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In addition to metabolic and cardiovascular disorders, obesity is associated with cognitive deficits in humans and animal models. We have previously shown that obesogenic high-fat and sugar diet intake during adolescence (adoHFSD) impairs hippocampus (HPC)-dependent memory in rodents. These results were obtained in males only and it remains to evaluate whether adoHFSD has similar effect in females. Therefore, here, we investigated the effects of adoHFSD consumption on HPC-dependent contextual fear memory and associated brain activation in male and female mice. Exposure to adoHFSD increased fat mass accumulation and glucose levels in both males and females but impaired contextual fear memory only in males. Compared with females, contextual fear conditioning induced higher neuronal activation in the dorsal and ventral HPC (CA1 and CA3 subfields) as well as in the medial prefrontal cortex in males. Also, adoHFSD-fed males showed enhanced c-Fos expression in the dorsal HPC, particularly in the dentate gyrus, and in the basolateral amygdala compared with the other groups. Finally, chemogenetic inactivation of the dorsal HPC rescued adoHFSD-induced memory deficits in males. Our results suggest that males are more vulnerable to the effects of adoHFSD on HPC-dependent aversive memory than females, due to overactivation of the dorsal HPC., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

High angular resolution imaging is an increasingly important capability in contemporary astrophysics. Of particular relevance to emerging fields such as the characterization of exoplanetary systems, imaging at the required spatial scales and contrast levels results in forbidding challenges in the correction of atmospheric phase errors, which in turn drives demanding requirements for precise wavefront sensing. Asgard is the next-generation instrument suite at the European Southern Observatory's Very Large Telescope Interferometer (VLTI), targeting advances in sensitivity, spectral resolution, and nulling interferometry. In this paper, we describe the requirements and designs of three core modules: Heimdallr, a beam combiner for fringe tracking, low order wavefront correction, and visibility science; Baldr, a Zernike wavefront sensor to correct high order atmospheric aberrations; and Solarstein, an alignment and calibration unit. In addition, we draw generalizable insights for designing such system and discuss integration plans.

Obesity is associated with neurocognitive dysfunction, including memory deficits. This is particularly worrisome when obesity occurs during adolescence, a maturational period for brain structures critical for cognition. In rodent models, we recently reported that memory impairments induced by obesogenic high-fat diet (HFD) intake during the periadolescent period can be reversed by chemogenetic manipulation of the ventral hippocampus (vHPC). Here, we used an intersectional viral approach in HFD-fed male mice to chemogenetically inactivate specific vHPC efferent pathways to nucleus accumbens (NAc) or medial prefrontal cortex (mPFC) during memory tasks. We first demonstrated that HFD enhanced activation of both pathways after training and that our chemogenetic approach was effective in normalizing this activation. Inactivation of the vHPC-NAc pathway rescued HFD-induced deficits in recognition but not location memory. Conversely, inactivation of the vHPC-mPFC pathway restored location but not recognition memory impairments produced by HFD. Either pathway manipulation did not affect exploration or anxiety-like behaviour. These findings suggest that HFD intake throughout adolescence impairs different types of memory through overactivation of specific hippocampal efferent pathways and that targeting these overactive pathways has therapeutic potential., Competing Interests: IB, ED, MN, AF, CD, CB, EC, PT, GF No competing interests declared, (© 2024, Bakoyiannis, Ducourneau et al.)

Cancer is a multifaceted disease characterised by uncontrolled cellular proliferation and metastasis, resulting in significant global mortality. Current therapeutic strategies, including surgery, chemotherapy, and radiation therapy, face challenges such as systemic toxicity and tumour resistance. Recent advancements have shifted towards targeted therapies that act selectively on molecular structures within cancer cells, reducing off-target effects. Mitochondria have emerged as pivotal targets in this approach, given their roles in metabolic reprogramming, retrograde signalling, and oxidative stress, all of which drive the malignant phenotype. Targeting mitochondria offers a promising strategy to address these mechanisms at their origin. Synthetic derivatives of natural compounds hold particular promise in mitochondrial-targeted therapies. Innovations in drug design, including the use of conjugates and nanotechnology, focus on optimizing these compounds for mitochondrial specificity. Such advancements enhance therapeutic efficacy while minimizing systemic toxicity, presenting a significant step forward in modern anticancer strategies. [ABSTRACT FROM AUTHOR]

