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Metalloporphyrins based on open-shell transition metals, such as Ni(II), exhibit typically fast excited-state relaxation. In this work, we shed light into the nonradiative relaxation mechanism in a nanographene-Ni(II) porphyrin conjugate. Variable temperature transient absorption and global fit analysis are combined to produce a picture of the relaxation pathways. At room temperature, photoexcitation of the lowest π-π* transition is followed by vibrational cooling in 1.6 ps, setting a short 20 ps temporal window wherein a small fraction of relaxed singlets radiatively decay to the ground state before intersystem crossing proceeds. Following intersystem crossing, triplets relax rapidly to the ground state (S 0 ) in a few tens of picoseconds. By performing measurements at low temperature, we provide evidence for a competition between two terminal relaxation pathways from the lowest (metal-centered) triplet to the ground state: a slow ground state relaxation process proceeding in time scales beyond 1.6 ns and a faster pathway dictated by a sloped conical intersection, which is thermally accessible at room temperature from the triplet state. The overall triplet decay at a given temperature is dictated by the interplay of these two contributions. This observation bears significance in understanding the underlying fast relaxation processes in Ni-based molecules and related transition metal complexes, opening avenues for potential applications for energy harvesting and optoelectronics.

The creation of complex hollow nanostructures with precise control over size and shape represents a great challenge in supramolecular soft materials. Here, we have further developed a bioinspired methodology for the formation of aqueous nanotubes of well-defined dimensions and pore coating through the self-assembly of amphiphiles that are chemically programmed with complementary nucleobases. These nanotubes are endowed with a hydrophobic lumen, whose diameter can be expanded as a function of the monomer length, in which apolar dyes can be efficiently encapsulated., (© 2024 The Author(s). Chemistry - A European Journal published by Wiley-VCH GmbH.)

Objective: Life expectancy and obesity prevalence are increasing worldwide, leading to an increase in the prevalence of cardiovascular disease. High-density lipoprotein (HDL) functionality and immunosenescence play key roles in cardiovascular disease, longevity, and quality of aging. Both molecular hallmarks of aging are impacted by obesity and metabolic syndrome and can be modulated by lifestyle. We aimed to evaluate the effect of a lifestyle intervention focused on an energy-reduced Mediterranean diet (erMedDiet), physical activity (PA), and behavioral support on HDL cholesterol efflux capacity (CEC) and immunosenescence., Method: CEC and immunosenescent T cells were determined in 60 participants from the control group (CG) and 56 from the intervention group (IG) of the PREDIMED-Plus trial at baseline and after 1 and 3 years of follow-up. PREDIMED-Plus is a randomized, controlled, parallel-group trial with an IG of erMedDiet, PA promotion, and behavioral support for weight loss and a CG of usual primary care advice. The sample included 116 volunteers from the PREDIMED-Plus-IMDEA subsample of the PREDIMED-Plus trial. Men aged 55 to 75 years and women aged 60 to 75 years with a body mass index between 27 and 40 kg/m 2 and metabolic syndrome were included., Results: Participants within the IG had significantly improved CEC (2.42% and 10.69% after 1 and 3 years of follow-up) and a decreased in senescent T cell profile (-3.32% ± 12.54% and -6.74% ± 11.2%, p  < 0.001, after 1 and 3 years of follow-up). Baseline obesity status impacted the response to the intervention., Conclusions: A weight loss intervention program with erMedDiet and PA ameliorated senescence markers.

This review aims to provide an overview of the progress in protein-based artificial photosystem design and their potential to uncover the underlying principles governing light-harvesting in photosynthesis. While significant advances have been made in this area, a gap persists in reviewing these advances. This review provides a perspective of the field, pinpointing knowledge gaps and unresolved challenges that warrant further inquiry. In particular, it delves into the key considerations when designing photosystems based on the chromophore and protein scaffold characteristics, presents the established strategies for artificial photosystems engineering with their advantages and disadvantages, and underscores the recent breakthroughs in understanding the molecular mechanisms governing light-harvesting, charge separation, and the role of the protein motions in the chromophore's excited state relaxation. By disseminating this knowledge, this article provides a foundational resource for defining the field of bio-hybrid photosystems and aims to inspire the continued exploration of artificial photosystems using protein design., (© 2024 The Protein Society.)

The peripherical protons of the dye molecule hypericin can undergo structural interconversion (tautomerization) between different isomers separated by a low energy barrier with rates that depends sensitively on the interaction with local chemical environment defined by the nature of host material. We investigate the deuterium (D) isotope effect of hypericin tautomerism at the single-molecule level to avoid ensemble averaging in different polymer matrices by a combined spectroscopic and computational approach. In the 'innocent' PMMA matrix only intramolecular isotope effects on the internal conversion channel and tautomerization are observed; while PVA specifically interacts with the probe via H- and D-bonding. This establishes a single molecular picture on intra- and intermolecular nano-environment effects to control chromophore photophysics and -chemistry., (© 2024 The Authors. ChemPhysChem published by Wiley-VCH GmbH.)

