Université Bourgogne Europe

Age-related diseases are often associated with a disruption of RedOx balance that can lead to lipid peroxidation with the formation of oxysterols, especially those oxidized on carbon-7: 7-ketocholesterol (also known as 7-oxo-cholesterol) and 7β-hydroxycholesterol. Like cholesterol, these oxysterols have 27 carbons, they are composed of a sterane nucleus and have a hydroxyl function in position 3. The oxysterols 7-ketocholesterol and 7β-hydroxycholesterol are mainly formed by cholesterol autoxidation and are biomarkers of oxidative stress. These two oxysterols are frequently found at increased levels in the biological fluids (plasma, cerebrospinal fluid), tissues and/or organs (arterial wall, retina, brain) of patients with age-related diseases, especially cardiovascular diseases, neurodegenerative diseases (mainly Alzheimer's disease), ocular diseases (cataract, age-related macular degeneration), and sarcopenia. Depending on the cell type considered, 7-ketocholesterol and 7β-hydroxycholesterol induce either caspase- dependent or -independent types of cell death associated with mitochondrial and peroxisomal dysfunctions, autophagy and oxidative stress. The caspase dependent type of cell death associated with oxidative stress and autophagy is defined as oxiapoptophagy. These two oxysterols are also inducers of inflammation. These biological features associated with the toxicity of 7-ketocholesterol, and 7β-hydroxycholesterol are often observed in patients with age-related diseases, suggesting an involvement of these oxysterols in the pathophysiology of these disorders. The cytotoxic effects of 7-ketocholesterol and 7β-hydroxycholesterol are counteracted on different cell models by representative nutrients of the Mediterranean diet: ω3 and ω9 fatty acids, polyphenols, and tocopherols. There are also evidences, mainly in cardiovascular diseases, of the benefits of α-tocopherol and phenolic compounds. These in vitro and in vivo observations on 7-ketocholesterol and 7β-hydroxycholesterol, which are frequently increased in age-related diseases, reinforce the interest of nutritherapeutic treatments to prevent and/or cure age-related diseases currently without effective therapies.

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Oxysterols can be derived from the diet, physiologically produced via specific enzymes, or are generated by autoxidation. These molecules have physiological properties and can also adversely affect vital organs. Indeed, some of them have pro-oxidant and pro-inflammatory activities and can lead to major pathologies. The present review focuses on oxysterols (7-ketocholesterol, 7β-hydroxycholesterol, 25-hydroxycholesterol, 27-hydroxycholesterol, 5,6α-epoxycholesterol, 5,6β-epoxycholesterol, and cholestane-3β, 5α, 6β-triol) involved either in cholesterol metabolism, age-related diseases (such as cardiovascular, neurodegenerative, and eye diseases, e.g., sarcopenia), and inflammatory diseases (especially Behcet’s disease and bowel and lung diseases (e.g., sarcoidosis, COVID-19)). Metabolic pathways associated with oxysterol-induced inflammation are discussed considering the cytokinic TLR4 pathway, non-cytokinic pathways, and the contribution of Ca2+ and K+ channels. Therapeutic approaches targeting oxysterol-induced inflammation either by natural or synthetic molecules are also presented.

Gravity, the force that structures the cosmos, also shapes human physiology. It influences skeletal, muscular, cardiovascular, respiratory, and neurological systems, sustaining balance, blood circulation, and functional capacity. Unlike other senses, the brain lacks a dedicated gravity-sensing region and instead relies on a distributed vestibular network, graviception, to interpret gravitational cues. On Earth, gravity-driven blood pooling in the legs triggers compensatory responses that preserve cerebral perfusion. In microgravity, these mechanisms are altered, leading to fluid shifts toward the head, visual disturbances, cerebral changes, and increased thrombosis risk. Prolonged spaceflight induces muscle atrophy, bone demineralization, cardiovascular deconditioning, and orthostatic intolerance upon return to Earth. Whether these changes represent "adaptation" or "deconditioning" remains debated, but the outcomes resemble the physiological decline of frailty and aging. Earth-based analogs, including bed rest, dry immersion, and parabolic flights, reproduce many of these effects, linking gravitational unloading to postural instability, orthostatic hypotension, falls, and fractures. Such complications often fuel a vicious cycle of immobility and functional decline, central to both chronic illness and geriatric care. Viewing spaceflight as a model of accelerated aging offers new opportunities for clinical innovation. Research in altered gravity environments provides insights into countermeasures that preserve muscle mass, cardiovascular stability, and postural control. Strategies such as targeted exercise, optimized fluid management, and even hypergravity interventions may not only safeguard astronaut health but also translate into novel therapies for older adults. By bridging space medicine and aging research, these approaches can help mitigate frailty, reduce health care burdens, and enhance quality of life.

