mechanisms has emerged as a promising anticancer strategy. Herein, we reported an aldehyde/catechol-functionalized hyaluronic acid (DAHA) and hydroxyethyl chitosan (HECS) decorated gold nanorod (GNR) platform for combined chemo-photothermal therapy of breast cancer. The DAHA was synthesized by conjugating dopamine onto oxidized hyaluronic acid. The nanoplatform was prepared by successively modifying GNR with DAHA via Au-catechol bonds, conjugating DOX onto DAHA moiety through Schiff base linkage, and coating HECS interlayer for charge-reversal and hyaluronic acid corona for tumor cell targeting. The resulting nanoplatform GNR-HADOXCH exhibited acid-triggered surface charge-reversal and pH/NIR dual-responsive drug release behaviors. The nanoplatform could be efficiently internalized into MCF-7 breast cancer cells and displayed greater cancer cell killing than individual modalities. Therefore, polysaccharide decoration could ensure the co-delivery of GNR and DOX into cancer cells, and the developed GNR-HADOXCH holds great potential for breast cancer treatment. Unlabelled Image • The versatile nanoplatform was prepared via a facile and effective self-assembly method. • The nanoplatform exhibited acid-triggered surface charge-reversal property. • The nanoplatform had pH/NIR dual-responsive drug release behavior. • Receptor recognition and charge-reversal dual-enhanced cellular internalization. • MCF-7 cells could be efficiently killed by combined chemo-photothermal therapy. [ABSTRACT FROM AUTHOR]

• Multifunctional PEG-b-polypeptide-decorated gold nanorod nanoplatform was developed. • DOX was conjugated onto the nanoplatform via pH-sensitive hydrazone linkage. • Release behavior of DOX from the nanoplatform was reduction/pH dual-responsive. • Combined photothermal chemotherapy achieved great anti-cancer efficacy in MCF-7 cells. The combination of chemotherapy and photothermal therapy is acknowledged as one of the most promising approaches in cancer treatment. Targeted delivery and controlled drug release are two important factors for combined chemo-photothermal therapy. In this study, a multifunctional nanoplatform based on gold nanorod (GNR) decorated with folate-conjugated poly(ethylene glycol)- b -poly(L-γ-glutamylhydrazine) (FEGGH) containing disulfide linker and dihydroxyphenyl groups was developed for targeted combined chemo-photothermal therapy of breast cancer. FEGGH was synthesized by ring-opening polymerization of γ-benzyl- l -glutamate -N- carboxyanhydride using folate/cystamine-heterobifunctionalized poly(ethylene glycol) as an initiator, following by hydrazinolysis and carbodiimide reactions. FEGGH was decorated onto GNR through Au-catechol bonds. Chemotherapeutic drug doxorubicin (DOX) was loaded onto the nanoplatform through pH-sensitive hydrazone linkage, obtaining final product FEGGHDOX-GNR. The DOX-loaded nanoplatform displayed excellent photostability and reduction/pH dual-responsive drug release behavior. Cytological studies demonstrated the effective internalization of FEGGHDOX-GNR into MCF-7 cells via folate-mediated endocytosis and additive therapeutic effect of combined photothermal-chemotherapy. These results indicate that our nanoplatform may be a promising strategy for targeted combined chemo-photothermal therapy of breast cancer. [ABSTRACT FROM AUTHOR]

This study examines the asymmetric volatility spillover effect using realized measures across 22 international stock markets. The findings suggest a high connectedness among global equity markets, with downside risk spillover significantly higher than upside risk spillover over time. Besides, Europe has a higher connectedness than the American and Asia-Pacific markets, and risk contagion is from the European and American developed markets to the Asia-Pacific regions. The study further identifies implied volatility index and market liquidity as the main positive determinants of risk spillover, which are robust across different rolling window lengths and horizons. We also find that the explanatory power is more significant during financial crises. • High-frequency data is used to analyze global asymmetric volatility spillover effects. • Over time, downside risk spillover surpasses upside risk spillover significantly. • Risk contagion is from the developed markets to the Asia-pacific regions. • Developed markets connected better than emerging markets. • VIX and market liquidity in risk-transmitting markets drive volatility spillover. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • AHA-decorated bifunctionalized HECS-GNR conjugate was developed. • DOX was loaded onto the conjugate via hydrazone linkage. • The conjugate displayed pH-responsive surface charge reversal and drug release. • The conjugate exhibited synergetic photothermal chemotherapy of breast cancer cells. Abstract Chemo-photothermal combination therapy is a promising strategy for cancer treatment. In this study, to achieve the combined photothermal-chemotherapy of breast cancer, a pH-sensitive oxidized hyaluronic acid-decorated dihydroxyphenyl/hydrazide bifunctionalized hydroxyethyl chitosan (DHHC)-gold nanorod (GNR) conjugate was developed. DHHC was synthesized by successive dihydroxyphenylation and hydrazidation of hydroxyethyl chitosan through carbodiimide reaction and click chemistry, respectively. The conjugate was obtained by chemically bonding DHHC onto GNR via Au-catechol bonds. Doxorubicin (DOX) was loaded onto the conjugate via an acid-labile hydrazone linkage with a drug loading content of 5.1%. DOX-loaded conjugate displayed good stability in neutral aqueous solutions and exhibited pH-responsive drug release and surface charge reversal behaviors. In vitro biological studies indicated that the conjugate could be effectively internalized by breast cancer MCF-7 cells and synergistic therapeutic effects were demonstrated, suggesting its great potential in combined photothermal-chemotherapy of breast cancer. [ABSTRACT FROM AUTHOR]

