Strong metal support interaction (SMSI) and MoO3 synergistic effect of Pt-based catalysts on the promotion of CO activity and sulfur resistance.

In industrial applications, Pt-based catalysts for CO oxidation have the dual challenges of CO self-poisoning and SO2 toxicity. This study used synthetic Keggin-type H3PMo12O40 (PMA) as the site of Pt, and the Pt-MoO3 produced by decomposition of PMA was anchored to TiO2 to construct the dual-interface structure of Pt-MoO3 and Pt-TiO2, abbreviated as Pt-P&M/TiO2. Pt-0.125P&M/TiO2 with a molar ratio of Pt to PMA of 8:1 showed both good CO oxidation activity and SO2 tolerance. In the CO activity test, the CO complete conversion temperature T100 of Pt-0.125P&M/TiO2 was 113 ℃ (compared with 135 ℃ for Pt/TiO2). In the SO2 resistance test, the conversion efficiency of Pt-0.125P&M/TiO2 at 170 ℃ remained at 60% after 72 h, while that of Pt/TiO2 was only 13%. H2-TPR and XPS tests revealed that lattice oxygen provided by TiO2 and hydroxyl produced by MoO3 increased the CO reaction rate on Pt. According to the DFT theoretical calculation, the electronegative MoO3 attracted the d-orbital electrons of Pt, which reduced the adsorption energy of CO and SO2 from - 4.15 eV and - 2.54 eV to - 3.56 eV and - 1.52 eV, respectively, and further weakened the influence of strong CO adsorption and SO2 poisoning on the catalyst. This work explored the relationship between catalyst structure and catalyst performance and provided a feasible technical idea for the design of high-performance CO catalysts in industrial applications.

Two-dimensional (n = 1) ferroelectric film solar cells.

Molecular ferroelectrics that have excellent ferroelectric properties, a low processing temperature, narrow bandgap, and which are lightweight, have shown great potential in the photovoltaic field. However, two-dimensional (2D) perovskite solar cells with high tunability, excellent photo-physical properties and superior long-term stability are limited by poor out-of-plane conductivity from intrinsic multi-quantum-well electronic structures. This work uses 2D molecular ferroelectric film as the absorbing layer to break the limit of multiple quantum wells. Our 2D ferroelectric solar cells achieve the highest open-circuit voltage (1.29 V) and the best efficiency (3.71%) among the 2D (n = 1) Ruddlesden-Popper perovskite solar cells due to the enhanced out-of-plane charge transport induced by molecular ferroelectrics with a strong saturation polarization, high Curie temperature and multiaxial characteristics. This work aims to break the inefficient out-of-plane charge transport caused by the limit of the multi-quantum-well electronic structure and improve the efficiency of 2D ferroelectric solar cells.

Duality-Induced Regularizer for Semantic Matching Knowledge Graph Embeddings.

Semantic matching models-which assume that entities with similar semantics have similar embeddings-have shown great power in knowledge graph embeddings (KGE). Many existing semantic matching models use inner products in embedding spaces to measure the plausibility of triples and quadruples in static and temporal knowledge graphs. However, vectors that have the same inner products with another vector can still be orthogonal to each other, which implies that entities with similar semantics may have dissimilar embeddings. This property of inner products significantly limits the performance of semantic matching models. To address this challenge, we propose a novel regularizer-namely, DUality-induced RegulArizer (DURA)-which effectively encourages the entities with similar semantics to have similar embeddings. The major novelty of DURA is based on the observation that, for an existing semantic matching KGE model (primal), there is often another distance based KGE model (dual) closely associated with it, which can be used as effective constraints for entity embeddings. Experiments demonstrate that DURA consistently and significantly improves the performance of state-of-the-art semantic matching models on both static and temporal knowledge graph benchmarks.

Effect of TiO2 Calcination Pretreatment on the Performance of Pt/TiO2 Catalyst for CO Oxidation.

In order to improve the CO catalytic oxidation performance of a Pt/TiO2 catalyst, a series of Pt/TiO2 catalysts were prepared via an impregnation method in this study, and various characterization methods were used to explore the effect of TiO2 calcination pretreatment on the CO catalytic oxidation performance of the catalysts. The results revealed that Pt/TiO2 (700 °C) prepared by TiO2 after calcination pretreatment at 700 °C exhibits a superior CO oxidation activity at low temperatures. After calcination pretreatment, the catalyst exhibited a suitable specific surface area and pore structure, which is beneficial to the diffusion of reactants and reaction products. At the same time, the proportion of adsorbed oxygen on the catalyst surface was increased, which promoted the oxidation of CO. After calcination pretreatment, the adsorption capacity of the catalyst for CO and CO2 decreased, which was beneficial for the simultaneous inhibition of the CO self-poisoning of Pt sites. In addition, the Pt species exhibited a higher degree of dispersion and a smaller particle size, thereby increasing the CO oxidation activity of the Pt/TiO2 (700 °C) catalyst.

