It is greatly intriguing yet remains challenging to construct single‐atomic photocatalysts with stable surface free energy, favorable for well‐defined atomic coordination and photocatalytic carrier ...mobility during the photoredox process. Herein, an unsaturated edge confinement strategy is defined by coordinating single‐atomic‐site Ni on the bottom‐up synthesized porous few‐layer g‐C3N4 (namely, Ni5‐CN) via a self‐limiting method. This Ni5‐CN system with a few isolated Ni clusters distributed on the edge of g‐C3N4 is beneficial to immobilize the nonedged single‐atomic‐site Ni species, thus achieving a high single‐atomic active site density. Remarkably, the Ni5‐CN system exhibits comparably high photocatalytic activity for CO2 reduction, giving the CO generation rate of 8.6 µmol g−1 h−1 under visible‐light illumination, which is 7.8 times that of pure porous few‐layer g‐C3N4 (namely, CN, 1.1 µmol g−1 h−1). X‐ray absorption spectrometric analysis unveils that the cationic coordination environment of single‐atomic‐site Ni center, which is formed by Ni‐N doping‐intercalation the first coordination shell, motivates the superiority in synergistic N–Ni–N connection and interfacial carrier transfer. The photocatalytic mechanistic prediction confirms that the introduced unsaturated Ni‐N coordination favorably binds with CO2, and enhances the rate‐determining step of intermediates for CO generation.
The unsaturated edge confinement Ni‐anchored g‐C3N4 system is designed by coordinating single‐atomic‐site Ni species on the bottom‐up synthesized porous few‐layer g‐C3N4. The high single‐atomic active site density and the cationic coordination environment are formed by Ni‐N doping‐intercalation, and motivate the superiority in improving the interfacial carrier dynamics, thus boosting the photocatalytic CO2 reduction activity.
The synthesis and the evaluation of the efficacy of a cycloruthenated complex, RuZ, is reported, to overcome multi‐drug resistance (MDR) in cancer cells. RuZ can self‐assemble into nanoaggregates in ...the cell culture medium, resulting in a high intracellular concentration of RuZ in MDR cancer cells. The self‐assembly significantly decreases oxygen consumption and inhibits glycolysis, which decreases cellular adenosine triphosphate (ATP) levels. The decrease in ATP levels and its low affinity for the ABCB1 and ABCG2 transporters (which mediate MDR) significantly increase the retention of RuZ by MDR cancer cells. Furthermore, RuZ increases cellular oxidative stress, inducing DNA damage, and, in combination with the aforementioned effects of RuZ, increases the apoptosis of cancer cells. Proteomic profiling analysis suggests that the RuZ primarily decreases the expression of proteins that mediate glycolysis and aerobic mitochondrial respiration and increases the expression of proteins involved in apoptosis. RuZ inhibits the proliferation of 35 cancer cell lines, of which 7 cell lines are resistant to clinical drugs. It is also active in doxorubicin‐resistant MDA‐MB‐231/Adr mouse tumor xenografts. To the best of our knowledge, the results are the first to show that self‐assembled cycloruthenated complexes are efficacious in inhibiting the growth of MDR cancer cells.
The cyclometalated Ru(II) complex, RuZ, is reported to be able to self‐assemble and accumulate in high levels in multi‐drug resistant cancer cells. RuZ significantly increases cancer cell death by dual metabolic inhibition and interactions with multiple biological targets. Overall, the results suggest that RuZ could represent a potential treatment for cancers including multi‐drug resistant cancers.
