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Hepatocellular carcinoma (HCC) is a prevalent primary liver cancer often associated with chronic hepatitis B virus infection (CHB) and liver cirrhosis (LC), underscoring the critical need for biomarker discovery to improve patient outcomes. Emerging as a promising avenue for biomarker development, proteomic technology leveraging liquid biopsy from small extracellular vesicles (sEV) offers new insights. Here, we evaluated various methods for sEV isolation and identified polysaccharide chitosan (CS) as an optimal approach. Subsequently, we employed optimized CS‐based magnetic beads (Mag‐CS) for sEV separation from serum samples of healthy controls, CHB, LC, and HBV‐HCC patients. Leveraging data‐independent acquisition mass spectrometry coupled with machine learning, we uncovered potential vesicular protein biomarker signatures (KNG1, F11, KLKB1, CAPNS1, CDH1, CPN2, NME2) capable of distinguishing HBV‐HCC from CHB, LC, and non‐HCC conditions. Collectively, our findings highlight the utility of Mag‐CS‐based sEV isolation for identifying early detection biomarkers in HBV‐HCC. [ABSTRACT FROM AUTHOR]

In this study, a silica boron modified phenolic resin foam (SiBPF) is prepared in a reactor under specific pressure and temperature and using supercritical CO2 (scCO2) as a physical foaming agent, to improve phenolic foam (PF) brittle and friable properties and avoid environmental pollution caused by conventional physical foaming. To determine the partially curing degree for foaming, the influence of partially curing time at partially curing degrees between 39.88% and 53.17% was studied. Further, through an orthogonal experimental method, the optimized foaming process parameters—partially curing time of 6 h, adsorption time of 9 h, foaming pressure of 1 MPa, and foaming temperature of 130°C—were determined. The SiBPF, thus prepared under the optimized conditions, exhibited a density of 0.2356 g/cm3, an average cell size of 86.66 μm, and a cell density of 7.10 × 106 cells/cm3. Its compressive strength was found to be 7.28 MPa, with a specific compressive strength of 30.90 MPa/g·cm−3. At 800°C, the carbon residue rate, thermal decomposition temperature T5%, and Tmax reached 77.61%, 355.21, and 702.70°C, respectively. The thermal conductivity of SiBPF was measured to be 0.0644 W/mK, with the rear temperature stabilizing at 60°C on a hot platform of 100°C. [ABSTRACT FROM AUTHOR]

Effective presentation of antigens by dendritic cells (DC) is essential for achieving a robust cytotoxic T lymphocytes (CTLs) response, in which cDC1 is the key DC subtype for high‐performance activation of CTLs. However, low cDC1 proportion, complex process, and high cost severely hindered cDC1 generation and application. Herein, the study proposes an in situ cDC1 recruitment and activation strategy with simultaneous inhibiting cancer stemness for inducing robust CTL responses and enhancing the anti‐tumor effect. Fms‐like tyrosine kinase 3 ligand (FLT3L), Poly I:C, and Nap‐CUM (NCUM), playing the role of cDC1 recruitment, cDC1 activation, inducing antigen release and decreasing tumor cell stemness, respectively, are co‐encapsulated in an in situ hydrogel vaccine (FP/NCUM‐Gel). FP/NCUM‐Gel is gelated in situ after intra‐tumoral injection. With the near‐infrared irradiation, tumor cell immunogenic cell death occurred, tumor antigens and immunogenic signals are released in situ. cDC1 is recruited to tumor tissue and activated for antigen cross‐presentation, followed by migrating to lymph nodes and activating CTLs. Furthermore, tumor cell stemness are inhibited by napabucasin, which can help CTLs to achieve comprehensive tumor killing. Collectively, the proposed strategy of cDC1 in situ recruitment and activation combined with stemness inhibition provides great immune response and anti‐tumor potential, providing new ideas for clinical tumor vaccine design. [ABSTRACT FROM AUTHOR]

