Drug-repurposing by virtual and experimental screening of PFKFB3 inhibitors for pancreatic cancer therapy.

Pancreatic cancer (PC) is the most frequently occurring cancer, with few effective treatments and a 5-year survival rate of only about 11%. It is characterized by stiff interstitium and pressure on blood vessels, leading to an increased glycolytic metabolism. PFKFB3 plays an important role in glycolysis, and its products (fructose-2,6-bisphosphate), which are allosteric PFK1 activators, limit the glycolytic rate. In this study, 14 PFKFB3 inhibitors were obtained by virtually screening the FDA-approved compound library. Subsequently, the in-vitro investigations confirmed that Lomitapide and Cabozantinib S-malate exhibit the excellent potential to inhibit PFKFB3. The combined administration of Lomitapide and Gemcitabine at a certain molar ratio indicated an enhanced anti-tumor effect in Orthotopic Pancreatic Cancer (OPC) models. This investigation provides a new treatment strategy for PC therapy.

Stabilized O3-Type Layered Sodium Oxides with Enhanced Rate Performance and Cycling Stability by Dual-Site Ti4+ /K+ Substitution.

High-capacity O3-type layered sodium oxides are considered one of the most promising cathode materials for the next generation of Na-ion batteries (NIBs). However, these cathodes usually suffer from low high-rate capacity and poor cycling stability due to structure deformation, native air sensitivity, and interfacial side reactions. Herein, a multi-site substituted strategy is employed to enhance the stability of O3-type NaNi0.5 Mn0.5 O2 . Simulations indicate that the Ti substitution decreases the charge density of Ni ions and improves the antioxidative capability of the material. In addition, the synergistic effect of K+ and Ti4+ significantly reduces the formation energy of Na+ vacancy and delivers an ultra-low lattice strain during the repeated Na+ extraction/insertion. In situ characterizations verify that the complicated phase transformation is mitigated during the charge/discharge process, resulting in greatly improved structure stability. The co-substituted cathode delivers a high-rate capacity of 97 mAh g-1 at 5 C and excellent capacity retention of 81% after 400 cycles at 0.5 C. The full cell paired with commercial hard carbon anode also exhibits high capacity and long cycling life. This dual-ion substitution strategy will provide a universal approach for the new rational design of high-capacity cathode materials for NIBs.

Design of Cu-Substituted O3-Type NaFe0.5 Mn0.5 O2 Cathode Materials for Sodium-Ion Batteries.

O3-type Fe/Mn-based layered oxide cathode materials with abundant reserves have a promising prospect in sodium-ion batteries. However, the electrochemical reversibility of most O3-type Fe/Mn-based oxide cathode materials is still not high enough. Herein, the effect of different Cu contents on the electrochemical properties of O3-NaFe0.50 Mn0.50 O2 materials is systematically investigated. The as-prepared NaFe0.30 Mn0.50 Cu0.20 O2 cathode achieves the synergistic optimization of the interface and bulk phase. It shows superior electrochemical performance, with an initial discharge specific capacity of 114 mAh g-1 at 0.1 C, a capacity retention rate of 94 % after 100 cycles at 0.5 C, and excellent chemical stability in air and water. In addition, the sodium ion full battery based on NaFe0.30 Mn0.50 Cu0.20 O2 cathode and hard carbon anode has a capacity retention rate of 81 % after 100 cycles. This research provides a useful approach for the preparation of low-cost and high-performance O3-type layered cathode materials.

Access to high-performance Li-rich layered oxide cathodes via ammonium phosphate surface treatment.

Ammonium phosphate ((NH4)3PO4) has been first used as a surface treatment reagent for Li-rich cathode materials. Compared to the conventional surface treatment, the samples treated with (NH4)3PO4 exhibit an ultra-high initial Coulomb efficiency of 98.0% and excellent cycling stability. This is mainly attributed to the simultaneous construction of surface integrated structures, including oxygen vacancies, spinel phases, and Li3PO4 coating. This study demonstrates the effectiveness of ammonium phosphate surface treatment and provides a new idea for designing other cathode materials.