This paper explores Text-to-Knowledge Graph (T2KG) construction, assessing Zero-Shot Prompting, Few-Shot Prompting, and Fine-Tuning methods with Large Language Models. Through comprehensive experimentation with Llama2, Mistral, and Starling, we highlight the strengths of FT, emphasize dataset size's role, and introduce nuanced evaluation metrics. Promising perspectives include synonym-aware metric refinement, and data augmentation with Large Language Models. The study contributes valuable insights to KG construction methodologies, setting the stage for further advancements.

We report on numerical predictions and experimental observations of a novel type of temporal localized dissipative structures that manifest themselves in the self-defocusing regime of driven nonlinear optical resonators with two polarization modes. These chiral dissipative solitons, which we term "polarization faticons," break both temporal and polarization symmetry and consist of two bright lobes of opposite polarization handedness, interlocked by a domain wall. Our study reveals that faticons are connected to a vectorial modulational instability, from which they can be excited through a collapsing dynamic. Faticons could offer a novel pathway for frequency comb generation in normal dispersion resonators. More generally, they offer new fundamental insights into vectorial localized dissipative structures and could be relevant to other multicomponent dissipative systems.

ABSTRACT: Patients with follicular lymphoma who experience disease progression within 24 months of diagnosis (POD24) have a lower survival. Positron emission tomography (PET) response and circulating tumor DNA (ctDNA) minimal residual disease (MRD) assessment at end of induction (EOI) may allow their early identification. A representative cohort of 141 patients from the RELEVANCE phase 3 trial with both available serum samples for ctDNA testing and PET images at randomization and at EOI (week 24) was investigated. Twelve percent were POD24. ctDNA was analyzed using a customized 130-kilobase capture panel, with phased variant (PV) enriched regions representing 39% of the panel. ctDNA was detected in 140 patients (99.3%) at baseline. To optimize specificity, only PVs, found in 124 patients (88%), were considered for ctDNA MRD assessment at EOI. Median progression-free survival (PFS) from EOI was not reached (NR) for the 112 patients with undetected ctDNA at EOI vs 17.7 months (95% confidence interval [CI], 1.4 to NR) for patients with positive ctDNA (MRD+) (P = .0038). Similarly, median PFS was NR for the 104 patients with undetected disease on PET at EOI vs 28.3 months (95% CI, 2.9 to NR; P = .0002) for patients with PET positivity. Both tests had a negative predictive value (NPV) of >90% for POD24. The positive predictive value was 58.3% for ctDNA MRD and 45% for PET but increased to 85.7% when both parameters were combined, without alteration of NPV. These data show that the combination of PET response and ctDNA MRD at EOI allows an early prediction of POD24, which may lead to a preemptive treatment decision. This trial was registered at www.clinicaltrials.gov as #NCT01650701.

Cyber-attack detection is crucial for securing Industrial Internet of Things (IIoT) systems. This study introduces advanced deep learning methodologies to identify potential cyber-attacks effectively in IIoT devices. Three novel stacked deep learning architectures, namely the StackMean, StackMax, and StackRF algorithms. These architectures aggregate and enhance the results of individual deep learning models. Specifically, StackMean computes average predicted class probabilities, StackMax selects maximum predicted class probabilities for more aggressive predictions, and StackRF leverages a random forest to aggregate base models. Theoretical analysis suggests that the proposed stacked deep learning model can boost detection accuracy compared to standalone single deep learning models. Moreover, these stacked models offer increased robustness against adversarial attacks by reducing reliance on specific neural network structures. Additionally, the synthetic minority oversampling technique (SMOTE) algorithm is integrated to address class imbalance challenges in the training dataset. Performance validation is conducted using three publicly available datasets. The detection performance is evaluated using five statistical scores. The results consistently indicate the superiority of the proposed stacked deep learning models over existing techniques. The effectiveness of the SMOTE algorithm is demonstrated through its ability to expand decision regions and minimize false negative signals during attack predictions. In addition, a statistical test is employed to compare the accuracy of individual models with the stacked models, demonstrating that the stacked models exhibit improved accuracy. By combining cutting-edge stacked deep learning architectures with strategic data augmentation techniques, this research significantly contributes to the robustness of cyber-attack detection within IIoT systems.

