Thermopressure Coupling Effect Mimicking Natural Graphite Formation to Enhance the Storage K-Ion Performance of Carbonaceous Heterostructures.

Borrowing from natural mechanisms for material design can lead to functional mimicry and improvement. Inspired by graphite formation, a thermopressure coupling strategy under micropressure (<400 Pa) is applied to prepare carbon anodes. A thermopressure response is discovered based on the cellulose precursor. Here, homologous graphene quantum dot/hard carbon (GQD/HC) heterostructures are synthesized. Under 181.4 Pa and 1,200 °C, the product shows a capacity of 310 mAh g-1, while the capacity of the direct carbonization product is only 120 mAh g-1. Prominently, the GQD/HC heterostructure displays marked mechanical strength and flexibility. The experimental and theoretical results illustrate the ion and electron transfer, coordination environment, and electronic states in the GQD/HC heterostructure and elaborate on the origin of the enhanced performance. The thermopressure coupling under micropressure mimics graphite formation, but the heterostructure has better properties than traditional carbon materials. Additionally, micropressure injects new vitality into material research.

Imaging parameters and clinical significance of posterior ligament complex injury in thoracolumbar fracture.

This study aims to investigate whether the combination of radiographs and computed tomography (CT) images can be used as an alternative means of magnetic resonance imaging examination or a preliminary screening method before examination, so as to improve the accuracy of determining the degree of posterior ligament complex injury in thoracolumbar fracture patients. From May 2011 to May 2019, the patients with thoracolumbar fracture were collected. A total of 150 patients were enrolled. The reference standard was 1.5T magnetic resonance imaging examination and lipid suppression sequence was applied. All radiographs and CT imaging results were measured in the Picture Archiving and Communication System workstation. The upper endplate angle and lower endplate angle, the percentage of vertebral height drop, the difference of inter-spinous process distance on CT images and the translation distance were statistically significant between the 2 groups (P < .05). Receiver operating characteristic curve showed that the diagnostic performance was excellent (all area under the curve > 0.7). To sum, the results showed that endplate angle + inter-spinous process distance on CT images combination had relatively high-quality diagnostic value for posterior ligamentous complex injury in thoracolumbar fracture patients.

An Unrevealed Molecular Function of Corannulene Buckybowl Glycoconjugates in Selective Tumor Annihilation by Targeting the Cancer-Specific Warburg Effect.

The biomedical application of corannulene π-bowls is historically limited by low solubility and bioavailability despite the potential in their unique electronic properties for new functional materials. Herein, the unexpected role and molecular mechanism of Corranulene π-bowls are uncovered in biomedical applications as an effective anticancer agent for Warburg effect mediated selective tumor targeting. The corannulene triazolyl monosaccharides Cor-sugars exhibit highly potent cytotoxicity against human cancer cells and effectively inhibit xenograft growth of hyperglycolytic tumors. Particularly, the galactose-conjugated Cor-gal exhibits superior in vivo anticancer efficacy in A549 tumor models with outstanding safety profile compared to doxorubicin. Moreover, the combined treatment of Cor-gal with immune checkpoint inhibitor results in an effective synergy in treating H460 human lung carcinoma. An uptake mechanism study reveals that Cor-sugars exploit tumor-specific glucose transporter glucose transporter 1 (GLUT1) for targeted cell delivery and intra-tumoral accumulation through the cancer-specific Warburg effect. Their significant anticancer activity is attributed to multiphasic DNA-binding and cell cycle alteration effects. This study uncovers new molecular properties of corannulene buckybowl and enabling their potential new applications in biomedical engineering.

The Astronomical Images in the First Chinese Treatise on the Telescope by Johann Adam Schall von Bell Revisited.

A reanalysis of the eight astronomical images that Johann Adam Schall von Bell incorporated in the first Chinese treatise on the telescope to illustrate the telescopic discoveries made by Galileo Galilei shows that they were borrowed from the works on telescopic astronomy by Galileo Galilei and Johann Georg Locher, a student of Christopher Scheiner. Except minor changes to both Galileo's illustrations of the telescopic view of the moon and nebulae and Locher's illustration of sunspots, Locher's images about the phases of Venus and Jovian satellites were redrawn presumably to convey a clearer commitment to Tycho Brahe's system of the world and most of the contents in Locher's image of Saturn was replaced by Schall's own observation. These changes seem to be the result of two important factors that confined the transcultural transmission of astronomical knowledge from Europe to China through the Jesuits in the seventeenth century, namely the official standpoint of the Catholic Church on the ongoing cosmological issues and the cultural tradition of Chinese astronomy.

