Although semiconductor materials such as vanadium pentoxide (V2O5) are promising non-plasmonic substrates for surface-enhanced Raman scattering (SERS) spectroscopy, their broader use is still hampered by their relatively low SERS enhancement. One strategy to overcome this limitation is to combine these materials with plasmonic noble metallic nanostructures. In this study, we investigate this approach for thin V2O5 nanostructural film decorated with Au (V2O5/Au) fabricated by sputter deposition and combined with thermal annealing. We found that SERS enhancement arises from both electromagnetic and chemical (charge-transfer) enhancement as well as it benefits from the morphology of the Au layer. The presence of the continuous Au film leads to a tremendous enhancement of the SERS signal of methylene blue (MB) as compared with Au-free V2O5 substrates. Under optimised conditions (an Au deposition time of 240 s), the SERS enhancement caused by the Au layer was found to be 1200-fold. Furthermore, spectral mapping across the V2O5/Au substrates shows that the relative standard deviation (RSD) of the SERS signal is less than 35 %, i.e., still sufficiently low for reliable detection. Finally, we successfully applied V2O5/Au substrates for sensitive detection of 5,10,15,20-tetrakis-(N-methyl-4-pyridyl)porphine (TMPyP), and 2,2'-bipyridine (BPy).
- Keywords
- Charge-transfer, Electromagnetic mechanism, Gold, Plasma-based deposition, SERS, Vanadium pentoxide,
- Publication type
- Journal Article MeSH
Ultra-thin, densely packed polymer brushes (PBs) with ultra-low fouling properties play a crucial role in recent developments of surface modification strategies for biomedical and biosensing technologies. However, micro-defects within PB structures can significantly impair their ultra-low fouling performance, thereby reducing their effectiveness and the application potential. Reliable detection of these micro-defects is essential for further evaluation and optimization of brush-based surfaces. In this study, we present a straightforward spectroscopic method for detection of micro-defects in PBs using Raman mapping. We employed random copolymer brushes of carboxybetaine methacrylamide (CBMAA) and N-(2-hydroxypropyl) methacrylamide (HPMAA) as examples of state-of-the-art ultra-low fouling PB systems prepared on a surface-enhanced Raman scattering (SERS)-active Ag nano-island layer fabricated on Au-coated glass substrates. Methylene blue, drop-deposited on the PB surface, is demonstrated as a suitable reporter molecule, providing spectroscopic information via both Raman and fluorescence signals. Analysis of the spectroscopic maps enabled not only the detection of micro-defects but also the differentiation between "shallow" and "deep" defects, providing detailed insights into the structural integrity of ultra-low fouling PBs.
- Keywords
- Low-fouling coating, Micro-defects, Polymer brush, Surface-enhanced Raman scattering, Surface-enhanced fluorescence,
- Publication type
- Journal Article MeSH
UNLABELLED: Cyanobacteria are ubiquitous aquatic organisms with a remarkable evolutionary history reaching as far as 1.9 Ga. They play a vital role in ecosystems yet also raise concerns due to their association with harmful algal blooms. Understanding the historical patterns and drivers behind these blooms is crucial for effective ecosystem management. Lake-sediment cores are valuable natural environmental archives, recording the histories of such blooms. Among others, phycocyanin, a pigment specific to cyanobacteria, emerges as a promising biomarker for reconstructing past cyanobacterial bloom events. However, due to the physicochemical properties of phycocyanin, there is no validated method available to extract and measure this pigment from complex sediment matrix. This study explores the applicability of hyperspectral imaging (HSI), a non-destructive technique, as a novel approach for high resolution in-situ detection and quantification of phycocyanin in lake sediments. Our experiments show that phycocyanin can be detected by HSI with an absorption trough at 620 nm (relative absorption band depth, RABD620). We established a semi-quantitative calibration of the spectral index RABD620 by conducting spiking experiments with phycocyanin standard (known phycocyanin mass) on organic-rich and mineral-rich sediments of varying water contents. We also assessed potential interference from chlorophyll a, another photosynthetic pigment, ensuring the reliability of hyperspectral phycocyanin measurements. Our findings demonstrate a significant correlation (R2 ranging from 0.37 to 0.997) between the RABD620 index and associated phycocyanin amounts in organic-rich and minerogenic sediments. This indicates the potential of the spectral index to directly measure in-situ biomarker concentrations on split sediment cores. Although confounding factors such as water and chlorophyll a content can influence the spectral signal, this method offers a rapid and non-destructive approach for studying historical cyanobacterial blooms in sedimentary records. This opens promising grounds for various applications, including ecosystem-health assessment and environmental change monitoring. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10933-024-00350-y.
