eNAMPT is a novel therapeutic target for mitigation of coronary microvascular disease in type 2 diabetes.

AIMS/HYPOTHESIS: Individuals with diabetes are at high risk of cardiovascular complications, which significantly increase morbidity/mortality. Coronary microvascular disease (CMD) is recognised as a critical contributor to the increased cardiac mortality observed in people with diabetes. Therefore, there is an urgent need for treatments that are specific to CMD. eNAMPT (extracellular nicotinamide phosphoribosyltransferase) is a damage-associated molecular pattern and TLR4 ligand, whose plasma levels are elevated in people with diabetes. This study was thus designed to investigate the pathogenic role of intracellular nicotinamide phosphoribosyltransferase (iNAMPT) and eNAMPT in promoting the development of CMD in a preclinical murine model of type 2 diabetes. METHODS: An inducible type 2 diabetic mouse model was generated by a single injection of low-dose streptozocin (75 mg/kg, i.p.) combined with a high-fat diet for 16 weeks. The in vivo effects of i/eNAMPT inhibition on cardiac endothelial cell (CEC) function were evaluated by using Nampt+/- heterozygous mice, chronic administration of eNAMPT-neutralising monoclonal antibody (mAb) or use of an NAMPT enzymatic inhibitor (FK866). RESULTS: As expected, diabetic wild-type mice exhibited significantly lower coronary flow velocity reserve (CFVR), a determinant of coronary microvascular function, compared with control wild-type mice. eNAMPT plasma levels or expression in CECs were significantly greater in diabetic mice than in control mice. Furthermore, in comparison with diabetic wild-type mice, diabetic Nampt+/- heterozygous mice showed markedly improved CFVR, accompanied by increased left ventricular capillary density and augmented endothelium-dependent relaxation (EDR) in the coronary artery. NAMPT inhibition by FK866 or an eNAMPT-neutralising mAb significantly increased CFVR in diabetic mice. Furthermore, administration of the eNAMPT mAb upregulated expression of angiogenesis- and EDR-related genes in CECs from diabetic mice. Treatment with either eNAMPT or NAD+ significantly decreased CEC migration and reduced EDR in coronary arteries, partly linked to increased production of mitochondrial reactive oxygen species. CONCLUSIONS/INTERPRETATION: These data indicate that increased i/eNAMPT expression contributes to the development of diabetic coronary microvascular dysfunction, and provide compelling support for eNAMPT inhibition as a novel and effective therapeutic strategy for CMD in diabetes.

Helical Bilayer Nanographenes: Impact of the Helicene Length on the Structural, Electrochemical, Photophysical, and Chiroptical Properties.

Helical bilayer nanographenes (HBNGs) are chiral π-extended aromatic compounds consisting of two π-π stacked hexabenzocoronenes (HBCs) joined by a helicene, thus resembling van der Waals layered 2D materials. Herein, we compare [9]HBNG, [10]HBNG, and [11]HBNG helical bilayers endowed with [9], [10], and [11]helicenes embedded in their structure, respectively. Interestingly, the helicene length defines the overlapping degree between the two HBCs (number of benzene rings involved in π-π interactions between the two layers), being 26, 14, and 10 benzene rings, respectively, according to the X-ray analysis. Unexpectedly, the electrochemical study shows that the lesser π-extended system [9]HBNG shows the strongest electron donor character, in part by interlayer exchange resonance, and more red-shifted values of emission. Furthermore, [9]HBNG also shows exceptional chiroptical properties with the biggest values of gabs and glum (3.6 × 10-2) when compared to [10]HBNG and [11]HBNG owing to the fine alignment in the configuration of [9]HBNG between its electric and magnetic dipole transition moments. Furthermore, spectroelectrochemical studies as well as the fluorescence spectroscopy support the aforementioned experimental findings, thus confirming the strong impact of the helicene length on the properties of this new family of bilayer nanographenes.

Extrahypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance.

Oxytocin increases the salience of both positive and negative social contexts and it is thought that these diverse actions on behavior are mediated in part through circuit-specific action. This hypothesis is based primarily on manipulations of oxytocin receptor function, leaving open the question of whether different populations of oxytocin neurons mediate different effects on behavior. Here we inhibited oxytocin synthesis in a stress-sensitive population of oxytocin neurons specifically within the medioventral bed nucleus of the stria terminalis (BNSTmv). Oxytocin knockdown prevented social stress-induced increases in social vigilance and decreases in social approach. Viral tracing of BNSTmv oxytocin neurons revealed fibers in regions controlling defensive behaviors, including lateral hypothalamus, anterior hypothalamus, and anteromedial BNST (BNSTam). Oxytocin infusion into BNSTam in stress naïve mice increased social vigilance and reduced social approach. These results show that a population of extrahypothalamic oxytocin neurons plays a key role in controlling stress-induced social anxiety behaviors.

sSLAM: Speeded-Up Visual SLAM Mixing Artificial Markers and Temporary Keypoints.

