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Multimodal cell-free DNA whole-genome TAPS is sensitive and reveals specific cancer signals
AbstractThe analysis of circulating tumour DNA (ctDNA) through minimally invasive liquid biopsies is promising for early multi-cancer detection and monitoring minimal residual disease. Most existing methods focus on targeted deep sequencing, but few integrate multiple data modalities. Here, we develop a methodology for ctDNA detection using deep (80x) whole-genome TET-Assisted Pyridine Borane Sequencing (TAPS), a less destructive approach than bisulphite sequencing, which permits the simultaneous analysis of genomic and methylomic data. We conduct a diagnostic accuracy study across multiple cancer types in symptomatic patients, achieving 94.9% sensitivity and 88.8% specificity. Matched tumour biopsies are used for validation, not for guiding the analysis, imitating an early detection scenario. Furthermore, in silico validation demonstrates strong discrimination (86% AUC) at ctDNA fractions as low as 0.7%. Additionally, we successfully track tumour burden and ctDNA shedding from precancerous lesions post-treatment without requiring matched tumour biopsies. This pipeline is ready for further clinical evaluation to extend cancer screening and improve patient triage and monitoring.
Oxidative toxicity mediated oophoritis alters ovarian growth in Channa punctatus under prolonged exposure to herbicide, paraquat dichloride
Unveiling the nexus between irradiation and phase reconstruction in tin-lead perovskite solar cells
AbstractTin-lead perovskites provide an ideal bandgap for narrow-bandgap perovskites in all-perovskite tandem solar cells, fundamentally improving power conversion efficiency. However, light-induced degradation in ambient air is a major issue that can hinder the long-term operational stability of these devices. Understanding the specifics of what occurs during this pathway provides the direction for improving device stability. In this study, we investigate the long-term stability problem of tin-lead perovskites under irradiation, counterintuitively discovering an irreversible phase reconstruction process. In-situ photoluminescence spectroscopy is used to monitor the reconstruction process, which involves the reaction of oxygen with photoexcited electrons to form superoxide. It is proposed that Pb-rich regions appear on the surface after Sn2+ oxidation, and these Pb-rich regions are reconstituted from the yellow phase of formamidinium lead iodide to the black phase with prolonged irradiation. This study highlights the phase reconstruction process during the degradation of tin-lead perovskites, providing valuable insights into the superoxide degradation mechanism and guiding further stability improvements for narrow-bandgap tin-lead perovskites and tandem solar cells.
Ribitol and ribose treatments differentially affect metabolism of muscle tissue in FKRP mutant mice
AbstractDystroglycanopathy is characterized by reduced or lack of matriglycan, a cellular receptor for laminin as well as other extracellular matrix proteins. Recent studies have delineated the glycan chain structure of the matriglycan and the pathway with key components identified. FKRP functions as ribitol-5-phosphate transferase with CDP-ribitol as the substrate for the extension of the glycan chain. Supplement of ribitol and ribose have been reported to increase the levels of CDP-ribitol in both cells and in muscles in vivo. Clinical trials with both ribitol and ribose have been reported for treating LGMD2I caused by mutations in the FKRP gene. Here we compared the comprehensive metabolite profiles of the skeletal muscle between ribitol-treated and ribose-treated FKRP mutant mice. The closely related pentose and pentitol show clearly differential impacts on metabolisms despite their similarity in enhancing the levels of CDP-ribitol and matriglycan synthesis. Supplement of ribitol changes lysophospholipid sub-pathway metabolite profiling with a trend towards normalization as reported in the muscle after AAV9-FKRP gene therapy. Ribose treatment significantly increases level of ribonate and elevates levels of advanced glycation end products. Further analysis is required to determine which metabolite is prudent to use for long-term daily treatment of dystroglycanopathies.
Ultra-light antennas via charge programmed deposition additive manufacturing
AbstractThe demand for lightweight antennas in 5 G/6 G communication, wearables, and aerospace applications is rapidly growing. However, standard manufacturing techniques are limited in structural complexity and easy integration of multiple material classes. Here we introduce charge programmed multi-material additive manufacturing platform, offering unparalleled flexibility in antenna design and the capability for rapid printing of intricate antenna structures that are unprecedented or necessitate a series of fabrication routes. Demonstrating its potential, we present a transmitarray antenna composed of an interconnected, multi-layered array of dielectric/conductive S-ring unit cells, reducing 94% mass of conventional antenna configurations. A fully printed circular polarized transmitarray system fed by a source and a Risley prism antenna system operating at 19 GHz both show close alignment between testing results and numerical simulations. This printing method establishes a universal platform, propelling discovery of new antenna designs and enabling data-driven design and optimizations where rapid production of antenna designs is crucial.
Hirudo extract ameliorates proliferative vitreoretinopathy by promoting autophagy and attenuating the THBS2/PI3K/Akt pathway
Diet-wide analyses for risk of colorectal cancer: prospective study of 12,251 incident cases among 542,778 women in the UK
AbstractUncertainty remains regarding the role of diet in colorectal cancer development. We examined associations of 97 dietary factors with colorectal cancer risk in 542,778 Million Women Study participants (12,251 incident cases over 16.6 years), and conducted a targeted genetic analysis in the ColoRectal Transdisciplinary Study, Colon Cancer Family Registry, and Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Alcohol (relative risk per 20 g/day=1.15, 95% confidence interval 1.09-1.20) and calcium (per 300 mg/day=0.83, 0.77–0.89) intakes had the strongest associations, followed by six dairy-related factors associated with calcium. We showed a positive association with red and processed meat intake and weaker inverse associations with breakfast cereal, fruit, wholegrains, carbohydrates, fibre, total sugars, folate, and vitamin C. Genetically predicted milk consumption was inversely associated with risk of colorectal, colon, and rectal cancers. We conclude that dairy products help protect against colorectal cancer, and that this is driven largely or wholly by calcium.
The persuasive role of generic-you in online interactions
AFM observation of protein translocation mediated by one unit of SecYEG-SecA complex
Identification of CT based radiomic biomarkers for progression free survival in head and neck squamous cell carcinoma
S100P is a ferroptosis suppressor to facilitate hepatocellular carcinoma development by rewiring lipid metabolism
Intraovarian platelet-rich plasma injection significantly improves blastocyst yield and quality in IVF patients
Enhancing photocatalytic hydrogen peroxide generation by tuning hydrazone linkage density in covalent organic frameworks
Integrating deformable CNN and attention mechanism into multi-scale graph neural network for few-shot image classification
Structural basis for the transport and regulation mechanism of the multidrug resistance-associated protein 2
Abstract Multidrug resistance-associated protein 2 (MRP2) is an ATP-powered exporter important for maintaining liver homeostasis and a potential contributor to chemotherapeutic resistance. Using cryogenic electron microscopy (cryo-EM), we determine the structures of human MRP2 in three conformational states: an autoinhibited state, a substrate-bound pre-translocation state, and an ATP-bound post-translocation state. In the autoinhibited state, the cytosolic regulatory (R) domain plugs into the transmembrane substrate-binding site and extends into the cytosol to form a composite ATP-binding site at the surface of nucleotide-binding domain 2. Substrate displaces the R domain, permitting conformational changes necessary for transport. These observations suggest that the R domain functions as a selectivity gauge, where only at sufficiently high concentrations can the substrate effectively initiate transport. Comparative structural analyzes of MRP2 bound to various substrates, as determined in this study and others, reveal how MRP2 recognizes a diverse array of compounds, supporting its role in multidrug resistance.