Ginsenoside Rh4 Facilitates the Sensitivity of Renal Cell Carcinoma to Ferroptosis via the NRF2 Pathway.

BACKGROUND: Renal cell carcinoma (RCC) is one of the most common malignancies of the urinary system and ferroptosis is considered as a promising therapeutic approach for treating RCC. Ginsenoside Rh4 (Rh4) was proved to have anticancer properties and play roles in ferroptosis. This study aimed to investigate the potential of ginsenoside Rh4 (Rh4) in enhancing the sensitivity of renal cell carcinoma (RCC) cells to ferroptosis and to elucidate the underlying mechanisms. METHODS: RCC cell lines of 786-O and ACHN were treated with RAS-selective lethal 3 (RSL3) and/or Rh4. Cell-viability assays were used to determine how Rh4 affected the sensitivity of RCC cells to RSL3-induced ferroptosis. Quantitative real-time polymerase chain reaction was conducted to examine the levels of ferroptosis-related genes. Additionally, the knockdown of nuclear factor E2-related factor 2 (NRF2) was performed to investigate the role of NRF2 in mediating the effects of Rh4. RESULTS: RSL3 suppressed the progression of RCC cells by inducing ferroptosis. Furthermore, Rh4 led to more RCC sensitivity to ferroptosis induced by RSL3. Rh4 downregulated the ferroptosis-related gene expression including superoxide dismutase 1 (p < 0.01), glutathione peroxidase 4 (p < 0.01), and catalase (p < 0.01), which was attenuated by NRF2 knockdown. This finding suggested that Rh4 exerted its sensitising effect on ferroptosis through the NRF2 pathway. CONCLUSIONS: Rh4 made RCC cells more sensitive to ferroptosis by inhibiting the NRF2 signaling and suppressing the expression of antioxidant enzymes. Therefore, combining Rh4 with ferroptosis-inducing reagents to treat RCC had potential therapeutic application.

Ginsenoside Rh4 Facilitates the Sensitivity of Renal Cell Carcinoma to Ferroptosis via the NRF2 Pathway

Background: Renal cell carcinoma (RCC) is one of the most common malignancies of the urinary system and ferroptosis is considered as a promising therapeutic approach for treating RCC. Ginsenoside Rh4 (Rh4) was proved to have anticancer properties and play roles in ferroptosis. This study aimed to investigate the potential of ginsenoside Rh4 (Rh4) in enhancing the sensitivity of renal cell carcinoma (RCC) cells to ferroptosis and to elucidate the underlying mechanisms. Methods: RCC cell lines of 786-O and ACHN were treated with RAS-selective lethal 3 (RSL3) and/or Rh4. Cell-viability assays were used to determine how Rh4 affected the sensitivity of RCC cells to RSL3-induced ferroptosis. Quantitative real-time polymerase chain reaction was conducted to examine the levels of ferroptosis-related genes. Additionally, the knockdown of nuclear factor E2-related factor 2 (NRF2) was performed to investigate the role of NRF2 in mediating the effects of Rh4. Results: RSL3 suppressed the progression of RCC cells by inducing ferroptosis. Furthermore, Rh4 led to more RCC sensitivity to ferroptosis induced by RSL3. Rh4 downregulated the ferroptosis-related gene expression including superoxide dismutase 1 (p < 0.01), glutathione peroxidase 4 (p < 0.01), and catalase (p < 0.01), which was attenuated by NRF2 knockdown. This finding suggested that Rh4 exerted its sensitising effect on ferroptosis through the NRF2 pathway. Conclusions: Rh4 made RCC cells more sensitive to ferroptosis by inhibiting the NRF2 signaling and suppressing the expression of antioxidant enzymes. Therefore, combining Rh4 with ferroptosis-inducing reagents to treat RCC had potential therapeutic application. (AU)

Curcumin Enhances the Anti-Cancer Efficacy of CDK4/6 Inhibitors in Prostate Cancer.

