Excited state mechanisms in crystalline carbazole: the role of aggregation and isomeric defects

The molecule of Carbazole (Cz) is commonly used as a building block in organic materials for optoelectronic applications, acting as light-absorbing, electron donor and emitting moiety. Crystals from Cz and derivatives display ultralong phosphorescence at room temperature. However, different groups have reported inconsistent quantum efficiencies for the same compounds. In a recent experimental study by Liu et al (Nature Materials 2021, 20, 175-180), the ultralong phosphoresce properties of Cz has been associated with the presence of small fractions of isomeric impurities from commercially available Cz. In this paper, we use state-of-the-art computational approaches to investigate light-induced processes in crystalline and doped Cz. We revisited the role of aggregation and isomeric impurities on the excited state pathways and analyse the mechanisms for exciton, Dexter energy transfer and electron transport based on Marcus and Marcus-Levich-Jortner theories. Our excited state mechanisms provide a plausible interpretation for the experimental results and support the formation of charge-separated states at the defect/Cz molecular interface. These results contribute to a better understanding of the factors enhancing the excited state lifetimes in organic materials and the role of doping with organic molecules

Identification of the direct regulon of NtcA during early acclimation to nitrogen starvation in the cyanobacterium Synechocystis sp. PCC 6803

In cyanobacteria, nitrogen homeostasis is maintained by an intricate regulatory network around transcription factor NtcA. Although mechanisms controlling NtcA activity appear to be well understood, its regulon remains poorly defined. To determine the NtcA regulon during the early stages of nitrogen starvation for the model cyanobacterium Synechocystis sp. PCC 6803, we performed chromatin immunoprecipitation, followed by sequencing (ChIP-seq), in parallel with transcriptome analysis (RNA-seq). Through combining these methods, we determined 51 genes activated and 28 repressed directly by NtcA. In addition to genes associated with nitrogen and carbon metabolism, a considerable number of genes without current functional annotation were among direct targets providing a rich reservoir for further studies. The NtcA regulon also included eight non-coding RNAs, of which Ncr1071, Syr6 and NsiR7 were experimentally validated, and their putative targets were computationally predicted. Surprisingly, we found substantial NtcA binding associated with delayed expression changes indicating that NtcA can reside in a poised state controlled by other factors. Indeed, a role of PipX as modulating factor in nitrogen regulation was confirmed for selected NtcA-targets. We suggest that the indicated poised state of NtcA enables a more differentiated response to nitrogen limitation and can be advantageous in native habitats of Synechocystis.Ministerio de Economia y Competitividad (MINECO) [BFU2013-41712, BIO2016-75634]; Junta de Andalucia-European Regional Funds (FEDER) [BIO-284, P12-BIO-1119]; FCT (Fundacao para a Ciencia e a Tecnologia) [PTDC/BIA-MIC/4418/2012, IF/00881/2013, UID/BIM/04773/2013-CBMR, UID/Multi/04326/2013-CCMAR]; School of Biomedical & Healthcare Sciences, Plymouth University Peninsula Schools of Medicine and Dentistryinfo:eu-repo/semantics/publishedVersio

Editorial: Recent insights into the double role of hydrogen peroxide in plants

Reactive oxygen species (ROS) of varied types can be yielded in plants at several primary sites (such as the chloroplast, mitochondria, and peroxisomes) under normal aerobic metabolism via processes including photosynthetic and respiratory electron transport chains. However, impaired oxidant-antioxidant balance and extreme growth conditions in plants are bound to cause increases in the cellular concentrations of radical and non-radical ROS such as superoxide anions (O2•−), hydroxyl radical (OH•), singlet oxygen (1O2), and hydrogen peroxide (H2O2). On the one hand, H2O2 has no unpaired electrons and is moderately reactive. Owing to its relative stability compared to other ROS and its capacity for diffusing through aquaporins in the membranes and over more considerable distances within the cell (Bienert et al., 2007), H2O2 acts as a stress signal transducer and contributes to numerous physiological functions in plants. On the other hand, H2O2 is a relatively long-lived molecule with a half-life of 1 ms, readily crosses biological membranes, and consequently can bring oxidative consequences far from the site of its formation (Neill et al., 2002; Sharma et al., 2012; Sehar et al., 2021). The Frontiers Research Topic “Recent Insights into the Double Role of Hydrogen Peroxide in Plants” highlighted the major mechanisms underlying the dual role of H2O2 in response to different abiotic stresses in plants. This Research Topic incorporated 19 publications, including 10 original research articles, 8 reviews, and one perspective article

Stereology shows that damaged liver recovers after protein refeeding

Objective: The aim of the present study was to investigate the putative effects of a low-protein diet on the three-dimensional structure of hepatocytes and determine whether this scenario could be reversed by restoring the adequate levels of protein to the diet. Methods: Using design-based stereology, the total number and volume of hepatocytes were estimated in the liver of mice in healthy and altered (by protein malnutrition) conditions and after protein renutrition. Results: This study demonstrated a 65% decrease in the liver volume (3302 mm3 for the control for undernourished versus 1141 mm3 for the undernourished group) accompanied by a 46% reduction in the hepatocyte volume (8223 μm3 for the control for undernourished versus 4475 μm3 for the undernourished group) and a 90% increase in the total number of binucleate hepatocytes (1 549 393 for the control for undernourished versus 2 941 353 for the undernourished group). Reinstating a normoproteinic diet (12% casein) proved to be effective in restoring the size of hepatocytes, leading to an 85% increase in the total number of uninucleate hepatocytes (15 988 560 for the undernourished versus 29 600 520 for the renourished group), and partially reversed the liver atrophy. Conclusions: Awareness of these data will add to a better morphologic understanding of malnutrition-induced hepatopathies and will help clinicians improve the diagnosis and treatment of this condition in humans and in veterinary practice