Tribological behavior at both tool/chip and tool/work material interfaces should be highly considered while simulating the machining process. In fact, it is no longer accurate to suppose one independent constant friction coefficient at the tool/chip interface, since in reality it depends on the applied contact conditions, including the sliding velocity and pressure. The contact conditions at both above mentioned interfaces may affect the thermal and mechanical phenomena and consequently the surface integrity predictions. In this article, the influence of contact conditions (sliding velocity) on the tribological behavior of uncoated tungsten carbide tool against OFHC copper work material was investigated. Series of tribology tests combined with numerical simulations of the contact process were performed under different sliding speeds and contact pressures, in order to identify the friction coefficient and the heat partition between OFHC copper and tungsten carbide. The friction coefficient in function of the sliding velocity was then integrated into a FE model of the orthogonal cutting of OFHC copper and applied to surface integrity prediction.

Overcoming the intrinsic linear scaling relationship that governs intermediate adsorption energies in oxygen evolution reaction (OER) electrocatalysis is crucial for unlocking higher catalytic efficiency beyond the limitations of the conventional adsorbate evolution mechanism (AEM). Here, we propose a lattice-engineering strategy to activate the oxide path mechanism (OPM)─a distinct reaction pathway that circumvents high-energy *OOH intermediates─by incorporating trace amounts of Ce into NiFe through a one-step electrodeposition process. The introduction of Ce induces pronounced lattice strain and abundant grain boundaries, shortening the Ni–Ni interatomic distance from 2.12 to 1.94 Å and constructing dual-metal site geometries that favor direct O–O coupling. This structural transformation not only increases the density of catalytically active sites but also triggers a pathway shift from AEM to OPM, thereby circumventing linear scaling constraints and enhancing intrinsic activity. Consequently, the NiFe-Ce/CeO 2 -0.01 catalyst exhibits an ultralow overpotential of 135 mV at 10 mA cm –2 and 332 mV at 500 mA cm –2, along with an operational lifetime exceeding 1000 h. When integrated into an alkaline water electrolyzer, the system delivers a current density of 1000 mA cm –2 at 1.71 V and maintains robust operation for over 850 h. This study establishes a direct structural–mechanistic correlation between lattice compression and OPM activation, offering a viable strategy to transcend linear scaling limitations and guiding the development of next-generation high-performance OER electrocatalysts.