A new role of GRP75-USP1-SIX1 protein complex in driving prostate cancer progression and castration resistance.

Prostate cancer (PC) is the second most common cancer with limited treatment option in males. Although the reactivation of embryonic signals in adult cells is one of the characteristics of cancer, the underlying protein degradation mechanism remains elusive. Here, we show that the molecular chaperone GRP75 is a key player in PC cells by maintaining the protein stability of SIX1, a transcription factor for embryonic development. Mechanistically, GRP75 provides a platform to recruit the deubiquitinating enzyme USP1 to inhibit K48-linked polyubiquitination of SIX1. Structurally, the C-terminus of GRP75 (433-679 aa) contains a peptide binding domain, which is required for the formation of GRP75-USP1-SIX1 protein complex. Functionally, pharmacological or genetic inhibition of the GRP75-USP1-SIX1 protein complex suppresses tumor growth and overcomes the castration resistance of PC cells in vitro and in xenograft mouse models. Clinically, the protein expression of SIX1 in PC tumor tissues is positively correlated with the expression of GRP75 and USP1. These new findings not only enhance our understanding of the protein degradation mechanism, but also may provide a potential way to enhance the anti-cancer activity of androgen suppression therapy.

Growth arrest and apoptosis induction in androgen receptor-positive human breast cancer cells by inhibition of USP14-mediated androgen receptor deubiquitination.

It has been well known that androgen receptor (AR) is critical to prostate cancer development and progression. It has also been documented that AR is expressed in more than 60% of breast tumors, which promotes the growth of estrogen receptor-negative (ER-)/AR-positive (AR+) breast cancer cells. Thus, AR might be a potential therapeutic target for AR-positive/ER-negative breast cancer patients. Previously we reported that in prostate cancer cells proteasome-associated deubiquitinase ubiquitin-specific protease 14 (USP14) stabilized AR protein level by removing its ubiquitin chain. In the current study, we studied the USP14-AR protein interaction and cell proliferation status after USP14 reduction or inhibition in breast cancer cells, and our results support the conclusion that targeting USP14 is a novel strategy for treating AR-responsive breast cancer. We found that inhibition of USP14 accelerated the K48-ubiquitination and proteasome-mediated degradation of AR protein. Additionally, both genetic and pharmacological inhibition of USP14 significantly suppressed cell proliferation in AR-responsive breast cancer cells by blocking G0/G1 to S phase transition and inducing apoptosis. Moreover, AR overexpression inhibited USP14 inhibition-induced events, suggesting that AR deubiquitination by USP14 is critical for breast cancer growth and USP14 inhibition is a possible strategy to treat AR-positive breast cancer.

A novel deubiquitinase inhibitor b-AP15 triggers apoptosis in both androgen receptor-dependent and -independent prostate cancers.

Prostate cancer (PCa) remains a leading cause of cancer-related death in men. Especially, a subset of patients will eventually progress to the metastatic castrate-resistant prostate cancer (CRPC) which is currently incurable. Deubiquitinases (DUBs) associated with the 19S proteasome regulatory particle are increasingly emerging as significant therapeutic targets in numerous cancers. Recently, a novel small molecule b-AP15 is identified as an inhibitor of the USP14/UCHL5 (DUBs) of the 19S proteasome, resulting in cell growth inhibition and apoptosis in several human cancer cell lines. Here, we studied the therapeutic effect of b-AP15 in PCa, and our results indicate that (i) b-AP15 decreases viability, proliferation and triggers cytotoxicity to both androgen receptor-dependent and -independent PCa cells in vitro and in vivo, associated with caspase activation, inhibition of mitochondria function, increased reactive oxygen species (ROS) generation and endoplasmic reticulum (ER) stress; (ii) pan-caspase inhibitor z-VAD-FMK and ROS scavenger N-acetyl-L-cysteine (NAC) efficiently block apoptosis but not proteasome inhibition induced by exposure of b-AP15; (iii) treatment with b-AP15 in androgen-dependent prostate cancer (ADPC) cells down-regulates the expression of androgen receptor (AR), which is degraded via the ubiquitin proteasome system. Hence, the potent anti-tumor effect of b-AP15 on both androgen receptor-dependent and -independent PCa cells identifies a new promising therapeutic strategy for prostate cancer.

Integrated analysis of tobacco miRNA and mRNA expression profiles under PVY infection provids insight into tobacco-PVY interactions.

