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Chemistry (Weinheim An Der Bergstrasse,... Jul 2024A series of fluorescent carbazole-coumarins exhibiting good photoluminescence quantum yields and thermally activated delayed fluorescence (TADF) properties have been...
A series of fluorescent carbazole-coumarins exhibiting good photoluminescence quantum yields and thermally activated delayed fluorescence (TADF) properties have been designed and synthetized using computer-aided density functional theory calculations. The TADF characteristics of the carbazole-coumarins were systematically explored both in solution and in the solid state, utilizing poly(methyl methacrylate) (PMMA) as a matrix. The study revealed that the introduction of carbazole units onto the coumarin benzene ring led to compounds with thermally induced reverse intersystem crossing and delayed fluorescence. The study further demonstrated the potential utility of these compounds in practical applications by incorporating them into a Cmr-PMMA-based sensor for molecular oxygen detection. The resulting sensor exhibited promising performance, highlighting the adaptability and efficacy of the synthesized TADF-carbazole-coumarin compounds for reversible molecular oxygen sensing.
PubMed: 38949777
DOI: 10.1002/chem.202401263 -
Annals of Biomedical Engineering Jun 2024Through their contractile and synthetic capacity, vascular smooth muscle cells (VSMCs) can regulate the stiffness and resistance of the circulation. To model the...
PURPOSE
Through their contractile and synthetic capacity, vascular smooth muscle cells (VSMCs) can regulate the stiffness and resistance of the circulation. To model the contraction of blood vessels, an active stress component can be added to the (passive) Cauchy stress tensor. Different constitutive formulations have been proposed to describe this active stress component. Notably, however, measuring biomechanical behaviour of contracted blood vessels ex vivo presents several experimental challenges, which complicate the acquisition of comprehensive datasets to inform complex active stress models. In this work, we examine formulations for use with limited experimental contraction data as well as those developed to capture more comprehensive datasets.
METHODS
First, we prove analytically that a subset of constitutive active stress formulations exhibits unstable behaviours (i.e., a non-unique diameter solution for a given pressure) in certain parameter ranges, particularly for large contractile deformations. Second, using experimental literature data, we present two case studies where these formulations are used to capture the contractile response of VSMCs in the presence of (1) limited and (2) extensive contraction data.
RESULTS
We show how limited contraction data complicates selecting an appropriate active stress model for vascular applications, potentially resulting in unrealistic modelled behaviours.
CONCLUSION
Our data provide a useful reference for selecting an active stress model which balances the trade-off between accuracy and available biomechanical information. Whilst complex physiologically motivated models' superior accuracy is recommended whenever active biomechanics can be extensively characterised experimentally, a constant 2nd Piola-Kirchhoff active stress model balances well accuracy and applicability with sparse contractile data.
PubMed: 38949730
DOI: 10.1007/s10439-024-03532-x -
Journal of Neurovirology Jun 2024HIV-associated neurocognitive disorders (HAND) is hypothesized to be a result of myeloid cell-induced neuro-inflammation in the central nervous system that may be...
BACKGROUND
HIV-associated neurocognitive disorders (HAND) is hypothesized to be a result of myeloid cell-induced neuro-inflammation in the central nervous system that may be initiated in the periphery, but the contribution of peripheral T cells in HAND pathogenesis remains poorly understood.
METHODS
We assessed markers of T cell activation (HLA-DR + CD38+), immunosenescence (CD57 + CD28-), and immune-exhaustion (TIM-3, PD-1 and TIGIT) as well as monocyte subsets (classical, intermediate, and non-classical) by flow cytometry in peripheral blood derived from individuals with HIV on long-term stable anti-retroviral therapy (ART). Additionally, normalized neuropsychological (NP) composite test z-scores were obtained and regional brain volumes were assessed by magnetic resonance imaging (MRI). Relationships between proportions of immune phenotypes (of T-cells and monocytes), NP z-scores, and brain volumes were analyzed using Pearson correlations and multiple linear regression models.
RESULTS
Of N = 51 participants, 84.3% were male, 86.3% had undetectable HIV RNA < 50 copies/ml, median age was 52 [47, 57] years and median CD4 T cell count was 479 [376, 717] cells/uL. Higher CD4 T cells expressing PD-1 + and/or TIM-3 + were associated with lower executive function and working memory and higher CD8 T cells expressing PD-1 and/or TIM-3 were associated with reduced brain volumes in multiple regions (putamen, nucleus accumbens, cerebellar cortex, and subcortical gray matter). Furthermore, higher single or dual frequencies of PD-1 + and TIM-3 + expressing CD4 and CD8 T-cells correlated with higher CD16 + monocyte numbers.