The incorporation of therapeutic ions like Sr 2+ , Si 4+ , Zn 2+ and Li + into biomaterials has become a promising approach to promote bone regeneration. However, the effects of Sr 2+ and Zn 2+ co-substitution on the crystal structure and properties of β-tricalcium phosphate (β-TCP) have not been elucidated well. In this study, Sr 2+ /Zn 2+ co-substituted β-tricalcium phosphate (SrZnTCP) nano-powders with different extents of substitution (0–4.8 mol%) were synthesized by poly(ethylene glycol)-assisted co-precipitation and subsequent heat treatment. The as-synthesized SrZnTCP nano-powders were characterized by x-ray diffraction, Fourier transform infrared spectroscopy, elemental analysis, Rietveld refinement and differential scanning calorimetry. The results showed that the conversion of calcium-deficient apatite to β-TCP was achieved after heat-treatment above 800 °C. The a -axis and c -axis lattice parameters gradually decreased with increasing level of Sr 2+ /Zn 2+ co-substitution in β-TCP lattice. Sr 2+ and Zn 2+ preferentially occupied the ninefold coordinated Ca (4) sites and the sixfold coordinated Ca (5) sites, respectively. The co-substitution of Sr 2+ and Zn 2+ for Ca 2+ significantly improved the thermal stability of β-TCP. The release rate of Zn 2+ from SrZnTCP depended on Ca 2+ concentration over 63-day immersion in PBS solution while that of Sr 2+ was not affected by Ca 2+ concentration. The amount of Sr 2+ released increased with increasing Sr 2+ content in SrZnTCP. Collectively, SrZnTCP showed great promise as a Sr 2+ /Zn 2+ -releasing biomaterial for bone repair, although no obvious mineralization was observed on β-TCP and SrZnTCP disc samples during 56 days of immersion in simulated body fluid. [ABSTRACT FROM AUTHOR]

• CIC-Gal nanomissiles were constructed by dual-coordination-driven self-assembly. • CIC-Gal nanomissiles showed prominent size/charge dual-transformability function. • CIC-Gal nanomissiles achieved synergistic chemotherapy/PDT/PTT in HCC. • CIC-Gal nanomissiles could induce ICD and promote CD8+ T cell infiltration into HCC. • CIC-Gal/αPD-1 combination activated robust systemic antitumor immunity in HCC. PD-1 blockade therapy holds great potential for curing hepatocellular carcinoma (HCC), but its efficacy is severely restrained by inefficient CD8+ T cells and abundant immunosuppressive myeloid-derived suppressor cells (MDSCs) in tumors. Moreover, the solid feature of HCC limits drugs' penetration depth. Herein, cisplatin/indocyanine green (ICG)-coloaded polysaccharide-based nanomissiles (CIC-Gal) with galactose-mediated tumor targeting ability and tumor microenvironment (TME)-responsive size/charge dual-transformability are constructed by coordination-driven self-assembly. The nanoparticles can efficiently accumulate in tumors and exert antitumor effects on HCC via combinational chemotherapy/phototherapy. Importantly, CIC-Gal nanoparticles may protect cisplatin from glutathione-mediated detoxification by depleting glutathione. Photodynamic therapy rather than photothermal therapy plays a predominant role in ICG-mediated phototherapy. Furthermore, CIC-Gal nanoparticles can induce prominent immunogenic cell death (ICD), promote dendritic cells maturation, and activate robust systemic antitumor immunity in combination with αPD-1, which efficiently eradicates primary tumors, inhibits distant tumor growth and lung metastasis, and prolongs survival of tumor-bearing mice by promoting CD8+ T cell infiltration in tumors, suppressing the expansion and trafficking of MDSCs, and reshaping immunostimulatory TME. Collectively, this study provides a drug-based coordination-driven polysaccharide nanomissile construction approach, and the CIC-Gal nanoparticles display a strong immunomicroenvironment-reeducating ability for potentiating HCC immunotherapy. [ABSTRACT FROM AUTHOR]

This paper investigates the impacts of personalized individual semantics (PIS) on consistency and consensus in Best–Worst method (BWM) with heterogeneous linguistic preference information. Firstly, a PIS driven consistency measurement and information transformation method is presented to analyze the consistency level of linguistic preference information (i.e., best-to-others and others-to-worst vectors) of each decision maker, and this is conducted by maximizing the consistency level of additive preference relation that converted from linguistic preference information via personalized numerical scales. Secondly, a PIS driven maximum consensus optimization model within the BWM framework is designed to yield the maximum consensus level among the additive preference relations generated from heterogeneous linguistic preference information by means of personalized numerical scales. Thirdly, a PIS-based heterogeneous linguistic consensus reaching process is put forward to promote the consensus establishment among decision makers. Finally, the validity of the proposed BWM framework is verified by a case study, a sensitive analysis, and a comparison analysis. [ABSTRACT FROM AUTHOR]