Environment landmarks are generally employed by visual SLAM (vSLAM) methods in the form of keypoints. However, these landmarks are unstable over time because they belong to areas that tend to change, e.g., shadows or moving objects. To solve this, some other authors have proposed the combination of keypoints and artificial markers distributed in the environment so as to facilitate the tracking process in the long run. Artificial markers are special elements (similar to beacons) that can be permanently placed in the environment to facilitate tracking. In any case, these systems keep a set of keypoints that is not likely to be reused, thus unnecessarily increasing the computing time required for tracking. This paper proposes a novel visual SLAM approach that efficiently combines keypoints and artificial markers, allowing for a substantial reduction in the computing time and memory required without noticeably degrading the tracking accuracy. In the first stage, our system creates a map of the environment using both keypoints and artificial markers, but once the map is created, the keypoints are removed and only the markers are kept. Thus, our map stores only long-lasting features of the environment (i.e., the markers). Then, for localization purposes, our algorithm uses the marker information along with temporary keypoints created just in the time of tracking, which are removed after a while. Since our algorithm keeps only a small subset of recent keypoints, it is faster than the state-of-the-art vSLAM approaches. The experimental results show that our proposed sSLAM compares favorably with ORB-SLAM2, ORB-SLAM3, OpenVSLAM and UcoSLAM in terms of speed, without statistically significant differences in accuracy.

Fiducial Objects: Custom Design and Evaluation.

Camera pose estimation is vital in fields like robotics, medical imaging, and augmented reality. Fiducial markers, specifically ArUco and Apriltag, are preferred for their efficiency. However, their accuracy and viewing angle are limited when used as single markers. Custom fiducial objects have been developed to address these limitations by attaching markers to 3D objects, enhancing visibility from multiple viewpoints and improving precision. Existing methods mainly use square markers on non-square object faces, leading to inefficient space use. This paper introduces a novel approach for creating fiducial objects with custom-shaped markers that optimize face coverage, enhancing space utilization and marker detectability at greater distances. Furthermore, we present a technique for the precise configuration estimation of these objects using multiviewpoint images. We provide the research community with our code, tutorials, and an application to facilitate the building and calibration of these objects. Our empirical analysis assesses the effectiveness of various fiducial objects for pose estimation across different conditions, such as noise levels, blur, and scale variations. The results suggest that our customized markers significantly outperform traditional square markers, marking a positive advancement in fiducial marker-based pose estimation methods.

UCO Physical Rehabilitation: New Dataset and Study of Human Pose Estimation Methods on Physical Rehabilitation Exercises.

Physical rehabilitation plays a crucial role in restoring motor function following injuries or surgeries. However, the challenge of overcrowded waiting lists often hampers doctors' ability to monitor patients' recovery progress in person. Deep Learning methods offer a solution by enabling doctors to optimize their time with each patient and distinguish between those requiring specific attention and those making positive progress. Doctors use the flexion angle of limbs as a cue to assess a patient's mobility level during rehabilitation. From a Computer Vision perspective, this task can be framed as automatically estimating the pose of the target body limbs in an image. The objectives of this study can be summarized as follows: (i) evaluating and comparing multiple pose estimation methods; (ii) analyzing how the subject's position and camera viewpoint impact the estimation; and (iii) determining whether 3D estimation methods are necessary or if 2D estimation suffices for this purpose. To conduct this technical study, and due to the limited availability of public datasets related to physical rehabilitation exercises, we introduced a new dataset featuring 27 individuals performing eight diverse physical rehabilitation exercises focusing on various limbs and body positions. Each exercise was recorded using five RGB cameras capturing different viewpoints of the person. An infrared tracking system named OptiTrack was utilized to establish the ground truth positions of the joints in the limbs under study. The results, supported by statistical tests, show that not all state-of-the-art pose estimators perform equally in the presented situations (e.g., patient lying on the stretcher vs. standing). Statistical differences exist between camera viewpoints, with the frontal view being the most convenient. Additionally, the study concludes that 2D pose estimators are adequate for estimating joint angles given the selected camera viewpoints.