Cancer refers to a group of diseases characterized by the uncontrolled growth of abnormal cells. Conventional cancer therapies, such as chemotherapy and radiation therapy, often encounter issues like toxicity and resistance, primarily due to their inability to effectively differentiate between cancerous and normal cells. As a result, these treatments frequently harm healthy cells, underscoring the urgent need for innovative and more effective cancer treatment strategies. This article aims to investigate the changes in the Bcl-2/Bax ratio over time and its stability, using the Atangana–Baleanu fractional derivative operators as a key factor in reproductive cancer. The article also discusses the potential application of this model to investigate the effects of the ABT-737 inhibitor on mitochondrial apoptosis under initial conditions. The methodology entails using a fixed-point approach to investigate existence and uniqueness, as well as exploring Hyers–Ulam stability results for the given model. The numerical schemes utilize the basic concepts of fractional calculus and Lagrange polynomial interpolation. We generate simulated graphical representations of these models for a variety of fractional-order values. Finally, we present the simulation results to confirm the effectiveness and practicality of the theoretical findings. [ABSTRACT FROM AUTHOR]

In this paper, a probabilistic methodology based on image analysis for identifying the postearthquake performance level of reinforced concrete shear walls is proposed. A databank of 270 surface crack maps of 87 rectangular reinforced concrete shear walls obtained from quasi-static experiments at different drift ratio values is employed to develop the methodology. The specimens included within the databank exhibit a diverse range of structural design parameters and geometric properties. The complexity of the surface crack patterns is extracted by succolarity, lacunarity, and generalized fractal dimensions of the images of specimen images. For a specific fractal geometry index, fragility functions are developed to determine the probability of exceedance from an ASCE 41-17-compliant seismic performance level. Four typical probability distributions are used to generate the fragility functions: lognormal, gamma Weibull, and beta. Two goodness of fit tests including the K–S test and the Lilliefors test are used to assess the fragility curves' fitness. The results show that, among the fractal geometry indices, succolarity has the best goodness of fit results, and the Weibull distribution fits the most seismic performance levels. In this study, seismic performance level indices are developed to optimize the goodness of fit by combining generalized fractal dimensions, lacunarity, and succolarity. A damaged wall specimen not in the databank at available performance levels is selected to present the application of the methodology. The results are also compared with other deterministic approaches available in the literature. By using the proposed methodology, the seismic performance level can be projected without the requirement for the structural characteristics data that are usually unavailable for seismically damaged buildings in the aftermath of an earthquake by only relying on image-derived data. [ABSTRACT FROM AUTHOR]

In this study, we analyzed the phytosociological data from four sample sites located in the Pannonian region. The study areas, ranging from 2.4 to 2.5 hectares, have been subjected to goat grazing and mowing for 24 years. N1: Nagyréde, an overgrazed pasture with 24 goats; N2: Nagyréde, a mown field; C1: Csokvaomány, a lightly grazed pasture with 12 goats; and meadow C2: Csokvaomány, a site that is both mown and grazed. Six phytosociological surveys were conducted randomly in each area. We also considered the conservation value, biomass production, and forage values. Phytosociological data were processed using hierarchical cluster analysis and the non-parametric Kruskal–Wallis test. The overgrazed pasture (N1) exhibited the most degraded vegetation community, dominated by weeds and disturbance-tolerant species. The overgrazed (N1) pasture had a low forage value because of the different timing of treatments. Even in the lightly grazed pasture (C1), the proportion of species indicative of degradation was significant. The species composition of the areas indicated that the mown and subsequently grazed area (C2) had outstanding values. The species richness of C2 was twice that of the mown field (N2). Based on the present study, a combination of light grazing pressure and mowing is the most suitable approach for managing and economically utilizing these grasslands. [ABSTRACT FROM AUTHOR]