Targeting Key Transporters in Tumor Glycolysis as a Novel Anticancer Strategy.

Increased glycolysis has been one of the metabolic characteristics known as the Warburg effect. The functional and therapeutic importance of the Warburg effect in targeted therapy is scientifically recognized and the glucose metabolic pathway has become a desirable target of anticancer strategies. Glucose transporters (GLUTs) play an important role in cancer glycolysis to sustain cancer cell proliferation, metastasis and survival. Utilizing the knowledge of differential expression and biological functions of GLUTs offers us the possibility of designing and delivering chemotherapeutics toward targeted tumor tissues for improved cancer selectivity. Inhibition of glucose uptake or glycolysis may effectively kill hypoxic cancer cells. Facilitative drug uptake via active transportation provides the potential opportunity to circumvent the drug resistance in chemotherapy. GLUTs as the hallmarks and biotargets of cancer metabolism enable the design and development of novel targeted theranostic agents. In this updated review, we examine the current scenario of the GLUTs as strategic targets in cancer and the unique concepts for discovery and development of GLUTs-targeted anticancer agents. We highlight the recent progresses on structural biology and underlying mechanism studies of GLUTs, with a brief introduction to the computational approaches in GLUT-mediated drug transport and tumor targeting.

Mechanistic and biological characteristics of different sugar conjugated 2-methyl malonatoplatinum(II) complexes as new tumor targeting agents.

Novel cis-2-methylmalonato(trans-R,R-cyclohexane-1,2-diamine)platinum(II) glycoconjugates derived from different sugar motifs, namely, glucose (Glu-Me-Pt), mannose (Man-Me-Pt) and galactose (Gal-Me-Pt) were designed and synthesized based on the third generation clinical drug oxaliplatin for potential glucose transporters (GLUTs) mediated tumor targeting. All platinum(II) glycoconjugates were characterized by 1H NMR, 13C NMR, IR, HRMS as well as 195Pt-NMR analysis. Despite their substantial improvement in water solubility, the conjugates exhibited comparable or better in vitro cytotoxicities than oxaliplatin determined in six different human cancer cell lines. Glu-Me-Pt has been shown to be more effective than cisplatin and oxaliplatin with improved therapeutic index in leukemia-bearing DBA/2 mice model. The potential GLUT transportability of the complexes was investigated using cell-based fluorescent competition assay and GLUT inhibitor mediated cell viability analysis in GLUT over-expressing HT29 cell line. Each sugar motif was found to be useful to enable the platinum(II) complexes as substrate for GLUT mediated cell uptake. In vitro DNA adduct formation analysis has been investigated for the first time for this class of compounds to reveal the intrinsic differences in antitumor activity between the malonatoplatinum(II) glycoconjugates and oxaliplatin. The intrinsic DNA reactivity of the platinum(II)-sugar conjugates was found as Gal-Me-Pt > Glu-Me-Pt > Man-Me-Pt ≈ oxaliplatin by kinetic study on the formation of platinum(II) adducts with guanosine-5'-monophosphate (5'-GMP). The results from this study demonstrate the usefulness of glucose, mannose and galactose as alternative sugar motif on glycoconjugation for GLUT mediated drug design and pharmaceutical R&D, and the obtained fundamental results also support the potential of the GLUT targeted platinum(II)-sugar conjugates as lead compounds for further pre-clinical evaluation.

Fluorescent 6-amino-6-deoxyglycoconjugates for glucose transporter mediated bioimaging.