OBJECTIVE: This study aimed to investigate the potential of combining cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors with curcumin (Cur), a natural compound known for its anti-aging properties, to enhance the anti-cancer efficacy in prostate cancer (PCa). METHODS: The cell viability was determined by cell counting kit-8 assay, colony forming assay and cell invasion. The cell cycle and mRNA levels of p16 (cyclin dependent kinase inhibitor 2A, CDKN2A), p21 (cyclin dependent kinase inhibitor 1A, CDKN1A) and Rb (RB transcriptional corepressor) were detected by flow cytometry and quantitative real-time polymerase chain reaction, respectively. SA-ß-gal staining and interleukin 6 (IL6) mRNA levels were used to evaluate cell aging. Western blot was used to detect mechanistic targets of rapamycin (mTOR) and signal transducer and activator of transcription 3 (STAT3) pathways. Moreover, Sphere formation assay and mRNA levels of aldehyde dehydrogenase (ALDH) 1A1, CD44 and Nanog were used to determine cell stemness. RESULTS: The combination of LY2835219 (LY, CDK4/6 inhibitor) and Cur exhibited a synergistic inhibitory effect on PCa cell proliferation (p < 0.01) and invasion (p < 0.01) and Rb gene expression (p < 0.05), as well as a synergistic promotive effect on p61 expression (p < 0.01), p21 expression (p < 0.01) and cell cycle G1 arrest in PCa cells (p < 0.05) compared with LY or Cur alone. LY and LY + Cur increased the SA-ß-gal-stained cells (p < 0.01). mTOR (p < 0.01) and STAT3 pathway (p < 0.01) were decreased by LY + Cur (p < 0.01). Furthermore, LY + Cur conditioned medium (CM) inhibited cell stemness by decreasing cell spheres (p < 0.05), ALDH1A1 (p < 0.01), CD44 (p < 0.01) and Nanog (p < 0.01) compared with LY CM. CONCLUSIONS: The findings of this study suggested that the combination of CDK4/6 inhibitor and curcumin may have clinical implications for the treatment of PCa.

Curcumin Enhances the Anti-Cancer Efficacy of CDK4/6 Inhibitors in Prostate Cancer

Objective: This study aimed to investigate the potential of combining cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors with curcumin (Cur), a natural compound known for its anti-aging properties, to enhance the anti-cancer efficacy in prostate cancer (PCa). Methods: The cell viability was determined by cell counting kit-8 assay, colony forming assay and cell invasion. The cell cycle and mRNA levels of p16 (cyclin dependent kinase inhibitor 2A, CDKN2A), p21 (cyclin dependent kinase inhibitor 1A, CDKN1A) and Rb (RB transcriptional corepressor) were detected by flow cytometry and quantitative real-time polymerase chain reaction, respectively. SA-β-gal staining and interleukin 6 (IL6) mRNA levels were used to evaluate cell aging. Western blot was used to detect mechanistic targets of rapamycin (mTOR) and signal transducer and activator of transcription 3 (STAT3) pathways. Moreover, Sphere formation assay and mRNA levels of aldehyde dehydrogenase (ALDH) 1A1, CD44 and Nanog were used to determine cell stemness. Results: The combination of LY2835219 (LY, CDK4/6 inhibitor) and Cur exhibited a synergistic inhibitory effect on PCa cell proliferation (p < 0.01) and invasion (p < 0.01) and Rb gene expression (p < 0.05), as well as a synergistic promotive effect on p61 expression (p < 0.01), p21 expression (p < 0.01) and cell cycle G1 arrest in PCa cells (p < 0.05) compared with LY or Cur alone. LY and LY + Cur increased the SA-β-gal-stained cells (p < 0.01). mTOR (p < 0.01) and STAT3 pathway (p < 0.01) were decreased by LY + Cur (p < 0.01). Furthermore, LY + Cur conditioned medium (CM) inhibited cell stemness by decreasing cell spheres (p < 0.05), ALDH1A1 (p < 0.01), CD44 (p < 0.01) and Nanog (p < 0.01) compared with LY CM. Conclusions: The findings of this study suggested that the combination of CDK4/6 inhibitor and curcumin may have clinical implications for the treatment of PCa (AU)

Solvent Effects on the Catalyst Ink and Layer Microstructure for Anion Exchange Membrane Fuel Cells.