Stressed hepatocytes promote liver fibrosis through communications with hepatic stellate cells (HSCs) during chronic liver injury. However, intra‐hepatocyte players that facilitate such cell‐to‐cell communications are largely undefined. It is previously reported that hepatocyte E4BP4 is potently induced by ER stress and hepatocyte deletion of E4bp4 protects mice from high‐fat diet‐induced liver steatosis. Here how hepatocyte E4bp4 deficiency impacts the activation of HSCs and the progression toward MASH‐associated liver fibrosis is examined. Hepatic E4BP4 is increased in mouse models of NASH diet‐ or CCl4‐induced liver fibrosis. Hepatocyte‐specific E4bp4 deletion protected mice against NASH diet‐induced liver injury, inflammation, and fibrosis without impacting liver steatosis. Hepatocyte E4BP4 overexpression activated HSCs in a medium transfer experiment, whereas hepatocyte E4bp4 depletion did the opposite. RNA‐Seq analysis identified the pro‐fibrogenic factor OPN as a critical target of E4BP4 within hepatocytes. Antibody neutralization or shRNA depletion of Opn abrogated hepatocyte E4BP4‐induced HSC activation. E4BP4 interacted with and stabilized YAP, an established activator of OPN. Loss of hepatic Yap blocked OPN induction in the liver of Ad‐E4bp4‐injected mice. Hepatocyte E4BP4 induces OPN via YAP to activate HSCs and promote liver fibrosis during diet‐induced MASH. Inhibition of the hepatocyte E4BP4‐OPN pathway could offer a novel therapeutic avenue for treating MASLD/MASH. [ABSTRACT FROM AUTHOR]

Despite the high incidence of dry mouth in postmenopausal women, its underlying mechanisms and therapeutic interventions remain underexplored. Using ovariectomized (OVX) mouse models, here this study identifies ferroptosis, an iron‐dependent regulated cell death, as a central mechanism driving postmenopausal salivary gland (SG) dysfunction. In the OVX‐SGs, TGFβ signaling pathway is enhanced with the aberrant TGFβ2 expression in SG mesenchymal cells. Intriguingly, TGFβ2 treatment reduces iron‐storing ferritin levels, leading to lipid peroxidation and ferroptotic death in SG epithelial organoids (SGOs). Mechanistically, TGFβ2 promotes the autophagy‐mediated ferritin degradation, so‐called ferritinophagy. A notable overexpression of the type III TGFβ receptor (TβRIII) is found in the OVX‐SGs and TGFβ2‐treated SGOs, while the silencing of TβRIII mitigates the ferroptosis‐mediated deleterious effects of TGFβ2 on SGOs. Finally, administration of ferroptosis inhibitor, Liproxstatin‐1 (Lip‐1), improves saliva secretion in OVX mice. Present findings collectively suggest a link between TGFβ signaling, ferroptosis, and SG injury, offering new therapeutic avenues for postmenopausal xerostomia. [ABSTRACT FROM AUTHOR]

The ability of myeloid cells to recognize and differentiate endogenous or exogenous ligands rely on the presence of different transmembrane protein receptors. C-type lectin receptors (CLRs), defined by the presence of a conserved structural motif called C-type lectin-like domain (CTLD), are a crucial family of receptors involved in this process, being able to recognize a diverse range of ligands from glycans to proteins or lipids and capable of initiating an immune response. The Dectin-1 and Dectin-2 clusters involve two groups of CLRs, with genes genomically linked within the natural killer cluster of genes in both humans and mice, and all characterized by the presence of a single extracellular CTLD. Fundamental immune cell functions such as antimicrobial effector mechanisms as well as internalization and presentation of antigens are induced and/or regulated through activatory, or inhibitory signalling pathways triggered by these receptors after ligand binding. In this review, we will discuss the most recent concepts regarding expression, ligands, signaling pathways and functions of each member of the Dectin clusters of CLRs, highlighting the importance and diversity of their functions. This review discusses the most recent concepts regarding expression, ligands, signaling pathways and functions of each member of the Dectin clusters of C-type lectin receptors, highlighting the importance and diversity of their functions. [ABSTRACT FROM AUTHOR]

