Pharmacogenomic profiling reveals molecular features of chemotherapy resistance in IDH wild-type primary glioblastoma

Background Although temozolomide (TMZ) has been used as a standard adjuvant chemotherapeutic agent for primary glioblastoma (GBM), treating isocitrate dehydrogenase wild-type (IDH-wt) cases remains challenging due to intrinsic and acquired drug resistance. Therefore, elucidation of the molecular mechanisms of TMZ resistance is critical for its precision application. Methods We stratified 69 primary IDH-wt GBM patients into TMZ-resistant (n = 29) and sensitive (n = 40) groups, using TMZ screening of the corresponding patient-derived glioma stem-like cells (GSCs). Genomic and transcriptomic features were then examined to identify TMZ-associated molecular alterations. Subsequently, we developed a machine learning (ML) model to predict TMZ response from combined signatures. Moreover, TMZ response in multisector samples (52 tumor sectors from 18 cases) was evaluated to validate findings and investigate the impact of intra-tumoral heterogeneity on TMZ efficacy. Results In vitro TMZ sensitivity of patient-derived GSCs classified patients into groups with different survival outcomes (P = 1.12e−4 for progression-free survival (PFS) and 3.63e−4 for overall survival (OS)). Moreover, we found that elevated gene expression of EGR4, PAPPA, LRRC3, and ANXA3 was associated to intrinsic TMZ resistance. In addition, other features such as 5-aminolevulinic acid negative, mesenchymal/proneural expression subtypes, and hypermutation phenomena were prone to promote TMZ resistance. In contrast, concurrent copy-number-alteration in PTEN, EGFR, and CDKN2A/B was more frequent in TMZ-sensitive samples (Fishers exact P = 0.0102), subsequently consolidated by multi-sector sequencing analyses. Integrating all features, we trained a ML tool to segregate TMZ-resistant and sensitive groups. Notably, our method segregated IDH-wt GBM patients from The Cancer Genome Atlas (TCGA) into two groups with divergent survival outcomes (P = 4.58e−4 for PFS and 3.66e−4 for OS). Furthermore, we showed a highly heterogeneous TMZ-response pattern within each GBM patient usingin vitro TMZ screening and genomic characterization of multisector GSCs. Lastly, the prediction model that evaluates the TMZ efficacy for primary IDH-wt GBMs was developed into a webserver for public usage (http://www.wang-lab-hkust.com:3838/TMZEP) Conclusions We identified molecular characteristics associated to TMZ sensitivity, and illustrate the potential clinical value of a ML model trained from pharmacogenomic profiling of patient-derived GSC against IDH-wt GBMs

Expeditious and eco-friendly hydrothermal polymerization of PEDOT nanoparticles for binderfree high performance supercapacitor electrodes

Poly(3,4-ethylenedioxythiophene) (PEDOT) is a promising conjugated polymer that has attracted attention because of its outstanding electronic properties, useful for a wide range of applications in energy storage devices. However, synthesis of high-quality PEDOT occurs via vapour phase polymerization and chemical vapour deposition techniques using extrinsic hard templates or complicated experimental setups. This study introduces a simple hydrothermal polymerization technique using ferric chloride (FeCl3) as an oxidizing agent to overcome the above drawback, which results in good conductive, crystalline PEDOT nanodendrites and nanospheres. The effects of varying the molar ratio of FeCl3 oxidant were investigated in terms of the structural, morphological and electrochemical properties of PEDOT. The supercapacitive performance of the as-polymerized PEDOT nanostructures was determined by fabricating an electrode without the aid of organic binders or conductive additives. PEDOT nanodendrites polymerized using 2.5 molar ratio of FeCl3 demonstrated enhanced electrochemical performance with a maximum specific capacitance of 284 F g-1 with high energy density of 39.44 W h kg-1 at 1 A g-1 current density in 1 M H2SO4 electrolyte. Moreover, the sample possessed higher conductivity, better specific surface area, improved electrochemical properties, comparable crystallinity, and excellent cycling stability after 5000 charge/discharge cycles than the other PEDOT nanostructures. Importantly, the results establish that these materials afford good redox behaviors with better conductivity suitable for the development of an organic electrode-based supercapacitor with high specific charge capacity and stability

