Aneuploidy is prevalent in cancer and has complicated roles in tumorigenesis. Paradoxically, artificially engineered aneuploidy in normal cells reduces cellular fitness by inducing proteotoxic and genotoxic stresses. A better molecular understanding of the multifaceted roles of aneuploidy in cancer evolution offers promising avenues for future cancer therapies.
View Article and Find Full Text PDFBackground: The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) has increased worldwide. In recent years, fecal microbiota transplantation (FMT) has become an important promising method for the treatment of MASLD. However, the mechanism remains unclear.
View Article and Find Full Text PDFNon-small cell lung cancer (NSCLC) is a highly prevalent and aggressive malignancy, where early diagnosis and therapeutic intervention are pivotal for enhancing patient prognosis. Nonetheless, the lack of reliable biomarkers remains a substantial hurdle in clinical practice. In this study, we identified dysregulated microRNAs (miRNAs) in NSCLC, revealing a significant downregulation of miR-3202 and an upregulation of miR-3182.
View Article and Find Full Text PDFThe Colavita visual dominance effect refers to the phenomenon in which tend to respond only or preferentially to visual stimuli of bimodal audiovisual stimulus. Previous evidence has indicated that sensory dominance can be modulated by top-down expectation. However, it remains unclear how expectations directed toward a single sensory modality influence Colavita visual dominance at the electrophysiology level.
View Article and Find Full Text PDFHeterogeneous electro-Fenton (EF) technology is an efficient approach for antibiotics degradation, but the effective mineralization of pollutants in complex actual water remains challenging due to the susceptibility of hydroxyl radical (∙OH) to environmental influences. Herein, a Fe-single atom anchored porous hollow carbon sphere (FeHCS) material with nano-confinement structure was designed for simultaneously catalyzing HO to produce ∙OH and O. Benefiting from oxidation of ∙OH and selective reaction of alkyl group with O, the kinetic constant (k) of the FeHCS-based EF system achieves 4.
View Article and Find Full Text PDFChromosomes in eukaryotic cells undergo compaction at multiple levels and are folded into hierarchical structures to fit into the nucleus with limited dimensions. Three-dimensional genome organization needs to be coordinated with chromosome-templated processes, including DNA replication and gene transcription. As an ATPase molecular machine, the cohesin complex is a major driver of genome folding, which regulates transcription by modulating promoter-enhancer contacts.
View Article and Find Full Text PDFMultiple myeloma (MM) is a haematological lymphoid malignancy marked by significant morbidity due to severe complications. Despite advances in targeted therapies, including proteasome inhibitors and the BCL-2 inhibitor venetoclax, drug resistance frequently occurs, with the underlying mechanisms poorly understood. This study investigates the role of lysosome-associated protein transmembrane 5 (LAPTM5) in conferring resistance to venetoclax in relapsed MM.
View Article and Find Full Text PDFFront Psychol
December 2024
The congruency sequence effect (CSE) refers to the reduction in the congruency effect in the current trial after an incongruent trial compared with a congruent trial. Although previous studies widely suggested that CSE was observed only in the modality repeat condition, few studies have reported that CSE could also appear in the modality switch condition. However, it remains unclear whether these conflicting findings were caused by partial repetition effects under modality transition conditions.
View Article and Find Full Text PDFPhotocatalytic conversion of carbon dioxide (CO) to fuel provides an ideal pathway to achieving carbon neutrality. One significant hindrance in achieving the reduction of CO to higher energy density multicarbon products (C) was the difficulty in coupling C-C bonds efficiently. Copper (Cu) is considered the most suitable metal catalyst for C-C coupling to form C products in the CO reduction reaction (CORR), but it encounters challenges such as low product selectivity and slow catalytic efficiency.
View Article and Find Full Text PDFIntroduction: Endothelin-1 (ET-1) regulates renal and vascular function, but the clinical utility of selective ET receptor antagonists has been limited due to associated fluid retention. The mechanisms underlying fluid retention remain poorly understood but could be a consequence of changes in ET-1 binding to the unantagonized ET receptor, either through increased ET-1 or non-selective ET.
Methods: A mathematical model of ET-1 kinetics was developed to quantify effects of ET antagonist exposure and selectivity on concentrations of ET-1 and its complexes with ET and ET receptors.
The photocatalytic co-reduction of CO and N is a sustainable method for urea synthesis under mild conditions. However, high-yield synthesis of urea is a challenge due to the sluggish kinetics of the C-N coupling reaction. Herein, we have successfully engineered a Z-scheme photocatalyst, SrTiO-FeS-CoWO, for boosting photocatalytic urea synthesis via enhancing the initial CO and N adsorption step and reducing the energy barrier for the C-N coupling reaction.