Immune checkpoint blockade treatment is highly effective in microsatellite-instable (MSI) colorectal cancer. However, microsatellite-stable (MSS) tumors, which represent 95% of metastatic colorectal cancer, are intrinsically resistant to immunotherapy. In this study, we sought to better understand the mechanisms of resistance to anti-PD-L1 therapy in colorectal cancer by characterizing the immune profiles of MSS and MSI tumor models. Although both tumor types presented intratumoral CD8+ T-cell responses and PD-L1 expression, the exhausted CD8+ T-cell phenotypes differed. In MSS tumors, exhausted CD8+ T cells coexpressed PD-1 and T-cell immunoglobulin and ITIM domain (TIGIT) and exhibited a terminal exhausted profile with low cytokine secretion and limited cytotoxic function. In contrast, PD-1+ CD8+ T cells in MSI tumors did not express TIGIT and displayed higher cytokine and cytotoxic activities. Interestingly, immunosuppressive M2-like tumor-associated macrophages (TAM) accumulated in MSI tumors and positively correlated with PD-1+ TIGIT+ CD8+ T-cell frequency. M2-like TAM depletion reduced TIGIT expression, increased CD8+ T-cell function, and improved efficacy of PD-L1 blockade. Transcriptomic analysis revealed elevated COX1/2 expression in TAMs in MSS tumors compared with MSI tumors. COX2 and prostaglandin E2 (PGE2) receptor inhibition impeded TIGIT expression and restored CD8+ T-cell activity, whereas PGE2 triggered TIGIT upregulation in CD8+ T cells. Single-cell, spatial, and bulk transcriptomic data from patients with colorectal cancer substantiated the correlation between elevated TIGIT in CD8+ T-cell and COX1/2 in TAMs. Together, these data uncover the role of the TAM axis in inhibiting PD-L1 efficacy in MSS colorectal cancer and support the utility of combining anti-PD-L1 therapy with TIGIT blockade, PGE2 treatment, or M2-like TAM inhibition in colorectal cancer. SIGNIFICANCE: Targeting PGE2 signaling activated by tumor-associated macrophages sensitizes microsatellite-stable colon tumors to immune checkpoint blockade by limiting the emergence of an exhausted PD-1+ TIGIT+ CD8+ T population.

Idiopathic pulmonary fibrosis (IPF) is a progressive disease characterized by an excessive collagen deposition ultimately leading to tissue stiffening and functional decline.Beyond IPF, other progressive pulmonary fibrosis are often associated with connective tissue diseases and may develop in 18-32% of patients.Therapeutic options are limited to nintedanib and pirfenidone which are only able to reduce fibrosis progression without curing it.The current lack of biomarker to accurately assess and predict disease progression and therapy efficacy for IPF remains a major clinical concern.Methods: In our study, collagen deposition was monitored in bleomycin-induced lung fibrosis in mice by in vivo molecular imaging using a collagen-targeted radiopharmaceutical, [ 68 Ga]Ga-NODAGA-collagelin. Fibrosis progression was also monitored using computed tomography, the gold standard technique to detect lung fibrosis in patients. Results:We demonstrated that the bleomycin-induced increase in collagen lung content can be accurately quantified by [ 68 Ga]Ga-NODAGA-collagelin PET imaging in correlation with disease stage and severity.The lung uptake of [ 68 Ga]Ga-NODAGA-collagelin was mainly found in fibrotic areas of lungs in bleomycin-receiving mice.Most interestingly, [ 68 Ga]Ga-NODAGA-collagelin PET imaging allowed the in vivo non-invasive monitoring of nintedanib efficacy as well as the anti-fibrotic effect of the JAK inhibitor, tofacitinib.Conclusion: Thus, collagen-targeted PET imaging appears as a promising non-invasive tool for staging, monitoring and prediction of disease progression and therapy efficacy towards personalized medicine in IPF.

Hydrogen (H 2 ) has gained a lot of interest as an alternative energy vector, to reduce greenhouse gas emission issues caused by the fossil fuel industry. However, to make hydrogen a real energy carrier in a decarbonated economy, a secure and sustainable supply chain is needed. This approach requires notably safe storage and efficient strategies for recycling of raw materials. We discuss in this survey the state-of-the-art in the field of chemical hydrogen storage (CHS) materials, considering two possible vectors: ammonia borane and hydrosilanes. Regardless of the vector, to achieve real use, it is necessary to understand both the performance of the system and its life cycle, which relates to catalysts structure, and the activation of chemical bonds with efficient and complete catalytic cycles. We give herein an overview of hydrolysis and/or alcoholysis from metals, using coordination complexes, molecular supported catalysts or other materials, including nanocatalysts, with a focus on mechanistic information and understanding. Notably, the studies related to these two vectors can be considered somewhat complementary. Thus, the set of bibliographic report on ammonia borane is very documented in efficient catalytic systems, while its recycling remains at a very early stage. In comparison, hydrosilanes have been much less addressed specifically as a vector for hydrogen, while their reactivity at the molecular scale benefits from a relevant understanding from coordination chemistry studies. In addition, both hydrosilane polymerization and solvolysis reaction enables the release of H 2 , and produces by-products of which added value is already established. This opening the way to economical strategies where recycling can be optional. Nevertheless, the reversibility of hydrosilanes chemistry in H 2 uptake remains attractive and is another option to develop.

