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Aim： Cathepsin L （CTSL）, a lysosomal acid cysteine protease, is known to play important roles in tumor metastasis and chemotherapy resistance. In this study we investigated the molecular mechanisms underlying the regulation of chemoresistance by CTSL in human lung cancer cells. Methods： Human lung cancer A549 cells, A549/PTX （paclitaxel-resistant） cells and A549/DDP （cisplatin-resistant） cells were tested. The resistance to cisplatin or paclitaxel was detected using MTT and the colony-formation assays. Actin remodeling was observed with FITC-Phalloidin fluorescent staining or immunofluorescence. A wound-healing assay or Transwell assay was used to assess the migration or invasion ability. The expression of CTSL and epithelial and mesenchymal markers was analyzed with Western blotting and immunofluorescence. The expression of EMT-associated transcription factors was measured with Western blotting or q-PCR. BALB/c nude mice were implanted subcutaneously with A549 cells overexpressing CTSL, and the mice were administered paclitaxel （10, 15 mg/kg, ip） every 3 d for 5 times.Results： Cisplatin or paclitaxel treatment （10-80 ng/mL） induced CTSL expression in A549 cells. CTSL levels were much higher in A549/PTX and A549/DDP cells than in A549 cells. Silencing of CTSL reversed the chemoresistance in A549/DDP and A549/TAX cells, whereas overexpression of CTSL attenuated the sensitivity of A549 cells to cisplatin or paclitaxel. Furthermore, A549/DDP and A549/TAX cells underwent morphological and cytoskeletal changes with increased cell invasion and migration abilities, accompanied by decreased expression of epithelial markers （E-cadherin and cytokeratin-18） and increased expression of mesenchymal markers （N-cadherin and vimentin）, as well as upregulation of EMT-associated transcription factors Snail, Slug, ZEB1 and ZEB2. Silencing of CTSL reversed EMT in A549/DDP and A549/TAX cells; In contrast, overexpression of CTSL induced EMT in A549 cells. In xenograft nude mouse model, the mice implanted with A549 cells overexpressing CTSL exhibited significantly reduced sensitivity to paclitaxel treatment, and increased expression of EMT-associated proteins and transcription factors in tumor tissues. Conclusion： Cisplatin and paclitaxel resistance is associated with CTSL upregulation-induced EMT in A549 cells. Thus, CTSL-mediated EMT may be exploited as a target to enhance the efficacy of cisplatin or paclitaxel against lung cancer and other types of malignancies

Development of active and durable electrocatalyst for oxygen reduction reaction (ORR) remains one challenge for the polymer electrolyte membrane fuel cell (PEMFC) technology. Pt-based nanomaterials show the greatest promise as electrocatalyst for this reaction among all current catalytic structures. This review focuses on Pt-based ORR catalyst material development and covers the past achievements, current research status and perspectives in this research field. In particular, several important categories of Pt-based catalytic structures and the research advances are summarized. Key factors affecting the catalyst activity and durability are discussed. An outlook of future research direction of ORR catalyst research is provided.

Although polymer electrolyte membrane fuel cells （PEMFCs） have received broad attention due to their virtually zero emission, high power density, and high efficiency, at present the limited stability of the electrocatalysts used in PEMFCs is a critical limitation to their large-scale commercialization. As a type of popularly used electrocatalyst material, carbon black supported platinum （Pt/C）--although highly efficient--undergoes corrosion of carbon, Pt dissolution, Ostwald ripening, and aggregation of Pt nanoparticles （NPs） under harsh chemical and electro- chemical oxidation conditions, which results in performance degradation of the electrocatalysts. In order to overcome these disadvantages, many groups have tried to improve the carbon support materials on which Pt is loaded. It has been found that some novel carbon nanomaterials and noncarbon materials with high surface areas, sufficient anchoring sites, high electrical conductivities, and high oxidation resistance under the strongly oxidizing condition in PEMFCs are ideal alternative supports. This review highlights the following aspects： （i） Recent advances in using novel carbon nanomaterials and noncarbon support materials to enhance the long-term durability of electrocatalysts; （ii） solutions to improve the electrical conductivity, surface area, and the strong interaction between metal and supports; and （iii） the synergistic effects in hybrid supports which help improve the stability of electrocatalysts.