Tumor immune escape caused by low levels of tumor immunogenicity and immune checkpoint‐dependent suppression limits the immunotherapeutic effect. Herein, a "two‐way regulation" epigenetic therapeutic strategy is proposed using a novel nano‐regulator that inhibits tumor immune escape by upregulating expression of tumor‐associated antigens (TAAs) to improve immunogenicity and downregulating programmed cell death 1 ligand 1 (PD‐L1) expression to block programmed death‐1 (PD‐1)/PD‐L1. To engineer the nano‐regulator, the DNA methyltransferase (DNMT) inhibitor zebularine (Zeb) and the bromodomain‐containing protein 4 (BRD4) inhibitor JQ1 are co‐loaded into the cationic liposomes with condensing the toll‐like receptor 9 (TLR9) agonist cytosine‐phosphate‐guanine (CpG) via electrostatic interactions to obtain G‐J/ZL. Then, asparagine–glycine–arginine (NGR) modified material carboxymethyl‐chitosan (CMCS) is coated on the surface of G‐J/ZL to construct CG‐J/ZL. CG‐J/ZL is shown to target tumor tissue and disassemble under the acidic tumor microenvironment (TME). Zeb upregulated TAAs expression to improve the immunogenicity; JQ1 inhibited PD‐L1 expression to block immune checkpoint; CpG promote dendritic cell (DC) maturation and reactivated the ability of tumour‐associated macrophages (TAM) to kill tumor cells. Taken together, these results demonstrate that the nano‐regulator CG‐J/ZL can upregulate TAAs expression to enhance T‐cell infiltration and downregulate PD‐L1 expression to improve the recognition of tumor cells by T‐cells, representing a promising strategy to improve antitumor immune response. [ABSTRACT FROM AUTHOR]

Cation‐disordered Rocksalt oxides (DRXs) are a promising new class of cathode materials for Li‐ion batteries due to their natural abundance, low cost and great electrochemical performance. High entropy strategy in Mn‐based DRXs appears to be an effective strategy for improving the rate capability, but it suffers from challenges including capacity degradation. The present paper reports a new group of high entropy DRXs (HE DRX) based on Ni2+‐Nb5+ pair; the structural and chemical evolution upon cycling of DRXs with an increasing transition metal (TM) species are systematically investigated. An explanation is proposed for how the crystal field stability energy determines that HE DRX could exist in single Rocksalt solid solution structures. We further reveal that the charge compensation mechanism in HE DRX is the result of various TM synergistic effect. More importantly, through various in situ and ex situ techniques and theoretical calculation, the effective integration of more TM cation species within the HE DRX framework promotes better Li+ diffusion and improves lattice oxygen stability, consequently increasing capacity upon cycling. [ABSTRACT FROM AUTHOR]

In this work, high temperature and large temperature gradient are addressed for the first time in the topology optimization of thermo‐elastic structures. The conventional assumption of constant material properties (CMPs) is broken through with the full consideration of temperature‐dependent material properties (TDMPs) including thermal conductivity, elastic tensor, and coefficient of thermal expansion. Nonlinear heat conduction is thus implemented to give varying temperature fields in thermoelasticity. The maximum displacement of the specified region is taken as the objective function in the formulation of the optimization problem. The Kreisselmeier‐Steinhauser (KS) function is employed to approximate the regional maximum displacement/temperature. Corresponding sensitivity analyses, which are carried out using the adjoint method, theoretically reveal how TDMPs affect the thermo‐elastic optimization problem. Typical numerical examples are investigated to validate the proposed approach. The results show that the use of TDMPs produces optimized structures of high fidelity with displacements precisely predicted and temperature constraints rigorously satisfied under large temperature gradient, while thermo‐elastic analysis and optimization with CMPs lead to undesirable designs with significant inaccuracy. [ABSTRACT FROM AUTHOR]