Influence of opioids on immune function in patients with cancer pain: from bench to bedside

In patients with cancer, opioids are principally used for the management of acute surgical and chronic cancer-related pain. However, opioids have many non-analgesic effects, including direct and indirect effects on cancer cells and on anti-tumour immunity (NK cells, macrophages and T-cells). Direct effects on immune cells are manifested via opioid and non-opioid toll-like receptors, whereas indirect effects are manifested via the sympathetic nervous system and hypothalamic–pituitary–adrenal axis. Opioids can also decrease/alter immune cell infiltration into the tumour micro-environment. Animal models have shown that this is not a class effect, in that morphine and fentanyl suppress NK cell cytotoxicity; buprenorphine does not affect NK cell cytotoxicity, whereas tramadol increases NK cell cytotoxicity, reducing metastasis. In healthy individuals, morphine suppresses and fentanyl enhances NK cell cytotoxicity. In patients undergoing surgery, fentanyl decreased and tramadol increased NK cell cytotoxicity; clinical outcomes were not determined. Meta-analyses of opioid-sparing surgical studies report an association between improved recurrence-free and/or overall survival with regional/neuraxial anaesthesia compared with systemic opioids. In patients receiving opioids for non-surgical cancer-related pain, morphine has variable effects on immunity; clinical outcomes were not assessed. Although there is a potential association between systemic opioid administration and shorter survival in cancer patients with a prognosis of months to years, studies have not been designed to primarily assess survival, as a consequence of which causality cannot be apportioned. Pain is immunosuppressive, so analgesia is important. Opioids for cancer-related pain will continue to be recommended until definitive data on the effects of opioids on clinical outcomes in specific patient groups becomes available

Association of VAV2 and VAV3 polymorphisms with cardiovascular risk factors

Hypertension, diabetes and obesity are cardiovascular risk factors closely associated to the development of renal and cardiovascular target organ damage. VAV2 and VAV3, members of the VAV family proto-oncogenes, are guanosine nucleotide exchange factors for the Rho and Rac GTPase family, which is related with cardiovascular homeostasis. We have analyzed the relationship between the presence of VAV2 rs602990 and VAV3 rs7528153 polymorphisms with cardiovascular risk factors and target organ damage (heart, vessels and kidney) in 411 subjects. Our results show that being carrier of the T allele in VAV2 rs602990 polymorphism is associated with an increased risk of obesity, reduced levels of ankle-brachial index and diastolic blood pressure and reduced retinal artery caliber. In addition, being carrier of T allele is associated with increased risk of target organ damage in males. On the other hand, being carrier of the T allele in VAV3 rs7528153 polymorphism is associated with a decreased susceptibility of developing a pathologic state composed by the presence of hypertension, diabetes, obesity or cardiovascular damage, and with an increased risk of developing altered basal glycaemia. This is the first report showing an association between VAV2 and VAV3 polymorphisms with cardiovascular risk factors and target organ damage

Development of a patient-centred intervention to improve knowledge and understanding of antibiotic therapy in secondary care.

Background: We developed a personalised antimicrobial information module co-designed with patients. This study aimed to evaluate the potential impact of this patient-centred intervention on short-term knowledge and understanding of antimicrobial therapy in secondary care. Methods: Thirty previous patients who had received antibiotics in hospital within 12 months were recruited to co-design an intervention to promote patient engagement with infection management. Two workshops, containing five focus-groups were held. These were audio-recorded. Data were analysed using a thematic framework developed deductively based on previous work. Line-by-line coding was performed with new themes added to the framework by two researchers. This was used to inform the development of a patient information module, embedded within an electronic decision support tool (CDSS).The intervention was piloted over a four-week period at Imperial College Healthcare NHS Trust on 30 in-patients. Pre- and post-intervention questionnaires were developed and implemented to assess short term changes in patient knowledge and understanding and provide feedback on the intervention. Data were analysed using SPSS and NVIVO software. Results: Within the workshops, there was consistency in identified themes. The participants agreed upon and co-designed a personalised PDF document that could be integrated into an electronic CDSS to be used by healthcare professionals at the point-of-care. Their aim for the tool was to provide individualised practical information, signpost to reputable information sources, and enhance communication between patients and healthcare professionals.Eighteen out of thirty in-patients consented to participant in the pilot evaluation with 15/18(83%) completing the study. Median (range) age was 66(22-85) years. The majority were male (10/15;66%). Pre-intervention, patients reported desiring further information regarding their infections and antibiotic therapy, including side effects of treatment. Deployment of the intervention improved short term knowledge and understanding of individuals infections and antibiotic management with median (IQR) scores improving from 3(2-5)/13 to 10(6-11)/13. 13/15(87%) reported that they would use the intervention again. Conclusion: A personalised, patient-centred intervention improved understanding and short-term knowledge of infections and antibiotic therapy in participating patients'. Long term impact on attitudes and behaviours post discharge will be further investigated