Current research on organic light emitters which utilize multiple resonance-induced thermally activated delayed fluorescence (MR-TADF) materials is gaining significant interest because of the materials' ability to efficiently generate color-pure blue emission. However, the underlying reasons for high color purity remain unclear. It is shown here that these emitters share a common electronic basis, which is deduced from resonance structure considerations following Clar's rule, and which is termed as "poly-heteroaromatic omni-delocalization" (PHOD). The simple and clear design rules derived from the PHOD concept allow extending the known chemical space by new structural motifs. Based on PHOD, a set of novel high-efficiency color-pure emitters with brilliant deep-blue hue is specifically designed., (© 2024 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.)

The absorption and emission spectral shapes of a flexible organic probe, the distyrylbenzene (DSB) dye, are simulated accounting for the effect of different environments of increasing complexity, ranging from a homogeneous, low-molecular- weight solvent, to a long-chain alkane, and, eventually, a channel-forming organic matrix. Each embedding is treated explicitly, adopting a mixed quantum-classical approach, the Adiabatic Molecular Dynamics - generalized vertical Hessian (Ad-MD|gVH) model, which allows a direct simulation of the environment-induced constraining effects on the vibronic spectral shapes. In such a theoretical framework, the stiff modes of the dye are described at a quantum level within the harmonic approximation, including Duschinsky mixing effects, while flexible degrees of freedom of the solute (e. g. torsions) and those of the solvent are treated classically by means of molecular dynamics sampling. Such a setup is shown to reproduce the distinct effects exerted by the different environments in varied thermodynamic conditions. Besides allowing for a first-principles rationale on the supramolecular mechanism leading to the experimental spectral features, this result represents the first successful application of the Ad-MD|gVH method to complex embeddings and supports its potential application to other heterogeneous environments, such as for instance, pigment-protein complexes or organic dyes adsorbed into metal-organic frameworks., (© 2024 Wiley-VCH GmbH.)

Flexible optoelectronics is the need of the hour as the market moves toward wearable and conformable devices. Crystalline π-conjugated materials offer high performance as active materials compared to their amorphous counterpart, but they are typically brittle. This poses a significant challenge that needs to be overcome to unfold their potential in optoelectronic devices. Unveiling the molecular packing topology and identifying interaction descriptors that can accommodate strain offers essential guiding principles for developing conjugated materials as active components in flexible optoelectronics. The molecular packing and interaction topology of eight crystal systems of dicyano-distyrylbenzene derivatives are investigated. Face-to-face π-stacks in an inclined orientation relative to the bending surface can accommodate expansion and compression with minimal molecular motion from their equilibrium positions. This configuration exhibits good compliance towards mechanical strain, while a similar structure with a criss-cross arrangement capable of distributing applied strain equally in opposite directions enhances the flexibility. Molecular arrangements that cannot reversibly undergo expansion and compression exhibit brittleness. In the isometric CT crystals, the disproportionate strength of the interactions along the bending plane and orthogonal directions makes these materials sustain a moderate bending strain. These results provide an updated explanation for the elastic bending in semiconducting π-conjugated crystals., (© 2024 Wiley-VCH GmbH.)

Objective: To estimate the prevalence of epilepsy and febrile seizures and their association with genotype, i.e., 15q11-q13 deletions, uniparental chromosome 15 disomy (UPD) and other mutations, in the population with Prader-Willi syndrome (PWS)., Methods: A systematic search of Medline, Scopus, Web of Science and the Cochrane Library was conducted. Studies estimating the prevalence of seizures, epilepsy and febrile seizures in the PWS population were included. Meta-analyses of the prevalence of epilepsy and febrile seizures and their association with genotype using the prevalence ratio (PR) were performed., Results: Fifteen studies were included. The prevalence of epilepsy was 0.11 (0.07, 0.15), similar to the prevalence of febrile seizures, with a prevalence of 0.09 (0.05, 0.13). The comparison "deletion vs. UPD" had a PR of 2.03 (0.90, 4.57) and 3.76 (1.54, 9.18) for epilepsy and febrile seizures., Conclusions: The prevalence of seizure disorders in PWS is higher than in the general population. In addition, deletions in 15q11-q13 may be associated with a higher risk of seizure disorders. Therefore, active screening for seizure disorders in PWS should improve the lives of these people. In addition, genotype could be used to stratify risk, even for epilepsy, although more studies or larger sample sizes are needed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In developing an organic light-emitting diode (OLED) panel for a foldable smartphone (specifically, a color filter on encapsulation) aimed at reducing power consumption, the use of a new optically clear adhesive (OCA) that blocks UV light was crucial. However, the incorporation of a UV-blocking agent within the OCA presented a challenge, as it restricted the traditional UV-curing methods commonly used in the manufacturing process. Although a visible-light curing technique for producing UV-blocking OCA was proposed, its slow curing speed posed a barrier to commercialization. Our study introduces a highly efficient photo-initiating system (PIS) for the rapid production of UV-blocking OCAs utilizing visible light. We have carefully selected the photocatalyst (PC) to minimize electron and energy transfer to UV-blocking agents and have chosen co-initiators that allow for faster electron transfer and more rapid PC regeneration compared to previously established amine-based co-initiators. This advancement enabled a tenfold increase in the production speed of UV-blocking OCAs, while maintaining their essential protective, transparent, and flexible properties. When applied to OLED devices, this OCA demonstrated UV protection, suggesting its potential for broader application in the safeguarding of various smart devices., (© 2024. The Author(s).)