Photothermal therapy (PTT) is a promising strategy for cancer treatment, but its clinical application relies heavily on accurate tumor positioning and effective combination. Nanotheranostics has shown superior application in precise tumor positioning and treatment, bringing potential opportunities for developing novel PTT‐based therapies. Here, a nanotheranostic agent is proposed to enhance magnetic resonance imaging (MRI)/ near‐infrared fluorescence imaging (NIRFI) imaging‐guided photo‐induced triple‐therapy for cancer. Thermosensitive liposomes co‐loaded with SPIONs/IR780 and Abemaciclib (SIA‐TSLs), peptide ACKFRGD, and click group 2‐cyano‐6‐amino‐benzothiazole (CABT) are co‐modified on the surface of SIA‐TSLs to form SIA‐αTSLs. ACKFRGD can be hydrolyzed to expose the 1, 2‐thiolamino groups in the presence of cathepsin B in tumors, which click cycloaddition with the cyano group on CABT, resulting in the formation of SIA‐αTSLs aggregates. The aggregation of SIA‐αTSLs in tumors enhances the MRI/NIRFI imaging capability and enables precise PTT. Photo‐induced triple‐therapy enhances precision cancer therapy. First, PTT ablates specific tumors and induces ICD via localized photothermal. Second, local tumor heating promotes the rupture of SIA‐αTSLs, which release Abemaciclib to block the tumor cell cycle and inhibit Tregs proliferation. Third, injecting GM‐CSF into tumor tissue leads to recruitment of dendritic cells and initiation of antitumor immunity. Collectively, these results present a promising nanotheranostic strategy for future cancer therapy. [ABSTRACT FROM AUTHOR]

Compositing dielectric and magnetic components have been proven effective in optimizing electromagnetic (EM) wave absorption, in which the dielectric loss capacity can be reinforced by the polarization effects of hetero‐substitutions. Here, the dielectric polarization through the energy transformation between the relatively complex permeability and permittivity in nitrogen‐doped carbon nanocages (NCNs) with sub‐nanometer Fe clusters is further boosted. As a transition state between single Fe atoms and Fe3O4 nanoparticles hetero‐substitutions, these subnanometer Fe clusters confined in NCNs can be achieved by carbonizing FePc@ZIF‐8 composites at 900 °C. Benefitting from their unique structures, an enhanced dielectric loss tangent of 1.57 is obtained at 10 GHz, which is 3.0 and 1.6 times higher than those of single Fe atoms and Fe3O4 nanoparticles hetero‐substitutions, respectively. Furthermore, the minimum reflection loss can reach −64.75 dB at 7.1 GHz (2.7 mm) and the effective absorption bandwidth is 6.2 GHz (11.8–18 GHz, covering the full P‐band) at 1.7 mm. The present study provides intrinsic insight into the dielectric polarization behaviors in subnanometer hetero‐substitutions, inspiring the design of high‐performance EM absorption materials. [ABSTRACT FROM AUTHOR]

Eliminating primary tumor ("roots") and inhibiting associated‐circulating tumor cells (associated‐CTCs, "seeds") are vital issues that need to be urgently addressed in cancer therapy. Associated‐CTCs, which include single CTCs, CTC clusters, and CTC–neutrophil clusters, are essential executors in metastasis and the cause of metastasis‐related death in cancer patients. Herein, a "roots and seeds" multipoint costriking nanodevice (GV‐Lipo/sorafenib (SF)/digitoxin (DT)) is developed to eliminate primary tumors and inhibit the spread of associated‐CTCs for enhancing metastasis inhibition and the therapeutic effect on hepatocellular carcinoma (HCC). GV‐Lipo/SF/DT eliminates primary tumor cells by the action of SF, thus reducing CTC production at the roots and improving the therapeutic effect on HCC. GV‐Lipo/SF/DT inhibits associated‐CTCs effectively via the enhanced identification and capture effects of glypican‐3 and/or vascular cell adhesion molecule 1 (VCAM1) targeting, dissociating CTC clusters using DT, blocking the formation of CTC–neutrophil clusters using anti‐VCAM1 monoclonal antibody, and killing CTCs with SF. It is successfully verified that GV‐Lipo/SF/DT increases the CTC elimination efficiency in vivo, thus effectively preventing metastasis, and shows enhanced antitumor efficacy in both an H22‐bearing tumor model and orthotopic HCC models. Overall, the "roots and seeds" multipoint costriking strategy may open a new cancer treatment model for the clinic. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Advanced microwave absorbing materials (MAMs) are urgently required to eliminate and attenuate microwaves to address the ubiquitous microwave radiations and interference. In this contribution, we report the microwave absorption application of a two‐dimensional (2D) semiconductive metal‐organic framework (MOF), i.e., CuHT (HT = 4‐hydroxythiophenol), without any pyrolysis at high temperature. Owing to the suitable electrical conductivity (2.69 × 10–4 S·cm–1), CuHT renders remarkable microwave absorption performance, with the minimum reflection loss (RLmin) of –50.9 dB and the effective absorption bandwidth of 4.2 GHz (7.7—10.9 GHz) at a thickness of 1.74 mm. Based on DFT calculation, microwave attenuation is mainly originated from resistance loss due to the conducting planes of honeycomb‐like Cu2S layers. Thanks to the facile kilogram‐scale synthesis, CuHT holds great potential for future microwave absorption applications. [ABSTRACT FROM AUTHOR]