Shape memory polymers (SMPs), a type of promising smart materials, are gradually applied into digital light processing (DLP) technology to realize four-dimensional (4D) printing. However, there is ...still a great lack of shape memory photosensitive resins suitable for DLP. In this work, novel acrylate-based photosensitive resins designed for DLP are prepared to fabricate SMP parts with tert-Butyl acrylate/1, 6-hexanediol diacrylate (tBA/HDDA) networks. The influence of crosslinker concentration on the shape memory and mechanical properties is systematically investigated. The results show that the developed SMP with 10 wt% crosslinker can withstand 16 consecutive cycles and retain extremely high shape recovery ratio of 100% even after 14 cycles, the one with 20 wt% crosslinker possesses the best shape fixity ratio of over 96%, and the storage modulus can reach up to 1.48 × 103 MPa with 50 wt% crosslinker. Furthermore, these 4D printed SMPs only spends 7–13 s in the 180° shape recovery, indicating a good shape recovery rate. This work confirms that the designed SMPs have potential applications in many areas due to their excellent shape memory performance, and provides valuable guidance for the shape memory properties optimization of other SMPs.
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•A new type of shape memory polymer is developed by digital light processing technology to achieve 4D printing.•The correlation of crosslinker concentration and shape memory properties is established.•The printed shape memory polymer parts show desirable shape recovery ratio and durable cycle life.•The shape memory mechanism is comprehensively revealed.
Nine dissimilar biochars, produced from varying feedstock at different pyrolysis temperatures, are appraised with respect to concentrations of potentially toxic elements, specifically, metals, ...metalloids and polycyclic aromatic hydrocarbons (PAHs). Concentrations of the metals and metalloids varied with the following ranges (mg kg−1): 0.02–0.94, Cd; 0.12–6.48, Cr; 0.04–13.2, Cu; 0.1–1.37, Ni; 0.06–3.87, Pb; 0.94–207, Zn and 0.03–0.27, As. Σ16PAH concentrations (16 Environmental Protection Agency (EPA) PAHs) range between 0.08 mg kg−1 to 8.7 mg kg−1. Subsequent comparison with background soil concentrations, concentration applied to the regulation of composted materials (Publicly Available Specification (PAS 100)) and European Union (EU) regulations relating to the application of sewage sludge to agricultural land suggest low risk associated with the concentrations of PTEs observed in biochar. Collectively, results suggest that environmental impacts attributable to metals, metalloids and PAHs associated with biochar following its application to soil are likely to be minimal.
► Concentrations of PTEs varied with feedstock and temperature of production. ► Of the PTEs Zn (0.94–207 mg kg−1) was of most priority. ► PTE levels did not infringe guidance values for compost or sewage sludge. ► Biochar (<100 t ha−1) is unlikely to make any real difference to PTE concentrations in soil.
Environmental impacts attributable to metals, metalloids and PAHs associated with biochar following its application to soil are likely to be minimal.
Overexpression of ATP-binding cassette (ABC) transporters is one of the most important mechanisms responsible for the development of multidrug resistance (MDR). Selonsertib, a serine/threonine kinase ...inhibitor, targets apoptosis signal-regulating kinase 1 (ASK1) and is now in phase III clinical trial for the treatment of non-alcoholic steatohepatitis (NASH). In this study, we investigated whether selonsertib could reverse MDR-mediated by ABC transporters, including ABCB1, ABCG2, ABCC1 and ABCC10. The results showed that selonsertib significantly reversed ABCB1- and ABCG2-mediated MDR, but not MDR-mediated by ABCC1 or ABCC10. Mechanism studies indicated that the reversal effect of selonsertib was related to the attenuation of the efflux activity of ABCB1 and ABCG2 transporters, without the protein level decrease or change in the subcellular localization of ABCB1 or ABCG2. Selonsertib stimulated the ATPase activity of ABCB1 and ABCG2 in a concentration-dependent manner, and in silico docking study showed selonsertib could interact with the substrate-binding sites of both ABCB1 and ABCG2. This study provides a clue into a novel treatment strategy, which includes a combination of selonsertib with antineoplastic drugs to attenuate MDR-mediated by ABCB1 or ABCG2 in cancer cells overexpressing these transporters.
•Selonsertib, a selective ASK1 inhibitor, significantly overcome MDR in cancer.•Selonsertib stimulates the ATPase activity of ABCB1 and ABCG2.•Selonsertib interacts with the substrate-binding sites of both ABCB1 and ABCG2.•The combination of selonsertib with anticancer drugs could be a novel treatment strategy to evade MDR in cancer.