In the present study, poly( N ɛ -acryloyl- l -lysine)/hyaluronic acid (pLysAAm/HA) interpenetrating network (IPN) hydrogels were successfully fabricated through the combination of hydrazone bond crosslinking and photo-crosslinking reactions. The HA hydrogel network was first synthesized from 3,3′-dithiodipropionate hydrazide-modified HA and polyethylene glycol dilevulinate by hydrazone bond crosslinking. The pLysAAm hydrogel network was prepared from N ɛ -acryloyl- l -lysine and N , N ′-bis(acryloyl)-( l )-cystine by photo-crosslinking. The resultant pLysAAm/HA hydrogels had a good shape recovery property after loading and unloading for 1.5 cycles (up to 90%) and displayed a highly porous microstructure. Their compressive moduli were at least 5 times higher than that of HA hydrogels. The pLysAAm/HA hydrogels had an equilibrium swelling ratio of up to 37.9 and displayed a glutathione-responsive degradation behavior. The results from in vitro biocompatibility evaluation with pre-osteoblasts MC3T3-E1 cells revealed that the pLysAAm/HA hydrogels could support cell viability and proliferation. Hematoxylin and eosin staining indicated that the pLysAAm/HA hydrogels allowed cell and tissue infiltration, confirming their good in vivo biocompatibility. Therefore, the novel pLysAAm/HA IPN hydrogels have great potential for bone tissue engineering applications. [ABSTRACT FROM AUTHOR]

A modified internal circulation (MIC) anaerobic reactor with an external hydraulic circulation system to strengthen mass transfer between sludge and substrates was used to treat dyeing wastewater and its performance was evaluated. During 110 days of operation, the MIC anaerobic reactor underwent three stages: start-up stage, improving stage, and steady stage. At the steady stage, COD removal efficiency, VFA concentration, and biogas production were approximately 85%, 158 mg/L and 1.65 L/L d, respectively. The color removal efficiency was from 77% to 90% in the whole experiment. Compared with the initial granular sludge, the sludge grew bigger with the portion of the granular diameter over 2 mm increasing from 77.9% to 85.5% and the suspended solid (SS) concentration increased from 66.1 to 75.9 g/L. The external circulation system not only shortened the startup time of the IC reactor treating wastewater, but also improved the pollutants removal in anaerobic reactor with a reasonable hydraulic upflow velocity. However, excessive hydraulic upflow velocity (40.9 m/h) caused the granular sludge disintegration and a decline in COD removal. Evaluation of the MIC reactor using the modified Stover–Kincannon model revealed the maximum removal rate constant ( U max ) and saturation value constant ( K B ) of 31.25 g/L d and 34.94 g/L d, respectively. [ABSTRACT FROM AUTHOR]

In financial markets, the presence of background risk may affect investors’ investments. This article develops a fuzzy portfolio selection model with background risk, based on the definitions of the possibilistic return and possibilistic risk. For the returns of assets obey LR-type possibility distribution, we propose a specific portfolio selection model with background risk. Then, a numerical study is carried out by using the data concerning some stocks. Based on the data, we obtain the efficient frontier of the possibilistic portfolio with background risk, and compare it with the efficient frontier of the portfolio without background risk. Finally, we conclude that the background risk can better reflect the investment risk of the real economy environment which make the investors choose a more suitable portfolio to them. [ABSTRACT FROM AUTHOR]

An ideal scaffold in bone tissue-engineering strategy should provide biomimetic extracellular matrix-like architecture and biological properties. Poly(γ-benzyl-L-glutamate) (PBLG) has been a popular model polypeptide for various potential biomedical applications due to its good biocompatibility and biodegradability. This study developed novel bimodal porous PBLG polypeptide scaffolds via a combination of biotemplating method and in situ ring-opening polymerization of γ-benzyl-L-gIutamate N-carboxyanhydride (BLG-NCA). The PBLG scaffolds were characterized by proton nuclear magnetic resonance spectroscopy, X-ray diffraction, differential scanning calorimetry, scanning electron microscope (SEM) and mechanical test. The results showed that the semi-crystalline PBLG scaffolds exhibited an anisotropic porous structure composed of honeycomb-like channels (100–200μm in diameter) and micropores (5–20μm), with a very high porosity of 97.4±1.6%. The compressive modulus and glass transition temperature were 402.8±20.6 kPa and 20.2°C, respectively. The in vitro biocompatibility evaluation with MC3T3-E1 cells using SEM, fluorescent staining and MTT assay revealed that the PBLG scaffolds had good biocompatibility and favored cell attachment, spread and proliferation. Therefore, the bimodal porous polypeptide scaffolds are promising for bone tissue engineering. [ABSTRACT FROM AUTHOR]

Abstract: In this paper, we discuss the valuation of equity warrants in the geometric fractional Brownian environment based on the equilibrium condition. Using the conditional expectation we present a fractional pricing model for equity warrants and analyze the influence of the Hurst parameter. Then we propose an optimization procedure to obtain the valuation of equity warrants. Some numerical examples are given to demonstrate the pricing results by comparing different pricing models. Furthermore, we provide an empirical study to show how to apply our model in realistic contexts, and these comparative results of different pricing models show that the pricing model proposed in this paper matches the actual price quite well. [Copyright &y& Elsevier]