CONCLUSIONS
This study reinforces evidence that T cells, particularly those with immune exhaustion phenotypes, are associated with neurocognitive impairment and brain atrophy in people living with HIV on ART. Relationships revealed between T-cell immune exhaustion and inflammatory in CD16 monocytes uncover interrelated cellular processes likely involved in the immunopathogenesis of HAND.
PubMed: 38949728
DOI: 10.1007/s13365-024-01223-w -
Antonie Van Leeuwenhoek Jul 2024Biological control is a promising approach to enhance pathogen and pest control to ensure high productivity in cash crop production. Therefore, PGPR biofertilizers are...
Biological control is a promising approach to enhance pathogen and pest control to ensure high productivity in cash crop production. Therefore, PGPR biofertilizers are very suitable for application in the cultivation of tea plants (Camellia sinensis) and tobacco, but it is rarely reported so far. In this study, production of a consortium of three strains of PGPR were applied to tobacco and tea plants. The results demonstrated that plants treated with PGPR exhibited enhanced resistance against the bacterial pathogen Pseudomonas syringae (PstDC3000). The significant effect in improving the plant's ability to resist pathogen invasion was verified through measurements of oxygen activity, bacterial colony counts, and expression levels of resistance-related genes (NPR1, PR1, JAZ1, POD etc.). Moreover, the application of PGPR in the tea plantation showed significantly reduced population occurrences of tea green leafhoppers (Empoasca onukii Matsuda), tea thrips (Thysanoptera:Thripidae), Aleurocanthus spiniferus (Quaintanca) and alleviated anthracnose disease in tea seedlings. Therefore, PGPR biofertilizers may serve as a viable biological control method to improve tobacco and tea plant yield and quality. Our findings revealed part of the mechanism by which PGPR helped improve plant biostresses resistance, enabling better application in agricultural production.
Topics: Animals; Plant Diseases; Nicotiana; Pseudomonas syringae; Pest Control, Biological; Camellia sinensis; Insecta; Thysanoptera; Disease Resistance; Plant Development; Biological Control Agents; Hemiptera
PubMed: 38949726
DOI: 10.1007/s10482-024-01975-9 -
Ecotoxicology (London, England) Jun 2024In recent years, the presence of Pharmaceutical Active Compounds (PhACs) in ecosystems has become a serious environmental problem due to their capacity to induce harmful...
In recent years, the presence of Pharmaceutical Active Compounds (PhACs) in ecosystems has become a serious environmental problem due to their capacity to induce harmful effects at extremely low concentrations in both humans and wildlife. Water treatment plants have not been designed to remove these types of compounds efficiently. Thus, the detection of these pollutants is essential to evaluate their negative impacts and is one of the emerging issues in environmental chemistry. The main objective of this study is to determine the bacterial toxicity of two PhACs (both individually and as a mixture) through the quantification of bioluminescence inhibition in the marine bacteria Aliivibrio fischeri, a commonly used method in short-term toxicity tests. In this work, Acetaminophen and Edaravone, two drugs approved by the Food and Drug Administration, have been studied. The acute toxicity of these PhACs has been tested at two exposure times (5 and 15 min) and different concentrations, by estimation of the median effective concentration (EC) for each individual compound or in combination at different concentrations. Moreover, the EC of the binary mixtures Acetaminophen/Edaravone have been forecast using two traditional predictive models, Concentration Addition and Independent Action. The results show that toxicity decreases with exposure time and depends on the concentration tested. Furthermore, a novel semi-empirical Van Laar-based model has been proposed and validated with the experimental data from this study and literature data, obtaining satisfactory estimations of the EC for binary mixtures.
PubMed: 38949723
DOI: 10.1007/s10646-024-02772-w -
Journal of Neuroimmune Pharmacology :... Jul 2024Amorfrutin B is a selective PPARγ modulator that we demonstrated to be a promising neuroprotective compound in cellular models of stroke and perinatal asphyxia....
Amorfrutin B Compromises Hypoxia/Ischemia-induced Activation of Human Microglia in a PPARγ-dependent Manner: Effects on Inflammation, Proliferation Potential, and Mitochondrial Status.