Background : Arterial stiffness and atherosclerosis are known risk factors for cardiovascular morbidity and mortality. Vegetarian diets have been associated with cardiovascular benefits, including improvements in metabolic parameters. However, the impact of a vegetarian diet on cardiovascular parameters, specifically arterial stiffness and atherosclerosis, in healthy individuals remains unclear. Thus, this study aims to analyze differences in arterial stiffness and atherosclerosis between vegetarian and omnivorous diets in healthy subjects. Methods : A systematic review and meta-analysis were conducted following established guidelines. PubMed, Scopus, Web of Science, and Cochrane Library databases were searched for studies examining the association between vegetarian and omnivorous diets with arterial stiffness and atherosclerosis. Cross-sectional studies reporting carotid to femoral pulse wave velocity (cf-PWv) as a measure of arterial stiffness and carotid intima media thickness (c-IMT) as a measure of atherosclerosis were included. Data were synthesized using random effects models, and sensitivity analyses, meta-regressions, and assessment of publication bias were performed. Results : Ten studies were included in the systematic review, and seven studies were included in the meta-analysis. The pooled analysis demonstrated that individuals following a vegetarian diet had differences in the levels of arterial stiffness (cf-PWv) compared to those following an omnivorous diet (MD: -0.43 m s -1 ; 95% CI: -0.63, -0.23). Similarly, atherosclerosis (c-IMT) was found to be different in individuals adhering to a vegetarian dietary pattern (MD = -29.86 mm; 95% CI: -58.41, -1.32). Conclusions : Our findings suggest that a vegetarian diet is associated with improved arterial stiffness and reduced atherosclerosis in healthy individuals. These results support the inclusion of a well-balanced vegetarian dietary pattern in the prevention and management of cardiovascular diseases. However, further research is needed to explore the effects of a vegetarian diet on arterial health in diverse populations and to assess long-term cardiovascular outcomes.

Non-alcoholic steatohepatitis (NASH) is one of the fastest growing liver diseases worldwide, and oxidative stress is one of NASH main key drivers. Nicotinamide adenine dinucleotide phosphate (NADPH) is the ultimate donor of reductive power to a number of antioxidant defences. Here, we explored the potential of increasing NADPH levels to prevent NASH progression. We used nicotinamide riboside (NR) supplementation or a G6PD-tg mouse line harbouring an additional copy of the human G6PD gene. In a NASH mouse model induced by feeding mice a methionine-choline deficient (MCD) diet for three weeks, both tools increased the hepatic levels of NADPH and ameliorated the NASH phenotype induced by the MCD intervention, but only in female mice. Boosting NADPH levels in females increased the liver expression of the antioxidant genes Gsta3, Sod1 and Txnrd1 in NR-treated mice, or of Gsr for G6PD-tg mice. Both strategies significantly reduced hepatic lipid peroxidation. NR-treated female mice showed a reduction of steatosis accompanied by a drop of the hepatic triglyceride levels, that was not observed in G6PD-tg mice. NR-treated mice tended to reduce their lobular inflammation, showed a reduction of the NK cell population and diminished transcription of the damage marker Lcn2. G6PD-tg female mice exhibited a reduction of their lobular inflammation and hepatocyte ballooning induced by the MCD diet, that was related to a reduction of the monocyte-derived macrophage population and the Tnfa, Ccl2 and Lcn2 gene expression. As conclusion, boosting hepatic NADPH levels attenuated the oxidative lipid damage and the exhausted antioxidant gene expression specifically in female mice in two different models of NASH, preventing the progression of the inflammatory process and hepatic injury., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Quantifying the dynamics of normal modes and how they interact with other excitations is of central importance in condensed matter. Spin-lattice coupling is relevant to several sub-fields of condensed matter physics; examples include spintronics, high-T c superconductivity, and topological materials. However, experimental approaches that can directly measure it are rare and incomplete. Here we use time-resolved X-ray diffraction to directly access the ultrafast motion of atoms and spins following the coherent excitation of an electromagnon in a multiferroic hexaferrite. One striking outcome is the different phase shifts relative to the driving field of the two different components. This phase shift provides insight into the excitation process of such a coupled mode. This direct observation of combined lattice and magnetization dynamics paves the way to access the mode-selective spin-lattice coupling strength, which remains a missing fundamental parameter for ultrafast control of magnetism and is relevant to a wide variety of materials., (© 2023. The Author(s).)