Understanding the complex solvent effects on the microstructures of ink and catalyst layer (CL) is crucial for the development of high-performance anion exchange membrane fuel cells (AEMFCs). Herein, we study the solvent effects within the binary solvent ink system composed of water, isopropyl alcohol (IPA), commercial anion exchange ionomer, and Pt/C catalyst. The results show that the Pt/C particles and ionomer tend to form large aggregates wrapped with a thick ionomer layer in IPA-rich ink and promote the formation of large mesopores within the CL. With the increase of the water content in the ink, Pt/C particles are more likely to bridge to each other through wrapped FAA to form a well-connected three-dimensional network. The CL fabricated using water-rich ink shows smaller pores, higher porosity, and a more homogeneous ionomer network without the formation of large aggregates. Based on these results, we propose that the properties of the solvent mixture, including dielectric constant (ε) and solubility parameter (δ), affect the coulomb interaction of charged particles and surface tension at interfaces, which in turn affects the microstructure of ink and CL. By leveraging the solvent effects, we optimize the CL microstructures and improve the performance of AEMFC. These results may guide the rational design and fabrication of AEMFCs.

Amorphous Cr2WO6-Modified WO3 Nanowires with a Large Specific Surface Area and Rich Lewis Acid Sites: A Highly Efficient Catalyst for Oxidative Desulfurization.

The oxidative desulfurization (ODS) of fuel oils is of great significance for environmental protection, and the development of efficient ODS heterogeneous catalysts is highly desired. Herein, we have designed and synthesized a novel material of amorphous Cr2WO6-modified WO3 (a-Cr2WO6/WO3) nanowires (3-6 nm) with a large specific surface area of 289.5 m2·g-1 and rich Lewis acid sites. The formation of such a unique nanowire is attributed to the adsorption of Cr3+ cations on non-(001) planes of WO3. In the ODS process, the a-Cr2WO6/WO3 nanowires can efficiently oxidize benzothiophene (BT), dibenzothiophene (DBT), and 4,6-dimethyldibenzothiophene (4,6-DMDBT) to their corresponding sulfones in a quasi-microemulsion reaction system and possess the highest activity (Ea = 55.4 kJ/mol) for DBT: 99.0% of 15,000 ppm DBT with 2600 ppm S can be removed (70 °C, H2O2 as the oxidant). The improvement in ODS activity from most of WO3 catalysts is owing to the sufficient active sites and enhanced adsorption of DBT on the basis of structural features of a-Cr2WO6/WO3 nanowires. Combined with free radical capture experiments, a possible ODS mechanism of W(O2) peroxotungstate route based on surface -OH groups is reasonably proposed. Moreover, the a-Cr2WO6/WO3 nanowires have good stability and can be synthesized on a large scale, suggesting its potential applications as an efficient heterogeneous catalyst.

CoP/RGO-Pd Hybrids with Heterointerfaces as Highly Active Catalysts for Ethanol Electrooxidation.

The ethanol oxidation reaction is of critical importance to the commercial viability of direct ethanol fuel cell technology. However, owing to the poor C-C bond cleavage capability, almost all ethanol oxidation is incomplete and suffers from low selectivity toward the C1 pathway. Herein, under the support of theoretical calculations that the heterointerfaces between CoP and Pd can reduce the energy barrier of C-C bond cleavage, rich heterointerfaces in CoP/RGO-Pd hybrids were designed to improve ethanol electrooxidation performance through enhancing the selectivity toward the C1 pathway. The experimental results show that the faradaic efficiency of the C1 pathway of CoP/RGO-Pd hybrids is as high as 27.6%, surpassing most reported catalysts in the literature. As a result of this enhancement, CoP/RGO-Pd10 exhibits mass activity as high as 4597 mA·mgPd-1 and specific activity as high as 10 mA·cm-2, which are much higher than those of other Pd-based electrocatalysts.

N-Doped amorphous MoSx for the hydrogen evolution reaction.