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International policymakers prioritize financial stability and inclusion, but often view them as separate goals, overlooking potential overlap and trade-offs. If synergies and trade-offs between the two concepts are not recognized and understood, policy design may yield less-than-ideal results. This paper provides a systematic review of the theoretical literature on financial inclusion and financial stability as well as empirical research initiatives examining the relationship between the two concepts. We found that current studies do not always present a unified theoretical approach or conceptual framework to explain the channels of the relationship between financial inclusion and stability. Empirical studies to date offer divergent views on the financial inclusion and stability nexus. While some studies are inconclusive, some also suggest that financial inclusion has a positive and significant impact on financial stability, as explained by the institutional theory. While other studies, supported by the aggressive credit expansion theory, reveal that financial inclusion can have a negative influence on financial stability. Through this comprehensive review, we intend to improve awareness and cohesion among scholars and policy makers of financial inclusion and financial stability while also facilitating the development of solid foundations to address future research and policy making challenges. [ABSTRACT FROM AUTHOR]

Background: Leptin, an adipokine essential for regulating energy balance, exerts important effects on brain function, notably within the hippocampus, a region integral to learning and memory. Leptin resistance, characterized by diminished responsiveness to elevated leptin levels, disrupts hippocampal function and exacerbates both obesity and cognitive impairments. Scope: This review critically examines how leptin resistance impairs hippocampal synaptic plasticity processes, specifically affecting long-term potentiation (LTP) and long-term depression (LTD), which are crucial for cognitive performance. Findings: Recent research highlights that leptin resistance disrupts N-methyl-D-aspartate (NMDA) receptor dynamics and hippocampal structure, leading to deficits in spatial learning and memory. Additionally, high-fat diets (HFDs), which contribute to leptin resistance, further deteriorate hippocampal function. Potential therapeutic strategies, including leptin sensitizers, show promise in mitigating brain disorders associated with leptin resistance. Complementary interventions such as caloric restriction and physical exercise also enhance leptin sensitivity and offer potential benefits to alleviating cognitive impairments. Aims of the review: This review synthesizes recent findings on the molecular pathways underlying leptin resistance and its impact on synaptic transmission and plasticity in the hippocampus. By identifying potential therapeutic targets, this work aims to provide an integrated approach for addressing cognitive deficits in obesity, ultimately improving the quality of life for affected individuals. [ABSTRACT FROM AUTHOR]

Cancer neuroscience is an emerging field that investigates the intricate relationship between the nervous system and cancer, gaining increasing recognition for its importance. The central nervous system governs the development of the nervous system and directly affects brain tumors, and the peripheral nervous system (PNS) shapes the tumor microenvironment (TME) of peripheral tumors. Both systems are crucial in cancer initiation and progression, with recent studies revealing a more intricate role of the PNS within the TME. Tumors not only invade nerves but also persuade them through remodeling to further promote malignancy, creating a bidirectional interaction between nerves and cancers. Notably, immune cells also contribute to this communication, forming a triangular relationship that influences protumor inflammation and the effectiveness of immunotherapy. This review delves into the intricate mechanisms connecting the PNS and tumors, focusing on how various immune cell types influence nerve‒tumor interactions, emphasizing the clinical relevance of nerve‒tumor and nerve‒immune dynamics. By deepening our understanding of the interplay between nerves, cancer, and immune cells, this review has the potential to reshape tumor biology insights, inspire innovative therapies, and improve clinical outcomes for cancer patients. [ABSTRACT FROM AUTHOR]