Abstract: In this paper, we generalize the traditional on-line leasing problem to the case where the equipment is depreciable and the investor can always sell the used equipment for a positive price, which is an essential feature of many practical leasing problems. The traditional risk–reward model for the case with a certain forecast has been discussed for the on-line leasing of depreciable equipment. On the basis of this, an improved risk–reward model with a probability forecast is obtained here and presented as the main result. A relationship between the two risk–reward models, in which the latter includes the former as a special case, is proved. Numerical analysis shows that the competitive performance is significantly improved in the risk–reward models. [Copyright &y& Elsevier]

Abstract: This paper studies the problem of on-line leasing of depreciable equipment. We first discuss deterministic strategies for the problem for situations with and without interest rates, respectively. Competitive ratios are used to evaluate the performance of on-line algorithms. The optimal competitive ratio of the deterministic strategy is therefore obtained. As randomization can boost performance, the randomized strategy for on-line leasing of depreciable equipment with oblivious adversary is further proposed. The main difference between the deterministic algorithm and the randomized algorithm is that the introduction of an interest rate decreases the optimal deterministic competitive ratio while it increases that of the latter. By comparison, we find that the introduction of a depreciation factor improves the competitive performance and the model is more practical for on-line leasing of depreciable equipment. Finally, we conclude that the competitive ratio is closely related to the transaction costs and the profitability in the leasing business. [Copyright &y& Elsevier]

Polysaccharide hydrogels are promising candidate matrices for recapitulating the characteristics of extracellular matrix (ECM) in breast tumors in terms of their structure and composition. Herein, to obtain an ECM-mimetic matrix, hydroxyethyl chitosan (HECS) hydrogels were prepared through Schiff-base crosslinking reaction using dialdehyde hyaluronic acid as crosslinker. The obtained HECS hydrogels displayed a highly porous structure, a stiffness comparable to that of breast tissue, and a fast water-absorption speed. The amount of crosslinker had great effects on the swelling and rheological behaviors of the HECS hydrogels. Preliminary results from in vitro biological assessments confirmed that MCF-7 cells incubated within HECS hydrogels preferred to grow into three-dimensional spheroids. Importantly, the cells displayed enhanced migrative capability and upregulated expression levels of MMP-2, TGF-β and VEGF in comparison to two-dimension cultured cells. Hence, the HECS hydrogels show great promise as a biomimetic ECM in constructing breast tumor models. [ABSTRACT FROM AUTHOR]

Spasmolytic polypeptide-expressing metaplasia (SPEM) is characterized by mucus cell morphologies at the base of gastric glands, which is considered advanced SPEM when accompanied with an increase in transcripts associated with intestinal-type gastric cancer. Weiwei decoction (WWD) was modified from "Si-Jun-Zi Tang," which has been used for thousands of years in China against gastric atrophy and metaplasia. To investigate the effects and potential mechanisms of WWD against advanced SPEM. Liquid chromatography-mass spectrometry was employed to analyze the constituents of WWD. Five-month-infected Helicobacter pylori (H. pylori) Sydney strain 1 C57BL/6J mice and 6-week-old ATPase H+/K+ transporting subunit alpha-knockout mice (Atp4a −/−) were given folic acid (1.95 mg/kg) or WWD (13.65 g/kg, 27.30 g/kg, 54.60 g/kg) by gavage for one month. WWD demonstrated beneficial effects on gastric mucosal pathology and mucus secretion. In H. pylori -infected mice, WWD effectively reduced the expression of GSII and inhibited the mRNA levels of key markers associated with advanced SPEM, including Clu , Cftr , Wfdc2 , Dmbt1 , and Gpx2. Similarly, in Atp4a −/− mice, WWD significantly decreased the expressions of GSII and Clusterin, and inhibited the mRNA levels of Wfdc2 , Cftr , Dmbt1 , and Gpx2. Notably, WWD restored the expression of markers for chief cells (PGC, GIF) and parietal cells (ATP4A), particularly in the medium- and high-dose groups, indicating its potential anti-atrophy effect on H. pylori -infected and Atp4a −/− mice. WWD administration resulted in a decline in TFF2 expression to baseline levels, suggesting that the mucous protection mediated by TFF2 was unaffected. Furthermore, the infiltration of CD163+F4/80+ M2 macrophages in the gastric mucosa of H. pylori -infected mice was reduced after WWD treatment, indicating a potential modulatory role of WWD on M2 macrophages. WWD exerted protective effects against SPEM in H. pylori -infected and Atp4a −/− mice. The optimal doses of WWD were found to be medium doses in H. pylori -infected mice and high doses in Atp4a −/− mice. These effects include inhibition of transcripts associated with intestinal-type gastric adenocarcinoma, restoration of ATP4A and PGC expression, and reduction of M2 macrophage infiltration. These findings provide valuable insights into the therapeutic effects of WWD on advanced SPEM and highlight its potential as a treatment option. [Display omitted] • Weiwei decoction (WWD) has been used in treating gastric atrophy and metaplasia in China for over 20 years. • This study investigates WWD's effects against advanced Spasmolytic polypeptide-expressing metaplasia (SPEM) in mice. • WWD improves gastric mucosal pathology and suppresses intestinal-type gastric adenocarcinoma-associated transcripts. • WWD has the potential to restore ATP4A and PGC expression, decrease M2 macrophage infiltration, and protect against SPEM mice. [ABSTRACT FROM AUTHOR]