Novel self-assembled architectures have received a growing amount of attention and have significant potential for application in catalysis/electrocatalysis. Herein, we take advantage of the unique coordination and self-assembly properties of arginine for the preparation of dendritic PtCu bimetallic nanoassemblies with tunable chemical composition and structure. Strong interactions between the arginine molecules are key in driving the self-assembly of primary nanocrystals. In addition, the strong coordination interactions between arginine and metal ions is responsible for the formation of Pt-Cu alloys. We also investigated the electrocatalytic activity of various dendritic PtCu bimetallic nanoassemblies towards the methanol oxidation reaction. PtBCUl nanoassemblies exhibited excellent electrocatalytic activity and stability in comparison with other PtCu bimetallic nanoassemblies （PtlCu3, PtlCu~） and commercial Pt black, due to their unique dendritic structures and the synergistic effect between the Pt and Cu atoms.

Ionomer impregnation represents a milestone in the evolution of polymer electrolyte fuel cell (PEFC) catalyst layers. Ionomer acts as the binder, facilitates proton transport, and thereby drastically improves catalyst utilization and effectiveness. However, advanced morphological and functional characterizations have revealed that up to 60% of Pt nanoparticles can be trapped in the micropores of carbon support particles. Ionomer clusters and oxygen molecules can hardly enter into micropores, leading to low Pt utilization and effectiveness. Moreover, the ionomer thin-films covering Pt nanoparticles can cause significant mass transport loss especially at high current densities. Ionomer-free ultra-thin catalyst layers (UTCLs) emerge as a promising alternative to reduce Pt loading by improving catalyst utilization and effectiveness, while theoretical issues such as the proton conduction mechanism remain puzzling and practical issues such as the rather narrow operation window remain unsettled. At present, the development of PEFC catalyst layer has come to a crossroads: staying ionomer-impregnated or going ionomer-free. It is always beneficial to look back into the past when coming to a crossroads. This paper addresses the characterization and modeling of both the conventional ionomer-impregnated catalyst layer and the emerging ionomer-free UTCLs, featuring advances in characterizing microscale distributions of Pt particles, ionomer, support particles and unraveling their interactions; advances in fundamental understandings of proton conduction and flooding behaviors in ionomer-free UTCLs; advances in modeling of conventional catalyst layers and especially UTCLs; and discussions on high-impact research topics in characterizing and modeling of catalyst layers.

Diallyl trisulfide （DATS）, a garlic organosulfide, has shown excellent chemopreventive potential. Cisplatin （DDP） is widely used to treat solid malignant tumors, but causing serious side effects. In the current study, we attempted to elucidate the chemopreventive mechanisms of DATS in human gastric cancer BGC-823 cells in vitro, and to investigate whether DATS could enhance the anti-tumor efficacy of DDP and improve quality of life in BGC-823 xenograft mice in vivo. Treatment with DATS （25-400 pmol/L） dose-dependently inhibited the viability of BGC-823 cells in vitro with an IC5o of 115.2＋4.3 pmol/L after 24 h drug exposure. DATS （50-200 pmol/L） induced cell cycle arrest at G2/M phase in BGC-823 cells, which correlated with significant accumulation of cyclin A2 and B1. DATS also induced BGC-823 cell apoptosis, which was accompanied by the modulation of Bcl-2 family members and caspase cascade activation. In BGC-823 xenograft mice, administration of DATS （20-40 mg.kg-1.d-1, ip） dose-dependently inhibited tumor growth and markedly reduced the number of Ki-67 positive cells in tumors. Interestingly, combined administration of DATS （30 mg.kg-1.d-1, ip） with DDP （5 mg/kg, every 5 d, ip） exhibited enhanced anti-tumor activity with fewer side effects. We showed that treatment of BGC-823 cells with DATS in vitro and in vivo significantly activated kinases such as p38 and JNK/MAPK and attenuated the Nrf2/Akt pathway. This study provides evidence that DATS exerts anticancer effects and enhances the antitumor efficacy of DDP, making it a novel candidate for adjuvant therapy for gastric cancer.