Background: In recent decades, there has been a startling rise in the number of cancer patients worldwide, which has led to an amazing upsurge in the development of novel anticancer treatment candidates. On a positive note, arylpiperazines have garnered attention in cancer research due to their potential as scaffolds for developing anticancer agents. These compounds exhibit a diverse array of biological activities, including cytotoxic effects against cancer cells. Indeed, one of the key advantages of arylpiperazines lies in their ability to interact with various molecular targets implicated in cancer pathogenesis. Aim: Here, we focus on the chemical structures of several arylpiperazine derivatives, highlighting their anti-proliferative activity in different tumor cell lines. The modular structure, diverse biological activities, and potential for combination therapies of arylpiperazine compounds make them valuable candidates for further preclinical and clinical investigations in the fight against cancer. Conclusion: This review, providing a careful analysis of different arylpiperazines and their biological applications, allows researchers to refine the chemical structures to improve potency, selectivity, and pharmacokinetic properties, thus advancing their therapeutic potential in oncology. [ABSTRACT FROM AUTHOR]

In this paper, bisection and extended-balanced singular perturbation methods are used to calculate the H8-norm of the transfer function of a linear DAEs system for the particular case D = 0. In the beginning the approaches' algorithms and error analysis are provided separately. Next, the methods are employed to calculate the H∞-norms of a numerical example pertaining to an automotive gas turbine model, and the error limits are used to check the norms in the suitable range, respectively. Ultimately, every solution is compared individually with the problem's H∞-norm values, which are retrieved from MATLAB. [ABSTRACT FROM AUTHOR]

In recent years, the continuous development of innovative nanopharmaceuticals is expanding their biomedical and clinical applications. Nanomedicines are being revolutionized to circumvent the limitations of unbound therapeutic agents as well as overcome barriers posed by biological interfaces at the cellular, organ, system, and microenvironment levels. In many ways, the use of nanoconfigured delivery systems has eased challenges associated with patient differences, and in our opinion, this forms the foundation for their potential usefulness in developing innovative medicines and diagnostics for special patient populations. Here, we present a comprehensive review of nanomedicines specifically designed and evaluated for disease management in the pediatric population. Typically, the pediatric population has distinguishing needs relative to those of adults majorly because of their constantly growing bodies and age-related physiological changes, which often need specialized drug formulation interventions to provide desirable therapeutic effects and outcomes. Besides, child-centric drug carriers have unique delivery routes, dosing flexibility, organoleptic properties (e.g., taste, flavor), and caregiver requirements that are often not met by traditional formulations and can impact adherence to therapy. Engineering pediatric medicines as nanoconfigured structures can potentially resolve these limitations stemming from traditional drug carriers because of their unique capabilities. Consequently, researchers from different specialties relentlessly and creatively investigate the usefulness of nanomedicines for pediatric disease management as extensively captured in this compilation. Some examples of nanomedicines covered include nanoparticles, liposomes, and nanomicelles for cancer; solid lipid and lipid-based nanostructured carriers for hypertension; self-nanoemulsifying lipid-based systems and niosomes for infections; and nanocapsules for asthma pharmacotherapy. [ABSTRACT FROM AUTHOR]

Introduction: Cesarean section it is the most frequently applied surgical application. Every surgical procedure creates an inflammation. Neutrophil to lymphocyte ratio (NLR), which can be easily obtained from complete blood count, is used as subclinical systemic inflammatory markers. In this study, our aim is to understand the effect of the duration of the cesarean section on subclinical inflammation by looking at the neutrophil/lymphocyte ratio and the effect of this period on blood loss and postoperative recovery Methods: We included a total of 188 operations between the ages of 18-45 in our study and created 2 groups according to the duration of the cesarean section. When grouped as short (0-39 min) and long (≥40 min) according to the operation time, NOL change was higher in the group with longer operation duration, but no significant difference was found in both groups. Similarly, although the decrease in hemoglobin was higher in the group with a long operation time, no significant difference was found. No difference was observed between the two groups in terms of wound healing on the postoperative 10th day. When we look at our other parameters, we found a significant relationship between those whose cesarean section ended within 40 minutes and those who had their first cesarean section. Results: As a result of our study, we could not detect a significant difference in the duration of the cesarean section operations performed in our clinic on the postoperative parameters. Conclusion: Although supportive studies are needed, it shows that the surgical rules of cesarean section operate correctly under optimal conditions. [ABSTRACT FROM AUTHOR]