Potato virus Y (PVY) is a globally and economically important pathogen of potato, tobacco, tomato and other staple crops and caused significant yield losses and reductions in quality.To explore the molecular PVY-host interactions, we analysed changes in the miRNA and mRNA profiles of tobacco in response to PVY infection. A total of 81 differentially expressed miRNAs belonging to 29 families and 8133 mRNAs were identified. The Gene Ontology (GO) enrichment analyses showed that genes encoding the DNA/RNA binding, catalytic activity and signalling molecules were all significantly enriched. Moreover, 88 miRNA-mRNA interaction pairs were identified through a combined analysis of the two datasets. We also found evidence showing that the virus-derived siRNAs (vsiRNAs) from the PVY genome target tobacco translationally controlled tumor protein (NtTCTP) mRNA and mediate plant resistance to PVY. Together, our findings revealed that both miRNA and mRNA expression patterns can be changed in response to PVY infection and novel vsiRNA-plant interactions that may regulate plant resistance to PVY. Both provide fresh insights into the virus-plant interactions.

Platinum-containing compound platinum pyrithione suppresses ovarian tumor proliferation through proteasome inhibition.

BACKGROUND: Ovarian carcinoma is one of the most aggressive gynecological malignant neoplasms and makes up 25-30% of all cancer cases of the female genital tract. Currently, resistance to traditional chemotherapy is a great challenge for patients with Epithelial ovarian cancer (EOC). Therefore, identifying novel agents for EOC treatment is essential and urgent. METHOD: MTS assay was used to analyze the cell viability and proliferation of cancer cells. Flow cytometry was employed to analyze cell cycle distribution and cell apoptosis. Protein signaling pathways were detected by western blot and immunohistochemical staining. Nude mouse experiment was performed to test the in vivo effect of platinum pyrithione (PtPT). RESULTS: PtPT is a chemically well-characterized synthetic complex of platinum that potently inhibits proteasome-associated deubiquitinases USP14 and UCHL5 activity and shows selective cytotoxicity to multiple cancer cells without damaging DNA. We found that PtPT significantly accumulated ubquitinated-proteins and suppressed the proliferation of multiple EOC cells. Additionally, PtPT induced G2 phase arrest and apoptosis in both A2780 and SKOV3 cells. More importantly, animal experiments showed that PtPT dramatically suppressed the growth of EOC xenografts without obvious side effects. CONCLUSION: These results suggest that through proteasome inhibition, PtPT significantly suppressed the proliferation of EOC in vitro and in vivo and could be developed as a novel agent for EOC treatment in the future.

Proteasome-associated deubiquitinase ubiquitin-specific protease 14 regulates prostate cancer proliferation by deubiquitinating and stabilizing androgen receptor.

Androgen receptor (AR) is frequently over-expressed and plays a critical role in the growth and progression of human prostate cancer. The therapy attempting to target AR signalling was established in decades ago but the treatment of prostate cancer is far from being satisfactory. The assignable cause is that our understanding of the mechanism of AR regulation and re-activation remains incomplete. Increasing evidence suggests that deubiquitinases are involved in the regulation of cancer development and progression but the specific underlying mechanism often is not elucidated. In the current study, we have identified ubiquitin-specific protease 14 (USP14) as a novel regulator of AR, inhibiting the degradation of AR via deubiquitinating this oncoprotein in the androgen-responsive prostate cancer cells. We found that (i) USP14 could bind to AR, and additionally, both genetic and pharmacological inhibition of USP14 accelerated the ubiquitination and degradation of AR; (ii) downregulation or inhibition of USP14 suppressed cell proliferation and colony formation of LNcap cells and, conversely, overexpression of USP14 promoted the proliferation; and (iii) reduction or inhibition of USP14 induced G0/G1 phase arrest in LNcap prostate cancer cells. Hence, we conclude that USP14 promotes prostate cancer progression likely through stabilization of AR, suggesting that USP14 could be a promising therapeutic target for prostate cancer.

Ubiquitin-specific protease 14 regulates cardiac hypertrophy progression by increasing GSK-3ß phosphorylation.

Cardiac hypertrophy, a compensatory response to various stimuli in the heart, independently predicts cardiovascular ailments and related deaths. Increasing evidence indicates ubiquitin-proteasome signaling contributes to cardiac hypertrophy regulation. Here, we identified ubiquitin-specific protease 14 (USP14), a 19S proteasome associated deubiquitinase (DUB), as a novel target for cardiac hypertrophy therapy via inhibition of the GSK-3ß pathway. Indeed, USP14 expression was increased in an animal model of abdominal aorta constriction. In an angiotensin II (AngII) induced primary neonatal rat cardiomyocyte hypertrophy model, USP14 expression was increased in a time-dependent manner, and reduced USP14 deubiquitinase activity or USP14 knockdown resulted in lower expression levels of the myocardial hypertrophy specific marker ß-MHC, and subsequent decreased GSK-3ß phosphorylation. In conclusion, USP14 mediates the development of cardiac hypertrophy by promoting GSK-3ß phosphorylation, suggesting that USP14 might represent a novel therapeutic target for cardiac hypertrophy treatment.