Immune checkpoint blockade (ICB) therapy revolutionizes cancer therapeutics. However, the effectiveness of ICB therapy is restricted. Focusing on the tumor itself and the immune system, an integrated nanoaircraft carrier that coloaded three therapeutic agents (NNG/OTC) to eradicate tumor cells, enhance T‐cells intratumoral infiltration, and relieve the inhibition of tumor immunosuppressive microenvironment (TIM) is designed. First, tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL) is used to combine with oxaliplatin for reducing tumor burden. Second, oxaliplatin is used to elicit immunogenic cell death and combine with cytosine‐phosphate‐guanine (CpG) to promote dendritic cells maturation, ultimately increasing T‐cells intratumoral infiltration. Third, CpG is further used to repolarize M2 type of tumor‐associated macrophages, thus reversing immunosuppression of TIM. The nanoaircraft carrier can effectively arrive at the tumor site and detach small‐sized nanoparticles under a high concentration of matrix metalloproteinase‐2, which promotes deep tumor penetration. Under the mediation of targeting ligands, three therapeutic agents loaded in small‐sized nanoparticles could be launched to their target cells. NNG/OTC modulates the antitumor immunity and exhibits excellent tumor inhibition when in combination with ICB therapy, indicating the increased response of ICB therapy. Collectively, NNG/OTC can co‐deliver various drugs with different physicochemical properties and provide a promising strategy for enhancing ICB therapy. [ABSTRACT FROM AUTHOR]

Immune checkpoint therapy promotes cytotoxic T lymphocytes (CTLs) activity to eliminate tumors. Nevertheless, their effectiveness in solid tumors is limited by inadequate infiltration of CTLs and suppressive tumor microenvironment (TME). Herein, an anti‐PD‐1 antibody coupled chemo‐photothermal integrated nanoplatform (A/Au@MSMs‐P) is proposed to reshape antitumor immunity against cancer. The matrix metalloproteinase‐2 (MMP‐2) responsive A/Au@MSMs‐P promotes the separation of abemaciclib‐loaded gold‐silica nanoparticles (A/Au@MSMs) and anti‐PD‐1 antibody, achieving a triple‐coordinated strategy to enhance checkpoint blockade therapy. First, chemo‐photothermal therapy of A/Au@MSMs induces cell cycle arrest in G1 phase and promotes tumor cells apoptosis to achieve local ablation. Second, immunogenic death of tumor cells promotes the maturation of dendritic cells and recruits antigen‐specific CTLs into tumor tissue to promote immune activation. Third, abemaciclib markedly suppresses the proliferation of regulatory T cells (Tregs) to alleviate the immunosuppression of the TME and potentiates the effectiveness of CTLs. This triple‐coordinated strategy not only reshapes the antitumor immunity to enhance checkpoint blockade, but also cooperates with chemo‐photothermal therapy, leading to improved antitumor efficiency and prolonged survival rate. Taken together, this study presents a promising strategy for improving checkpoint therapy response and has great potential in future cancer therapy. [ABSTRACT FROM AUTHOR]

