Identification and vitro verification of the potential drug targets of active ingredients of Chonglou in the treatment of lung adenocarcinoma based on EMT-related genes.

Lung adenocarcinoma (LUAD) is the main histological type of lung cancer with an unfavorable survival rate. Metastasis is the leading LUAD-related death with Epithelial-Mesenchymal Transition (EMT) playing an essential role. The anticancer efficacies of the active ingredients in Chonglou have been widely reported in various cancers. However, the potential therapeutic targets of the Chonglou active ingredients in LUAD patients remain unknown. Here, the network pharmacology and bioinformatics were performed to analyze the associations of the clinical characteristics, immune infiltration factors and m6A-related genes with the EMT-related genes associated with LUAD (EMT-LUAD related genes), and the molecular docking, STRING, GO, and KEGG enrichment for the drug targets of Chonglou active ingredients associated with EMT (EMT-LUAD-Chonglou related genes). And, cell viability analysis and cell invasion and infiltration analysis were used to confirm the theoretical basis of this study. A total of 166 EMT-LUAD related genes were identified and a multivariate Cox proportional hazards regression model with a favorable predictive accuracy was constructed. Meanwhile, the immune cell infiltration, immune cell subsets, checkpoint inhibitors and the expression of m6A-related genes were significantly associated with the risk scores for EMT-LUAD related genes with independent significant prognostic value of all included LUAD patients. Furthermore, 12 EMT-LUAD-Chonglou related genes with five core drug targets were identified, which participated in LUAD development through extracellular matrix disassembly, collagen metabolic process, collagen catabolic process, extracellular matrix organization, extracellular structure organization and inflammatory response. Moreover, we found that the active ingredients of Chonglou could indeed inhibit the progression of lung adenocarcinoma cells. These results are oriented towards EMT-related genes to achieve a better understanding of the role of Chonglou and its targets in osteosarcoma development and metastasis, thus guiding future preclinical studies and facilitating clinical translation of LUAD treatment.

Tailoring Dense, Orientation-Tunable, and Interleavedly Structured Carbon-Based Heat Dissipation Plates.

The controllability of the microstructure of a compressed hierarchical building block is essential for optimizing a variety of performance parameters, such as thermal management. However, owing to the strong orientation effect during compression molding, optimizing the alignment of materials perpendicular to the direction of pressure is challenging. Herein, to illustrate the effect of the ordered microstructure on heat dissipation, thermally conductive carbon-based materials are fabricated by tailoring dense, orientation-tunable, and interleaved structures. Vertically aligned carbon nanotube arrays (VACNTs) interconnected with graphene films (GF) are prepared as a 3D core-ordered material to fabricate compressed building blocks of O-VA-GF and S-VA-GF. Leveraging the densified interleaved structure offered by VACNTs, the hierarchical O-VA-GF achieves excellent through-plane (41.7 W m-1 K-1 ) and in-plane (397.9 W m-1 K-1 ) thermal conductivities, outperforming similar composites of S-VA-GF (through-plane: 10.3 W m-1 K-1 and in-plane: 240.9 W m-1 K-1 ) with horizontally collapsed carbon nanotubes. As heat dissipation plates, these orderly assembled composites yield a 144% and 44% enhancement in the cooling coefficient compared with conventional Si3 N4 for cooling high-power light-emitting diode chips.

Preparation and In Vitro Bioactivity Study of a Novel Hollow Mesoporous Bioactive Glass Nanofiber Scaffold.

In this study, a novel three-dimensional hollow mesoporous bioactive glass nanofiber scaffold has been synthesized with a template-assisted sol-gel method using bacterial cellulose (BC) as a template and nonionic triblock copolymer (P123) as a pore-directing agent, ethyl orthosilicate (TEOS), calcium nitrate tetrahydrate (CN), and triethyl phosphate (TEP) as glass precursors. Scanning and transmission electron microscopies, X-ray diffraction, nitrogen adsorption-desorption, and nuclear magnetic resonance method were applied to characterize the morphology, crystal structure, and chemical structure of the mesoporous bioactive glass nanofiber scaffold. Furthermore, the in vitro bioactivity and biocompatibility were also explored. The obtained scaffold depicted nanofiber-like morphology and interconnected three-dimensional network structure that replicated the BC template. The scaffold showed a large specific surface area (230.0 cm2 g-1) and pore volume (0.2 m3 g-1). More importantly, the scaffold exhibited excellent apatite-forming ability and cellular biocompatibility. We believe that the hollow mesoporous bioactive glass nanofiber scaffold has great potential application in bone tissue regeneration.