The complex photokinetics of donor-acceptor-donor triads with varying flexible spacer lengths (n = 4-10 carbon atoms) are investigated in liquid and solid solution, as well as in crystals, by steady-state and transient fluorescence spectroscopy combined with computational studies. For the short spacer (n = 4) in a liquid solution, dynamic charge-transfer (CT) state formation with subsequent, efficient exciplex emission is observed, effectively competing with quenching through electron transfer (eT) via a radical ion pair. In a solid solution, a fluorescent CT static complex is formed upon freezing for all spacer lengths. This allows the observations of a former seminal report on stimuli-responsive high-contrast fluorescence on/off switching in films of the triads to be reassigned (Adv. Mater. 2012, 24, 5487), now providing a holistic picture on varying spacer length. In fact, external stimuli of the film by modulating the geometry of the CT complex, which results in on/off fluorescence switching (for n > 4) or in a change of the emission color (n = 4). The work thus demonstrates how in-depth analysis of complex photophysics can be put to practical use in materials science., (© 2023 Wiley-VCH GmbH.)

In the United States (US), new firefighters' fitness and health behaviors deteriorate rapidly after fire academy graduation. Over the long-term, this increases their risks for chronic diseases. This study protocol describes the proposed usability testing and pilot study of a newly designed and developed healthy lifestyle smartphone app, "Surviving & Thriving", tailored towards young US firefighters. "Surviving & Thriving" will provide interactive educational content on four lifestyle factors; nutrition, sleep, physical activity, and resilience, and include a personalized journey, habit tracker, and elements of gamification to promote engagement and long-term healthy behavior change. The first phase of the app development entails alpha testing by the research team and pre-beta testing by a fire service expert panel which will help refine the app into a pre-consumer version. Upon completion of the full app prototype, beta 'usability' testing will be conducted among new fire academy graduates from two New England fire academies to collect qualitative and quantitative feedback via focus groups and satisfaction surveys, respectively. A last phase of piloting the app will evaluate the app's efficacy at maintaining/improving healthy lifestyle behaviors, mental health metrics, and physical fitness metrics. We will also evaluate whether firefighters' perceived "health cultures" scores (ratings of each fire station's/fire department's environments as to encouraging/discouraging healthy behaviors) modify the changes in health metrics after utilizing the app for three to six months. This novel user-friendly app seeks to help new firefighters maintain/improve their health and fitness more effectively, reducing their risk of lifestyle-related chronic disease. Firefighters who can establish healthy habits early in their careers are more likely to sustain them throughout their lives., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hershey, Bouziani, Chen, Lidoriki, Hadkhale, Huang, Filippou, López-Gil, Gribble, Lan, Sotos-Prieto and Kales.)

Porphyrins, a type of heterocyclic aromatic compounds consisting of tetrapyrroles connected by four substituted methine groups, are appealing building blocks for solar energy applications. However, their photosensitization capability is limited by their large optical energy gap, which results in a mismatch in absorption toward efficient harvesting of the solar spectrum. Porphyrin π-extension by edge-fusing with nanographenes can be employed for narrowing their optical energy gap from 2.35 to 1.08 eV, enabling the development of porphyrin-based panchromatic dyes with an optimized energy onset for solar energy conversion in dye-sensitized solar fuel and solar cell configurations. By combining time-dependent density functional theory with fs transient absorption spectroscopy, it is found that the primary singlets, which are delocalized across the entire aromatic part, are transferred into metal centred triplets in only 1.2 ps; and subsequently, relax toward ligand-delocalized triplets. This observation implies that the decoration of the porphyrin moiety with nanographenes, while having a large impact on the absorption onset of the novel dye, promotes the formation of a ligand-centred lowest triplet state of large spatial extension, potentially interesting for boosting interactions with electron scavengers. These results reveal a design strategy for broadening the applicability of porphyrin-based dyes in optoelectronics., (© 2023 Wiley-VCH GmbH.)

Background & Aims: To date, no specific drugs are available for non-alcoholic fatty liver disease (NAFLD), though the effect of fish oil supplementation on improving fibrosis in patients with NAFLD has been evaluated. N-3 polyunsaturated fatty acids (n-3 PUFA) may modulate the concentration of microRNAs (miRNAs) and fibroblast growth factor (FGF)-21, which have been identified as non-invasive markers of liver fibrosis. The present study aims to evaluate whether n-3 PUFA supplementation can modulate miRNA-122 and FGF-21 and improve liver fibrosis and steatosis, measured by transient hepatic elastography (THE), in individuals with NAFLD., Methods: A randomized, double-blind, placebo-controlled clinical trial will be conducted to evaluate the effect of 4 g/day supplementation of fish oil (2100 mg EPA and 924 mg DHA) in patients with NAFLD over a 6-month period. Fifty-two patients aged >19 years will be randomly assigned to either a placebo (olive oil) or treatment (fish oil) group. Anthropometric data, food intake, physical activity, body composition, resting energy expenditure (evaluated using indirect calorimetry), liver enzymes, platelets, lipids and glucose profile, inflammatory markers (such as C-reactive protein, neutrophil/lymphocyte, platelet/lymphocyte, and monocyte/lymphocyte ratios), miRNA-122 and FGF-21 concentration, and incorporation of fatty acids into the erythrocyte membrane (analyzed using gas chromatography) as well as the degree of liver fibrosis and steatosis assessed using THE (Fibroscan® Touch 502, Paris, France) and liver biomarkers Steato-Brazilian Longitudinal Study of Adult Health, Fatty Liver Index, NAFLD Fibrosis Score, Fibrosis-4 score, and FibroScan-AST score will be evaluated at the beginning and end of the treatment. Continuous variables with normal distribution will be compared between placebo and intervention groups using Student's T test for independent samples; continuous non-parametric variables will be compared using Dunn or Mann-Whitney test. Associations between categorical variables will be analyzed using the chi-square test, and within-group differences will be evaluated using the Wilcoxon signed-ranks test. The criterion for determining significance will be set at 5%., Conclusion: The present study protocol will investigate the supplementation of EPA-rich fish oil as an alternative treatment for NAFLD and its feasibility in affecting the concentration of miRNA-122 and FGF-21 markers. Its findings will offer valuable contributions to the literature., Registration: ReBEC number RBR-8dp876., Competing Interests: Declaration of conflict of interest The authors have no conflicts of interest to declare., (Copyright © 2023 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