Simultaneous Detection of Circularly Polarized Luminescence and Raman Optical Activity in an Organic Molecular Lemniscate.

Circularly polarized luminescence (CPL) and Raman optical activity (ROA) were observed in a single spectroscopic experiment for a purely organic molecule, an event that had so far been limited to lanthanide-based complexes. The present observation was achieved for [16]cycloparaphenylene lemniscate, a double macrocycle constrained by a rigid 9,9'-bicarbazole subunit, which introduces a chirality source and allows the molecule to be resolved into two configurationally stable enantiomers. Distortion of oligophenylene loops in this lemniscular structure produces a large magnetic transition dipole moment while maintaining the π-conjugation-induced enhancement of the Raman signal, causing the appearance of the CPL/ROA couple. A two-photon mechanism is proposed to explain the population of the lowest-energy excited electronic state prior to the simultaneous emission-scattering event.

Raman and ROA analyses of twisted anthracenes: connecting vibrational and electronic/photonic structures.

In this article the Raman and Raman Optical Activity (ROA) spectra of a series of enantiomeric twisted anthracenes are presented. The evolution of their vibrational spectra is understood in the context of the variation of π-electron delocalization as a result of the twisting imparted by the belt structure and in terms of the modulation of the resonance Raman/ROA effects which are photonic properties also tuned by anthracene twisting. The Raman/ROA vibrational spectra are simulated by several theoretical approaches to account for their vibrational and electronic properties including the theoretical evaluation of resonance effects. We furthermore incorporate a vibrational and ROA activity dissection analysis as provided in the Pyvib2 program valid to establish correlations among vibrational modes of different molecules with different electronic structures and equivalent vibrational dynamics. This paper is one of the very first attempts to use ROA spectroscopy in π-conjugated molecules with twisted and helical morphologies that contrast with the well-known cases of ROA studies of chiral helicenes in which the impact of π-electron delocalization in the electronic/photonic/vibrational (Raman/ROA) spectra is negligible.

Raman Optical Activity (ROA) as a New Tool to Elucidate the Helical Structure of Poly(phenylacetylene)s.

Poly(phenylacetylene)s are a family of helical polymers constituted by conjugated double bonds. Raman spectra of these polymers show a structural fingerprint of the polyene backbone which, in combination with its helical orientation, makes them good candidates to be studied by Raman optical activity (ROA). Four different well-known poly(phenylacetylene)s adopting different scaffolds and ten different helical senses have been prepared. Raman and ROA spectra were recorded and allowed to establish ROA-spectrum/helical-sense relationships: a left/right-handed orientation of the polyene backbone (Mhelix /Phelix ) produces a triplet of positive/negative ROA bands. Raman and ROA spectra of each polymer exhibited the same profile, and the sign of the ROA spectrum was opposite to the lowest-energy electronic circular dichroism (ECD) band, indicating a resonance effect. Resonance ROA appears then as an indicator of the helical sense of poly(phenylacetylene)s, especially for those with an extra Cotton band in the ECD spectrum, where a wrong helical sense is assigned based on ECD, while ROA alerts of this misassignment.

[All]-S,S-dioxide Oligo-Thienylenevinylenes: Synthesis and Structural/Electronic Shapes from Their Molecular Force Fields.

Oligo-S,S-dioxothienylenevinylenes have been prepared by transferring oxygen atoms to the sulfur atoms using the HOF⋅CH3 CN complex. Their photophysical properties are presented in comparison with their thiophenevinylene congeners. Together with their vibrational properties and molecular force fields, this study allows for the interpretation of the alteration of aromaticity and inter-ring exocyclic π-conjugation in this series.

Long rylene nanoribbons express polyacetylene-like signatures at their edges.

Oligorylenes have been the focus of research during the journey toward intrinsically conducting polyrylene. Recently, the description of diradicaloid and tetraradicaloid properties in long oligorylene molecules has revived the old question about their electronic structures which is of current interest in the context of the properties of graphene nanoribbons. Here we show that the armchair edges of smaller oligorylenes are embedded within aromatic units and they transform into armchair cis-polyacetylenic structures for octarylene and longer. Concomitantly, the short zig-zag edges of oligorylenes stabilize diradicaloid and multiradical states. This electronic transformation is proved experimentally by Raman spectroscopy and supported by theoretical modelling.