Oncogenetic Function and Prognostic Value of DNA Topoisomerase II Alpha in Human Malignances: A Pan-Cancer Analysis.

Increasing studies have revealed significant associations between TOP2A with oncogenesis and prognosis of human cancers; however, pan-cancer analysis has not been reported. Here, we explored the potential carcinogenic function and the association with clinical outcomes of TOP2A in 33 different human cancers. The results showed that TOP2A was amplified in 31 investigated cancers; TOP2A expression was significantly associated with metastasis of six different cancers and significantly associated with the survival of patients in ten different cancers; TOP2A-encoded protein was obviously upregulated in five available cancers; phosphorylated TOP2A protein at S1106 was significantly upregulated in all six available cancers. Moreover, TOP2A expression was found to be associated with the cancer-associated immune cell infiltration, including fibroblasts, Tregs, and macrophages. In addition, the Kyoto encyclopedia of genes and genomes (KEGG) pathway and Gene Ontology (GO) enrichment analyses revealed a most significant association between TOP2A with the Wnt signaling pathway and DNA conformation change. This work provides a comprehensive knowledge of TOP2A in different cancers, including carcinogenic function, prognostic values for metastasis, and clinical outcomes.

Intratibial Osteosarcoma Cell Injection to Generate Orthotopic Osteosarcoma and Lung Metastasis Mouse Models.

Osteosarcoma is the most common primary bone cancer in children and adolescents, with lungs as the most common metastatic site. The five-year survival rate of osteosarcoma patients with pulmonary metastasis is less than 30%.Therefore, the utilization of mouse models mimicking the osteosarcoma development in humans is of great significance for understanding the fundamental mechanism of osteosarcoma carcinogenesis and pulmonary metastasis to develop novel therapeutics. Here, detailed procedures are reported to generate the primary osteosarcoma and pulmonary metastasis mouse models via intratibia injection of osteosarcoma cells. Combined with the bioluminescence or X-ray live imaging system, these living mouse models are utilized to monitor and quantify osteosarcoma growth and metastasis. To establish this model, a basement membrane matrix containing osteosarcoma cells was loaded in a micro-volume syringe and injected into one tibia of each athymic mouse after being anesthetized. The mice were sacrificed when the primary osteosarcoma reached the size limitation in the IACUC-approved protocol. The legs bearing osteosarcoma and the lungs with metastasis lesions were separated. These models are characterized by a short incubation period, rapid growth, severe lesions, and sensitivity in monitoring the development of primary and pulmonary metastatic lesions. Therefore, these are ideal models for exploring the functions and mechanisms of specific factors in osteosarcoma carcinogenesis and pulmonary metastasis, the tumor microenvironment, and evaluating the therapeutic efficacy in vivo.

Inverse Vulcanization of a Natural Monoene with Sulfur as Sustainable Electrochemically Active Materials for Lithium-Sulfur Batteries.

A novel soluble copolymer poly(S-MVT) was synthesized using a relatively quick one-pot solvent-free method, inverse vulcanization. Both of the two raw materials are sustainable, i.e., elemental sulfur is a by-product of the petroleum industry and 4-Methyl-5-vinylthiazole (MVT) is a natural monoene compound. The microstructure of poly(S-MVT) was characterized by FT-IR, 1H NMR, XPS spectroscopy, XRD, DSC SEM, and TEM. Test results indicated that the copolymers possess protonated thiazole nitrogen atoms, meso/macroporous structure, and solubility in tetrahydrofuran and chloroform. Moreover, the improved electronic properties of poly(S-MVT) relative to elemental sulfur have also been investigated by density functional theory (DFT) calculations. The copolymers are utilized successfully as the cathode active material in Li-S batteries. Upon employment, the copolymer with 15% MVT content provided good cycling stability at a capacity of ∼514 mA h g-1 (based on the mass of copolymer) and high Coulombic efficiencies (∼100%) over 100 cycles, as well as great rate performance.