Herein, the functions of a N dopant in crystalline MoS2 catalysts during the electrochemical hydrogen evolution reaction (HER) were reported via a combined experimental and first-principles approach. However, studies on the N doping of amorphous MoSx, which is a more active catalyst, have not been reported to date. In this study, via a simple method, we fabricated N-doped amorphous MoSx for the first time and studied the correlations between the N dopant and the HER performance. Via X-ray photoelectron spectroscopy and theoretical formation energy calculations, we have found that a N dopant in basal plane S2- plays a very important role in the improvement of the HER performance and remains stable during this dynamic transformation process. A N dopant in basal plane S2- can increase the number of active sites toward the HER and enhance the conductivity of the catalysts as well as a N dopant in c-MoS2. In addition to this, the first-principles calculations further suggested that a N dopant in basal plane S2- could improve the activity of unsaturated MoV active sites by bringing its hydrogen adsorption free energy closer to zero. As a result, N-doped amorphous MoSx possesses an overpotential of 143 mV at 10 mA cm-2 and a Tafel slope of 57 mV dec-1, much better than those of a-MoSx. These results provide useful insights for the future development of nonmetal-doped MoSx catalysts in the HER.

Facile synthesis of self-assembled ultrathin α-FeOOH nanorod/graphene oxide composites for supercapacitors.

A one-pot facile, impurity-free hydrothermal method to synthesize ultrathin α-FeOOH nanorods/graphene oxide (GO) composites is reported. It is directly synthesized from GO and iron acetate in water solution without inorganic or organic additives. XRD, Raman, FT-IR, XPS and TEM are used to characterize the samples. The nanorods in composites are single crystallite with an average diameter of 6nm and an average length of 75nm, which are significantly smaller than GO-free α-FeOOH nanorods. This can be attributed to the confinement effect and special electronic influence of GO. The influences of experimental conditions including reaction time and reactant concentration on the sizes of nanorods have been investigated. It reveals that the initial Fe2+ concentration and reaction time play an important role in the synthetic process. Furthermore, a possible nucleation-growth mechanism is proposed. As electrode materials for supercapacitors, the α-FeOOH nanorods/GO composite with 20% iron loading has the largest specific capacitance (127Fg-1 at 10Ag-1), excellent rate capability (100Fg-1 at 20Ag-1) and good cyclic performance (85% capacitance retention after 2000 cycles), which is much better than GO-free α-FeOOH nanorods. This unique structure results in rapid electrolyte ions diffusion, fast electron transport and high charging-discharging rate. In virtue of the superior electrochemical performance, the α-FeOOH nanorods/GO composite material has a promising application in high-performance supercapacitors.

New Water Vapor Barrier Film Based on Lamellar Aliphatic-Monoamine-Bridged Polysilsesquioxane.

Siloxane-based hybrid lamellar materials with ordered nanostructure units paralleling to the substrate have been widely used for water vapor barrier. However, it is very difficult to control the orientation of the lamellar units at molecular level. In this Research Article, a new lamellar bridged polysilsesquioxane (BPSQ) film, whose voids between lamellae were filled by pendant alkyl chains in the organic bridge, was prepared via the stoichiometric reaction between 3-glycidoxypropyltrimethoxysilane and aliphatic monoamine at 60 °C without catalyst. Experimental evidence obtained from FT-IR, MS, NMR, and GIXRD techniques suggested that the as-prepared BPSQ films were constructed by lamellar units with disordered orientation. Nonetheless, they possessed satisfactory water vapor barrier performance for potassium dihydrogen phosphate (KDP) and deuterated potassium dihydrogen phosphate (DKDP) optical crystals, and the water vapor transmission rate through BPSQ film with thickness of 25 µm was as low as 20.3 g·m(-2)·d(-1). Those results proved that filling the voids between molecular lamellae with alkyl chains greatly weakened the effect of lamellar unit orientation on the vapor barrier property of BPSQ film.

Integrated copper-nickel oxide mesoporous nanowire arrays for high energy density aqueous asymmetric supercapacitors.

An integrated (Cu,Ni)O mesoporous nanowire array was fabricated by a simple hydrothermal method with subsequent annealing, which with optimized Cu : Ni ratio = 1 : 1 delivers a high specific capacitance of 1710 F g-1. The further assembled aqueous asymmetric supercapacitor (Cu,Ni)O(+)//activated carbon(-) demonstrates high energy/power densities and long cycle life.

Transparent and Dense Ladder-Like Alkylene-Bridged Polymethylsiloxane Coating with Enhanced Water Vapor Barrier Property.