View Article and Find Full Text PDFWith the rapid development of the Internet of Things, location-based services are becoming increasingly important, especially in indoor environments. Visible light positioning (VLP) has garnered widespread attention due to its high accuracy, low cost, and immunity to the radio frequency electromagnetic interference. However, traditional VLP relies on line-of-sight paths, making it impractical in complex and dynamic indoor environments.
View Article and Find Full Text PDFAims: GLP-1 receptor agonists (GLP-1 RAs) are proven therapies for type 2 diabetes mellitus (T2DM) and overweight or obesity. We performed non-clinical and first-in-human (FIH) evaluation of ECC5004/AZD5004, an oral small-molecule GLP-1 RA.
Materials And Methods: ECC5004 was profiled in cell lines overexpressing human GLP-1R, in glucose-stimulated insulin secretion (GSIS) assays in a human β-cell line and non-human primates (NHPs).
Although Zeolitic Imidazolate Framework-8 (ZIF-8) shows significant promise in chemodynamic therapy of bacterial infections due to its large specific surface area and enzyme-like activity, it still faces a considerable gap compared to natural enzymes. The dependency on low pH and high concentrations of hydrogen peroxide ((HO) is a major factor limiting the clinical progress of nanozymes. Single-atom nanozymes (SA-zyme), which exhibit superior catalytic performance, are expected to overcome this limitation.
View Article and Find Full Text PDFEnviron Sci Technol
November 2024
The nonradical oxidation pathway for pollutant degradation in Fenton-like catalysis is favorable for water treatment due to the high reaction rate and superior environmental robustness. However, precise regulation of such reactions is still restricted by our poor knowledge of underlying mechanisms, especially the correlation between metal site conformation of metal atom clusters and pollutant degradation behaviors. Herein, we investigated the electron transfer and pollutant oxidation mechanisms of atomic-level exposed Ag atom clusters (Ag) loaded on specifically crafted nitrogen-doped porous carbon (NPC).
View Article and Find Full Text PDFClear cell renal cell carcinoma (ccRCC) represents a highly heterogeneous kidney malignancy associated with the poorest prognosis. The metastatic potential of advanced ccRCC tumors is notably high, posing significant clinical challenges. There is an urgent imperative to develop novel therapeutic approaches to address ccRCC metastasis.
View Article and Find Full Text PDFCotadutide is a glucagon-like peptide-1 (GLP-1) and glucagon receptor agonist that may improve kidney function in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). In this phase 2b study, patients with T2D and CKD (estimated glomerular filtration rate [eGFR] of 20 or more and under 90 mL/min per 1.73 m and urinary albumin-to-creatinine ratio [UACR] over 50 mg/g) were randomized 1:1:1:1:1 to 26 weeks' treatment with standard of care plus subcutaneous cotadutide uptitrated to 100, 300, or 600 μg, or placebo daily (double-blind), or the GLP-1 agonist semaglutide 1 mg once weekly (open-label).
View Article and Find Full Text PDFExhaustive exercise is known to induce muscle damage characterized by inflammation and oxidative stress. Although "regular" and "weekend warrior" exercise regimens have been shown to confer comparable health benefits in human studies, such as reduced risks of all-cause, cardiovascular disease (CVD), and cancer mortality, their differential impacts on muscle damage post-exhaustive exercise remain unclear. This study aimed to compare the effects of long-term, moderate-intensity (LTMI) and short-term, high-intensity (STHI) training modalities, matched for total exercise volume, on gut microbiota, short-chain fatty acids (SCFAs), and exhaustive exercise-induced muscle damage in mice, as well as to evaluate the correlation between these factors.
View Article and Find Full Text PDFFor electrochemical application in seawater or brine, continuous scaling on cathodes will form insulation layers, making it nearly impossible to run an electrochemical reaction continuously. Herein, we report our discovery that a cathode consisting of conical nanobundle arrays with hydrophobic surfaces exhibits a unique scaling-free function. The hydrophobic surfaces will be covered with microbubbles created by electrolytic water splitting, which limits scale crystals from standing only on nanotips of conical nanobundles, and the bursting of large bubbles formed by the accumulation of microbubbles will cause a violent disturbance, removing scale crystals automatically from nanotips.
View Article and Find Full Text PDFCPT Pharmacometrics Syst Pharmacol
September 2024
Cotadutide is a dual glucagon-like peptide-1 (GLP-1)/glucagon receptor agonist. Gastrointestinal adverse effects are known to be associated with GLP-1 receptor agonism and can be mitigated through tolerance development via a gradual up-titration. This analysis aimed to characterize the relationship between exposure and nausea incidence and to optimize titration schemes.
View Article and Find Full Text PDFPlant Biotechnol J
November 2024
As an essential macronutrient, phosphorus (P) is often a limiting nutrient because of its low availability and mobility in soils. Drought is a major environmental stress that reduces crop yield. How plants balance and combine P-starvation responses (PSRs) and drought resistance is unclear.
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