Disulfide Bond-Based SN38 Prodrug Nanoassemblies with High Drug Loading and Reduction-Triggered Drug Release for Pancreatic Cancer Therapy.

Purpose: Chemotherapy is a significant and effective therapeutic strategy that is frequently utilized in the treatment of cancer. Small molecular prodrug-based nanoassemblies (SMPDNAs) combine the benefits of both prodrugs and nanomedicine into a single nanoassembly with high drug loading, increased stability, and improved biocompatibility. Methods: In this study, a disulfide bond inserted 7-ethyl-10-hydroxycamptothecin (SN38) prodrug was rationally designed and then used to prepare nanoassemblies (SNSS NAs) that were selectively activated by rich glutathione (GSH) in the tumor site. The characterization of SNSS NAs and the in vitro and in vivo evaluation of their antitumor effect on a pancreatic cancer model were performed. Results: In vitro findings demonstrated that SNSS NAs exhibited GSH-induced SN38 release and cytotoxicity. SNSS NAs have demonstrated a passive targeting effect on tumor tissues, a superior antitumor effect compared to irinotecan (CPT-11), and satisfactory biocompatibility with double dosage treatment. Conclusion: The SNSS NAs developed in this study provide a new method for the preparation of SN38-based nano-delivery systems with improved antitumor effect and biosafety.

Alkaloid Derivative (Z)-3ß-Ethylamino-Pregn-17(20)-en Inhibits Triple-Negative Breast Cancer Metastasis and Angiogenesis by Targeting HSP90α.

Metastasis is an important cause of cancer-related death. Previous studies in our laboratory found that pregnane alkaloids from Pachysandra terminalis had antimetastatic activity against breast cancer cells. In the current study, we demonstrated that treatment with one of the alkaloid derivatives, (Z)-3ß-ethylamino-pregn-17(20)-en (1), led to the downregulation of the HIF-1α/VEGF/VEGFR2 pathway, suppressed the phosphorylation of downstream molecules Akt, mTOR, FAK, and inhibited breast cancer metastasis and angiogenesis both in vitro and in vivo. Furthermore, the antimetastasis and antiangiogenesis effects of 1 treatment (40 mg/kg) were more effective than that of Sorafenib (50 mg/kg). Surface plasmon resonance (SPR) analysis was performed and the result suggested that HSP90α was a direct target of 1. Taken together, our results suggested that compound 1 might represent a candidate antitumor agent for metastatic breast cancer.

Plasma-Wind-Assisted In2S3 Preparation with an Amorphous Surface Structure for Enhanced Photocatalytic Hydrogen Production.

Photocatalytic production from water is considered an effective solution to fossil fuel-related environmental concerns, and photocatalyst surface science holds a significant interest in balancing photocatalysts' stability and activity. We propose a plasma-wind method to tune the surface properties of a photocatalyst with an amorphous structure. Theoretical calculation shows that the amorphous surface structure can cause an unsaturated coordination environment to adjust the electron distribution, forming more adsorption sites. Thus, the photocatalyst with a crystal-amorphous (C-A) interface can strengthen light absorption, harvest photo-induced electrons, and enrich the active sites, which help improve hydrogen yield. As a proof of concept, with indium sulfide (In2S3) nanosheets used as the catalyst, an impressive hydrogen production rate up to 457.35 µmol cm-2 h-1 has been achieved. Moreover, after plasma-assisted treatment, In2S3 with a C-A interface can produce hydrogen from water under natural outdoor conditions. Following a six-hour test, the rate of photocatalytic hydrogen evolution is found to be 400.50 µmol cm-2 g-1, which demonstrates that a catalyst prepared through plasma treatment is both effective and highly practical.

Alkaloid derivative ION-31a inhibits breast cancer metastasis and angiogenesis by targeting HSP90α.