- Keywords
- Algal blooms, Cyanobacteria, Environmental change, Paleolimnology, Pigments,
- Publication type
- Journal Article MeSH
UNLABELLED: This study investigates the underlying mechanisms driving the formation of the largest known burial site of the Northern European Mesolithic, Yuzhniy Oleniy Ostrov (YOO). Radiogenic strontium isotope analysis (87Sr/86Sr) was used to identify group dynamics within the cemetery and examine the site's place within local and supra-regional networks. The analysis of 57 humans and 31 animals was supported by the creation of an environmental baseline which identified four key geological zones and defines the strontium characteristics of Lake Onega. Only two individuals had strontium values indicating time spent outside of Lake Onega's northern shores, where the majority of the burial population is likely to have resided. These results suggest that the YOO cemetery predominantly served as a burial place for those with semi-permanent residence in this area, with no significant evidence for gender-based relocation patterns indicative of patri- or matrilocal residency. However, materials seem to have travelled towards Lake Onega even over great distances and the presence of the two outlier individuals suggests these exchanges also involved long-distance travel of people. Our results align with an increasing number of studies that suggest a high degree of residential stability for Late Mesolithic foraging groups relying primarily on aquatic resources, yet simultaneously places the Lake Onega community within a wider Mesolithic communication network. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12520-024-02129-8.
- Keywords
- Bioarchaeology, Geology, Hunter-gatherer-fishers, Mesolithic, Mobility, Strontium,
- Publication type
- Journal Article MeSH
Plasma flows with enhanced dynamic pressure, known as magnetosheath jets, are often found downstream of collisionless shocks. As they propagate through the magnetosheath, they interact with the surrounding plasma, shaping its properties, and potentially becoming geoeffective upon reaching the magnetopause. In recent years (since 2016), new research has produced vital results that have significantly enhanced our understanding on many aspects of jets. In this review, we summarise and discuss these findings. Spacecraft and ground-based observations, as well as global and local simulations, have contributed greatly to our understanding of the causes and effects of magnetosheath jets. First, we discuss recent findings on jet occurrence and formation, including in other planetary environments. New insights into jet properties and evolution are then examined using observations and simulations. Finally, we review the impact of jets upon interaction with the magnetopause and subsequent consequences for the magnetosphere-ionosphere system. We conclude with an outlook and assessment on future challenges. This includes an overview on future space missions that may prove crucial in tackling the outstanding open questions on jets in the terrestrial magnetosheath as well as other planetary and shock environments.
- Keywords
- Bow shock, Foreshock, Magnetopause, Magnetosheath, Magnetosheath jets, Solar wind,
- Publication type
- Journal Article MeSH
- Review MeSH
Reversed-phase ultrahigh-performance liquid chromatography-mass spectrometry (RP-UHPLC/MS) method is optimized for the quantitation of a large number of lipid species in biological samples, primarily in human plasma and serum. The method uses a C18 bridged ethylene hybrid (BEH) column (150 × 2.1 mm; 1.7 μm) for the separation of lipids from 23 subclasses with a total run time of 25 min. Lipid species separation allows the resolution of isobaric and isomeric lipid forms. A triple quadrupole mass spectrometer is used for targeted lipidomic analysis using multiple reaction monitoring (MRM) in the positive ion mode. Data are evaluated by Skyline software, and the concentrations of analytes are determined using internal standards per each individual lipid class.