Although gemcitabine has been considered as the first-line drug for advanced pancreatic cancer (PC), development of resistance to gemcitabine severely limits the effectiveness of this chemotherapy, ...and the underlying mechanism of gemcitabine resistance remains unclear. Various factors, such as ATP binding cassette (ABC) transporters, microRNAs and their downstream signaling pathways are included in chemoresistance to gemcitabine. This study investigated the potential mechanisms of microRNAs and ABC transporters related signaling pathways for PC resistance to gemcitabine both in vivo and in vitro.
Immunohistochemistry and Western blotting were applied to detect the expression of ABC transporters. Molecular docking analysis was performed to explore whether gemcitabine interacted with ABC transporters. Gain-of-function and loss-of-function analyses were performed to investigate the functions of hsa-miR-3178 in vitro and in vivo. Bioinformatics analysis, Western blotting and dual-luciferase reporter assay were used to confirm the downstream regulatory mechanisms of hsa-miR-3178.
We found that P-gp, BCRP and MRP1 were highly expressed in gemcitabine-resistant PC tissues and cells. Molecular docking analysis revealed that gemcitabine can bind to the ABC transporters. Hsa-miR-3178 was upregulated in gemcitabine resistance PANC-1 cells as compared to its parental PANC-1 cells. Moreover, we found that hsa-miR-3178 promoted gemcitabine resistance in PC cells. These results were also verified by animal experiments. RhoB was down-regulated in gemcitabine-resistant PC cells and it was a downstream target of hsa-miR-3178. Kaplan-Meier survival curve showed that lower RhoB expression was significantly associated with poor overall survival in PC patients. Rescue assays demonstrated that RhoB could reverse hsa-miR-3178-mediated gemcitabine resistance. Interestingly, hsa-miR-3178 promoted gemcitabine resistance in PC by activating the PI3K/Akt pathway-mediated upregulation of ABC transporters.
Our results indicate that hsa-miR-3178 promotes gemcitabine resistance via RhoB/PI3K/Akt signaling pathway-mediated upregulation of ABC transporters. These findings suggest that hsa-miR-3178 could be a novel therapeutic target for overcoming gemcitabine resistance in PC.
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Drug resistance is a major obstacle in the field of pre-clinical and clinical therapeutics. The development of novel technologies and targeted therapies have yielded new modalities to ...overcome drug resistance, but multidrug resistance (MDR) remains one of the major challenges in the treatment of cancer. The ubiquitin-proteasome system (UPS) has a central role in regulating the levels and activities of a multitude of proteins as well as regulation of cell cycle, gene expression, response to oxidative stress, cell survival, cell proliferation and apoptosis. Therefore, inhibition of the UPS could represent a novel strategy for the treatment and overcoming of drug resistance in chemoresistant malignancies. In 2003, bortezomib was approved by the FDA for the treatment of multiple myeloma (MM). However, due to its limitations, second generation proteasome inhibitors (PIs) like carfilzomib, ixazomib, oprozomib, delanzomib and marizomib were introduced which displayed clinical activity in bortezomib-resistant tumors. Past studies have demonstrated that proteasome inhibition potentiates the anti-cancer efficacy of other chemotherapeutic drugs by: i) decreasing the expression of anti-apoptotic proteins such as TNF-α and NF-kB, ii) increasing the levels of Noxa, a pro-apoptotic protein, iii) activating caspases and inducing apoptosis, iv) degrading the pro-survival protein, induced myeloid leukemia cell differentiation protein (MCL1), and v) inhibiting drug efflux transporters. In addition, the mechanism of action of the immunoproteasome inhibitors, ONX-0914 and LU-102, suggested their therapeutic role in the combination treatment with PIs. In the current review, we discuss various PIs and their underlying mechanisms in surmounting anti-tumor drug resistance when used in combination with conventional chemotherapeutic agents.
