Search Results (61)

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, projected to affect 55% globally by 2040. Up to one-third of NAFLD patients develop non-alcoholic steatohepatitis (NASH), with 40% progressing to fibrosis. However, there are currently few reliable tools to predict disease progression. Impaired mitochondrial dynamics, characterized by dysregulated fission, fusion, and mitophagy, have emerged as key events in NAFLD pathophysiology, contributing to hepatocyte death and inflammation. This study explored the transition from steatosis to NASH through transcriptomic analyses, including data from patients with steatosis and those with NASH at different fibrosis stages. By identifying a transcriptomic signature associated with disease progression, the study revealed increased expression of genes involved in mitochondrial dynamics in NASH compared to steatosis and during NASH-related fibrosis. Histological analyses highlighted the central role of Dynamin-related protein 1 (Drp1), a dynamin GTPase essential for mitochondrial fission and mitophagy. In human liver biopsies, Drp1 expression progressively increased from NAFLD to NASH and NASH-related fibrosis and cirrhosis, predominantly in Kupffer cells. These finding suggest Drp1 is a potential driver of the transition to more severe liver damage, making it a promising biomarker for NASH development and progression and a potential therapeutic target in metabolic disorders. Full article

Background/Objectives: Hot-melt extrusion (HME) has become a key technology in pharmaceutical formulation, particularly for enhancing the solubility of poorly soluble Active Pharmaceutical Ingredients (APIs). While horizontal HME is widely adopted, vertical HME remains underexplored despite its potential benefits in footprint reduction, feeding efficiency, temperature control, and integration into continuous manufacturing. This study investigates vertical HME as an innovative approach in order to optimize drug polymer interactions and generate stable amorphous dispersions with controlled release behavior. Methods: Extrusion trials were conducted using a vertical hot-melt extruder developed by Rondol Industrie (Nancy, France). Acetylsalicylic acid (ASA) supplied by Seqens (Écully, France) was used as a model API and processed with Soluplus^® and Kollidon^® 12 PF (BASF, Ludwigshafen, Germany). Various process parameters (temperature, screw speed, screw profile) were explored. The extrudates were characterized by powder X-ray diffraction (PXRD) and small-angle X-ray scattering (SAXS) to evaluate crystallinity and microstructure. In vitro dissolution tests were performed under sink conditions using USP Apparatus II to assess drug release profiles. Results: Vertical HME enabled the formation of homogeneous amorphous solid dispersions. PXRD confirmed the absence of residual crystallinity, and SAXS revealed nanostructural changes in the polymer matrix influenced by drug loading and thermal input. In vitro dissolution demonstrated enhanced drug release rates compared to crystalline ASA, with good reproducibility. Conclusions: Vertical HME provides a compact, cleanable, and modular platform that supports the development of stable amorphous dispersions with controlled release. It represents a robust and versatile solution for pharmaceutical innovation, with strong potential for cost-efficient continuous manufacturing and industrial-scale adoption. Full article

We report the synthesis and characterization of five novel metal complexes. Three of them are vanadium complexes with the general formula [VO(Lⁿ)₂], where Lⁿ are Schiff bases derived from the condensation of 2-carbaldehyde-8-hydroxyquinoline with either 4-(2-aminoethyl)morpholine (L¹), 3-morpholinopropylamine (L²) or 1-(2-aminoethyl)piperidine (L³). The two other metal complexes are [Ni(L¹)₂] and [Fe(L¹)₂]Cl. They were characterized by analytical, spectroscopic (Fourier transform infrared, UV-visible absorption), and mass spectrometric techniques as well as by single-crystal X-ray diffraction (for all [VO(Lⁿ)₂] complexes and [Ni(L¹)₂]). While, in the crystal structure, the V(IV)O complexes show distorted square–pyramidal geometry with the ligands bound as bidentate through quinolate NO donors, the Ni(II) complex shows octahedral geometry with two ligand molecules coordinated through NNO donors. Stability studies in aqueous media revealed that the vanadium complexes are not stable, undergoing oxidation to VO₂(L), which was corroborated by ⁵¹V NMR and MS. This behavior is also observed in organic media, though at a significantly slower rate. The Ni complex exhibited small spectral changes over time in aqueous media. Nonetheless, all compounds show enhanced stability in the presence of bovine serum albumin (BSA). Fluorescence studies carried out for the Ni(II) and Fe(III) complexes indicate reversible binding to albumin. The cytotoxicity of the L¹ metal complexes was assessed on melanoma (B16F10 and A375) and colon cancer (CT-26 and HCT-116) cell lines, with 5-fluorouracil (5-FU) as a reference drug. The V- and Ni complexes showed the lowest IC₅₀ values (<10 μM) in either A375 or HCT-116 cells after 48 h of incubation, while the Fe(III) complex presented minimal antiproliferative effects. The complexes were generally more cytotoxic to human than murine cancer cells. Synergistic in vitro studies with 5-FU revealed antagonism in most cases, except in A375 cells, where an additive effect was observed for the combination with the V-complex. Overall, these compounds show promising potential for cancer treatment, mostly for melanoma. Full article