Programmed cell death ligand 2 (PD-L2), a ligand for the receptor programmed cell death 1 (PD-1), has an identity of 34% with its twin ligand PD-L1 and exhibits higher binding affinity with PD-1 than PD-L1. However, the role of PD-L2 in non-small cell lung cancer (NSCLC) progression, especially tobacco-induced cancer progression, has not been fully understood. Here, we found that PD-L2 promoted tumor growth in murine models with recruitment of regulatory T cells (Tregs). In patients with NSCLC, PD-L2 expression level in tumor samples was higher than in counterpart normal controls and was positively associated with patients' response to anti-PD-1 treatment. Mechanismly, PD-L2 bound its receptor Repulsive guidance molecule B (RGMB) on cancer cells and activated extracellular signal-regulated kinase (Erk) and nuclear factor κB (NFκB), leading to increased production of chemokine CCL20, which recruited Tregs and contributed to NSCLC progression. Consistently, knockdown of RGMB or NFκB p65 inhibited PD-L2-induced CCL20 production, and silencing of PD-L2 repressed Treg recruitment by NSCLC cells. Furthermore, cigarette smoke and carcinogen benzo(a)pyrene (BaP) upregulated PD-L2 in lung epithelial cells via aryl hydrocarbon receptor (AhR)-mediated transcription activation, whose deficiency markedly suppressed BaP-induced PD-L2 upregulation. These results suggest that PD-L2 mediates tobacco-induced recruitment of Tregs via the RGMB/NFκB/CCL20 cascade, and targeting this pathway might have therapeutic potentials in NSCLC. [ABSTRACT FROM AUTHOR]

Inhibitors of the transforming growth factor–β (TGF-β) pathway are potentially promising antifibrotic therapies, but nonselective simultaneous inhibition of all three TGF-β homologs has safety liabilities. TGF-β1 is noncovalently bound to a latency-associated peptide that is, in turn, covalently bound to different presenting molecules within large latent complexes. The latent TGF-β–binding proteins (LTBPs) present TGF-β1 in the extracellular matrix, and TGF-β1 is presented on immune cells by two transmembrane proteins, glycoprotein A repetitions predominant (GARP) and leucine-rich repeat protein 33 (LRRC33). Here, we describe LTBP-49247, an antibody that selectively bound to and inhibited the activation of TGF-β1 presented by LTBPs but did not bind to TGF-β1 presented by GARP or LRRC33. Structural studies demonstrated that LTBP-49247 recognized an epitope on LTBP-presented TGF-β1 that is not accessible on GARP- or LRRC33-presented TGF-β1, explaining the antibody's selectivity for LTBP-complexed TGF-β1. In two rodent models of kidney fibrosis of different etiologies, LTBP-49247 attenuated fibrotic progression, indicating the central role of LTBP-presented TGF-β1 in renal fibrosis. In mice, LTBP-49247 did not have the toxic effects associated with less selective TGF-β inhibitors. These results establish the feasibility of selectively targeting LTBP-bound TGF-β1 as an approach for treating fibrosis. Editor's summary: Transforming growth factor–β (TGF-β) drives fibrosis in many tissues, but treatments that globally inhibit TGF-β signaling affect the immune system and are cardiotoxic. Jackson et al. developed an antibody that specifically bound to the latent form of TGF-β1 presented in the extracellular matrix and prevented its release. The antibody did not have toxic effects in mice and did not bind to latent complexes of TGF-β2 or TGF-β3 or to the latent forms of TGF-β1 presented on immune cells. In two rodent models of kidney fibrosis, systemic treatment with the antibody reduced fibrosis. The specificity of this approach may enable the safe targeting of TGF-β to treat fibrotic diseases (see also the Focus by Hinz). —Annalisa M. VanHook [ABSTRACT FROM AUTHOR]