Amorfrutin B is a selective PPARγ modulator that we demonstrated to be a promising neuroprotective compound in cellular models of stroke and perinatal asphyxia. Although neuronal mechanisms of amorfrutin B-evoked neuroprotection have been identified, none of them reflects the actions of the compound on microglia, which play a pivotal role in brain response to hypoxia/ischemia. Here, we provide evidence for amorfrutin B-induced effects on human microglia subjected to hypoxia/ischemia; the compound counteracts inflammation, and influences mitochondrial status and proliferation potential in a PPARγ-dependent manner. Post-treatment with amorfrutin B decreased the IBA1 fluorescence intensity, reduced caspase-1 activity, and downregulated IL1B/IL-1β and TNFA but not IL10/IL-10 expression, which was upregulated. Amorfrutin B also stimulated PPARγ signaling, as evidenced by increased mRNA and/or protein levels of PPARγ and PGC1α. In addition, amorfrutin B reversed the hypoxia/ischemia-evoked effects on mitochondria-related parameters, such as mitochondrial membrane potential, BCL2/BCL2 expression and metabolic activity, which were correlated with diminished proliferation potential of microglia. Interestingly, the inhibitory effect of amorfrutin B on the proliferation potential and mitochondrial function of microglia is opposite to the stimulatory effect of amorfrutin B on mouse neuronal survival, as evidenced by increased neuronal viability and reduced neurodegeneration. In summary, this study showed for the first time that amorfrutin B compromises hypoxia/ischemia-induced activation of human microglia in a PPARγ-dependent manner, which involves inhibiting inflammation, normalizing mitochondrial status, and controlling proliferation potential. These data extend the protective potential of amorfrutin B in the pharmacotherapy of hypoxic/ischemic brain injury, targeting not only neurons but also activated microglia.
Topics: PPAR gamma; Humans; Microglia; Cell Proliferation; Mitochondria; Hypoxia-Ischemia, Brain; Inflammation; Cells, Cultured; Neuroprotective Agents
PubMed: 38949694
DOI: 10.1007/s11481-024-10135-9 -
Autophagy Jul 2024A growing number of studies link dysfunction of macroautophagy/autophagy to the pathogenesis of diseases such as Alzheimer disease (AD). Given the global importance of...
A growing number of studies link dysfunction of macroautophagy/autophagy to the pathogenesis of diseases such as Alzheimer disease (AD). Given the global importance of autophagy for homeostasis, how its dysfunction can lead to specific neurological changes is puzzling. To examine this further, we compared the global deactivation of autophagy in the adult mouse using the iKO with the impact of AD-associated pathogenic changes in autophagic processing of synaptic proteins. Isolated forebrain synaptosomes, rather than total homogenates, from iKO mice demonstrated accumulation of synaptic proteins, suggesting that the synapse might be a vulnerable site for protein homeostasis disruption. Moreover, the deactivation of autophagy resulted in impaired cognitive performance over time, whereas gross locomotor skills remained intact. Despite deactivation of autophagy for 6.5 weeks, changes in cognition were in the absence of cell death or synapse loss. In the symptomatic APP PSEN1 double-transgenic mouse model of AD, we found that the impairment in autophagosome maturation coupled with diminished presence of discrete synaptic proteins in autophagosomes isolated from these mice, leading to the accumulation of one of these proteins in the detergent insoluble protein fraction. This protein, SLC17A7/Vglut, also accumulated in iKO mouse synaptosomes. Taken together, we conclude that synaptic autophagy plays a role in maintaining protein homeostasis, and that while decreasing autophagy interrupts normal cognitive function, the preservation of locomotion suggests that not all circuits are affected similarly. Our data suggest that the disruption of autophagic activity in AD may have relevance for the cognitive impairment in this adult-onset neurodegenerative disease. : 2dRAWM: 2-day radial arm water maze; AD: Alzheimer disease; Aβ: amyloid-beta; AIF1/Iba1: allograft inflammatory factor 1; APP: amyloid beta precursor protein; ATG7: autophagy related 7; AV: autophagic vacuole; CCV: cargo capture value; Ctrl: control; DLG4/PSD-95: discs large MAGUK scaffold protein 4; GFAP: glial fibrillary acidic protein; GRIN2B/NMDAR2b: glutamate ionotropic receptor NMDA type subunit 2B; LTD: long-term depression; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; m/o: months-old; PNS: post-nuclear supernatant; PSEN1/PS1: presenilin 1; SHB: sucrose homogenization buffer; SLC32A1/Vgat: solute carrier family 32 member 1; SLC17A7/Vglut1: solute carrier family 17 member 7; SNAP25: synaptosome associated protein 25; SQSTM1/p62: sequestosome 1; SYN1: synapsin I; SYP: synaptophysin ; SYT1: synaptotagmin 1; Tam: tamoxifen; VAMP2: vesicle associated membrane protein 2; VCL: vinculin; wks: weeks.
PubMed: 38949671
DOI: 10.1080/15548627.2024.2368335 -
Journal of Clinical Rheumatology :... Jul 2024The help-seeking process in rheumatoid arthritis (RA) patients is challenging, and its study is limited in Latin America. The study describes the real-life journey...
INTRODUCTION
The help-seeking process in rheumatoid arthritis (RA) patients is challenging, and its study is limited in Latin America. The study describes the real-life journey before patients' incorporation into an early arthritis clinic (EAC) and its impact on baseline and 1-year cumulative disease activity levels.