- Keywords
- High-throughput lipidomics, Mass spectrometry, Plasma, Quantitation, Reversed-phase, Serum, Ultrahigh-performance liquid chromatography,
- MeSH
- Chromatography, Reverse-Phase * methods MeSH
- Mass Spectrometry methods MeSH
- Liquid Chromatography-Mass Spectrometry MeSH
- Humans MeSH
- Lipidomics * methods MeSH
- Lipids * analysis MeSH
- High-Throughput Screening Assays methods MeSH
- Software MeSH
- Tandem Mass Spectrometry methods MeSH
- Chromatography, High Pressure Liquid methods MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Lipids * MeSH
PURPOSE: To evaluate treatment outcomes and toxicity in patients with stage T1-3N0M0 oral cancer treated with surgery followed by high-dose-rate brachytherapy (HDR-BT). METHODS AND MATERIALS: Retrospective study of 50 patients with stage T1-T3N0 tongue and floor-of-mouth cancer who underwent tumour excision (+ elective neck dissection) followed by postoperative HDR-BT due to the presence of negative prognostic factors (close or positive resection margins, lymphovascular and/or perineural invasion, deep invasion). The plastic tube technique (dose: 18 x 3 Gy b.i.d.) was used. Survival outcomes, toxicity, and prognostic factors were evaluated. RESULTS: At a median follow-up of 81 months (range, 4-121), actuarial 5-year local control (LC), nodal control (NC) and progression-free survival (PFS) rates were 79%, 69%, and 64%. After salvage treatment (surgery + external beam radiotherapy), LC, NC, and PFS increased to 87%, 77%, and 72.3%, respectively. Five-year overall survival and cancer-specific survival (CSS) rates were 73% and 77%. Treatmentrelated toxicity included two cases of mandibular osteoradionecrosis and five cases of small soft tissue necrosis. T stage was significantly correlated with nodal control (p=0.02) and CSS (p=0.04). Tumour grade correlated with DFS (p=0.01). CONCLUSION: Postoperative HDR-BT 18 x 3 Gy b.i.d. seems to be an effective method in patients with T1-3N0M0 oral cancer with negative prognostic factors after tumour resection.
- Keywords
- Brachytherapy, Early oral cancer, Postoperative treatment,
- MeSH
- Brachytherapy * methods adverse effects MeSH
- Radiotherapy Dosage MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Mouth Neoplasms * radiotherapy surgery pathology mortality MeSH
- Prognosis MeSH
- Retrospective Studies MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Neoplasm Staging MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
In esophageal squamous cell carcinoma, genetic activation of NRF2 increases resistance to chemotherapy and radiotherapy, which results in a significantly worse prognosis for patients. Therefore NRF2-activated cancers create an urgent clinical need to identify new therapeutic options. In this context, we previously identified the geldanamycin family of HSP90 inhibitors, which includes 17DMAG, to be synthetic lethal with NRF2 activity. As the first-generation of geldanamycin-derivative drugs were withdrawn from clinical trials due to hepatotoxicity, we designed second-generation compounds with C19-substituted structures in order to inhibit glutathione conjugation-mediated hepatotoxicity. In this study, using a variety of in vitro and in vivo cancer models, we found that C19-substituted 17DMAG compounds maintain their enhanced toxicity profile and synthetic lethal interaction with NRF2-NQO1-activated cancer cells. Importantly, using a xenograft mouse tumor model, we found that C19-substituted 17DMAG displayed significant anticancer efficacy against NRF2-NQO1-activated cancer cells without causing hepatotoxicity. These results clearly demonstrate the improved clinical potential for this new class of HSP90 inhibitor anticancer drugs, and suggest that patients with NRF2-NQO1-activated esophageal carcinoma may benefit from this novel therapeutic approach.