• A method for the MADM with the linguistic distribution is proposed. • The disappointment behaviors of decision makers are considered. • The disappointment almost stochastic dominance relationship is defined. • The properties of the disappointment almost stochastic dominance relationship are discussed. • The disappointment almost stochastic dominance degrees are defined. In the existing studies of the multi-attribute decision making problem (MADM) with linguistic distributions, the decision makers are assumed to be completely rational. However, in real life MADM problems, the decision makers sometimes exhibit the disappointment behaviors over different linguistic assessments. Thus, in this paper a method is proposed for the MADM with the linguistic distributions, in which the disappointment behaviors of decision makers are considered. In the proposed method, the decision matrix with numerical distribution is obtained by the numerical scale model. Based on the defined disappointment almost stochastic dominance (DASD) relationship and DASD degree, the DASD relationship and the DASD degree matrices with respect to all criteria are then calculated, respectively. Next, the ranking results are determined based on the net DASD degrees. Finally, a numerical example and a comparison analysis are provided to discuss the effectiveness of the proposal. [ABSTRACT FROM AUTHOR]

Abstract In recent years, the sparsity-promoting reconstruction method based on the compressed sensing theory has been rapidly developed and applied to seismic data reconstruction. Many achievements have been made toward providing high-quality reconstruction by using undersampled data. However, the problem of insufficient reconstruction in null traces still hinders us a lot in practical applications, especially for complex seismic data. Aiming to solve this problem, we made full use of the sparsity characteristics of seismic data in multiple sparse transform domains and jointly reconstructed seismic data to realize the complementary advantages of multiple sparse transforms; As such, we propose a high-precision seismic data recovery method with multi-domain sparsity constraints based on curvelet and high-resolution Radon transforms. Numerical examples by synthetic and real data showed that the new approach can achieve a better reconstruction result than the commonly used curvelet-based recovery method. Integrated with the curvelet transform to develop new recovery method, the high-resolution Radon transform has more advantages than the conventional Radon transform for overcoming the shortcomings associated with the insufficient reconstruction of high-amplitude events. At the same time, the method is also applicable for developing new reconstruction methods by combining other sparse transforms depending on the characteristics of seismic data. The reconstruction method with multi-domain sparsity constraints can easily be extended to three-dimensional situation. Highlights • A better seismic data recovery with multi-domain sparsity constraints is proposed. • Sparse representation with curvelet and Radon transforms for complex seismic data. • A joint recovery scheme is easily implemented based on sequential inversion. • New method improves the recovery effect of seismic data with high-amplitude events. • Sparse Radon transform is superior to conventional one for joint data recovery. [ABSTRACT FROM AUTHOR]

Highlights • Multifunctional hyaluronic acid/hydroxyethyl chitosan nanocomplexes were prepared. • DOX and ALA were loaded into polysaccharide nanocomplexes via Schiff base linkage. • Nanocomplexes displayed pH-responsive surface charge reversal and drug release. • Active targeting enhanced additive effect of chemotherapy and photodynamic therapy. Abstract Combination of chemotherapy and photodynamic therapy has emerged as a promising anticancer strategy. Polysaccharide-based nanoparticles are being intensively explored as drug carriers for different forms of combination therapy. In this study, novel multifunctional polysaccharide-based nanocomplexes were prepared from aldehyde-functionalized hyaluronic acid and hydroxyethyl chitosan via sequential self-assembly method. Stable nanocomplexes were obtained through both Schiff's base bond and electrostatic interactions. Chemotherapeutics doxorubicin and pro-photosensitizer 5-aminolevulinic acid were chemically conjugated onto the nanocomplexes via Schiff base linkage. Anti-HER2 antibody as targeting moiety was decorated onto the surface of nanocomplexes. The obtained near-spherical shaped nanocomplexes had an average size of 140 nm and a zeta potential of −24.6 mV, and displayed pH-responsive surface charge reversal and drug release. Active targeting strategy significantly enhanced the cellular uptake of nanocomplexes and combined anticancer efficiency of chemo-photodynamic dual therapy in breast cancer MCF-7 cells. These results suggested that the nanocomplexes had great potential for targeted combination therapy of breast cancer. [ABSTRACT FROM AUTHOR]

Hydrogels fabricated from natural polysaccharides may serve as ideal scaffolds for tissue engineering because of their similarity to the extracellular matrices. In this study, novel hydrogel scaffolds with bubble-like porous structure were prepared from hydroxyethyl chitosan (HECS) and cellulose (CEL) by a combination of chemical crosslinking, particle-leaching using silicon dioxide particles as porogen and freeze-drying method. The morphology, compression stress-strain curves, wettability, and swelling and rheological behaviors of the HECS/CEL scaffolds were characterized by SEM, mechanical test, contact angle measurement and rheometer. HECS/CEL scaffolds had good comprehensive performances and could reach equilibrium swelling state in water within 20s. The results from in vitro biocompatibility evaluated using SEM, live/dead cell viability and MTT assays demonstrated that the HECS/CEL scaffolds could well support the attachment, spreading and proliferation of osteoblastic MC3T3-E1 cells and showed good biocompatibility. Therefore, the novel HECS/CEL scaffolds may be promising for bone tissue engineering applications. [ABSTRACT FROM AUTHOR]