Redox-Active Chiroptical Switching in Mono- and Bis-Iron Ethynylcarbo[6]helicenes Studied by Electronic and Vibrational Circular Dichroism and Resonance Raman Optical Activity.

Introducing one or two alkynyl-iron moieties onto a carbo[6]helicene results in organometallic helicenes (2 a,b) that display strong chiroptical activity combined with efficient redox-triggered switching. The neutral and oxidized forms have been studied in detail by electronic and vibrational circular dichroism, as well as by Raman optical activity (ROA) spectroscopy. The experimental results were analyzed and spectra were assigned with the help of first-principles calculations. In particular, a recently developed method for ROA calculations under resonance conditions has been used to study the intricate resonance effects on the ROA spectrum of mono-iron ethynylhelicene 2 a.

Isomerism, Diradical Signature, and Raman Spectroscopy: Underlying Connections in Diamino Oligophenyl Dications.

A diradical dication of a 4,4'-di(bis(1,4-methylphenyl)amino)-p-terphenyl oligomer has been characterized in solid-state by Raman spectroscopy and thermo-spectroscopy together with quantum chemical calculations. The diradical character has been evaluated on the basis of the Raman spectra and as a function of temperature. A complete understanding of the nature of the changes in solid state has been provided based on a pseudo-Jahn-Teller effect, which is feasible owing to the fine balance between quinoidal/aromatic extension among consecutive rings and steric crowding. This study contributes to the further comprehension of the molecular and electronic structures of these particular diradical molecules with strong implications on the understanding of the nature of chemical bonds in the limits of high electronic correlation or π-conjugation.

Fingerprints of Through-Bond and Through-Space Exciton and Charge π-Electron Delocalization in Linearly Extended [2.2]Paracyclophanes.

New stilbenoid and thiophenic compounds terminally functionalized with donor-donor, acceptor-acceptor, or donor-acceptor moieties and possessing a central [2.2]paracyclophane unit have been prepared, and their properties interpreted in terms of through-bond and through space π-electron delocalization (i.e., π-conjugations). Based on photophysical data, their excited-state properties have been described with a focus on the participation of the central [2.2]paracyclophane in competition with through-bond conjugation in the side arms. To this end, two-photon and one-photon absorption and emission spectroscopy, as a function of temperature, solvent polarity, and pressure in the solid state have been recorded. Furthermore, charge delocalization through the [2.2]paracyclophane in the neutral state and in the oxidized species (radical cations, dications and radical trications) has been investigated, allowing the elucidation of the vibrational Raman fingerprint of through-space charge delocalization. Thus, a complementary approach to both "intermolecular" excitation and charge delocalizations in [2.2]paracyclophane molecules is shown which can serve as models of charge and exciton migration in organic semiconductors.

Solvent-Directed Helical Stereomutation Discloses Pathway Complexity on N-Heterotriangulene-Based Organogelators.

The chiroptical features of supramolecular polymers formed from N-heterotriangulenes 1-3 have been investigated by circular dichroism (ECD) and vibrational circular dichroism (VCD) techniques. In solution, the CD spectra demonstrate that the helicity of the aggregates depends on only the stereogenic centres located at the peripheral chains. In the gel state, the chiroptical features are conditioned by the point chirality of the stereogenic centres and by the achiral solvent utilised. Sonication of the gels formed in CCl4 reveals both kinetic and thermodynamic phases. These findings reveal the presence of pathway complexity in the gel state triggered by sonication. The described solvent-induced helical stereomutation demonstrates that the gel state can be utilised as an outstanding benchmark for investigating uncommon chiroptical effects and to explore the rules of chirality transmission.

Push-Pull-Type Polychlorotriphenylmethyl Radicals: New Two-Photon Absorbers and Dyes for Generation of Photo-Charges.

Tri(4-iodo-2,3,5,6-tetrachlorophenyl)methane (2) is reported as a general building block for the synthesis of various π-conjugated polychlorotriphenylmethyl (PTM) radicals. Three push-pull-type triphenylamine-substituted PTM radicals with different substitution patterns were prepared and all exhibited intense inter-valence charge-transfer bands and large two-photon absorption (TPA) cross sections. Moreover, increase of solvent polarity also resulted in improved TPA response. The charge-transfer character of the relevant excited states provoked the efficient photo-generation of charges, anions in the PTM and cations in the amine arms, driven by the amphoteric redox character and the small coupling between donor and acceptor.