Squeal refers to a sustained high-intensity noise resulting from friction-induced vibrations. Although it is known that it originates from mode coupling, the conditions under which it occurs are still unclear, especially regarding the contact conditions. In this paper, pin-on-disc experimental tests are conducted in order to investigate the conditions of squeal occurrence. The tests are highly instrumented: they involve in particular a detailed measurement of near-surface temperature evolution in the pin using 16 thermocouples and a discrete monitoring of the evolution of surface profiles. As expected, the squealing frequency is closely related to the temperature level. However, the mean temperature level alone is not sufficient to predict the occurrence of squeal, especially at low temperatures. The study of local temperature elevations over the pin surface coupled with surface observations allows for assessing the evolution of macroscopic contact localization during tests at low temperatures. The contact localization is shown to be related to squeal episodes: at low temperatures, the contact is localized near the corners of the pin surface, and squeal is found to occur only in situations where the contact is evenly balanced over the corners, which is highly influenced by the initial pin surface profile. This shows that the conditions of squeal occurrence are driven in a significant extent by thermomechanical processes. Full article

Background/Objectives: Inflammation is a vital response of the immune system, frequently linked to the development and progression of numerous chronic and autoimmune diseases. Targeting inflammation represents an attractive strategy to prevent and treat these pathologies. In this context, many pathways, including pro-inflammatory cytokines secretion, NFκB activation, reactive oxygen species (ROS) production, inflammasome activation and arachidonic acid metabolism could be highlighted and addressed. Several plant materials have traditionally been used as effective and non-harmful anti-inflammatory agents. However, well-established scientific evidence is lacking, and their mechanisms of action remain unclear. The current article compares the effects of seven plant extracts, including Quercus robur L. (Oak), Plantago lanceolata L. (narrowleaf plantain), Plantago major L. (broadleaf plantain), Helichrysum stoechas L. (immortelle or helichrysum), Leontopodium nivale alpinum Cass. (edelweiss), Medicago sativa L. (alfafa) and Capsella bursa-pastoris Moench (shepherd’s purse) on different inflammatory pathways. Results: All of the plant extracts significantly affected ROS production, but their action on cytokine production was more variable. As the Quercus robur extract showed the highest efficacy in our models, it was subsequently assessed on several inflammatory signaling pathways. Quercus robur significantly decreased the secretion of IFNγ, IL-17a, IL-12, IL-2, IL-1β and IL-23 in stimulated human leucocytes, and the expression of TNFα, IL-6, IL-8, IL-1β and CXCL10 in M1-like macrophages. Additionally, a significant reduction in PGE2 secretion, COX2, NLRP3, caspase1 and STAT3 expression and NFκB p65 phosphorylation was observed. Conclusions: Our results clearly indicate that Quercus robur has a potent anti-inflammatory effect, making it a promising candidate for both the treatment and prevention of inflammation and related diseases, thereby promoting overall well-being. Full article

Wastewater surveillance is a powerful public health tool which gained global prominence during the COVID-19 pandemic. This article describes the development and implementation of the national wastewater surveillance network in France: SUM’EAU. Preliminary work included defining a sampling strategy, evaluating/optimising analytical methods, launching a call for tenders to select network laboratories and producing wastewater monitoring indicators. SUM’EAU was then deployed in three stages: (i) a pilot study, (ii) the transfer of analytical activities from the National Reference Laboratory to four selected network laboratories, and (iii) the extension of the system to additional sampling sites. Currently, SUM’EAU monitors SARS-CoV-2 across 54 wastewater treatment plants in mainland France. Once a week on business days, 24 h flow-proportional composite samples are collected at plant inlets and transported at 5 °C (±3 °C) to partner laboratories for analysis. The analytical process involves sample concentration, RNA extraction, and digital RT-PCR/q-RT-PCR to detect and quantify the presence of the SARS-CoV-2 genome in wastewater. Subsequently, data are transferred to Santé publique France, the French National Public Health Agency, for analysis and interpretation. While SUM’EAU has been instrumental in monitoring the COVID-19 pandemic and holds significant potential for broader application, securing sustainable funding for its operation remains a major challenge. Full article