Background: Helicobacter pylori (H. pylori) is a common human pathogenic bacterium that is associated with gastric diseases. The current leading clinical therapy is combination antibiotics, but this treatment has safety issues, especially the induction of drug resistance. Therefore, developing a safe and effective vaccine against H. pylori is one of the best alternatives. Objective: To develop Saccharomyces cerevisiae (S. cerevisiae)‐based oral vaccines and then demonstrate the feasibility of this platform for preventing H. pylori infection in the absence of a mucosal adjuvant. Materials and Methods: Saccharomyces cerevisiae (S. cerevisiae)‐based oral vaccines, including EBY100/pYD1‐UreB and EBY100/pYD1‐VacA, were generated and analyzed by Western blot, Immunofluorescence analysis, flow cytometric assay, and indirect enzyme‐link immunosorbent assay (ELISA). Further, antibody responses induced by oral administration of EBY100/pYD1‐UreB, EBY100/pYD1‐VacA, or EBY100/pYD1‐UreB + EBY100/pYD1‐VacA were measured in a mouse model. Lastly, the vaccinated mice were infected with H. pylori SS1, and colonization in the stomach were evaluated. Results: Saccharomyces cerevisiae‐based H. pylori oral vaccines were successfully constructed. Mice orally administered with EBY100/pYD1‐UreB, EBY100/pYD1‐VacA, or EBY100/pYD1‐UreB + EBY100/pYD1‐VacA exhibited a significant humoral immune response as well as a mucosal immune response. Importantly, S. cerevisiae‐based oral vaccines could effectively reduce bacterial loads with statistical significance after H. pylori infection. Conclusions: Our study shows that S. cerevisiae‐based platforms can serve as an alternative approach for the future development of promising bacterial oral vaccine candidates. [ABSTRACT FROM AUTHOR]

Combination therapy is a current hot topic in cancer treatment. Multiple synergistic effects elicited by combined drugs are essential in improving antitumor activity. Herein, a pH‐triggered charge and size dual switchable nanocage co‐loaded with abemaciclib and IMD‐0354 (PA/PI‐ND) is reported, exhibiting a novel triple‐interlocked combination of chemotherapy, immunotherapy, and chemoimmunotherapy. The charge reversal polymer NGR‐poly(ethylene glycol)‐poly(l‐lysine)‐dimethylmaleic anhydride (NGR‐PEG‐PLL‐DMA, ND) in PA/PI‐ND promotes the pH‐triggered charge reversal from negative to positive and size reduction from about 180 to 10 nm in an acidic tumor microenvironment, which greatly enhances cellular uptake and tumor tissue deep penetration. With the PA/PI‐ND triple‐interlocked combination therapy, the chemotherapeutic effect is enhanced by the action of abemaciclib to induce cell cycle arrest in the G1 phase, together with the reduction in cyclin D levels caused by IMD‐0354. The dual anti‐tumor promoting immunotherapy is achieved by abemaciclib selectively inhibiting the proliferation of regulatory T cells (Tregs) and by IMD‐0354 promoting tumor‐associated macrophage (TAM) repolarization from an M2 to M1 phenotype. Furthermore, PA/PI‐ND has improved anti‐tumor efficiency resulting from the third synergistic effect provided by chemoimmunotherapy. Taken together, PA/PI‐ND is a promising strategy to guide the design of future drug delivery carriers and cancer combination therapy. [ABSTRACT FROM AUTHOR]

The thermodynamic and electrochemical properties of ionic liquids produce a broad spectrum of unconventional phenomena both microscopically and macroscopically. However, despite numerous theoretical and experimental studies, the fundamental roles of the relevant interactions such as electrostatic interactions and hydrogen bonding often remain unclear at the molecular level. The complexity of the molecular interactions typically increases when ionic liquids dissolve polymers or polar substances such as water. Accordingly, recent studies have revealed new features of ionic liquids. Further insights into the role of the molecular polarity of ionic liquids are required. This article presents an overview of the important phenomena of ionic liquids concerning soft‐matter sciences based on selected experimental and theoretical studies. We focus on the effect of the dielectric response of ionic liquids to distinguish ionic liquids from common inorganic salts, such as alkali metal halides. [ABSTRACT FROM AUTHOR]