Co-delivery of chemotherapeutic drug and small interfering RNA (siRNA) within a single nanovehicle has emerged as a promising combination therapy approach to treating cancers because of their synergistic effect. Nanocarrier delivery systems with low cytotoxicity and high efficiency are needed for such a purpose. In this study, a novel folate-conjugated PEGylated cationic triblock copolymer, poly(acrylhydrazine)- block -poly(3-dimethylaminopropyl methacrylamide)- block -poly(acrylhydrazine) (PAH- b -PDMAPMA- b -PAH), was synthesized and evaluated as a stimuli-sensitive vehicle for the targeted co-delivery of doxorubicin (DOX) and Bcl-2 siRNA into breast cancer MCF-7 cells. The synthetic process of the PEGylated triblock copolymer involved sequential reversible addition-fragmentation chain transfer polymerization, PEGylation and removal of tert -butoxy carbamate protecting groups. Folate-conjugated and/or -unconjugated poly(ethylene glycol) segments were grafted onto PAH- b -PDMAPMA- b -PAH via a reduction-sensitive disulfide linkage. The synthetic polymers were characterized by 1 H NMR and gel permeation chromatography. The PEGylated triblock copolymer could chemically conjugate DOX onto PAH blocks via pH-responsive hydrazone bonds and simultaneously complex negatively charged Bcl-2 siRNA with cationic PDMAPMA blocks through electrostatic interactions at N/P ratios ≥ 32:1 to form multifunctional nanomicelleplexes. The nanomicelleplexes exhibited spherical shape, possessed a positively charged surface with a zeta potential of + 22.5 mV and had a desirable and uniform particle size of 187 nm. In vitro release studies revealed that the nanomicelleplexes could release DOX and Bcl-2 siRNA in a reduction and pH dual-sensitive manner and the payload release was significantly enhanced in a reductive acidic environment mimicking the endosomes/lysosomes of cancer cells compared to under physiology conditions. Furthermore, the release of both DOX and siRNA was found to follow Higuchi kinetic model. Confocal laser scanning microscopy, flow cytometry and MTT analyses confirmed that, compared with folate-undecorated nanomicelleplexes, folate-decorated nanomicelleplexes could more effectively co-deliver DOX and Bcl-2 siRNA into MCF-7 cells and showed a stronger cell-killing effect. The pristine PEGylated triblock copolymer exhibited good cytocompatibility. Moreover, co-delivery of DOX and Bcl-2 siRNA achieved a significant synergistic antitumor efficacy. These findings suggested that the folate-decorated PEGylated cationic triblock copolymer might be a promising vehicle for targeted intracellular co-delivery of DOX and siRNA in MCF-7 cells, representing a potential clinical combination therapy for breast cancer treatment. [ABSTRACT FROM AUTHOR]

Though much progress in utilizing tissue engineering technology to investigate tumor development in vitro has been made, the effective management of human melanoma is still a challenge in clinic due to lack of suitable 3D culture systems. In this study, we prepared a poly(γ-benzyl- l -glutamate)/poly(lactic acid) (PBLG/PLA) nanofiber membrane by electrospinning and demonstrated its suitability as a matrix for 3D culture of melanoma cells in vitro . The electrospun PBLG/PLA nanofiber membrane displayed a smooth and uniform fibrous morphology and had a desirable water contact angle of 79.3 ± 0.6°. The average diameter of PBLG/PLA nanofibers was 320.3 ± 95.1 nm that was less than that (516.2 ± 163.3 nm) of pure PLA nanofibers. The addition of PBLG into PLA decreased the cold crystallization peak of PLA fibers from 93 to 75 °C. The in vitro biocompatibility of PBLG/PLA nanofiber membrane was evaluated with B16F10 cells using PLA nanofiber membrane as control. It was found that, compared to PLA nanofiber membrane, PBLG/PLA nanofiber membrane could better support cell viability and proliferation, as indicated by MTT assay and live-dead staining. SEM results revealed that PBLG/PLA rather than PLA nanofiber membrane promoted the generation of tumoroid-like structures. These findings clearly demonstrated that the electrospun PBLG/PLA nanofiber membrane could mimick the extracellular matrix of melanoma microenvironment and be a promising platform for 3D cell culture. [ABSTRACT FROM AUTHOR]

Glucagon-like peptide (GLP-1) is an endogenous hormone that induces insulin secretion from pancreatic islets and modified forms are used to treat diabetes mellitus type 2. Understanding how GLP-1 interacts with its receptor (GLP-1R) can potentially lead to more effective drugs. Modeling and NMR studies of the N-terminus of GLP-1 suggest a β-turn between residues Glu9-Phe12 and a kinked alpha helix between Val16-Gly37. N-terminal turn constraints attenuated binding affinity and activity (compounds 1–8 ). Lys-Asp (i, i+4) crosslinks in the middle and at the C-terminus increased alpha helicity and cAMP stimulation without much effect on binding affinity or beta-arrestin 2 recruitment (compounds 9–18 ). Strategic positioning of helix-inducing constraints and amino acid substitutions (Tyr16, Ala22) increased peptide helicity and produced ten-fold higher cAMP potency (compounds 19–28 ) over GLP-1(7–37)-NH 2 . The most potent cAMP activator (compound 23 ) was also the most potent inducer of insulin secretion. [ABSTRACT FROM AUTHOR]