MicroRNAs (miRNAs) regulate gene expression and might resist adverse physicochemical conditions, which makes them potential biomarkers. They are being investigated as biomarkers of dairy production systems, based on the variations in their levels in raw milk depending on animal diet and management. Whether miRNA levels can serve as biomarkers for dairy products remains unclear, since technological or culinary treatments, such as fermentation, may alter their levels. Here, 10 cow dairy farms were sampled in Asturias (north-west Spain) and milk samples were subjected to microwave heating or used to produce yogurt or cheese. Total RNA was isolated from raw milk and three derived products, and levels of seven miRNAs, selected based on previous studies as possible milk production system biomarkers, were assessed by RT-qPCR. The treatments decreased levels of all miRNAs to some extent. These results also imply that cheesemaking increases the concentration of miRNAs in this product; raw milk and cheese supposedly may provide similar concentrations of miRNAs, higher than those of yogurt and microwaved milk. They also indicate that the content of certain miRNAs in raw milk cannot necessarily be extrapolated to other dairy products.

A new series of donor-acceptor-donor (D-A-D) structures derived from arylethynyl 1 H -benzo[ d ]imidazole was synthesized and processed into single crystals with the goal of testing such crystals' ability to act as optical waveguides. Some crystals displayed luminescence in the 550-600 nm range and optical waveguiding behavior with optical loss coefficients around 10 -2 dB/μm, which indicated a notable light transport. The crystalline structure, confirmed by X-ray diffraction, contains internal channels that are important for light propagation, as we previously reported. The combination of a 1D assembly, a single crystal structure, and notable light emission properties with low losses from self-absorption made 1 H -benzo[ d ]imidazole derivatives appealing compounds for optical waveguide applications.

Reversible and sub-lethal stresses to the mitochondria elicit a program of compensatory responses that ultimately improve mitochondrial function, a conserved anti-aging mechanism termed mitohormesis. Here, we show that harmol, a member of the beta-carbolines family with anti-depressant properties, improves mitochondrial function and metabolic parameters, and extends healthspan. Treatment with harmol induces a transient mitochondrial depolarization, a strong mitophagy response, and the AMPK compensatory pathway both in cultured C2C12 myotubes and in male mouse liver, brown adipose tissue and muscle, even though harmol crosses poorly the blood-brain barrier. Mechanistically, simultaneous modulation of the targets of harmol monoamine-oxidase B and GABA-A receptor reproduces harmol-induced mitochondrial improvements. Diet-induced pre-diabetic male mice improve their glucose tolerance, liver steatosis and insulin sensitivity after treatment with harmol. Harmol or a combination of monoamine oxidase B and GABA-A receptor modulators extend the lifespan of hermaphrodite Caenorhabditis elegans or female Drosophila melanogaster. Finally, two-year-old male and female mice treated with harmol exhibit delayed frailty onset with improved glycemia, exercise performance and strength. Our results reveal that peripheral targeting of monoamine oxidase B and GABA-A receptor, common antidepressant targets, extends healthspan through mitohormesis., (© 2023. The Author(s).)

Luminescent metal-organic frameworks are an emerging class of optical sensors, able to capture and detect toxic gases. Herein, we report the incorporation of synergistic binding sites in MOF-808 through post-synthetic modification with copper for optical sensing of NO 2 at remarkably low concentrations. Computational modelling and advanced synchrotron characterization tools are applied to elucidate the atomic structure of the copper sites. The excellent performance of Cu-MOF-808 is explained by the synergistic effect between the hydroxo/aquo-terminated Zr 6 O 8 clusters and the copper-hydroxo single sites, where NO 2 is adsorbed through combined dispersive- and metal-bonding interactions., (© 2023. The Author(s).)

Perylene bisimide (PBI) dyes are known as red, maroon and black pigments, whose colors depend on the close π-π stacking arrangement. However, contrary to the luminescent monomers, deep-red and black PBI pigments are commonly non- or only weakly fluorescent due to (multiple) quenching pathways. Here, we introduce N-alkoxybenzyl substituted PBIs that contain close π stacking arrangement (exhibiting d π-π ≈ 3.5 Å, and longitudinal and transversal displacements of 3.1 Å and 1.3 Å); however, they afford deep-red emitters with solid-state fluorescence quantum yields (Φ F ) of up to 60%. Systematic photophysical and computational studies in solution and in the solid state reveal a sensitive interconversion of the PBI-centred locally excited state and a charge transfer state, which depends on the dihedral angle (θ) between the benzyl and alkoxy groups. This effectively controls the emission process, and enables high Φ F by circumventing the common quenching pathways commonly observed for perylene black analogues., (© 2023. The Author(s).)