Organic-inorganic hybrid composites have been well-studied as water vapor barrier materials for their long diffusion length of water vapor in coatings which can be realized by improving the aspect ratio of inorganic components and regularity of nanostructure in coatings. In this paper, dense organic-inorganic hybrid coating based on ladder-like alkylene-bridged polymethylsiloxane (ABPMS) was successfully fabricated through the hydrosilylation reaction between polymethylhydrosiloxane and diene (1,5-hexadiene or 1,7-octadiene) in toluene under Pt/C catalysis. Its ladder-like structure was verified by 29Si magic angle spinning (MAS) NMR, 13C MAS NMR, and in-plane and out-of-plane glance-incident X-ray diffraction (GIXRD) techniques. Its corresponding coating showed excellent water vapor barrier ability for a typical water-soluble crystal, potassium dihydrogen phosphate (KDP). When treated in 50% relative humidity (RH) condition at 25 °C for 8 months, the ABPMS coating with 100 nm thickness displayed a very low transmittance loss of 1.6% compared with the high transmittance loss of 10% for uncoated KDP. Moreover, the ABPMS coating showed good ultraviolet radiation resistance, thermal stability, low mechanical property, and excellent compatibility with hydrophobic antireflective (AR) coatings.

Contamination-resistant silica antireflective coating with closed ordered mesopores.

Porous silica optical antireflective (AR) coatings prepared by traditional sol-gel method have been extensively used for high power laser systems, but a serious drawback is that contamination existing in the high vacuum is easily absorbed by the disordered open pore structure, resulting in a fast decrease in transmittance. To improve the stability of transmittance in vacuum, a contamination-resistant silica AR coating with ordered mesopores completely closed by hydrophobic-oleophobic groups was successfully developed on a fused quartz substrate. The ordered mesopores in the coating were controlled under the direction of surfactant F127 via an evaporation-induced-self-assembling process and then were closed by post-grafting long chain fluoroalkylsilane. The grazing incidence small angle X-ray scattering (GISAXS) and the X-ray reflectivity (XRR) results indicated that the mesopores in the coating constructed a Fmmm orthorhombic symmetry structure with a (010) plane parallel to the substrate. Cage-like mesopores were confirmed by nitrogen adsorption-desorption analysis. The obtained coatings showed low surface roughness, excellent abrase-resistance and high transmittance of 100% on quartz substrate. Especially, the decrease of transmittance tested with polydimethylsiloxane pollution in vacuum within one-month was as small as 0.02%. The laser induced damage threshold was up to 59.8 J cm(-2) at a 12 ns laser pulse of 1053 nm wavelength. This work provides an alternative way to fabricate AR coatings with high stability.

CoFe2O4 and/or Co3Fe7 loaded porous activated carbon balls as a lightweight microwave absorbent.

In order to prepare a lightweight and efficient microwave absorbent, porous activated carbon balls (PACB) were used to load Fe(3+) and Co(2+) ions, because the PACB carrier has a high specific surface area of 800 m(2) g(-1) and abundant pores, including micropores and macropores. The loaded Fe(3+) and Co(2+) ions in the PACB composite were transformed into magnetic CoFe2O4 and/or Co3Fe7 particles during subsequent heat-treatment under an Ar atmosphere. According to the XRD and SEM results, the magnetic particles were embedded in the PACB macropores and showed different crystalline phases and morphologies after heat-treatment. CoFe2O4 flakes with spinel structure were obtained at approximately 450 °C, and were then transformed into loose quasi-spheres between 500 °C and 600 °C, where CoFe2O4 and Co3Fe7 coexisted because of the partial reduction of CoFe2O4. Co3Fe7 microspheres appeared above 700 °C. The density of the magnetic PACB composites was in the range of 2.2-2.3 g cm(-3). The as-synthesized PACB composites exhibited excellent microwave absorbability, which was mainly attributed to the magnetism of CoFe2O4 and Co3Fe7, as well as the presence of graphitized carbon. The minimum reflection loss value of the CoFe2O4-Co3Fe7-PACB composite reached -32 dB at 15.6 GHz, and the frequency of microwave absorption obeyed the quarter-wavelength matching model, showing a good match between dielectric loss and magnetic loss. The microwave reflection loss (RL) value could be modulated by adjusting the composition and thickness of the PACB composite absorbent. PACB composites with CoFe2O4-Co3Fe7 are a promising candidate for lightweight microwave absorption materials.