In this study, the in-situ synthesized TiB/Ti-6Al-4Vceramic-matrix nanocomposites with greatly enhanced hardness and wear resistant property have been prepared via selective laser melting (SLM) using ...a simple mixture of microsized Ti-6Al-4V and TiB2 powders. In order to provide a valuable reference for fabricating TiB/Ti-6Al-4V parts with metallographic features, effects of reinforcement content on microstructure and mechanical properties have been systematically investigated. It is found that during SLM process, the additive particles TiB2 are totally transformed into need-like nanoscaled TiB phase, and the microstructure of composites is composed of mutual parallel strips architecture with TiB rich in some regions but lean in the other regions. The SLM-producedTiB/Ti-6Al-4 V composites exhibit superior nanohardness of 6.0 GPa, which is much higher than its traditional sintering counterpart. Moreover, the in-site synthesized TiB reinforcement can remarkably improve in the wear resistance properties, the wear loss of TiB-free sample is approximately 2 times than that of the sample with 3 wt% TiB2.
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•In-situ synthesized TiB/Ti-6Al-4V nanocomposites have been prepared via SLM.•The need-like nanoscaled TiB phase formation and evolution mechanism during SLM is discussed in detail.•The interface orientation relationship between TiB and Ti matrix has been investigated.•The SLM-producedTiB/Ti-6Al-4V composites exhibit superior hardness and outstanding wear resistant property.
This review discusses different forms of nanomaterials generated from chitosan and its derivatives for controlled drug delivery. Nanomaterials are drug carriers with multiple features, including ...target delivery triggered by environmental, pH, thermal responses, enhanced biocompatibility, and the ability to cross the blood-brain barrier. Chitosan (CS), a natural polysaccharide largely obtained from marine crustaceans, is a promising drug delivery vector for therapeutics and diagnostics, owing to its biocompatibility, biodegradability, low toxicity, and structural variability. This review describes various approaches to obtain novel CS derivatives, including their distinct advantages, as well as different forms of nanomaterials recently developed from CS. The advanced applications of CS-based nanomaterials are presented here in terms of their specific functions. Recent studies have proven that nanotechnology combined with CS and its derivatives could potentially circumvent obstacles in the transport of drugs thereby improving the drug efficacy. CS-based nanomaterials have been shown to be highly effective in targeted drug therapy.
Biochar addition to soil has been proposed to improve plant growth by increasing soil fertility, minimizing bioaccumulation of toxic metal(liod)s and mitigating climate change. Sewage sludge (SS) is ...an attractive, though potentially problematic, feedstock of biochar. It is attractive because of its large abundance; however, it contains elevated concentrations of metal(loid)s and other contaminants. The pyrolysis of SS to biochar (SSBC) may be a way to reduce the availability of these contaminants to the soil and plants. Using rice plant pot experiments, we investigated the influence of SSBC upon biomass yield, bioaccumulation of nutrients, and metal(loid)s, and green housegas (GHG) emissions. SSBC amendments increased soil pH, total nitrogen, soil organic carbon and available nutrients and decreased bioavailable As, Cr, Co, Ni, and Pb (but not Cd, Cu, and Zn). Regarding rice plant properties, SSBC amendments significantly (P ≤ 0.01) increased shoot biomass (71.3-92.2%), grain yield (148.8-175.1%), and the bioaccumulation of phosphorus and sodium, though decreased the bioaccumulation of nitrogen (except in grain) and potassium. Amendments of SSBC significantly (P ≤ 0.05) reduced the bioaccumulation of As, Cr, Co, Cu, Ni, and Pb, but increased that of Cd and Zn, though not above limits set by Chinese regulations. Finally regarding GHG emissions, SSBC significantly (P < 0.01) reduced N2O emissions and stimulated the uptake/oxidation of CH4 enough to make both the cultivated and uncultivated paddy soil a CH4 sink. SSBC can be beneficial in rice paddy soil but the actual associated benefits will depend on site-specific conditions and source of SS; long-term effects remain a further unknown.
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