In various applications, dry friction could induce vibrations. A well-known example is frictional braking systems in ground transportation vehicles involving a sliding contact between a rotating and a stationary part. In such scenarios, the emission of high-intensity noise, commonly known as squeal, can present human health risks based on the noise’s intensity, frequency, and occurrences. Despite the importance of squeal in the context of advancing urbanization, the parameters determining its occurrence remain uncertain due to the complexity of the involved phenomena. This study aims to identify a relevant operando indicator for predicting squeal occurrences. To this end, a pin-on-disc test rig was developed to replicate various contact conditions found in road profiles and investigate resulting squealing. Each test involves a multimodal instrumentation, complemented by surface observations. It is illustrated that the enhanced thermal indicator identified is relevant because it is sensitive to the thermomechanical and tribological phenomena involved in squealing. Full article

Many video-based eye trackers rely on detecting and tracking ocular features, a task that can be negatively affected by a number of individual or environmental factors. In this context, the aim of this study was to practically evaluate how the use of a scleral contact lens with two integrated near-infrared lasers (denoted CLP) could improve the tracking robustness in difficult lighting conditions, particularly outdoor ones. We assessed the ability of the CLP (on a model eye) to detect the lasers and to deduce a gaze position with an accuracy better than 1° under four lighting conditions (1 lx, 250 lx, 50 klux and alternating 1 lx /250 lx) on an artificial eye. These results were compared to the ability of a commercial eye tracker (Pupil Core) to detect the pupil on human eyes with a confidence score equal to or greater than 0.9. CLP provided good results in all conditions (tracking accuracy and detection rates). In comparison, the Pupil Core performed well in all indoor conditions (99% detection) but failed in outdoor conditions (9.85% detection). In conclusion, the CLP presents strong potential to improve the reliability of video-based eye-trackers in outdoor conditions by providing easy trackable feature. Full article

In this paper, we present the design of a fractional-order sliding mode observer (FO-SMO) for actuator fault estimation in a quadrotor unmanned aerial vehicle (QUAV) system. Actuator faults can significantly compromise the stability and performance of QUAV systems; therefore, early detection and compensation are crucial. Sliding mode observers (SMOs) have recently demonstrated their accuracy in estimating faults in QUAV systems under matched uncertainties. However, existing SMOs encounter difficulties associated with chattering and sensitivity to initial conditions and noise. These challenges significantly impact the precision of fault estimation and may even render fault estimation impossible depending on the magnitude of the fault. To address these challenges, we propose a new fractional-order SMO structure based on the Caputo derivative definition. To demonstrate the effectiveness of the proposed FO-SMO in overcoming the limitations associated with classical SMOs, we assess the robustness of the FO-SMO under three distinct scenarios. First, we examined its performance in estimating actuator faults under varying initial conditions. Second, we evaluated its ability to handle significant chattering phenomena during fault estimation. Finally, we analyzed its performance in fault estimation under noisy conditions. For comparison purposes, we assess the performance of both observers using the Normalized Root-Mean-Square Error (NRMSE) criterion. The results demonstrate that our approach enables more accurate actuator fault estimation, particularly in scenarios involving chattering phenomena and noise. In contrast, the performance of classical (non-fractional) SMO suffers significantly under these conditions. We concluded that our FO-SMO is more robust to initial conditions, chattering phenomena, and noise than the classical SMO. Full article

We investigate the zero-error coding for computing problems with encoder side information. An encoder provides access to a source X and is furnished with side information $g\left(Y\right)$. It communicates with a decoder that possesses side information Y and aims to retrieve $f(X,Y)$ with zero probability of error, where f and g are assumed to be deterministic functions. In previous work, we determined a condition that yields an analytic expression for the optimal rate $R^{*}\left(g\right)$; in particular, it covers the case where $P_{X,Y}$ is full support. In this article, we review this result and study the side information design problem, which consists of finding the best trade-offs between the quality of the encoder’s side information $g\left(Y\right)$ and $R^{*}\left(g\right)$. We construct two greedy algorithms that give an achievable set of points in the side information design problem, based on partition refining and coarsening. One of them runs in polynomial time. Full article

The aminated sodium lignosulfonate (AELS) was prepared through a Mannich reaction and characterized via FT-IR, TG, SEM and XPS in this study. Subsequently, the adsorption capacity of AELS for methyl blue (MB) was evaluated under various conditions such as pH, adsorbent dosage, contact time, initial concentration and temperature. The adsorption kinetics, isotherms and thermodynamics of AELS for methyl blue were investigated and analyzed. The results were found to closely adhere to the pseudo-second-order kinetic model and Langmuir isotherm model, suggesting a single-molecular-layer adsorption process. Notably, the maximum adsorption capacity of AELS for methyl blue (153.42 mg g⁻¹) was achieved under the specified conditions (T = 298 K, M_AELS = 0.01 g, pH = 6, V_MB = 25 mL, C₀ = 300 mg L⁻¹). The adsorption process was determined to be spontaneous and endothermic. Following five adsorption cycles, the adsorption capacity exhibited a minimal reduction from 118.99 mg g⁻¹ to 114.33 mg g⁻¹, indicating good stability. This study contributes to the advancement of utilizing natural resources effectively and sustainably. Full article

