Synthesis and biological evaluation of novel bi-gold mitocans in lung cancer cells

Mitochondria are promising drug target for cancer treatment. We previously demonstrated that a bi-gold compound BGC2a was more potent than the mono-gold drug auranofin in suppressing cancer cells due to increased gold atom number that led to higher drug accumulation in and thereby inhibition of mitochondria. To exploit the potential of this new strategy, we further designed and synthesized a series of bi-gold mitocans, the compounds targeting mitochondria. The results showed that most of the newly synthesized mitocans exhibited obviously lower IC50 than auranofin, an old drug that is repurposed in clinical trials for cancer treatment. The best mitocan C3P4 was nearly 2-fold more potent than BGC2a in human non-small cell lung cancer A549 cells and mantle cell lymphoma Jeko-1 cells, exhibiting substantial colony formation-suppressing and tumor-suppressing effects in A549 cells xenograft model. C3P4 induced apoptosis in a dose-dependent manner and arrested cell cycle at G0/G1 phase. The mechanistic study showed that C3P4 significantly increased the global reactive oxygen species and mitochondrial superoxide level, and reduced the mitochondrial membrane potential. C3P4 preferentially accumulated in mitochondria as measured by the gold content and substantially inhibited oxygen consumption rate and ATP production. These results further validated our hypothesis that targeting mitochondria would be promising to develop more potent anticancer agents. C3P4 may be further evaluated as a drug candidate for lung cancer treatment

Concentration of Healthcare Resources in China: The Spatial–Temporal Evolution and Its Spatial Drivers

This paper estimated and evaluated the spatial–temporal evolution of the concentration of healthcare resources (HCRs), in 31 provinces in China between 2004 and 2017, by using the entropy method. The spatial Durbin model (SDM) was used to further analyze the mechanisms behind the spatial driving forces at the national and regional levels. The findings revealed that: (i) The concentration of HCRs differed significantly among eastern, central, and western regions. The eastern, followed by the central region, had the highest concentration. Going east to west, the concentration of HCRs in the first echelon decreased, while it increased in the second and third echelons; (ii) places with higher concentrations clustered, while those with lower concentrations agglomerated; and (iii) economic development, population size, and urbanization promoted concentration. Education facilitated HCR concentration in the eastern and central regions, income stimulated HCR concentration in the eastern and western regions, and fiscal expenditure on healthcare promoted HCR concentration in the eastern region. Economic development inhibited HCR concentration in neighboring regions, population size restrained HCR concentration in neighboring areas in the western region, urbanization and income curbed HCR concentration in neighboring areas in the eastern and western regions, and fiscal expenditure on healthcare hindered HCR concentration in neighboring areas in the eastern region. Policy recommendations were proposed toward optimizing allocation of healthcare resources, increasing support for healthcare and education, and accelerating urbanization

Piezoelectric Applications of Low-Dimensional Composites and Porous Materials

Low-dimensional (LD) materials, with atomically thin anisotropic structures, exhibit remarkable physical and chemical properties, prominently featuring piezoelectricity resulting from the absence of centrosymmetry. This characteristic has led to diverse applications, including sensors, actuators, and micro- and nanoelectromechanical systems. While piezoelectric effects are observed across zero-dimensional (0D), one-dimensional (1D), and two-dimensional (2D) LD materials, challenges such as effective charge separation and crystal structure imperfections limit their full potential. Addressing these issues requires innovative solutions, with the integration of LD materials with polymers, ceramics, metals, and other porous materials proving a key strategy to significantly enhance piezoelectric properties. This review comprehensively covers recent advances in synthesizing and characterizing piezoelectric composites based on LD materials and porous materials. The synergistic combination of LD materials with other substances, especially porous materials, demonstrates notable performance improvements, addressing inherent challenges. The review also explores future directions and challenges in developing these composite materials, highlighting potential applications across various technological domains

Improvement the Flame Retardancy and Thermal Conductivity of Epoxy Composites via Melamine Polyphosphate-Modified Carbon Nanotubes