Breast cancer has become the number one killer of women. In our previous study, an active compound, ION-31a, with potential anti-metastasis activity against breast cancer was identified through the synthesis of ionone alkaloid derivatives. In the present study, we aimed to identify the therapeutic target of ION-31a. We used a fluorescence tag labeled probe, molecular docking simulation, and surface plasmon resonance (SPR) analysis to identify the target of ION-31a. The main target of ION-31a was identified as heat shock protein 90 (HSP90). Thus, ION-31a is a novel HSP90 inhibiter that could suppress the metastasis of breast cancer and angiogenesis significantly in vitro and in vivo. ION-31a acts via inhibiting the HSP90/hypoxia inducible factor 1 alpha (HIF-1α)/vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR2) pathway and downregulating downstream signal pathways, including protein kinase B (AKT)/mammalian target of rapamycin (mTOR), AKT2/protein kinase C epsilon (PKCζ), extracellular regulated kinase 1/2 (ERK1/2), focal adhesion kinase (FAK), and mitogen-activated protein kinase 14 (p38MAPK) pathways. ION-31a affects multiple effectors implicated in tumor metastasis and has the potential to be developed as an anti-metastatic agent to treat patients with breast cancer.

The synergistic antitumor activity of 3-(2-nitrophenyl) propionic acid-paclitaxel nanoparticles (NPPA-PTX NPs) and anti-PD-L1 antibody inducing immunogenic cell death.

Cancer immunotherapy is a strategy that is moving to the frontier of cancer treatment in the current decade. In this study, we show evidence that 3-(2-nitrophenyl) propionic acid-paclitaxel nanoparticles (NPPA-PTX NPs), act as immunogenic cell death (ICD) inducers, stimulating an antitumor response which results in synergistic antitumor activity by combining anti-PD-L1 antibody (aPD-L1) in vivo. To investigate the antitumor immunity induced by NPPA-PTX NPs, the expression of both ICD marker calreticulin (CRT) and high mobility group box 1 (HMGB1) were analyzed. In addition, the antitumor activity of NPPA-PTX NPs combined with aPD-L1 in vivo was also investigated. The immune response was also measured through quantitation of the infiltration of T cells and the secretion of pro-inflammatory cytokines. The results demonstrate that NPPA-PTX NPs induce ICD of MDA-MB-231 and 4T1 cells through upregulation of CRT and HMGB1, reactivating the antitumor immunity via recruitment of infiltrating CD3+, CD4+, CD8+ T cells, secreting IFN-γ, TNF-α, and the enhanced antitumor activity by combining with aPD-L1. These data suggest that the combined therapy has a synergistic antitumor activity and has the potential to be developed into a novel therapeutic regimen for cancer patients.

Electrolytes for Lithium- and Sodium-Metal Batteries.

High-energy-density batteries have attracted significant attention due to the huge demand in electric transportation in future. Metal-based batteries, especially lithium metal batteries (LMBs) and sodium metal batteries (SMBs), have been hot research topics nowadays. The uncontrolled growth of metal dendrites has retarded the development of LMBs and SMBs. Various electrolytes have been explored to meet the demand of high-performance metal-based batteries, such as additives-contained electrolytes, polymer electrolytes, and solid-state electrolytes. To guide the development of electrolytes in LMBs and SMBs, we organize this roadmap to give out the status of present research and future challenges in this field. We also hope that the readers can get the knowledge and ideas from this roadmap.

Enhancing Anti-Tumor Activity of Sorafenib Mesoporous Silica Nanomatrix in Metastatic Breast Tumor and Hepatocellular Carcinoma via the Co-Administration with Flufenamic Acid.

INTRODUCTION: Because tumor-associated inflammation is a hallmark of cancer treatment, in the present study, sorafenib mesoporous silica nanomatrix (MSNM@SFN) co-administrated with flufenamic acid (FFA, a non-steroidal anti-inflammatory drug (NSAID)) was investigated to enhance the anti-tumor activity of MSNM@SFN. METHODS: Metastatic breast tumor 4T1/luc cells and hepatocellular carcinoma HepG2 cells were selected as cell models. The effects of FFA in vitro on cell migration, PGE2 secretion, and AKR1C1 and AKR1C3 levels in 4T1/luc and HepG2 cells were investigated. The in vivo anti-tumor activity of MSNM@SFN co-administrating with FFA (MSNM@SFN+FFA) was evaluated in a 4T1/luc metastatic tumor model, HepG2 tumor-bearing nude mice model, and HepG2 orthotopic tumor-bearing nude mice model, respectively. RESULTS: The results indicated that FFA could markedly decrease cell migration, PGE2 secretion, and AKR1C1 and AKR1C3 levels in both 4T1/luc and HepG2 cells. The enhanced anti-tumor activity of MSNM@SFN+FFA compared with that of MSNM@SFN was confirmed in the 4T1/luc metastatic tumor model, HepG2 tumor-bearing nude mice model, and HepG2 orthotopic tumor-bearing nude mice model in vivo, respectively. DISCUSSION: MSNM@SFN co-administrating with FFA (MSNM@SFN+FFA) developed in this study is an alternative strategy for improving the therapeutic efficacy of MSNM@SFN via co-administration with NSAIDs.