BACKGROUND Traditional hot water blanching has a slow heat transfer rate, whereas radiofrequency (RF) heating has the advantages of a much faster heating rate and a higher penetration depth. In the present study, RF heating was applied to improve heating uniformity for subsequent blanching experiments involving potato cuboids. Potato cuboids were treated in a pilot-scale, RF heating system (27.12 MHz, 6 kW) under different operating conditions. RESULTS The dielectric constant increased first and then decreased with temperature, whereas the loss factor increased as the temperature increased. The results of the present study reveal that the electrode gap, sample height and NaCl solution had significant effects ( P < 0.05) on the temperature distribution and heating uniformity of the sample after RF heating. The optimum RF heating uniformity was obtained at an electrode gap of 120 mm, a sample height of 60 mm and when immersed in NaCl solution of 0.5 s m-1. The central heating pattern was presented in a sample. Cold spots were located at the edge of the top surface of the sample. CONCLUSION The present study shows the great potential of RF heating for the blanching of vegetables. Future studies should aim to determine changes in the texture and nutrient contents of vegetables during RF heating. © 2017 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Rod-shaped bacterial cells are polarized, with many organelles confined to a polar cellular site. In polar flagellates, FlhF and FlhG, a multiple-domain ( B- N- G) GTPase and a MinD-like ATPase respectively, function as a cognate pair to regulate flagellar localization and number as revealed in V ibrio and P seudomonas species. In this study, we show that FlhFG of S hewanella oneidensis ( SoFlhFG), a monotrichous γ-proteobacterium renowned for respiratory diversity, also play an important role in the flagellar polar placement and number control. Despite this, SoFlhFG exhibit distinct features that are not observed in the characterized counterparts. Most strikingly, the G domain of SoFlhF determines the polar placement, contrasting the N domain of the V ibrio cholerae FlhF. The SoFlhF N domain in fact counteracts the function of the G domain with respect to the terminal targeting in the absence of the B domain. We further show that GTPase activity of SoFlhF is essential for motility but not positioning. Overall, our results suggest that mechanisms underlying the polar placement of organelles appear to be diverse, even for evolutionally relatively conserved flagellum. [ABSTRACT FROM AUTHOR]

H2 production from water splitting by a photocatalytic process is one route that can be used to solve global issues related to energy depletion and environmental pollution, and it has attracted a great amount of attention in both the academic and industrial fields. TiO2 nanotube arrays are intensively investigated as TiO2 catalysts. In comparison to a TiO2 powder catalyst, the nanotube arrays have specific advantages, including a large surface area, easy retrievability, uniformly ordered structure, and size-dependent properties, all of which make them attractive in wide applications including H2 generation. In recent years, a large amount of work has been done and great progress has been achieved in this field. In this review, we summarize synthetic strategies to prepare TiO2 nanotube arrays and their modification methods, and we highlight recent progress in the generation of H2 on TiO2 nanotube-array-based materials. Finally, challenges associated with industrial application of this photocatalytic technique are also emphasized. [ABSTRACT FROM AUTHOR]

As a most conserved complex molecular machine made up of a large number of structural subunits, the flagellum is under tight regulation by hierarchical arrangements. Although variations in polar flagellar systems are found, most of them are restricted to multiple-copy components, such as flagellins and stators. Therefore, these features are regarded to be peripheral relative to the comprehensive conservation. In this study, however, we present evidence to show that the difference in highly conserved polar flagellar systems can be surprisingly profound, even at the heart of the classical regulatory hierarchy. In Gram-negative S hewanella oneidensis, two-component system FlrBC, whose counterpart is essential for flagellar biosynthesis and motility by directly controlling expression of class III genes in polarly flagellated bacteria such as V ibrio cholerae, is dispensable for the process. The system directly controls expression of the flaA gene, encoding a flagellin of weak motility. We further show that the ratio of two flagellins, FlaA and FlaB, determines motility of a flagellum. More strikingly, overproduction of FlrC results in a peritrichously multi-flagellated phenotype, and FlrC is likely to function as an activator in its unphosphorylated form for transcription of the flaA gene, contrasting the previously characterized counterpart. [ABSTRACT FROM AUTHOR]