Two novel fluorescent bioprobes, namely, 6N-Gly-Cy3 and 6N-Gly-Cy5, were designed and synthesized for real-time glucose transport imaging as well as potentially useful tracer for galactokinase metabolism. The structure of the bioprobes was fully characterized by 1H NMR, 13C NMR, IR, and HRMS. The fluorescence properties, glucose transporter (GLUT) specificity, and the quenching and safety profiles were studied. The cellular uptake of both bioprobes was competitively diminished by d-glucose, 2-deoxy-d-glucose and GLUT specific inhibitor in a dose-dependent manner in human colon cancer cells (HT29). Comparison study results revealed that the 6N-derived bioprobes are more useful for real-time imaging of cell-based glucose uptake than the structurally similar fluorescent tracer 6-NBDG which was not applicable under physiological conditions. The up to 96 h long-lasting quenching property of 6N-Gly-Cy5 in HT29 suggested the potential applcability of the probe for cell labeling in xenograft transplantation as well as in vivo animal imaging studies.

Methyl 6-Amino-6-deoxy-d-pyranoside-Conjugated Platinum(II) Complexes for Glucose Transporter (GLUT)-Mediated Tumor Targeting: Synthesis, Cytotoxicity, and Cellular Uptake Mechanism.

Methyl 6-aminodeoxy-d-pyranoside-derived platinum(II) glycoconjugates were designed and synthesized based on the clinical drug oxaliplatin for glucose transporter (GLUT)-mediated tumor targeting. In addition to a substantial improvement in water solubility, the conjugates exhibited cytotoxicity similar to or higher than that of oxaliplatin in six different human cancer cell lines. GLUT-mediated transport of the complexes was investigated with a cell-based fluorescence competition assay and GLUT-inhibitor-mediated cytotoxicity analysis in a GLUT-overexpressing human colorectal adenocarcinoma (HT29) cell line. The antitumor effect of the aminodeoxypyranoside-conjugated platinum(II) complexes was found to depend significantly on the GLUT inhibitor, and the cellular uptake of the molecules was regulated by GLUT-mediated transport. The results from this study demonstrate the potential advantages of aminodeoxypyranosides as sugar motifs for glycoconjugation for Warburg-effect-targeted drug design. These fundamental results also support the potential of aminodeoxypyranoside-conjugated platinum(II) complexes as lead compounds for further preclinical evaluation.

Cyanine-based 1-amino-1-deoxyglucose as fluorescent probes for glucose transporter mediated bioimaging.

Two novel cyanine-based 1-amino-1-deoxy-ß-glucose conjugates (Glu-1N-Cy3 and Glu-1N-Cy5) were designed, synthesized and their fluorescence characteristics were studied. Both Glu-1N-Cy3 and Glu-1N-Cy5 accumulate in living HT29 human colon cancer cells, which overexpress glucose transporters (GLUTs). The cellular uptake of the bioprobes was inhibited by natural GLUT substrate d-glucose and 2-deoxy-d-glucose. The GLUT specificity of the probes was validated with quercetin, which is both a permeant substrate via GLUTs and a high-affinity inhibitor of GLUT-mediated glucose transport. Competitive fluorometric assay for GLUT substrate cell uptake revealed that Glu-1N-Cy3 and Glu-1N-Cy5 are 5 and 10 times more sensitive than 2-NBDG, a leading fluorescent glucose bioprobe. This study provides fundamental data supporting the potential of these two conjugates as new powerful tools for GLUT-mediated theranostics, in vitro and in vivo molecular bioimaging and drug R&D.

Scalable preparation of ultrathin silica-coated Ag nanoparticles for SERS application.

Silica-coated Ag nanoparticles (Ag@SiO2 NPs) have been successfully prepared by a scalable flame spray pyrolysis (FSP) technique with production rate up to 4 g/h in laboratory-scale. The ultrathin SiO2 shell, with a thickness 1 nm, not only effectively avoids the intersintering of Ag nanoparticles core at the high temperature, but also serves as a protective layer of the SERS-active nanostructure. The silica-coated Ag nanoparticles form agglomerates in the large temperature gradient zone, which with several nanometers gaps from each other but not contact. Such an intriguing feature can result in more Raman hot-spots generated at the gaps among Ag core active sites, which will beneficial for the whole SERS substrate enhancement. The results demonstrate that a maximum enhancement factor can reach ~10(5) with a detectable concentration as low as 10(-10) M for rhodamine 6G (R6G) molecules, indicating that the as-obtained unique nanostructure will be a promising candidate for SERS applications.