In this study, novel poly(γ-benzyl l -glutamate)/poly(lactic- co -glycolic acid)/bioglass (PBLG/PLGA/BG) composite scaffolds with different weight ratios were fabricated using a negative NaCl-templating method. The morphology, compression modulus and degradation kinetics of the scaffolds were characterized. The results showed that the PBLG/PLGA/BG composite scaffolds with a weight ratio of 5:5:1, namely PBLG5PLGA5BG composite scaffolds, displayed a pore size range of 50–500 μm, high compressive modulus (566.6 ± 8.8 kPa), suitable glass transition temperature (46.8 ± 0.2 °C) and low degradation rate (> 8 weeks). The in vitro biocompatibility of the scaffolds was evaluated with MC3T3-E1 cells by live-dead staining, MTT and ALP activity assays. The obtained results indicated that the PBLG5PLGA5BG composite scaffolds were more conducive to the adhesion, proliferation and osteoblastic differentiation of MC3T3-E1 cells than PBLG and PBLG/PLGA composite scaffolds. The in vivo biocompatibility of the scaffolds was evaluated in both SD rat subcutaneous model and rabbit tibia defect model. The results of H&E, Masson's trichrome and CD34 staining assays demonstrated that the PBLG5PLGA5BG composite scaffolds allowed the ingrowth of tissue and microvessels more effectively than PBLG/PLGA composite scaffolds. The results of digital radiography confirmed that the PBLG5PLGA5BG composite scaffolds significantly improved in vivo osteogenesis. Collectively, the PBLG5PLGA5BG composite scaffolds could be a promising candidate for tissue engineering applications. [ABSTRACT FROM AUTHOR]

A comb-like amphiphilic copolymer methoxypolyethylene glycol- graft -poly( l -lysine)- block -poly( l -phenylalanine) (mPEG- g -PLL- b -Phe) was successfully synthesized. To synthesize mPEG- g -PLL- b -Phe, diblock copolymer PLL- b -Phe was first synthesized by successive ring-opening polymerization of α-amino acid N-carboxyanhydrides followed by the removal of benzyloxycarbonyl protecting groups, and then mPEG was grafted onto PLL- b -Phe by reductive amination via Schiff's base formation. The chemical structures of the copolymers were identified by 1 H NMR. mPEG- g -PLL- b -Phe copolymer had a critical micelle concentration of 6.0 mg/L and could self-assemble in an aqueous solution into multicompartment nanomicelles with a mean diameter of approximately 78 nm. The nanomicelles could encapsulate doxorubicin (DOX) through hydrophobic and π–π stacking interactions between DOX molecules and Phe blocks and simultaneously complex P-gp siRNA with cationic PLL blocks via electrostatic interactions. The DOX/P-gp siRNA-loaded nanomicelles showed spherical morphology, possessed narrow particle size distribution and had a mean particle size of 120 nm. The DOX/P-gp siRNA-loaded nanomicelles exhibited pH-responsive release behaviors and displayed accelerated release under acidic conditions. The DOX/P-gp siRNA-loaded nanomicelles were efficiently internalized into MCF-7 cells, and DOX released could successfully reach nuclei. In vitro cytotoxicity assay demonstrated that the DOX/P-gp siRNA-loaded nanomicelles showed a much higher cytotoxicity in MCF-7 cells than DOX-loaded nanomicelles due to their synergistic killing effect and that the blank nanomicelles had good biocompatibility. Thus, the novel comb-like mPEG- g -PLL- b -Phe nanomicelles could be a promising vehicle for co-delivery of chemotherapeutic drug and genetic material. [ABSTRACT FROM AUTHOR]

• Nanozyme-assisted PDT nanoplatform was prepared by an innovative dual coordination. • Obtained nanoplatform showed tri-enzyme activity to potentiate ROS generation efficacy. • Obtained nanoplatform-mediated ROS storm could induce immunogenic cell death. • Nanoplatform/αPD-1 combination could induce robust systemic antitumor immunity. Induction of immunogenic tumor cell death (ICD) is a promising strategy to potentiate immune checkpoint blockade (ICB) efficacy. However, it is still a huge challenge to develop efficient ICD-inducing nanomedicine. Herein, a copper nanozyme-assisted photodynamic therapy (PDT) nanoplatform nHACI was developed to achieve efficient ICD induction and robust systemic antitumor immune response through amplifying intracellular oxidative stress. The nHACI was fabricated from hydrazided hyaluronan and Cu2+ through an innovative hydrazide-copper coordination and in situ mineralization process, followed by loading of photosensitizer indocyanine green (ICG) via ICG-copper coordination. The nHACI exhibited superior drug loading efficiency, tumor microenvironment-responsive degradation behavior, and Fenton-like, glutathione oxidase-like and catalase-like triple activities. Importantly, it could not only deplete glutathione and concurrently generate 1O 2 and ·OH that amplified oxidative stress and induced ICD but also downregulate the proportion of M2 macrophages in tumors. The combination of nHACI-based PDT and PD-1 blockade could efficiently eradicate primary tumors, inhibit distant tumor growth and lung metastasis, and prevent tumor recurrence, demonstrating activation of robust systemic antitumor immune response. Collectively, this study presents a novel coordination assembly approach and nHACI holds great potential in eradicating primary tumors and potentiating ICB therapy via inducing ICD. [ABSTRACT FROM AUTHOR]