Electrochemical supercapacitor behaviour of functionalized candle flame carbon soot

The electrochemical supercapacitor behaviour of bare, washed and nitric acid functionalized candle flame carbon soots were reported. Crystallinity and the morphology of the candle soots were recorded using X-ray diffraction analysis, scanning and transmission electron microscopy, respectively. The nitric acid functionalized candle soot showed an improved Brunauer-Emmett-Teller surface area of 137.93 from 87.495 m 2 g -1 of washed candle soot. The presence of various functional groups in candle soots and the development of oxygen functionalities in the functionalized candle soot were examined through Fourier transform infrared spectroscopy and energy-dispersive X-ray analysis. Raman spectra showed the characteristic peaks corresponding to the D (diamond) and G (graphite) phase of carbon present in the candle soots. The electrochemical characterization was performed by cyclic voltammetry, galvanostatic charge/discharge test and impedance spectroscopy in 1 M H 2 SO 4 electrolyte. The functionalized candle soot electrode showed an enhanced specific capacitance value of 187 F g -1 at 0.15 A g -1 discharge current density, which is much higher than that of bare and washed candle soot electrodes

A high performance PEDOT/PEDOT symmetric supercapacitor by facile in-situ hydrothermal polymerization of PEDOT nanostructures on flexible carbon fibre cloth electrodes

Achievement of conducting polymer based symmetric supercapacitor with high specific capacitance and long cyclic stability is a very challenging and a complicated approach. Generally, the specific capacitance and stability of the conducting polymer system have been improved by forming composite with metal oxides or carbon based nanomaterials. In this present work, we demonstrated a simple and straightforward strategy for the deposition of bare PEDOT nanostructures on flexible 3D carbon fibre cloth (CFC) via in situ hydrothermal polymerization technique. The hydrot hermally polymerized electrodes were easily assembled into PEDOT/PEDOT symmetrical supercapacitor without using any organic binders and conductive additives. This symmetric supercapacitor exhibited significantly high specific capacitance of 203 F g −1 at 5 mV s −1 scan rate with high energy density of 4.4 W h kg −1 and power density of 40.25 kW kg −1 in 1 M H 2 SO 4 electrolyte, which is highest value reported for this material as a symmetric device. More importantly, the formation of 3D PEDOT nanostructure with flexible carbon cloth affords an efficient and stable electrode for facile electron transfer in symmetrical supercapacitor and delivered a long device stability with capacitance retention of ∼86% after 12,000 charge/discharge cycles

Highly Flexible and Planar Supercapacitors Using Graphite Flakes/Polypyrrole in Polymer Lapping Film

Flexible supercapacitor electrodes have been fabricated by simple fabrication technique using graphite nanoflakes on polymer lapping films as flexible substrate. An additional thin layer of conducting polymer polypyrrole over the electrode improved the surface conductivity and exhibited excellent electrochemical performances. Such capacitor films showed better energy density and power density with a maximum capacitance value of 37 mF cm \u3c sup \u3e -2 \u3c /sup \u3e in a half cell configuration using 1 M H \u3c inf \u3e 2 \u3c /inf \u3e SO \u3c inf \u3e 4 \u3c /inf \u3e electrolyte, 23 mF cm \u3c sup \u3e -2 \u3c /sup \u3e in full cell, and 6 mF cm \u3c sup \u3e -2 \u3c /sup \u3e as planar cell configuration using poly(vinyl alcohol) (PVA)/phosphoric acid (H \u3c inf \u3e 3 \u3c /inf \u3e PO \u3c inf \u3e 4 \u3c /inf \u3e ) solid state electrolyte. Moreover, the graphite nanoflakes/polypyrrole over polymer lapping film demonstrated good flexibility and cyclic stability. (Graph Presented)