Mitochondrial epitranscriptomics refers to the modifications occurring in all the different RNA types of mitochondria. Although the number of mitochondrial RNA modifications is less than those in cytoplasm, substantial evidence indicates that they play a critical role in accurate protein synthesis. Recent evidence supported those modifications in mitochondrial RNAs also have crucial implications in mitochondrial-related diseases. In the light of current knowledge about the involvement, the association between mitochondrial RNA modifications and diseases arises from studies focusing on mutations in both mitochondrial and nuclear DNA genes encoding enzymes involved in such modifications. Here, we review the current evidence available for mitochondrial RNA modifications and their role in metabolic disorders, and we also explore the possibility of using them as promising targets for prevention and early detection. Finally, we discuss future directions of mitochondrial epitranscriptomics in these metabolic alterations, and how these RNA modifications may offer a new diagnostic and theragnostic avenue for preventive purposes. This article is categorized under: RNA Processing > RNA Editing and Modification., (© 2022 The Authors. WIREs RNA published by Wiley Periodicals LLC.)

The enormous societal impact of the ongoing COVID-19 pandemic has been particularly harsh for some social groups, such as the elderly. Recently, it has been suggested that senescent cells could play a central role in pathogenesis by exacerbating the pro-inflammatory immune response against SARS-CoV-2. Therefore, the selective clearance of senescent cells by senolytic drugs may be useful as a therapy to ameliorate the symptoms of COVID-19 in some cases. Using the established COVID-19 murine model K18-hACE2, we demonstrated that a combination of the senolytics dasatinib and quercetin (D/Q) significantly reduced SARS-CoV-2-related mortality, delayed its onset, and reduced the number of other clinical symptoms. The increase in senescent markers that we detected in the lungs in response to SARS-CoV-2 may be related to the post-COVID-19 sequelae described to date. These results place senescent cells as central targets for the treatment of COVID-19, and make D/Q a new and promising therapeutic tool., (© 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Cyanoarene-based photocatalysts (PCs) have attracted significant interest owing to their superior catalytic performance for radical anion mediated photoredox catalysis. However, the factors affecting the formation and degradation of cyanoarene-based PC radical anion (PC •‒ ) are still insufficiently understood. Herein, we therefore investigate the formation and degradation of cyanoarene-based PC •‒ under widely-used photoredox-mediated reaction conditions. By screening various cyanoarene-based PCs, we elucidate strategies to efficiently generate PC •‒ with adequate excited-state reduction potentials (E red * ) via supra-efficient generation of long-lived triplet excited states (T 1 ). To thoroughly investigate the behavior of PC •‒ in actual photoredox-mediated reactions, a reductive dehalogenation is carried out as a model reaction and identified the dominant photodegradation pathways of the PC •‒ . Dehalogenation and photodegradation of PC •‒ are coexistent depending on the rate of electron transfer (ET) to the substrate and the photodegradation strongly depends on the electronic and steric properties of the PCs. Based on the understanding of both the formation and photodegradation of PC •‒ allows for the highly efficient photoredox catalyzed dehalogenation of aryl/alkyl halides at a PC loading as low as 0.001 mol% with a high oxygen tolerance. The present work provides new insights into the reactions of cyanoarene-based PC •‒ allows for the highly efficient photoredox catalyzed dehalogenation of aryl/alkyl halides at a PC loading as low as 0.001 mol% with a high oxygen tolerance. The present work provides new insights into the reactions of cyanoarene-based PC •‒ in photoredox-mediated reactions., (© 2023. The Author(s).)