Cantharidin inhibits osteosarcoma proliferation and metastasis by directly targeting miR-214-3p/DKK3 axis to inactivate ß-catenin nuclear translocation and LEF1 translation.

Background: As the leading primary bone cancer in adolescents and children, osteosarcoma patients with metastasis show a five-year-survival-rate of 20-30%, without improvement over the past 30 years. Wnt/ß-catenin is important in promoting osteosarcoma development. DKK3 is a Wnt/ß-catenin antagonist and predicted to have the specific binding site in 3'-UTR with miR-214-3p. Methods: miR-214-3p and DKK3 levels were investigated in human osteosarcoma tissues and cells by RT-qPCR; the prognostic importance of DKK3 level in osteosarcoma patients was determined with Log-rank test; direct binding between DKK3 with miR-214-3p was identified with targetscan; anti-osteosarcoma mechanism of cantharidin was investigated by miR-214-3p silence/over-expression with or without cantharidin treatment, and nuclear/cytoplasmic protein assay in osteosarcoma cells. Results: Down-regulated DKK3 indicated poor prognosis of osteosarcoma patients. Up-regulated miR-214-3p promoted proliferation and migration, while suppressed apoptosis of osteosarcoma cells by increasing ß-catenin nuclear translocation and LEF1 translation via degradation of DKK3. Cantharidin suppressed viabilities, migration and invasion, while promoted cell cycle arrest and apoptosis in 143B and U-2 OS cells via down-regulating miR-214-3p to up-regulate DKK3, thus inhibited p-GSK-3ß expression, ß-catenin nuclear translocation and LEF1 translation. Meanwhile, cantharidin inhibited tumor growth in xenograft-bearing mice with 143B cell injection in tibia. Conclusion: miR-214-3p mediated Wnt/ß-catenin/LEF1 signaling activation by targeting DKK3 to promote oncogenesis of osteosarcoma; cantharidin inhibited proliferation and metastasis of osteosarcoma cells via down-regulating miR-214-3p to up-regulate DKK3 and decrease ß-catenin nuclear translocation, indicating that cantharidin may be a prospective candidate for osteosarcoma treatment by targeting miR-214-3p/DKK3/ß-catenin signaling.

Two-Dimensional GeTe: Air Stability and Photocatalytic Performance for Hydrogen Evolution.

As a key method to convert solar into chemical energy, photocatalytic water decomposition has garnered attention. Moreover, the development of graphene and graphene-like two-dimensional (2D) materials has brought fresh vitality in the field of photocatalysis. Here, we prepared two to four layers of GeTe nanosheets by ultrasonic-assisted liquid-phase exfoliation in argon and air, which we referred to as Ar-GeTe and O-GeTe, respectively. The photocatalytic hydrogen production potential of 2D GeTe was experimentally investigated for the first time. The results indicated that minimally layered GeTe samples are indirect-gap semiconductors with the GeTe band gap increasing after oxidation. All samples have suitable band positions that can drive photocatalytic water splitting into H2 under mild conditions, providing maximum hydrogen evolution rates of 1.13 mmol g-1 h-1 (Ar-GeTe) and 0.54 mmol g-1 h-1 (O-GeTe). With density functional theory computations, the structural stability of GeTe in air was discussed, revealing that oxygen atoms could easily combine with Ge to form a more stable structure, thus impacting the photocatalytic performance of 2D GeTe. Therefore, the light requirement and oxygen deficiency of the material give an advantage in the field of energy supply in space.

A nanostructured porous carbon/MoO2 composite with efficient catalysis in polysulfide conversion for lithium-sulfur batteries.