Cu@C composite nanotube array and its application as an enzyme-free glucose sensor.

We report a novel hydrothermal method for the synthesis of a Cu@C nanotube array on a centimeter-scale substrate for the first time. In this hydrothermal reaction process, employing the carbon coated ZnO nanorod array as an inexpensive and partially sacrificial template, along with the ZnO dissolving in the alkaline atmosphere, the formed Cu particles deposit and grow on the carbon surface gradually. Importantly, the carbon shell of the template is not only essential to the preservation of the array configuration, but also makes a significant contribution to the final nanostructure. Such a method provides a morphology-reservation transformation when various shaped carbon-containing templates are adopted. Moreover, this designed Cu@C array has been demonstrated as an excellent electrode material for an enzyme-free glucose sensor in terms of sensitivity (1200 µA mM( - 1) cm( - 2)) and significantly lower applied potential (-0.2 V). Our results present the first preparation of the Cu@C composite nanotube array and may open up an opportunity for rational design of advanced electrode materials for enzyme-free glucose sensors.

Two novel hierarchical homogeneous nanoarchitectures of TiO2 nanorods branched and P25-coated TiO2 nanotube arrays and their photocurrent performances.

We report here for the first time the synthesis of two novel hierarchical homogeneous nanoarchitectures of TiO2 nanorods branched TiO2 nanotube arrays (BTs) and P25-coated TiO2 nanotube arrays (PCTs) using two-step method including electrochemical anodization and hydrothermal modification process. Then the photocurrent densities versus applied potentials of BTs, PCTs, and pure TiO2 nanotube arrays (TNTAs) were investigated as well. Interestingly, at -0.11 V and under the same illumination condition, the photocurrent densities of BTs and PCTs show more than 1.5 and 1 times higher than that of pure TNTAs, respectively, which can be mainly attributed to significant improvement of the light-absorbing and charge-harvesting efficiency resulting from both larger and rougher surface areas of BTs and PCTs. Furthermore, these dramatic improvements suggest that BTs and PCTs will achieve better photoelectric conversion efficiency and become the promising candidates for applications in DSSCs, sensors, and photocatalysis.

Large-scale uniform α-Co(OH)2 long nanowire arrays grown on graphite as pseudocapacitor electrodes.

Large-scale uniform α-Co(OH)2 nanowire arrays (NWAs) with an average length of ∼20 µm grown on pyrolytic graphite (PG) were successfully synthesized by a hydrothermal method at 120 °C. Ultrasonication test was carried out toward the as-made nanoarray products and the result demonstrated their robust adhesion to graphitic substrate. After 300 s of sonication testing, α-Co(OH)2 NWAs could still possess both integrated one-dimensional (1D) nanoarray architecture and good electronic connections with current collector. When investigated as electrochemical pseudocapacitor electrodes, α-Co(OH)2 NWAs exhibited good energy-storage performance in terms of high specific capacitance of 642.5 F/g, good rate capability, and excellent capacity retention. Our work not only presents a cost-effective and scale-up synthetic method for α-Co(OH)2 NWAs but also holds promise in general synthesis of long arrays of other metal hydroxides/oxide (TiO2, Fe2O3, SnO2, etc.) nanostructures on PG substrate by using α-Co(OH)2 NWAs as sacrificial templates.

Carbon-Coated SnO(2) Nanorod Array for Lithium-Ion Battery Anode Material.

Carbon-coated SnO(2) nanorod array directly grown on the substrate has been prepared by a two-step hydrothermal method for anode material of lithium-ion batteries (LIBs). The structural, morphological and electrochemical properties were investigated by means of X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and electrochemical measurement. When used as anodes for LIBs with high current density, as-obtained array reveals excellent cycling stability and rate capability. This straightforward approach can be extended to the synthesis of other carbon-coated metal oxides for application of LIBs.

High surface area ZnO-carbon composite tubular arrays based on the Kirkendall effect and in situ Zn evaporation.

High surface area ZnO-carbon composite tubular arrays on a ceramic substrate were successfully synthesized by a hydrothermal process and a subsequent nanoscale diffusion-related reaction within the carbonaceous species-coated ZnO rod arrays during 900 degrees C annealing.