Molecularly Imprinted Polymer (MIP)-based sensors have gained increasing attention in the field of food safety analysis due to their unique ability to selectively recognize and quantify chemical contaminants and allergens with interesting sensitivity. These synthetic receptors, often referred to as “plastic antibodies,” offer several advantages over conventional analytical methods, including high stability, cost-effectiveness, reusability, and compatibility with miniaturized sensor platforms. This review provides a comprehensive overview of recent advances in the design, fabrication, and application of MIP-based sensors for the detection of a broad range of food contaminants, including pesticides, antibiotics, mycotoxins, heavy metals, acrylamide, heterocyclic amines, allergens, viruses, and bacteria. Various transduction mechanisms—electrochemical, optical, thermal, and mass-sensitive—are discussed in relation to their integration with MIP recognition elements. The review also highlights the advantages and limitations of MIPs in comparison with traditional techniques such as ELISA and HPLC. Finally, we explore current challenges and emerging trends, including nanomaterial integration, multiplexed detection, and smartphone-based platforms, which are expected to drive future developments toward real-time, point-of-need, and regulatory-compliant food safety monitoring tools.

The functionalization of polycyclic aromatic hydrocarbons (PAHs) with N→B Lewis pairs, so-called borylative fusion, has recently emerged as a simple and powerful means to modulate their electronic and photophysical properties thanks to the extension of the π system. Herein, we considered a new class of PAHs appended with phosphine→borane Lewis pairs and investigated pyrene as well as anthracene derivatives. In these compounds, strong P→B interactions are enforced geometrically, but the π-system is not extended. Nevertheless, such P→B functionalization was found to significantly impact the optical and electrochemical properties. The P,B-functionalized PAHs display noticeably reduced HOMO-LUMO gaps and enhanced fluorescence. Both the number and position of P→B units turned out to play a significant role.

Simultaneously increasing the spectral bandwidth and average output power of mid-infrared supercontinuum sources remains a major challenge for their practical application. We particularly address this issue for the long mid-infrared spectral region through experimental developments of short tapered rods made from selenide glass by means of supercontinuum generation in the femtosecond regime. Our simple post-processing of glass rods unlocks potentially higher-power and coherent fiber-based supercontinuum sources beyond the 10-μm waveband. By using a 5-cm-long tapered Ge-Se-Te rod pumped at 6 μm, a supercontinuum spanning from 2 to 15 μm (3–14 μm) with an average output power of 93 mW (170 mW) is obtained for 500-kHz (1-MHz) repetition rate. Additional experiments on other glass families (silica and tellurite) covering distinct spectral regions are also reported to develop and support our analyses. We demonstrate that ultra-broadband spectral broadenings over entire glass transmission windows can be achieved in few-cm-long segments of tapered rods by a fine adjustment of input modal excitation. Numerical simulations are used to confirm the main contribution of the fundamental mode in the ultrafast nonlinear dynamics, as well as the possible preservation of coherence features. Our study opens a new route, to our knowledge, towards the power scaling of high-repetition-rate fiber supercontinuum sources over the full molecular fingerprint region.

G-quadruplexes (G4s) are challenging targets for chemical biology interventions, notably because of their dynamic topological polymorphism. We found that the antibiotic small- molecule colistin (COL) interacts specifically with a single subtype of G4 structures, the so-called parallel G4s. This interaction triggers the aggregation of the G4/COL complexes in a structure-specific manner, which can thus be separated from the bulk solution by centrifugation. This unprecedented mode of affinity-precipitation was exploited here to design the COL-induced RNA G4 precipitation and sequencing (CoRP-seq) protocol, which allows for the assessment of the prevalence of RNA G4s in the transcriptome of human cells in a straightforward manner. CoRP-seq shines by its ultraspecificity, simplicity, and practical convenience, which thus advances G4 mapping further and addresses unmet needs in the field of G4omics.