Lithium-sulfur batteries are considered as the next generation of energy storage systems because of their high theoretical specific capacity and energy density. Unfortunately, the sluggish reaction kinetics, weak adsorption toward to lithium polysulfides, and slow lithium ion diffusion impede the smooth electrochemical process, resulting in the lithium-sulfur batteries with the unsatisfactory cycling stability and rate performance. Since it is recognized that polar metal oxides and doped nitrogen in carbon materials have chemical interaction with lithium polysulfides, a nanostructured nitrogen-doped porous carbon/MoO2 composite is synthesized through a simple hydrothermal method by using graphene oxide nanoribbon and phosphomolybdic acid hydrate as precursors. The porous nanostructure promotes the charge and mass transport, while MoO2 nanoparticles immobilize lithium polysulfides via strong chemisorption and enhance the redox kinetics of polysulfides owing to the efficient catalytic activity in liquid-solid boundary. Consequently, the as-obtained nanostructured porous carbon/MoO2-based sulfur cathode exhibits low polarization, high initial discharge capacity (1403 mAh g-1 at 0.1 C), good rate capabilities (584 mAh g-1 at 4 C), and impressive cycling performance at 1 C (503 mAh g-1 after 500 cycles with capacity fade rate of 0.07% per cycle).

Two-dimensional gersiloxenes with tunable bandgap for photocatalytic H2 evolution and CO2 photoreduction to CO.

The discovery of graphene and graphene-like two-dimensional materials has brought fresh vitality to the field of photocatalysis. Bandgap engineering has always been an effective way to make semiconductors more suitable for specific applications such as photocatalysis and optoelectronics. Achieving control over the bandgap helps to improve the light absorption capacity of the semiconductor materials, thereby improving the photocatalytic performance. This work reports two-dimensional -H/-OH terminal-substituted siligenes (gersiloxenes) with tunable bandgap. All gersiloxenes are direct-gap semiconductors and have wide range of light absorption and suitable band positions for light driven water reduction into H2, and CO2 reduction to CO under mild conditions. The gersiloxene with the best performance can provide a maximum CO production of 6.91 mmol g-1 h-1, and a high apparent quantum efficiency (AQE) of 5.95% at 420 nm. This work may open up new insights into the discovery, research and application of new two-dimensional materials in photocatalysis.

Sonication-assisted liquid-phase exfoliated α-GeTe: a two-dimensional material with high Fe3+ sensitivity.

We describe sonication-assisted liquid-phase exfoliation of rhombohedral germanium telluride (α-GeTe) to obtain a good dispersion of α-GeTe nanosheets in ethanol. The thickness of the α-GeTe nanosheets is dependent on the exfoliation conditions, and few-layer α-GeTe nanosheets of 2-4 layers and even monolayer α-GeTe were obtained. We use first-principles calculations to investigate the structural, electronic, and optical properties of monolayer and bulk α-GeTe and compare the optical band gap of centrifugally fractionated α-GeTe nanosheet dispersions with the computational predictions. We demonstrate that few layer α-GeTe nanosheets are purified selectively through centrifugation, and they exhibit high sensitivity to Fe3+. The scalable production of two-dimensional α-GeTe nanosheets can be used in the future optoelectronic industry.

Two-Dimensional High-Quality Monolayered Triangular WS2 Flakes for Field-Effect Transistors.

Large-area uniform of single-crystal tungsten disulfide (WS2) is important for advanced optoelectronics based on two-dimensional (2D) atomic crystals. However, difficulties in controlling the interrelated growth parameters restrict its development in devices. Herein, we present the synthesis of triangular monolayered WS2 flakes with good uniformity and single crystal by adjusting the introduction time of sulfur precursor and the distances between the sources and substrates to control the nucleation density. Investigation of the morphology and structure by transmission electron microscopy and Raman spectroscopy indicates that a series of triangular (side length of 233 µm) monolayered WS2 flakes shows high-quality structure and homogenous crystallinity. Field-effect transistors based on the fabricated triangular monolayered WS2 with single crystal demonstrate environmentally stable charge transport with a field-effect mobility of 50.5 cm2/V s and current modulation Ion/ Ioff of ∼107. The results of this study pave the way for the application of monolayered WS2 in a multitude of 2D-material-based devices.