Three-dimensional （3D） hierarchical Pt-Cu tetragonal, highly branched, and dendritic superstructures have been synthesized by a facile template-free hydrothermal approach, showing growth patterns along （111, 110）, （111）, and （100） planes, respectively. These structures have been characterized by transmission electron microscopy （TEM）, X-ray diffraction （XRD）, energy dispersive X-ray spectroscopy （EDX）, inductively coupled plasma optical emission spectrometry （ICP-OES） and a detailed formation mechanism has been developed, which shows that the in situ formed 12 and the galvanic replacement reaction between Cu and Pt4, may guide the formation of these superstructures. The comparative electrocatalytic properties have been investigated for methanol and ethanol oxidation. Due to their interconnected arms, sufficient absorption sites, and exposed surfaces, these superstructures exhibit enhanced electrocatalytic performance for electro-oxidation of methanol and ethanol when compared with commercial Pt/C and Pt black.

Porous organic polymers （POPs） have recently emerged as promising candidates for catalyzing oxygen reduction reaction （ORR）. Compared to conventional Pt-based ORR catalysts, these newly developed porous materials, including both non-precious metal based catalysts and metal-free catalysts, are more sustainable and cost-effective. Their porous structures and large surface areas facilitate mass and electron transport and boost the ORR kinetics. This mini-review will give a brief summary of recent development of POPs as electrocatalysts for the ORR. Some design principles, different POP structures, key factors for their ORR catalytic performance, and outlook of POP materials will be discussed.

Oxaliplatin is a key drug in chemotherapy of colorectal cancer （CRC）. However, its efficacy is unsatisfied due to drug resistance of cancer ceils. In this study, we tested whether a natural agent, ursolic acid, was able to enhance the efficacy of oxaliplatin for CRC. Four CRC cell lines including SW480, SW620, LoVo, and RKO were used as in vitro models, and a SW620 xenograft mouse model was used in further in vivo study. We found that ursolic acid inhibited proliferation and induced apoptosis of all four cells and enhanced the cytotoxicity of oxaliplatin. This effect was associated with down-regulation of Bcl-xL, Bcl-2, survivin, activation of caspase-3, 8, 9, and inhibition of KRAS expression and BRAF, MEKll2, ERK1/2, p-38, JNK, AKT, IKKa, IKBa, and p65 phosphorylation of the MAPK, PI3K/AKT, and NF-KB signaling pathways. The two agents also showed synergistic effects against tumor growth in vivo. In addition, ursolic acid restored liver function and body weight of the mice treated with oxaliplatin. Thus, we concluded that ursolic acid could enhance the therapeutic effects of oxaliplatin against CRC both in vitro and in vivo, which offers an effective strategy to minimize the burden of oxaliplatin-induced adverse events and provides the groundwork for a new clinical strategy to treat CRC.

Heteroatom doping, precise composition control and rational morphology design are efficient strategies for producing novel nanocatalysts for the oxygen reduction reaction （ORR） in fuel cells. Herein, a cost-effective approach to synthesize nitrogen- and sulfur-codoped carbon nanowire aerogels using a hard templating method is proposed. The aerogels prepared using a combination of hydrothermal treatment and carbonization exhibit good catalytic activity for the ORR in alkaline solution. At the optimal annealing temperature and mass ratio between the nitrogen and sulfur precursors, the resultant aerogels show comparable electrocatalytic activity to that of a commercial Pt/C catalyst for the ORR. Importantly, the optimized catalyst shows much better long-term stability and satisfactory tolerance for the methanol crossover effect. These codoped aerogels are expected to have potential applications in fuel cells.