The Mediterranean diet (MD) is one of the healthiest ones and is associated with a lower incidence of cardiovascular and cerebrovascular diseases as well as cancer. Extra virgin olive oil (EVOO) is probably the most idiosyncratic component of this diet. EVOO has been attributed with many healthful effects, which may be due to its phenolic components, e.g. including hydroxytyrosol (HT). Recent studies suggest that EVOO and HT have molecular targets in human tissues and modulate epigenetic mechanisms. DNA methylation is one of the most studied epigenetic mechanisms and consists of the addition of a methyl group to the cytosines of the DNA chain. Given the purported health effects of EVOO (poly)phenols, we analyzed the changes induced by HT in DNA methylation, in a colorectal cancer cell line. Caco-2 cells were treated with HT for one week or with the demethylating agent 5'-azacytidine for 48 h. Global DNA methylation was assessed by ELISA. DNA bisulfitation was performed and Infinium Methylation EPIC BeadChips were used to analyze the specific methylation of CpG sites. We show an increase in global DNA methylation in Caco-2 cells after HT treatment, with a total of 32,141 differentially methylated (CpGs DMCpGs). Interestingly, our analyses revealed the endothelin receptor type A gene (EDNRA) as a possible molecular target of HT. In summary, we demonstrate that cellular supplementation with HT results in a specific methylome map and propose a potential gene target for HT., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest associated with this work., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Obesity is characterized by adipose tissue dysregulation and predisposes individuals to insulin resistance and type 2 diabetes. At the molecular level, adipocyte dysfunction has been linked to obesity-triggered oxidative stress and protein carbonylation, considering protein carbonylation as a link between oxidative stress and metabolic dysfunction. The identification of specific carbonylated proteins in adipose tissue could provide novel biomarkers of oxidative damage related to metabolic status (i.e prediabetes). Thus, we aimed at characterizing the subcutaneous and omental human adipose tissue carbonylome in obesity-associated insulin resistance., Methods: 2D-PAGE was used to identify carbonylated proteins, and clinical correlations studies and molecular biology approaches including intracellular trafficking, reactive oxygen species assay, and iron content were performed using in vitro models of insulin resistance., Results: The carbonylome of human adipose tissue included common (serotransferrin, vimentin, actin, and annexin A2) and depot-specific (carbonic anhydrase and α-crystallin B in the subcutaneous depot; and α-1-antitrypsin and tubulin in the omental depot) differences that point out the complexity of oxidative stress at the metabolic level, highlighting changes in carbonylated transferrin expression. Posterior studies using in vitro prediabetic model evidence alteration in transferrin receptor translocation, linked to the prediabetic environment. Finally, ligand-receptor molecular docking studies showed a reduced affinity for carbonylated transferrin binding to its receptor compared to wild-type transferrin, emphasizing the role of transferrin carbonylation in the link between oxidative stress and metabolic dysfunction., Conclusions: The adipose tissue carbonylome contributes to understanding the molecular mechanism driving adipocyte dysfunction and identifies possible adipose tissue carbonylated targets in obesity-associated insulin resistance.

Background: Online health data collection has gained a reputation over the last years to record and process information about health issues for implementing digital health., Objective: The research aim was to appraise two online methods (open and rewarded) to collect information about HRQoL and nutritional well-being and to compare the results between both surveyed populations., Methods: This cross-sectional study is framed on the NUTRiMDEA project. Online data through two different web-based methods (open survey and rewarded survey) were retrieved to assemble data related to sociodemographic, lifestyle (diet, physical activity and sleep patterns) and general health aspects, as well as HRQoL by an evidence-based form such as the SF-12 questionnaire, the IPAQ survey, and MEDAS-14, participants were adults (>18 years old)., Results: Overall, 17,332 participants responded to the open survey (OS, n  = 11,883) or the rewarded survey (RS, n  = 5449). About 65.1% of the participants were female, while the mean age was in the range of 40-70 years. There were significant differences ( p  < 0.05) between surveyed populations in sociodemographic, lifestyle (diet and physical activity), health and HRQoL data., Conclusions: This investigation implemented an evidence-based online questionnaire that collected demographic, lifestyle factors, phenotypic and health-related aspects as well as compared differential outcomes in HRQoL and nutritional/lifestyle well-being depending on the online mode data collection. Findings demonstrated dissimilarities in most aspects of health, HRQoL, dietary intake and physical activity records between both populations. Overall, OS sample was characterized as a healthier population with superior lifestyle habits than RS participants., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Dietary components can induce epigenetic changes through DNA methylation, histone modification, and regulation of microRNAs (miRNAs). Studies of diet-induced epigenetic regulation can inform anticipatory trials and fine-tune public health guidelines. We systematically reviewed data on the effect of extra virgin olive oil (EVOO) and its phenolic compounds (OOPCs) on the epigenetic landscape. We conducted a literature search using PubMed, Scopus, and Web of Science databases and scrutinized published evidence. After applying selection criteria (e.g., inclusion of in vitro, animal, or human studies supplemented with EVOO or its OOPCs), we thoroughly reviewed 51 articles, and the quality assessment was performed using the revised Cochrane risk of bias tool. The results show that both EVOO and its OOPCs can promote epigenetic changes capable of regulating the expression of genes and molecular targets involved in different metabolic processes. For example, oleuropein (OL) may be an epigenetic regulator in cancer, and hydroxytyrosol (HT) modulates the expression of miRNAs involved in the development of cancer, cardiovascular, and neurodegenerative diseases. We conclude that EVOO and its OOPCs can regulate gene expression by modifying epigenetic mechanisms that impact human pathophysiology. A full elucidation of the epigenetic effects of EVOO and its OOPCs may contribute to developing different pharma-nutritional strategies that exploit them as epigenetic agents. This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) as CRD42022320316., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Fasting exerts beneficial effects in mice and humans, including protection from chemotherapy toxicity. To explore the involved mechanisms, we collect blood from humans and mice before and after 36 or 24 hours of fasting, respectively, and measure lipid composition of erythrocyte membranes, circulating micro RNAs (miRNAs), and RNA expression at peripheral blood mononuclear cells (PBMCs). Fasting coordinately affects the proportion of polyunsaturated versus saturated and monounsaturated fatty acids at the erythrocyte membrane; and reduces the expression of insulin signaling-related genes in PBMCs. When fasted for 24 hours before and 24 hours after administration of oxaliplatin or doxorubicin, mice show a strong protection from toxicity in several tissues. Erythrocyte membrane lipids and PBMC gene expression define two separate groups of individuals that accurately predict a differential protection from chemotherapy toxicity, with important clinical implications. Our results reveal a mechanism of fasting associated with lipid homeostasis, and provide biomarkers of fasting to predict fasting-mediated protection from chemotherapy toxicity., (© 2022. The Author(s).)