2020 Roadmap on Carbon Materials for Energy Storage and Conversion.

Carbon is a simple, stable and popular element with many allotropes. The carbon family members include carbon dots, carbon nanotubes, carbon fibers, graphene, graphite, graphdiyne and hard carbon, etc. They can be divided into different dimensions, and their structures can be open and porous. Moreover, it is very interesting to dope them with other elements (metal or non-metal) or hybridize them with other materials to form composites. The elemental and structural characteristics offer us to explore their applications in energy, environment, bioscience, medicine, electronics and others. Among them, energy storage and conversion are extremely attractive, as advances in this area may improve our life quality and environment. Some energy devices will be included herein, such as lithium-ion batteries, lithium sulfur batteries, sodium-ion batteries, potassium-ion batteries, dual ion batteries, electrochemical capacitors, and others. Additionally, carbon-based electrocatalysts are also studied in hydrogen evolution reaction and carbon dioxide reduction reaction. However, there are still many challenges in the design and preparation of electrode and electrocatalytic materials. The research related to carbon materials for energy storage and conversion is extremely active, and this has motivated us to contribute with a roadmap on 'Carbon Materials in Energy Storage and Conversion'.

Ionic Liquid Assisted Electrospinning of Porous LiFe0.4 Mn0.6 PO4 /CNFs as Free-Standing Cathodes with a Pseudocapacitive Contribution for High-Performance Lithium-Ion Batteries.

In pursuit of high-performance cathode materials for lithium-ion batteries with high energy and power densities, porous LiFe0.4 Mn0.6 PO4 /CNF free-standing electrodes have been successfully prepared through a facile ionic liquid (IL) assisted electrospinning method. Owing to the hierarchical porosity and N-doped carbon layer derived from the ionic liquid, the resulting electrodes exhibited superior electrochemical performances with an improvement of conductivity and pseudocapacitive contribution, delivering a discharge capability of 162.7, 133.5, 114.5, and 102.6 mAh g-1 at the current rates of 0.1, 1, 5, and 10 C, respectively. It is highly expected that this facile IL-assisted electrospinning method will lead to further developments for other phosphate-based free-standing electrodes, which offers a new route in designing polyanionic cathodes for high-performance Li-ion batteries.

New Insights on the Fast Response of Poly(Ionic Liquid)s to Humidity: The Effect of Free-Ion Concentration.

The swelling mechanism is widely used to explain the response of ionic liquids (ILs) or poly(ionic liquid)s (PILs) to moisture. While a fairly broad consensus has been attained, there are still some phenomena that are not well explained. As a complement to the swelling mechanism, we systematically studied the free volume theory in the rapid response and recovery of PIL humidity performance. We chose poly(1-ethyl-3-vinylimidazolium bromide) (PIL-Br), poly(1-ethyl-3-vinylimidazolium tetrafluoroborate) (PIL-BF4) and poly(1-ethyl-3-vinylimidazolium bis(trifluoromethane sulfonimide)) (PIL-TFSI) as model materials and investigated the impact of PIL structure including anion type, film thickness and affinity to moisture on performance to obtain the humidity sensing mechanism for PILs based on free volume theory. Hence, we can combine free volume theory with the designed PIL structures and their affinity with moisture to obtain a high concentration of free ions in PIL sensing films. Furthermore, the PIL humidity sensors also show fast, substantial impedance changes with changing humidity for real-time monitoring of the human respiratory rate due to a fast response and recovery performance. Therefore, our findings develop a new perspective to understand the humidity performance of PILs based on free volume theory, resulting in fast response and recovery properties realized by the rational design of PIL sensing films.