This work investigated that the graphite felt anodized by NaOH, NH 4 HCO 3 , or H 2 SO 4 aqueous, and then as the cathode materials for in-situ hydrogen peroxide (H 2 O 2) production and its employed for rhodamine B (RhB) degradation via Electro-Fenton (EF) process. At −0.60 V (vs. SCE), after 120 min electrolysis, the H 2 O 2 yield by graphite felt which anodized by 0.2 M H 2 SO 4 achieved up 110.5 mg L−1 in 0.05 M Na 2 SO 4 electrolyte. Compared with the raw graphite felt used for cathode, the H 2 O 2 yield increased by 15.85 times under the same conditions. The results of Raman spectroscopy demonstrated that graphite felt anodized by H 2 SO 4 solution can be achieved the highest defect degree. For the degradation of RhB, the cathode which anodized by H 2 SO 4 solution has the highest removal rate. For the degradation rate of RhB, the effect of applied current density, Fe2+ ions concentration, pH value were investigated. In addition, suggested that the efficient Fe3+ reduction reaction on the cathode surface was an important reason of the high efficiency of RhB degradation. 5-times continuous runs indicated that the modified cathode has remarkable stability and reusability during the EF process. [Display omitted] • Graphite felt modified by anodic oxidation used for the cathode of Electro-Fenton technology. • Modification significantly improved the yield of H 2 O 2 and the degradation rate of RhB. • The effect of solution types of electrolyte on graphite felt modification was studied. • Investigated the effect factors of current density, Fe2+ concentration, pH for RhB removal rate. [ABSTRACT FROM AUTHOR]

It is still a huge challenge for concurrent highly efficient loading of chemotherapeutic agent and photosensitizer into single nanocarrier via stimuli-responsive linkages due to their different physicochemical properties and pharmacokinetics. Herein, based on the discovery of unique cisplatin-hydrazide and cisplatin-indocyanine green (ICG) coordination reactions, a multifunctional coordination nanoprodrug, cisplatin/ICG co-loaded hydrazided hyaluronan/bovine serum albumin (HBCI) nanoparticles, was developed by a desolvation-dual coordination process. The nanoprodrug exhibited ultrahigh drug loading efficiency and glutathione/NIR light dual-responsive drug release behavior. In vitro cellular studies demonstrated efficient internalization and apoptosis-inducing ability of the nanoprodrug in HepG2 cells. In vivo results confirmed the efficacious tumor accumulation and biosafety of HBCI nanoprodrug and synergistic effect of HBCI-based combined photodynamic chemotherapy on inhibiting tumor growth. Overall, this work not only provides a novel dual coordination approach for highly efficient loading of cisplatin and ICG but also verifies the therapeutic potential of HBCI nanoprodrug in combating hepatocellular carcinoma. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: On-line portfolio is a sequential investment algorithm during a long period and makes portfolio decision without any statistical assumption about the behavior of the market. A constant rebalanced portfolio (CRP) is an investment strategy which adopts the same portfolio vector on each trading period. Design of on-line portfolio algorithms which are competitive with the best constant rebalanced portfolio (BCRP) is a hot topic recently. In this paper, we present a new on-line portfolio selection strategy, which computes the new portfolio vector based completely on on-line learning of linear functions. The proposed algorithm is useful since it gives the investor a whole range of choices for the on-line portfolios. Using the technique of taking relative entropy as a distance function, we prove that the new algorithm is a universal portfolio, which exhibits the same asymptotic growth rate in normalized natural logarithmic wealth as the BCRP for any sequence of price relatives. Experiments on several New York Stock Exchange dates also show the good performance of the new strategy. [Copyright &y& Elsevier]

Abstract: The 3C-like protease (3CLpro) of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is one of the most promising targets for discovery of drugs against SARS, because of its critical role in the viral life cycle. In this study, a natural compound called quercetin-3-β-galactoside was identified as an inhibitor of the protease by molecular docking, SPR/FRET-based bioassays, and mutagenesis studies. Both molecular modeling and Q189A mutation revealed that Gln189 plays a key role in the binding. Furthermore, experimental evidence showed that the secondary structure and enzymatic activity of SARS-CoV 3CLpro were not affected by the Q189A mutation. With the help of molecular modeling, eight new derivatives of the natural product were designed and synthesized. Bioassay results reveal salient features of the structure–activity relationship of the new compounds: (1) removal of the 7-hydroxy group of the quercetin moiety decreases the bioactivity of the derivatives; (2) acetoxylation of the sugar moiety abolishes inhibitor action; (3) introduction of a large sugar substituent on 7-hydroxy of quercetin can be tolerated; (4) replacement of the galactose moiety with other sugars does not affect inhibitor potency. This study not only reveals a new class of compounds as potential drug leads against the SARS virus, but also provides a solid understanding of the mechanism of inhibition against the target enzyme. [Copyright &y& Elsevier]