Surface chemical modification of carbon nanotubes can enhance the compatibility with polymers and improve flame retardancy performances. In this work, the double bond active sites were constructed on the surface of carbon nanotubes modified by the γ-methacryloyloxypropyl trimethoxysilane (KH570). Glycidyl methacrylate (GMA) was further grafted onto the surface of carbon nanotubes via free radical polymerization. Finally, the flame retardant melamine polyphosphate (MPP) was bonded to the surface of carbon nanotubes by the ring-opening reaction. This modification process was proved to be achieved by infrared spectroscopy and thermogravimetric test. The carbon nanotubes modified by flame retardant were added into the epoxy matrix and cured to prepare flame retardant and thermal conductive composites. The flame retardancy of composites were studied by cone calorimetry, UL94 vertical combustion test and limiting oxygen index. The thermal conductivity of composites was characterized by laser thermal conductivity instrument. The results showed that when the addition amount of flame retardant MPP-modified carbon nanotubes in composites was 10 wt%, the flame retardant level of UL94 reached to V2, the limiting oxygen index increased from 25.1 of pure epoxy resin to 28.3, the PHRR of pure epoxy resin was reduced from 800 kW/m2 to 645 kW/m2 of composites and thermal conductivity of composites was enhanced from 0.21 W/m·K−1 of pure epoxy resin to 0.42 W/m·K−1 of the composites

Microstructure and Properties of Semisolid A356 Alloy Strip Affected by Nozzle Temperature of a Novel Micro Fused-Casting

The semisolid A356 alloy strip was prepared by a novel continuous micro fused-casting process. The microstructure evolution and mechanical property of A356 aluminum alloy strip with different nozzle temperatures were investigated. The nozzle temperature had great influences on the microstructure and property primarily accompanied with the crystal change in the fused-casting area through the cooling conditions. The results showed that the semisolid A356 alloy strip samples fabricated by micro fused-casting demonstrated good performances and uniform structures with the nozzle temperature at 593 degrees C and the stirring velocity at 700 r/min. The fine grains of the primary alpha-Al phase with average grain size of 51 mu m and shape factor up to 0.71 were obtained under the micro fused-casting process, and the ultimate average vickers hardness came up to 83.39 +/- 0.89 HV, and the tensile strength and elongation of the A356 alloy strip reached 245.32 MPa and 7.85%, respectively

Effect of Pouring Temperature on Microstructure and Properties of A356 Alloy Strip by a Novel Semisolid Micro Fused-Casting for Metal

A novel semisolid micro fused-casting (MFC) for preparing A356 alloy strips is proposed, and the effects of process parameters of pouring temperature on the microstructure and properties of A356 alloy strips are investigated. MFC means that the semisolid metal slurry was pressed out from the outlet of bottom of crucible to the movable plate, and directly solidified and formed layer by layer. The microstructure and properties of A356 semisolid alloy slurry were influenced by the cooling conditions. Results show that the aluminu alloy A356 strip samples fabricated by micro fused-casting had good performances and uniform structures with the pouring temperature at 595 degrees C and the substrate movement speed at 18 mm/s. The fine grains of the primary alpha-Al phase with average grain size of 53 mu m and shape factor up to 0.72 was obtained, the ultimate tensile strength of the aluminum alloy A356 strip reaches 243.79 +/- 3.91 MPa, while the average vickers hardness is 82.65 +/- 1.86 HV

Activated E2F activity induces cell death in papillary thyroid carcinoma K1 cells with enhanced Wnt signaling.

Disruption of Wnt signaling often happens in tumorigenesis, but whether Wnt signaling affects the early stages of thyroid tumor, such as papillary thyroid carcinoma, is still a question, especially in the papillary thyroid carcinoma without genomic RET/PTC mutation. In this study, we demonstrated the important function of Wnt signaling in papillary thyroid carcinoma K1 cells, which have no RET/PTC mutation. We found that K1 cells have enhanced Wnt signaling in comparison to normal thyroid cells. We further demonstrated that K1 cells require the enhanced Wnt signaling for growth and survival. Interestingly, we identified that enhancing E2F activity by either knockdown of Rb or overexpression of Cyclin D1 induces cell death in K1 cells. And we further revealed that the cell death is caused by enhanced oxidative stress. Our studies present a novel cell model to support the key roles of Wnt signaling in early stage of thyroid tumor, and also provide an alternative way to limit thyroid cancer