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Increase of intracellular Zn2+ concentration directly inhibits phospholipase Cε and suppresses inflammation and tumour formation in mice
Abstract Phospholipase Cε (PLCε) has been shown to augment inflammation and inflammation-associated carcinogenesis by inducing proinflammatory cytokine expression through activation of nuclear factor-κB (NF-κB), making it a candidate molecular target for development of anti-inflammatory and cancer-preventive agents. Aiming at developing its selective inhibitor, we carry out a high-throughput screening of 68,114 compounds by using a fluorogenic substrate and discover zinc pyrithione (ZPT) as an ε class-specific PLC inhibitor whose IC 50 value for phosphatidylinositol 4,5-bisphosphate is 7.5 µM. Further experiments show that Zn 2+ ion is the active principle of ZPT while the pyrithione moiety acts as an ionophore to raise the intracellular Zn 2+ concentration. Treatment with ZPT effectively inhibits activation of protein kinase D, nuclear entry of NF-κB and expression of proinflammatory molecules induced by lysophosphatidic acid in cultured colon epithelial cells. Moreover, administration of ZPT not only ameliorates dextran sulfate-induced inflammatory colitis but also inhibits malignant progression of intestinal tumours formed in Apc Min/+ mice. Furthermore, it displays growth-inhibitory and anti-metastatic activities toward xenografts of human colorectal cancer cells. These results support the notion that PLCε inhibitors may become promising anti-inflammatory, cancer-preventive and anti-cancer agents, and suggest that PLCε-inhibition may account for a molecular mechanism underlying the inflammation-moderating activity of zinc.
Assessment of quality of life after traumatic brain injury in adults from Armenia, Georgia, and Moldova using EQ-5D-5L
Universal efficiency boost in prethermal quantum heat engines at negative temperature
Abstract Heat engines near the adiabatic limit typically assume a working medium at thermal equilibrium. However, quantum many-body systems often showcase conservation laws that hinder thermalization, leading to prethermalization in exotic stationary phases. This work explores whether prethermalization enhances or reduces engine efficiency. We investigate Otto cycles in quantum systems with varying numbers of conserved quantities. We find that additional conservation laws reduce efficiency at positive temperatures, but enhance it in regimes of negative temperatures. Our findings stem from general thermodynamic inequalities for infinitesimal cycles, and we provide evidence for integrable models undergoing finite cycles using the theoretical framework of Generalized Hydrodynamics. The relevance of our results for quantum simulators is also discussed.
Effect of an educational intervention using the extended parallel process model on preventive lifestyle for metabolic syndrome among Iranian employees
The semantic structure of events consistently influences episodic memory recall over time in young and older adults
Abstract Remembering the past often involves constructing narratives that connect various events. Despite older adults retaining the temporal organization of events, it remains unclear whether content similarity between events influence their recall as they do in young adults. Moreover, it remains to be clarified whether such semantic influence is consistent over time. Here we adopted a naturalistic paradigm involving video-based event encoding and multiple recalls over a week to investigates how semantic relationships among events shape memory in young and older adults. Narratives describing the content of each video were transformed into a network of interconnected events based on semantic similarity. Each event was further segmented into central details (essential to the storyline), or peripheral details (contextual and perceptual information). We found that content similarity between events systematically influenced recall across testing sessions, and similarly in young and older adults. Furthermore, this benefit of the semantic structure of events predicted the amount of central but not peripheral details in participants’ narratives. Finally, repeated retrieval stabilized recall within individuals over time without promoting convergence among individuals of the same age group. Our findings highlight the need of using naturalistic stimuli to understand which forms of memory are preserved and preferred in ageing.