Hardware implementations of cryptographic primitives require protection against physical attacks and supply chain threats. This raises the question of secure composability of different attack countermeasures, i.e., whether protecting a circuit against one threat can make it more vulnerable against a different threat. In this article, we study the consequences of applying logic locking, a popular design-for-trust solution against intellectual property piracy and overproduction, to cryptographic circuits. We show that the ability to unlock the circuit incorrectly gives the adversary new powerful attack options. We introduce LEDFA (locking-enabled differential fault analysis) and demonstrate for several ciphers and families of locking schemes that fault attacks become possible (or consistently easier) for incorrectly unlocked circuits. In several cases, logic locking has made circuit implementations prone to classical algebraic attacks with no fault injection needed altogether. We refer to this “zero-fault” version of LEDFA by the term LEDA, investigate its success factors in-depth and propose a countermeasure to protect the logic-locked implementations against LEDA. We also perform test vector leakage assessment (TVLA) of incorrectly unlocked AES implementations to show the effects of logic locking regarding side-channel leakage. Our results indicate that logic locking is not safe to use in cryptographic circuits, making them less rather than more secure. Full article

Background: Primary cutaneous T-cell lymphomas (CTCLs) are rare lymphoproliferative malignancies characterized by significant morbidity and mortality in advanced disease stages. As curative approaches apart from allogeneic stem cell transplantation are lacking, establishing new treatment options, especially combination therapies, is crucial. Methods: This retrospective study included 11 patients with SS or MF receiving therapy with mogamulizumab in combination with ECP from four European expert centers. The response rates in the skin and blood as well as treatment use and adverse events (AE) were described. Results: 8/11 patients (73%) showed an overall response (OR) in the skin. The mean mSWAT decreased from 98.2 ± 40.8 to 34.6 ± 23.8. The overall response rate (ORR) in the blood was 64% with two complete responses. During combination therapy, the mean number of Sézary cells decreased from 3365.3 × 10⁶/L before treatment to 1268.6 × 10⁶/L. The mean minimum known period without progress was 7.2 months in the skin and 7.6 months in the blood. The most common AEs were mogamulizumab-associated rash (MAR) (45.5%), anemia (27.3%), lymphocytopenia (27.8%), and infusion related reaction (16.7%). No AE led to treatment discontinuation. Conclusions: Our study presents the combination of mogamulizumab and ECP as an effective therapy in the blood and skin in CTCL with good tolerability, similar to mogamulizumab monotherapy. Full article

The recent growth in maturity of paraffin-based hybrid propulsion systems reassesses the possibility to design an alternative Mars Ascent Vehicle (MAV) propelled by a European hybrid motor. As part of the Mars Sample Return (MSR) campaign, a Hybrid MAV would present potential advantages over the existent solid concept funded by NASA through offering increased performance, higher thermal resilience, and lower Gross Lift-Off Mass (GLOM). This study looks at the preliminary design of a two-stage European MAV equipped with HyImpulse’s hybrid engine called the Hyplox10. This Hybrid MAV utilizes the advantages inherent to this type of propulsion to propose an alternative MAV concept. After a careful analysis of previous MAV architectures from the literature, the vehicle is sized with all its components such as the propellant tanks and nozzle, and the configuration of the rocket is established. A detailed design of the primary structure is addressed. This is followed by a Finite Element Analysis (FEA), evaluating the structural integrity under the challenging conditions of Entry, Descent, and Landing (EDL) on Mars, considering both static and dynamic analyses. The outcome is a Hybrid MAV design that demonstrates feasibility and resilience in the harsh Martian environment, boasting a GLOM of less than 300 kg. Full article

This paper proposes a fault detection and isolation (FDI) scheme for a wind turbines subject to actuator faults in both the pitch system and the drive train system. The proposed scheme addresses fault detection and isolation problems using a fault estimation approach. The proposed approach considers the use of a particular class of sliding mode observers (SMOs) designed to maintain the sliding motion even in the presence of actuator faults. The fault detection problem is solved by reconstructing the actuator faults through an appropriate analysis of the nonlinear output error injection signal, which is required to keep the SMO in a sliding motion. To ensure accurate fault reconstruction, only two conditions are required, namely that the faults are bounded and they meet the matching condition. A scheme based on a bank of SMOs is proposed to solve the fault detection and isolation problem in the pitch system. For the drive train system, a scheme using only one SMO is proposed. The performance of the proposed FDI scheme is validated by using a wind turbine benchmark model subjected to several actuator faults. Normalized root mean square error (NRMSE) analysis is performed to evaluate the accuracy of the actuator fault estimations. Full article