The utilization of gelatin capsule waste (GCW) poses a challenge for the industry. This study investigates its potential as a functional food ingredient by evaluating the physico-chemical, rheological, and techno-functional properties of gelatin capsule waste powder (GCWP). To achieve this, the gelatin capsule waste (GCW) was mixed with maltodextrin at varying ratios (1:1, 1:2, 1:3, 1:4, and 1:5) and subjected to spray drying. The findings highlight maltodextrin’s crucial role in stabilizing the drying process, reducing stickiness, and enhancing handling and storage properties. All the obtained GCWP samples appeared light white and had a slightly sticky texture. The 1:5 (w/w) GCW-to-maltodextrin ratio produced the highest powder recovery with minimal stickiness, indicating enhanced drying efficiency. Increasing maltodextrin reduced gel strength, texture, and foaming properties while raising the glass transition temperature. The FTIR analysis indicated a decline in protein–protein interactions and increased polysaccharide interactions at higher maltodextrin levels. The rheological analysis demonstrated lower elastic and loss moduli with increased maltodextrin, affecting GCWP’s structural behavior. For overall properties, the GCW mixed with maltodextrin at a 1:1 ratio (GCW-1M) is recommended for future applications, particularly for its gelling characteristics. The GCW-1M, being rich in amino acids, demonstrates its potential as a functional food ingredient. However, certain properties, such as gel strength and powder stability (hygroscopicity and stickiness), require further optimization to enhance its industrial applicability as a functional food ingredient.

Musicians are often regarded as a positive example of brain plasticity and associated cognitive benefits. This emerges when experienced musicians (e.g., musicians with more than 10 years of music training and practice) are compared with nonmusicians. A frequently observed behavioral finding is a short-term memory advantage of the former over the latter. Although available meta-analysis reported that the effect size of this advantage is medium (Hedges’s g = 0.5), no literature study was adequately powered to estimate reliably an effect of such size. This multilab study has been ideated, realized, and conducted in lab by several groups that have been working on this topic. Our ultimate goal was to provide a community-driven shared and reliable estimate of the musicians’ short-term memory advantage (if any) and set a method and a standard for future studies in neuroscience and psychology comparing musicians and nonmusicians. Thirty-three research units recruited a total of 600 experienced musicians and 600 nonmusicians, a number that is sufficiently large to estimate a small effect size (Hedges’s g = 0.3) with a high statistical power (i.e., 95%). Subsequently, we measured the difference in short-term memory for musical, verbal, and visuospatial stimuli. We also looked at cognitive, personality, and socioeconomic factors that might mediate the difference. Musicians had better short-term memory than nonmusicians for musical, verbal, and visuospatial stimuli with an effect size of, respectively, Hedges’s g s = 1.08 (95% confidence interval [CI] = [0.94, 1.22]; large), 0.16 (95% CI = [0.02 0.30]; very small), and 0.28 (95% CI = [0.15, 0.41]; small). This work sets the basis for sound research practices in studies comparing musicians and nonmusicians and contributes to the ongoing debate on the possible cognitive benefits of musical training.

In preclinical mouse models of triple-negative breast cancer (TNBC), we show that a combination of chemotherapy with cisplatin (CDDP) and eribulin (Eri) was additive from an immunological point of view and was accompanied by the induction of an intratumoral immune and inflammatory response favored by the immunogenic cell death induced by CDDP, as well as by the vascular and tumor stromal remodeling induced by each chemotherapy. Unexpectedly, despite the favorable immune context created by this immunomodulatory chemotherapy combination, our models remained refractory to the addition of anti-PD-L1 immunotherapy. These surprising observations led us to discover that CDDP chemotherapy was simultaneously responsible for the production of TGF-β by several populations of cells present in tumors, which favored the emergence of different subpopulations of immune cells and cancer-associated fibroblasts characterized by immunosuppressive properties. Accordingly, co-treatment with anti-TGF-β restored the immunological synergy between this immunogenic doublet of chemotherapy and anti-PD-L1 in a CD8-dependent manner. Translational studies revealed the unfavorable prognostic effect of the TGF-β pathway on the immune response in human TNBC, as well as the ability of CDDP to induce this cytokine also in human TNBC cell lines, thus highlighting the clinical relevance of targeting TGF-β in the context of human TNBC treated with chemoimmunotherapy.