Meningococci drive host membrane tubulation to recruit their signaling receptors
Abstract Once passed into the bloodstream, bacterial pathogens have a limited time to interact with permissive receptors at the surface of host cells. Neisseria meningitidis has developed an extremely effective strategy allowing it to find its receptors in a few seconds. Here, we report that N. meningitidis type IV pili exploit the physical properties of host cells' plasma membranes to promote the formation of early tubular membrane structures essential for initial bacterial adhesion. These tubular structures, which form before any signaling events in host cells, concentrate and trap multiple plasma membrane-associated proteins in the vicinity of bacteria, thereby facilitating the selection, interaction and activation of specific adhesion and signaling receptors by bacterial ligands present on type IV pili. Our results define an additional paradigm for the recruitment of specific receptors by pathogenic bacteria, which depends on the physical property of bacterial pili to induce the formation of tubular plasma membrane structures enriched in integral plasma membrane receptors.
An explicit and rapid intersection algorithm of plane and NURBS surface in CNC surface machining
Optimizing the crystallinity of ZrO2 gate insulator in indium gallium zinc oxide thin-film transistors through atomic layer deposition process temperature control
Organocatalytic iminium-assisted asymmetric B(sp²)-to-B(sp³) transformation
Design of a wideband RF rectifier for enhanced wireless power transfer in biomedical implants supporting white space WiFi and LTE bands
Secure image encryption using a 4D chaotic system and Langton’s ant cellular automaton
Selective micropollutant degradation via nanoconfined core-shell heterostructures with robust resilience to water matrices
Construction of an evaluation index system for core literacy in physical education and health for Chinese college students
Qualitative study of kinesiophobia in patients with tumors after PICC catheterization
Terahertz photonic heterodyne spectral analysis with (sub-) kHz resolution and 6.5 THz frequency coverage
Abstract Spectrum analyzers and spectrometers are essential for designing sources, analyzing material properties, layer structures and fingerprinting substances. We present an ultra-wideband, continuous-wave photonic receiver with kHz-level spectral resolution in the terahertz domain for both heterodyne and homodyne detection. Employed as a spectrum analyzer front end, it records the emitted spectrum of a source under test, assessing spectral purity, spectral shape and undesired frequency components. It outperforms state-of-the-art electronic systems in terms of frequency coverage and system cost with a competitive spectral resolution and noise floor on the few aW/Hz level at room temperature. It covers the important frequencies above 1.5 THz, yet commercially inaccessible, where sources like quantum cascade lasers operate. When combined with a comb-based photonic source, we demonstrate hetero- and homodyne spectroscopy over an unprecedented frequency range from below 100 GHz to 6.5 THz and a very low noise floor. Locking the photonic system to GPS enables tracing back the measured parameters to SI units, being of key importance for metrological applications. The presented setups offer the broadest continuous-wave frequency coverage to date, combined with a sharp spectral resolution, enabling diverse applications ranging from fast non-destructive testing, astronomic high-resolution spectroscopy, to frequency-modulated RADAR.
Three distinct genetic lineages of Trichonephila clavata based on mitochondrial COI and genome-wide SNPs on the Korean Peninsula
Towards an RGB camera-based live repetition counter using auto correlation with action recognition for home rehabilitation
Isolable f-element diphosphene complexes by phosphinidene group transfer and coupling at uranium
Abstract The parent diphosphene (HPPH) molecule is of fundamental interest, but its reactive nature renders it challenging to isolate and study. Metal-stabilization is an attractive approach for studying HPPH, but molecular derivatives are limited to three complexes of p-/d-metals reflecting a scarcity of synthetic methods for rationally preparing HPPH complexes. Here, we introduce f-element HPPH complexes, adding to f-element diazenes (HNNH) that were first reported over thirty years ago. By utilizing 7λ 3 -phosphadibenzonorbornadiene and uranium(III) reagents we show how parent diphosphene, phosphinidiide, and diphosphorus motifs can all be constructed, developing synthetic approaches for this area. Computed reaction profiles reveal common, initial reaction steps that subsequently diverge depending on the ancillary ligands, radical nature of intermediates, and the 7λ 3 -phosphadibenzonorbornadiene P-substituent. Calculations demonstrate a surprising prevalence of open-shell radical intermediates, and that the redox chemistry is P-, not U-, centred. This work thus provides insights to inform future synthetic endeavours in this area.