- Keywords
- C19-position substituted geldanamycin derivatives, ESCC, HSP90, NQO1, NRF2-NQO1-activated cancer,
- MeSH
- Benzoquinones * pharmacology chemistry MeSH
- NF-E2-Related Factor 2 * metabolism genetics MeSH
- Humans MeSH
- Lactams, Macrocyclic * pharmacology chemistry MeSH
- Mice, Nude MeSH
- Mice MeSH
- NAD(P)H Dehydrogenase (Quinone) * metabolism genetics MeSH
- Cell Line, Tumor MeSH
- Esophageal Neoplasms * drug therapy metabolism pathology MeSH
- HSP90 Heat-Shock Proteins antagonists & inhibitors metabolism MeSH
- Antineoplastic Agents * pharmacology chemistry MeSH
- Esophageal Squamous Cell Carcinoma * drug therapy metabolism MeSH
- Xenograft Model Antitumor Assays MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Benzoquinones * MeSH
- NF-E2-Related Factor 2 * MeSH
- geldanamycin MeSH Browser
- Lactams, Macrocyclic * MeSH
- NAD(P)H Dehydrogenase (Quinone) * MeSH
- NFE2L2 protein, human MeSH Browser
- NQO1 protein, human MeSH Browser
- HSP90 Heat-Shock Proteins MeSH
- Antineoplastic Agents * MeSH
BACKGROUND: Patients with severe aortic stenosis present frequently (∼50%) with concomitant obstructive coronary artery disease. Current guidelines recommend combined surgical aortic valve replacement (SAVR) and coronary artery bypass grafting (CABG) as the preferred treatment. Transcatheter aortic valve implantation (TAVI) and fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) represent a valid treatment alternative. We aimed to test the non-inferiority of FFR-guided PCI plus TAVI versus SAVR plus CABG in patients with severe aortic stenosis and complex coronary artery disease. METHODS: This international, multicentre, prospective, open-label, non-inferiority, randomised controlled trial was conducted at 18 tertiary medical centres across Europe. Patients (aged ≥70 years) with severe aortic stenosis and complex coronary artery disease, deemed feasible for percutaneous or surgical treatment according to the on-site Heart Team, were randomly assigned (1:1) to FFR-guided PCI plus TAVI or SAVR plus CABG according to a computer-generated sequence with random permuted blocks sizes stratified by site. The primary endpoint was a composite of all-cause mortality, myocardial infarction, disabling stroke, clinically driven target-vessel revascularisation, valve reintervention, and life-threatening or disabling bleeding at 1 year post-treatment. The trial was powered for non-inferiority (with a margin of 15%) and if met, for superiority. The primary and safety analyses were done per an intention-to-treat principle. This trial is registered with ClinicalTrials.gov (NCT03424941) and is closed. FINDINGS: Between May 31, 2018, and June 30, 2023, 172 patients were enrolled, of whom 91 were assigned to the FFR-guided PCI plus TAVI group and 81 to the SAVR plus CABG group. The mean age of patients was 76·5 years (SD 3·9). 118 (69%) of 172 patients were male and 54 (31%) patients were female. FFR-guided PCI plus TAVI resulted in favourable outcomes for the primary endpoint (four [4%] of 91 patients) versus SAVR plus CABG (17 [23%] of 77 patients; risk difference -18·5 [90% CI -27·8 to -9·7]), which was below the 15% prespecified non-inferiority margin (pnon-inferiority<0·001). FFR-guided PCI plus TAVI was superior to SAVR plus CABG (hazard ratio 0·17 [95% CI 0·06-0·51]; psuperiority<0·001), which was driven mainly by all-cause mortality (none [0%] of 91 patients vs seven (10%) of 77 patients; p=0·0025) and life-threatening bleeding (two [2%] vs nine [12%]; p=0·010). INTERPRETATION: The TCW trial is the first trial to compare percutaneous treatment versus surgical treatment in patients with severe aortic stenosis and complex coronary artery disease, showing favourable primary endpoint and mortality outcomes with percutaneous treatment. FUNDING: Isala Heart Centre and Medtronic.
- MeSH
- Aortic Valve Stenosis * surgery complications MeSH
- Heart Valve Prosthesis Implantation methods MeSH
- Fractional Flow Reserve, Myocardial * MeSH
- Percutaneous Coronary Intervention * methods MeSH
- Coronary Artery Bypass * methods MeSH
- Humans MeSH
- Coronary Artery Disease * surgery complications therapy MeSH
- Prospective Studies MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Transcatheter Aortic Valve Replacement * methods MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Equivalence Trial MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