Iron Alkynyl Helicenes: Redox-Triggered Chiroptical Tuning in the IR and Near-IR Spectral Regions and Suitable for Telecommunications Applications.

The combination of a bis-alkynyl-helicene moiety with two iron centers leads to novel electroactive species displaying unprecedented redox-triggered chiroptical switching. Upon oxidation, strong changes of vibrational modes (either local or extended coupled modes) are detected by vibrational circular dichroism and Raman optical activity. Remarkably, the sign of the optical rotation at 1.54 µm (that is, at wavelengths typically used for telecommunications) changes upon oxidation while the topology and stereochemistry of the helicene remain unchanged.

Metabolic correction: a functional biochemical mechanism against disease--Part 2: mechanisms and benefits.

A healthy physiology depends on a plethora of complex interdependent biochemical reactions. In order for these reactions to occur suitably, the enzymes and cofactors that regulate their flow must be present in the proper balance. The term metabolic correction is used to describe a biochemical-physiological process that improves cellular biochemistry as a means to an individual's achieving metabolic or physiological optimization. Part 2 discusses how metabolic correction, through the increase of cofactors, can supply unmet enzyme needs and compensate for nutritional deficiencies induced by improper nutritional intake or by the increased demand for nutrients caused by genetics, health conditions, medications, or physical or environmental stressors. Nutrient insufficiencies are causing an increase in morbidity and mortality, at great cost to our society. In summary, metabolic correction improves enzymatic function and satisfies the increasing demand for nutrients. Metabolic correction can have a significant impact on the reduction of morbidity and mortality and their financial cost to our society and contribute to improving health and well-being.

Metabolic correction: a functional biochemical mechanism against disease--Part 1: concept and historical background.

Human physiology depends on countless biochemical reactions, numerous of which are co-dependent and interrelated. The speed and level of completion of reactions usually depend on the availability of precursors and enzymes. The enzymatic activity depends on the bioavailability of micronutrient cofactors such as vitamins and minerals. In order to achieve a healthy physiological state, the organism requires that biochemical reactions occur at a controlled rate. To achieve this state it is required that metabolic reactions reach what can be considered an optimal metabolic equilibrium. A combination of genetic makeup, dietary patterns, trauma, disease, toxins, medications, and environmental stressors can elevate the demand for the nutrients needed to reach this optimal metabolic equilibrium. In this, part 1, the general concept of metabolic correction is presented with an elaboration explaining how this concept is increasing in importance as we become aware of the presence of genetic variants that affect enzymatic reactions causing metabolic disturbances that themselves favor or promote the disease state. In addition, part 1 reviews how prominent scientists have contributed in fundamental ways to our understanding of the importance of micronutrients in health and disease and in the development of the metabolic correction concept.

[Metabolic correction: a biochemical option against diseases]. / Corrección metabólica: Una opción bioquímica contra las enfermedades.

Human development and its physiology depends on a number of complex biochemical body processes, many of which are interactive and codependent. The speed and the degree in which many physiological reactions are completed depend on enzyme activity, which in turn depends on the bioavailability of co-factors and micronutrients such as vitamins and minerals. To achieve a healthy physiological state, organism need that biochemical reactions occur in a controlled and specific way at a particular speed and level or grade fully completed. To achieve this, is required an optimal metabolic balance. Factors such as, a particular genetic composition, inadequate dietary consumption patterns, traumas, diseases, toxins and environmental stress all of these factors rising demands for nutrients in order to obtain optimal metabolic balance. Metabolic correction is a biochemical and physiological concept that explains how improvements in cellular biochemistry of an organism can help the body achieve metabolic and physiological optimization. We summarize the contribution of several pioneers in understanding the role of micronutrients in health management. The concept of metabolic correction is becoming a significant term due to the presence of genetic variants that affect the speed of reactions of enzymes, causing metabolic alterations that enhance or promote the state/development of multiple diseases. Decline in the nutritional value of the food we eat, the increase in demand for certain nutrients caused by normal development, diseases and medications induce, usually, nutrients consumption. These nutritional deficiencies and insufficiencies are causing massive economic costs due to increased morbidity and mortality in our society. In summary, metabolic correction improves the enzymatic function, which favors the physiological normal functions, thus, contributing to improving health and the welfare of the human being. The purpose of this paper is to describe and introduce the concept of optimal metabolic correction as a functional cost-effective mechanism against disease, in addition, to contribute to diseases prevention and regeneration of the body and health.