Well-Wrapped Li-Rich Layered Cathodes by Reduced Graphene Oxide towards High-Performance Li-Ion Batteries.

Layered lithium-rich manganese oxide (LLO) cathode materials have attracted much attention for the development of high-performance lithium-ion batteries. However, they have suffered seriously from disadvantages, such as large irreversible capacity loss during the first cycle, discharge capacity decaying, and poor rate performance. Here, a novel method was developed to coat the surface of 0.4Li2MnO3∙0.6LiNi1/3Co1/3Mn1/3O2 cathode material with reduced graphene-oxide (rGO) in order to address these drawbacks, where a surfactant was used to facilitate the well-wrapping of rGO. As a result, the modified LLO (LLO@rGO) cathode exhibits superior electrochemical performance including cycling stability and rate capability compared to the pristine LLO cathode. In particular, the LLO@rGO with a 0.5% rGO content can deliver a high discharge capacity of 166.3 mAh g-1 at a 5C rate. The novel strategy developed here can provide a vital approach to inhibit the undesired side reactions and structural deterioration of Li-rich cathode materials, and should be greatly useful for other cathode materials to improve their electrochemical performance.

A generalized strategy for the synthesis of two-dimensional metal oxide nanosheets based on a thermoregulated phase transition.

Two-dimensional (2D) metal oxide (MO) nanomaterials, like graphene, possess unique electrical, mechanical, optical and catalytic performances, and have attracted substantial research interest recently. However, it remains a challenge to easily obtain 2D MO nanosheets by a generalized synthetic pathway. Here, we report a general and facile strategy for the synthesis of 2D MO nanosheets induced by nonionic surfactant micelles. Notably, the novel strategy primarily relies on the thermoregulated phase transition of the micelles. The resulting 2D MO nanosheets show high specific surface areas. As a demonstration, Sb2O3 nanosheets synthesized by our method as anodes for sodium-ion batteries (SIBs) have a high reversible capacity of 420 mA h g-1 and a high capacity retention of 99% after 150 cycles at 0.1 A g-1. Mn3O4 nanosheets for supercapacitors have a remarkable specific capacitance of 127 F g-1 at a current density of 0.5 A g-1. Even at a large current density of 5 A g-1 after 10 000 cycles, 96% of the specific capacitance is retained, demonstrating the remarkable performance of these nanosheets for energy storage applications.

Antitumor activity of the bioreductive prodrug 3-(2-nitrophenyl) propionic acid-paclitaxel nanoparticles (NPPA-PTX NPs) on MDA-MB-231 cells: in vitro and in vivo.

BACKGROUND: 3-(2-Nitrophenyl) propionic acid-paclitaxel (NPPA-PTX) is a paclitaxel (PTX) bioreductive prodrug synthesized by our lab. We hypothesize that NPPA-PTX can self-assemble to form nanoparticles (NPs). MATERIALS AND METHODS: In the present research, the theoretical partition coefficient (XlogP) and Hansen solubility parameters of NPPA-PTX were calculated. NPPA-PTX nanoparticles prepared by NPPA-PTX and DSPE-PEG (NPPA-PTX:DSPE-PEG =1:0.1, w/w) (NPPA-PTX@PEG NPs) were prepared and characterized. The cellular uptake, in vitro antitumor activity, in vivo targeting effect, tumor distribution, in vivo antitumor activity, and safety of NPPA-PTX@PEG NPs were investigated. RESULTS: Our results indicate that NPPA-PTX can self-assemble to form NPPA-PTX@PEG NPs. Both the cellular uptake and safety of NPPA-PTX@PEG NPs were higher than those of Taxol. NPPA-PTX@PEG NPs could target tumor tissues by a passive targeting effect. In tumor tissues, NPPA-PTX@PEG NPs could completely transform into active PTX. The in vivo antitumor activity of NPPA-PTX@PEG NPs was confirmed in MDA-MB-231 tumor-bearing nude mice. CONCLUSION: The bioreductive prodrug NPPA-PTX could self-assemble to form NPs. The safety and antitumor activity of NPPA-PTX@PEG were confirmed in our in vitro and in vivo experiments. The NPPA-PTX@PEG NPs developed in this study could offer a new way of preparing bioreductive prodrug, self-assembled NPs suitable for antitumor therapy.

