Mismatch Repair Deficiency and Lynch Syndrome Among Adult Patients With Glioma.

PURPOSE: The Lynch syndrome (LS)-glioma association is poorly documented. As for mismatch repair deficiency (MMRd) in glioma, a hallmark of LS-associated tumors, there are only limited data available. We determined MMRd and LS prevalence in a large series of unselected gliomas, and explored the associated characteristics. Both have major implications in terms of treatment, screening, and prevention. METHODS: Somatic next-generation sequencing was performed on 1,225 treatment-naive adult gliomas referred between 2017 and June 2022. For gliomas with ≥1 MMR pathogenic variant (PV), MMR immunohistochemistry (IHC) was done. Gliomas with ≥1 PV and protein expression loss were considered MMRd. Eligible patients had germline testing. To further explore MMRd specifically in glioblastomas, isocitrate dehydrogenase (IDH)-wild type (wt), we performed IHC, and complementary sequencing when indicated, in a series of tumors diagnosed over the 2007-2021 period. RESULTS: Nine gliomas were MMRd (9/1,225; 0.73%). Age at glioma diagnosis was <50 years for all but one case. Eight were glioblastomas, IDH-wt, and one was an astrocytoma, IDH-mutant. ATRX (n = 5) and TP53 (n = 8) PV were common. There was no TERT promoter PV or EGFR amplification. LS prevalence was 5/1,225 (0.41%). One 77-year-old patient was a known LS case. Four cases had a novel LS diagnosis, with germline PV in MSH2 (n = 3) and MLH1 (n = 1). One additional patient had PMS2-associated constitutional mismatch repair deficiency. Germline testing was negative in three MSH6-deficient tumors. In the second series of glioblastomas, IDH-wt, MMRd prevalence was 12.5% in the <40-year age group, 2.6% in the 40-49 year age group, and 1.6% the ≥50 year age group. CONCLUSION: Screening for MMRd and LS should be systematic in glioblastomas, IDH-wt, diagnosed under age 50 years.

Hierarchical Cu@CuxO nanowires arrays-coated gold nanodots as a highly sensitive self-supported electrocatalyst for L-cysteine oxidation.

The sensitivity, selectivity, and stability of an electrochemical sensor for detecting small biomolecules can be significantly upgraded through properly controlling the morphology and chemical structure of electrocatalyst. Herein, we fabricated a unique hierarchical nanostructure based on Cu@CuxO nanowires (NWs) array uniformly depositing with a layer of gold nanoparticles (2-3 nm) through a simple electroless deposition process. The Au-Cu@CuxO NWs hybrid was successfully applied as a novel binder-free self-supported biosensor towards L-cysteine detection with low limit of detection (1.25 µM), wide linear detection range (1.25 µM-1.94 mM), long-term stability (four weeks), and excellent selectivity. In addition, the hybrid-based sensor accurately detected L-cysteine in real samples. It was found that the obtained nanostructure with the formation of strong interaction between Au and Cu phase produces synergistic effects, which improve exposed electroactive site number, accelerate charge transfer rate, and increase surface area, thereby boosting the sensing performance. The results open a potential way to develop electrochemical sensor for efficiently detecting not only L-cysteine but also other small molecules with high sensitivity, accuracy, stability, and cost-effectiveness in health care and disease diagnosis.

Nitrogen-Doped Graphene-Encapsulated Nickel Cobalt Nitride as a Highly Sensitive and Selective Electrode for Glucose and Hydrogen Peroxide Sensing Applications.

To explore a natural nonenzymatic electrode catalyst for highly sensitive and selective molecular detection for targeting biomolecules is a very challenging task. Metal nitrides have attracted huge interest as promising electrodes for glucose and hydrogen peroxide (H2O2) sensing applications due to their exceptional redox properties, superior electrical conductivity, and superb mechanical strength. However, the deprived electrochemical stability extremely limits the commercialization opportunities. Herein, novel nitrogen-doped graphene-encapsulated nickel cobalt nitride (Ni xCo3- xN/NG) core-shell nanostructures with a controllable molar ratio of Ni/Co are successfully fabricated and employed as highly sensitive and selective electrodes for glucose and H2O2 sensing applications. The highly sensitive and selective properties of the optimized core-shell NiCo2N/NG electrode are because of the high synergistic effect of the NiCo2N core and the NG shell, as evidenced by a superior glucose sensing performance with a short response time of <3 s, a wide linear range from 2.008 µM to 7.15 mM, an excellent sensitivity of 1803 µA mM-1 cm-2, and a low detection limit of 50 nM (S/N = 3). Furthermore, the core-shell NiCo2N/NG electrode shows excellent H2O2 sensing performances with a short response time of ∼3 s, a wide detection range of 200 nM to 3.4985 mM, a high sensitivity of 2848.73 µA mM-1 cm-2, and ultra-low limit detection of 200 nM (S/N = 3). The NiCo2N/NG sensor can also be employed for glucose and H2O2 detection in human blood serum, promising its application toward the determination of glucose and H2O2 in real samples.

Cu-Au nanocrystals functionalized carbon nanotube arrays vertically grown on carbon spheres for highly sensitive detecting cancer biomarker.

A three-dimensional hierarchical nanohybrid based on Cu-Au bimetallic nanocrystals integrated carbon nanotube arrays vertically grown on carbon spheres was successfully developed as an active platform for sensing application. Such nanohybrid can provide abundant active sites and act as an exceptional platform for immobilizing highly dense and well-dispersed carcinoembryonic antibody (anti-CEA) to sensitively detect CEA, an emerging biomarker of various cancer diseases. Due to the unique nanoarchitecture with altered electronic structure of Cu-Au bimetallic catalyst and enhanced interactions between components, such nanohybrid based biosensor demonstrated excellent electrochemical performance towards CEA detection with great sensitivity, wide linear detection range (0.025-25 ng/mL), very low limit of detection (0.5 pg/mL), and good selectivity. The results imply that this sensor has great potential to offer essential information for cancer diagnosis and management with great clinical importance.