In the present work a parametric investigation on hydrogen evolution by hydrolysis of ball-milled Al/graphite composite materials with water is reported. The results showed that the addition of NaCl produced some favorable effects on the completeness of the Al hydrolysis reaction with water, particularly at low NaCl weight percentage levels, but deteriorated the Al reactivity due to large size agglomerates formed during milling process. Using a fine aluminum powder could improve the aluminum hydrolysis reactivity and increase hydrogen generation rate. The hydrogen evolution measurements showed that Al in pellet form exhibited poor hydrolysis reactivity, and increasing the aging time significantly degraded the Al reactivity. The hydrogen evolution rate of the Al/graphite composite materials is also dependent on reaction temperature, and the maximum hydrogen generation rate of 52.4 cm3 min−1 g−1 Al was obtained if the reaction temperature was increased to 75 °C. [ABSTRACT FROM AUTHOR]

SUMMARY The discrete optimal orientation design of the composite laminate can be treated as a material selection problem dealt with by using the concept of continuous topology optimization method. In this work, a new bi-value coding parameterization (BCP) scheme of closed form is proposed to this aim. The basic idea of the BCP scheme is to 'code' each material phase using integer values of +1 and -1 so that each available material phase has one unique 'code' consisting of +1 and/or -1 assigned to design variables. Theoretical and numerical comparisons between the proposed BCP scheme and existing schemes show that the BCP has the advantage of an evident reduction of the number of design variables in logarithmic form. The benefit is particularly remarkable when the number of candidate materials becomes important in large-scale problems. Numerical tests with up to 36 candidate material orientations are illustrated for the first time to indicate the reliability and efficiency of the BCP scheme in solving this kind of problem. It proves that the BCP is an interesting and valuable scheme to achieve the optimal orientations for large-scale design problems. Besides, a four-layer laminate example is tested to demonstrate that the proposed BCP scheme can easily be extended to multilayer problems. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Attenuated salmonella have been reported to be capable of both selectively growing in tumors and expressing exogenous genes for tumor-targeted therapy. As 6-methoxypurine 2′-deoxyriboside (MoPdR) is similar to 6-methylpurine 2′-deoxyriboside in structure, we aimed to evaluate the antitumoral effect of the Escherichia coli purine nucleoside phosphorylase (ePNP) gene, using an attenuated salmonella-mediated delivery system, in combination with MoPdR. A novel mutant serovar Typhimurium (SC36) was used to carry the pEGFP-C1-ePNP vector that contains an enhanced green fluorescent protein and an ePNP gene under the control of the cytomegalovirus promoter. The function of the ePNP expression vector was confirmed in vitro using the enzymic conversion of MoPdR into methoxypurine. We also observed a high bystander effect induced by the ePNP/MoPdR system with a very low proportion (1%) of ePNP-positive cells and 5 µg/mL MoPdR, although the growth of parental cells was affected appreciably by MoPdR. The killing effect and increased apoptosis induced by SC36 carrying the ePNP expression vector (SC/ePNP) were detected by cytotoxicity assay and propidium iodide staining flow cytometry analysis, in combination with MoPdR. SC/ePNP was given orally to mice bearing mammary carcinomas, and its antitumor effect was evaluated. SC/ePNP plus MoPdR significantly inhibited tumor growth by approximately 86.6–88.7% and prolonged the survival of tumor-hosting mice. Our data support the view that MoPdR combined with the ePNP gene could be used in gene-directed enzyme prodrug therapy. Attenuated salmonella could be a promising strategy to improve ePNP/MoPdR bystander killing due to its preferential accumulation and anticancer activity in tumors. ( Cancer Sci 2008; 99: 1172–1179) [ABSTRACT FROM AUTHOR]

The title compound, C(13)H(11)N(3)O(3)S, was synthesized from 1H-1,2,4-triazole-5-thiol in a one pot reaction. The fused thia-zolo[3,2-b][1,2,4]triazole system is essentially coplanar with the benzene ring: they enclose an inter-planar angle of 1.37 (13)°. The olefinic double bond is in a Z conformation. In the crystal, C-H⋯N hydrogen bonds link the mol-ecules into double layers parallel to the ab plane.