Anti-tumour activity of low molecular weight heparin doxorubicin nanoparticles for histone H1 high-expressive prostate cancer PC-3M cells.

Nucleus-targeting drug delivery systems (NTDDs) deliver chemotherapeutic agents to nuclei in order to improve the efficacy of anti-tumour therapy. Histone H1 (H1) plays a key role in establishing and maintaining higher order chromatin structures and could bind to cell membranes. In the present study, we selected H1 as a target to prepare a novel H1-mediated NTDD. Low molecular weight heparin (LMHP) and doxorubicin (DOX) were combined to form LMHP-DOX. Then, a novel NTDD consisting of LMHP-DOX nanoparticles (LMHP-DOX NPs) was prepared by self-assembly. The characteristics of LMHP-DOX and LMHP-DOX NPs were investigated. Histone H1 high-expressive prostate cancer PC-3M cell line was selected as the cell model. Cellular uptake, and the in vitro and in vivo anti-tumour activity of LMHP-DOX NPs were evaluated on H1 high-expressive human prostate cancer PC-3M cells. Our results indicated that intact LMHP-DOX NPs mediated by H1 could be absorbed by H1 high-expressive PC-3M cells, escape from the lysosomes to the cytoplasm, and localize in the perinuclear region via H1-mediated, whereby DOX could directly enter the cell nucleus and quickly increase the concentration of DOX in the nuclei of H1 high-expressive PC-3M cells to enhance the apoptotic activity of cancer cells. The anti-coagulant activity of LMHP-DOX NPs was almost completely diminished in rat blood compared with that of LMHP, indicating the safety of LMHP-DOX NPs. Compared to traditional NTDD strategies, LMHP-DOX NPs avoid the complicated modification of nucleus-targeting ligands and provide a compelling solution for the substantially enhanced nuclear uptake of chemotherapeutic agents for the development of more intelligent NTDDs.

Preparation of mesoporous ZnAl2O4 nanoflakes by ion exchange from a Na-dawsonite parent material in the presence of an ionic liquid.

Herein, mesoporous ZnAl2O4 spinel nanoflakes were prepared by an ion-exchange method from a Na-dawsonite parent material in the presence of an ionic liquid, 1-butyl-2,3-dimethylimidazolium chloride ([bdmim][Cl]), followed by calcination at 700 °C for 2 h. The as-obtained products were characterized by several techniques such as X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and energy dispersive X-ray spectroscopy (EDX). The ZnAl2O4 nanoflakes with the thickness of ∼20 nm were composed of numerous nanoparticles, which resulted in a high specific surface area of 245 m2 g-1. The formation mechanism of the ZnAl2O4 nanoflakes was comprehensively investigated, and the results showed that a 2D growth process of the Zn6Al2(OH)16(CO3)·4H2O crystallites with the assistance of [bdmim][Cl] was the key for the induction of ZnAl2O4 nanoflakes. Moreover, mesopores were formed between adjacent nanoparticles due to the release of CO2 and H2O molecules from Zn6Al2(OH)16(CO3)·4H2O during the calcination process.

A highly selective and sensitive H2S sensor at low temperatures based on Cr-doped α-Fe2O3 nanoparticles.

Cr-doped α-Fe2O3 nanoparticles were synthesized by a low-cost and environmentally friendly hydrothermal route. Their gas sensing properties were investigated and the sensor showed high sensitivity and selectivity to H2S gas. Different Cr doping levels from 0 to 8.0 wt% were studied, and the sensor of 4.0 wt% Cr-doped α-Fe2O3 showed the largest response, with a response of 213 to 50 ppm H2S at 100 °C. The incorporation of Cr ions within α-Fe2O3 nanocrystals increases the specific surface area, and promotes the oxidation of H2S and oxygen adsorption in the air. Thus, the doping of Cr into α-Fe2O3 nanostructures would be a promising method for designing and fabricating high performance H2S gas sensors.