PATIENTS AND METHODS
The patient's journey was assessed through a questionnaire that captured the patient's path from the first disease-related symptom to the initial assessment in the EAC. A disease activity (28 joints evaluated)-erythrocyte sedimentation rate (DAS28-ESR) score >5.1 defined a high-disease activity level. The mean of individual consecutive DAS28-ESR scores summarized cumulative DAS28-ESR. Multiple logistic regression analysis identified factors associated with a DAS28-ESR score >5.1 at the first assessment. Linear regression analysis assessed the impact of general practitioner (GP)-first consultant and time on disease-modifying antirheumatic drugs (DMARDs) on baseline and cumulative DAS28-ESR scores.
RESULTS
Through January 2023, the EAC had 241 RA patients, among whom 209 (86.7%) completed the patients' journey questionnaire (PJQ) and 176 (84.2%) at least 1 year of follow-up. A GP was the first consultant in 76.6% of the patients, and only 12.4% were prescribed DMARDs. Patients had additional evaluations with either rheumatologists (38.6%) or other specialists (31.6%), and half of them were initiated DMARDs. GP-first consultant (adjusted odds ratio: 2.314, 95% confidence interval: 1.190-4.500, p = 0.013) and time on DMARDs (adjusted odds ratio: 0.738, 95% confidence interval: 0.585-0.929, p = 0.010) were associated with baseline DAS28-ESR score >5.1. The B coefficient magnitudes for GP-first consultant and time on DMARDs to predict cumulative DAS28 progressively decreased during the first year of follow-up.
CONCLUSIONS
Patients' journey before recent-onset RA diagnosis predicts first-year disease activity levels.
PubMed: 38949663
DOI: 10.1097/RHU.0000000000002098 -
ELife Jul 2024Secreted chemokines form concentration gradients in target tissues to control migratory directions and patterns of immune cells in response to inflammatory stimulation;...
Secreted chemokines form concentration gradients in target tissues to control migratory directions and patterns of immune cells in response to inflammatory stimulation; however, how the gradients are formed is much debated. Heparan sulfate (HS) binds to chemokines and modulates their activities. In this study, we investigated the roles of HS in the gradient formation and chemoattractant activity of CCL5 that is known to bind to HS. CCL5 and heparin underwent liquid-liquid phase separation and formed gradient, which was confirmed using CCL5 immobilized on heparin-beads. The biological implication of HS in CCL5 gradient formation was established in CHO-K1 (wild-type) and CHO-677 (lacking HS) cells by Transwell assay. The effect of HS on CCL5 chemoattractant activity was further proved by Transwell assay of human peripheral blood cells. Finally, peritoneal injection of the chemokines into mice showed reduced recruitment of inflammatory cells either by mutant CCL5 (lacking heparin-binding sequence) or by addition of heparin to wild-type CCL5. Our experimental data propose that co-phase separation of CCL5 with HS establishes a specific chemokine concentration gradient to trigger directional cell migration. The results warrant further investigation on other heparin-binding chemokines and allows for a more elaborate insight into disease process and new treatment strategies.
Topics: Chemokine CCL5; Animals; Heparitin Sulfate; Humans; Cricetulus; CHO Cells; Mice; Chemotaxis; Heparin; Phase Separation
PubMed: 38949655
DOI: 10.7554/eLife.93871 -
Nanoscale Jul 2024Possessing excellent electronic properties and high chemical stability, semiconducting n-type two-dimensional (2D) tin dioxide (SnO) nanosheets have been featured in...
Possessing excellent electronic properties and high chemical stability, semiconducting n-type two-dimensional (2D) tin dioxide (SnO) nanosheets have been featured in sensing and electrocatalysis applications recently. Derived from non-layered crystal structures, 2D SnO has abundant unsaturated dangling bonds existing at the surface, providing interfacial activity. How the surface chemistry alters the electronic properties of 2D SnO nanomaterials remains unexplored. In this study, we synthesised ultra-thin 2D SnO nanosheets using a liquid metal (LM) touch printing technique and investigated experimentally and theoretically how the interactions of organic solvents composed of alkyl and hydroxyl groups with the surface of LM-derived 2D SnO modulate the electronic properties. It was found that alkane solvents can physically absorb onto the SnO surface with no impact on the material conductivity. Alcohol-based solvents on the other hand interact with the SnO surface chemical absorptions primarily, in which oxygen atoms of hydroxyl groups in the alcohols form bonds with the surface atoms of SnO. The binding stability is determined by the length and configuration of the hydrocarbon chain in alcohols. As representative long-chain alcohols, 1-octanol and 1-pentanol attach onto the SnO surface strongly, lowering the binding energy of Sn and reducing the electron transfer ability of SnO nanosheets. Consequently, the electronic properties, conductivity and electronic mobility of SnO nanosheet-based electronic devices are decreased significantly.
PubMed: 38949653
DOI: 10.1039/d4nr01841a