Combined therapeutic effects of bortezomib and anacardic acid on multiple myeloma cells via activation of the endoplasmic reticulum stress response.

Bortezomib (Bor), a proteasome inhibitor, has marked therapeutic effects in multiple myeloma (MM), and its synergistic effects with other anticancer agents have been widely investigated. In the present study, endoplasmic reticulum (ER) stress was the target of the treatment strategy; anacardic acid (AA) and Bor induce ER stress, resulting in apoptosis of multiple myeloma cells. AA/Bor combination therapy exhibited overt cytotoxicity in MM cells, by synergistically reducing cell growth and promoting cell death. Notably, expression levels of the stress­associated molecules binding protein, phosphorylated eukaryotic initiation factor 2α, activating transcription factor 4 (ATF4) and CCAAT­enhancer binding protein homologous protein (CHOP) were increased following treatment. AA/Bor combination therapy­induced U266 cell cytotoxicity was partially reversed by ATF4 gene silencing and slightly enhanced by CHOP knockdown. The results of the present study suggest that AA/Bor combination may be a potential therapeutic strategy for MM treatment.

Multiple virus resistance using artificial trans-acting siRNAs.

Plant TAS gene encoded trans-acting siRNAs (ta-siRNAs) regulate the expression of target mRNAs by guiding their cleavage at the sequence complementary region as microRNAs. Since one TAS transcript is cleaved into multiple ta-siRNAs in a phased manner, TAS genes may be engineered to express multiple artificial ta-siRNAs (ata-siRNAs) that target multiple viruses at several distinct genomic positions. To test this hypothesis, the Arabidopsis TAS3a gene was engineered to express ata-siRNAs targeting the genome of Turnip mosaic virus (TuMV) and Cucumber mosaic virus (CMV). Transgenic Arabidopsis thaliana plants expressing these ata-siRNAs showed high level of resistance to both viruses. These results suggest that plant TAS genes can be modified to express artificial ta-siRNAs to confer multiple virus resistance and could have broad applications for future development in virus resistance strategies.

Two clinical drugs deubiquitinase inhibitor auranofin and aldehyde dehydrogenase inhibitor disulfiram trigger synergistic anti-tumor effects in vitro and in vivo.

Inhibition of proteasome-associated deubiquitinases (DUBs) is emerging as a novel strategy for cancer therapy. It was recently reported that auranofin (Aur), a gold (I)-containing compound used clinically to treat rheumatoid arthritis, is a proteasome-associated DUB inhibitor. Disulfiram (DSF), an inhibitor of aldehyde dehydrogenase, is currently in clinical use for treating alcoholism. Recent studies have indicated that DSF can also act as an antitumor agent. We investigated the effect of combining DSF and Aur on apoptosis induction and tumor growth in hepatoma cancer cells. Here we report that (i) the combined treatment of Aur and DSF results in synergistic cytotoxicity to hepatoma cells in vitro and in vivo; (ii) Aur and DSF in combination induces caspase activation, endoplasmic reticulum (ER) stress, and reactive oxygen species (ROS) production; (iii) pan-caspase inhibitor z-VAD-FMK could efficiently block apoptosis but not proteasome inhibition induced by Aur and DSF combined treatment, and ROS is not required for Aur+DSF to induce apoptosis. Collectively, we demonstrate a model of synergism between DSF and proteasome-associated DUB inhibitor Aur in the induction of apoptosis in hepatoma cancer cells, identifying a potential novel anticancer strategy for clinical use in the future.

Artificial TALE as a Convenient Protein Platform for Engineering Broad-Spectrum Resistance to Begomoviruses.

Transcription activator-like effectors (TALEs) are a class of sequence-specific DNA-binding proteins that utilize a simple and predictable modality to recognize target DNA. This unique characteristic allows for the rapid assembly of artificial TALEs, with high DNA binding specificity, to any target DNA sequences for the creation of customizable sequence-specific nucleases used in genome engineering. Here, we report the use of an artificial TALE protein as a convenient platform for designing broad-spectrum resistance to begomoviruses, one of the most destructive plant virus groups, which cause tremendous losses worldwide. We showed that artificial TALEs, which were assembled based on conserved sequence motifs within begomovirus genomes, could confer partial resistance in transgenic Nicotiana benthamiana to all three begomoviruses tested. Furthermore, the resistance was maintained even in the presence of their betasatellite. These results shed new light on the development of broad-spectrum resistance against DNA viruses, such as begomoviruses.