Excited-state absorption (ESA) spectra of π-conjugated compounds are frequently calculated by (quadratic response) time-dependent density functional theory, (QR) TD-DFT, often giving a reasonable representation of the experimental results despite the (known) incomplete electronic description. To investigate whether this is inherent to the method, we calculate here the ESA spectra of small-to-medium-sized oligophenylenevinylenes ( n PV) and oligothiophenes ( n T) using QR TD-DFT as well as CASPT2 based on CASSCF geometries. CASPT2 gives indeed a reliable, theoretically correct description of the ESA features for all compounds; the computational effort can be reduced without significant loss of accuracy using TD-DFT geometries. QR TD-DFT, based on BHandHLYP and CAM-/B3LYP functionals, fails on short n but provides a reasonable description for spectral positions of Ts but provides a reasonable description for spectral positions of n PVs and long n , on the other side, adapt approximately the MO scheme for alternant hydrocarbons just like in Ts , while contributions by two triplet excitations combined to a singlet (which inhibits an accurate treatment of polyenes with standard TD-DFT) do not play a relevant role in the current case. For such "well-behaved" systems, a reasonable representation of ESA spectra is found at the QR TD-DFT level due to the rather small energy shifts when including higher-order excitations. n Ts is, however, only partly due to the incomplete configuration description but, in particular, related to an improper MO description, resulting in an asymmetric energy spacing of the occupied vs unoccupied MOs in the DFT scheme. Longer n Ts , on the other side, adapt approximately the MO scheme for alternant hydrocarbons just like in n PVs , while contributions by two triplet excitations combined to a singlet (which inhibits an accurate treatment of polyenes with standard TD-DFT) do not play a relevant role in the current case. For such "well-behaved" systems, a reasonable representation of ESA spectra is found at the QR TD-DFT level due to the rather small energy shifts when including higher-order excitations.

Metabolic syndrome (MetS) is one of the most important medical problems around the world. Identification of patient´s singular characteristic could help to reduce the clinical impact and facilitate individualized management. This study aimed to categorize MetS patients using phenotypical and clinical variables habitually collected during health check-ups of individuals considered to have high cardiovascular risk. The selected markers to categorize MetS participants included anthropometric variables as well as clinical data, biochemical parameters and prescribed pharmacological treatment. An exploratory factor analysis was carried out with a subsequent hierarchical cluster analysis using the z-scores from factor analysis. The first step identified three different factors. The first was determined by hypercholesterolemia and associated treatments, the second factor exhibited glycemic disorders and accompanying treatments and the third factor was characterized by hepatic enzymes. Subsequently four clusters of patients were identified, where cluster 1 was characterized by glucose disorders and treatments, cluster 2 presented mild MetS, cluster 3 presented exacerbated levels of hepatic enzymes and cluster 4 highlighted cholesterol and its associated treatments Interestingly, the liver status related cluster was characterized by higher protein consumption and cluster 4 with low polyunsaturated fatty acid intake. This research emphasized the potential clinical relevance of hepatic impairments in addition to MetS traditional characterization for precision and personalized management of MetS patients., Competing Interests: JS-S reports grants from CIBEROBN, ISCIII (Spain), during the conduct of the study; non-financial support from Nut and Dried Fruit Foundation, personal fees from Instituto Danone Spain, other from Danone S.A., other from Font Vella Lanjaron, personal fees and grants from Eroski Distributors, grants from Nut and Dried Fruit Foundation, grants from Eroski Distributors, personal fees from Nut and Dried Fruit Foundation, outside the submitted work. ER reports grants, personal fees, non-financial support and other from California Walnut Commission, grants, personal fees, non-financial support and other from Alexion, personal fees, non-financial support and other from Ferrer International, personal fees from Amarin, personal fees, non-financial support and other from Danone, outside the submitted work. JL-M reports personal fees and non-financial support from AMGEN, personal fees and non-financial support from SANOFI, personal fees from MSD, personal fees from Laboratorios Dr. Esteve, personal fees from NOVO-NORDISK outside the submitted work., (Copyright © 2022 Micó, San-Cristobal, Martín, Martínez-González, Salas-Salvadó, Corella, Fitó, Alonso-Gómez, Wärnberg, Vioque, Romaguera, López-Miranda, Estruch, Tinahones, Lapetra, Serra-Majem, Bueno-Cavanillas, Tur, Martín Sánchez, Pintó, Delgado-Rodríguez, Matía, Vidal, Vázquez, García-Arellano, Pertusa-Martinez, Chaplin, Garcia-Rios, Muñoz Bravo, Schröder, Babio, Sorli, Gonzalez, Martinez-Urbistondo, Toledo, Bullón, Ruiz-Canela, Portillo, Macías-González, Perez-Diaz-del-Campo, García-Gavilán, Daimiel and Martínez.)