Institut de Chimie de Nice

Abstract Immune checkpoint inhibitors (ICI) have revolutionized cancer treatment, but their efficacy has now reached a plateau. ICIs are the first class of treatment targeting the crosstalk between immune and tumor cells, making it crucial to understand the complex interactions within the tumor microenvironment (TME) to enhance therapeutic responses. The elevated consumption of resources by cancer cells, coupled with limited vascularization, often results in a TME that is deficient in nutrients, leading to competition for resources between cancer and stromal cells. Consequently, targeting tumor metabolism has emerged as a promising strategy to improve the efficacy of ICIs. Through metabolomic analysis, we have identified metabolic alterations in melanoma cells that are resistant to ICIs, specifically an increase in arginine synthesis and upregulation of ASS1, the rate-limiting enzyme in this pathway. By using gain and loss of function models, as well as a pharmacological inhibitor specific for ASS1, we demonstrated that modulations in the expression or activity of ASS1 is associated with translational reprogramming, characterized by an inhibition of the cap-dependent mRNA translation mediated through mTORC1/4EBP1 axis. We also demonstrated that targeting ASS1 in vivo , resensitize tumors initially resistant to ICI. Taken together, our results highlight the interaction between modulations of arginine synthesis pathway, mRNA translation reprogramming, antitumor immunity, and restauration of sensitivity to anti-PD-1. Our work also demonstrates the therapeutic potential of targeting arginine synthesis pathway, and especially ASS1, to offer new treatments to patients suffering from cutaneous melanoma resistant to ICIs.

Although the interaction between groundwater (GW) and surface water (SW) has been the subject of numerous studies, few of them have focused on braided river environments. Yet these environments form essential freshwater resources and unique ecosystems. This work analyses GW-SW interactions in the Var River alluvial plain (30 km²), which is located in south-east France. The alluvial aquifer of the Var River is a crucial resource for the nearby, densely populated coastal area of the French Riviera. The objective is therefore twofold: i) to improve the conceptual understanding of GW-SW exchanges in an anthropized Mediterranean braided river, and ii) to support the operational management of the water resource. In order to achieve a multi-scale understanding of the different processes involved in GW-SW interactions, a multidisciplinary approach is being implemented in the Var alluvial plain. It incorporates methods from hydrometry, hydrogeophysics, geochemistry, aerial and satellite imaging, hydrosedimentology and numerical modelling. Here, we show results obtained by combining two methods: unmanned aerial vehicle (UAV)-based infrared thermal imagery and electrical resistivity tomography (ERT). Thermal infrared imaging of the Var riverbed was carried out in July 2025 (when piezometric levels began to decrease) using a light-weight UAV, and ERT was performed at four study sites along the river between September and November 2025 (when piezometric levels were at their lowest). The results obtained led to a new conceptualization of the connectivity and interactions between the river and the aquifer. This conceptualization is intended to be further enriched by combining more results from the multidisciplinary approach, particularly from a fully integrated modelling of surface and subsurface flows.

The uneven detection of prebiotic organic compounds in meteorites-where amino acids and nucleobases are commonly identified but sugars remain rare and poorly characterized-limits our understanding of extraterrestrial organic chemistry. This discrepancy is striking given that laboratory simulations of interstellar ice chemistry readily produce complex sugars. Here we report the simultaneous analysis of sugar and amino acid enantiomers in a meteorite sample. Multiple aldoses were detected in the Orgueil meteorite, including ribose, arabinose, xylose, lyxose, and the ketopentose ribulose, several of which display near-racemic distributions consistent with an extraterrestrial origin. Recovery experiments demonstrate that sugar abundances are severely underestimated. Despite this limitation, pentose abundances are comparable to those of some C4-C5 amino acid enantiomers, implying higher true concentrations. These results indicate efficient abiotic sugar formation in space and suggest that meteorites may have delivered a broader range of prebiotically relevant sugars to early Earth than previously recognized.

In an effort to reduce global dependence on fossil-based polymers and advance toward a more sustainable materials industry, research over recent decades has increasingly focused on the development of bio-based polymers and broadening their potential applications. Within this context, the present study investigates nanocomposites based on poly(butylene succinate-co-butylene adipate) (PBSA), reinforced with two types of nanofillers: silicon dioxide nanoparticles (SiO2 NPs) and cellulose nanofibrils (CNFs). The main objective of this work is to examine how the morphology, geometry, and chemical nature of the nanofillers influence the thermal, mechanical, and barrier properties of PBSA, as well as its biodegradability. For each nanofiller, three formulations were prepared, containing 1, 2, and 5 wt% of filler, respectively. Scanning electron microscopy (SEM) analysis confirmed good dispersion and minimal aggregation in the SiO2-based systems, whereas marked aggregation was observed in the CNF-based samples. Thermal analysis indicated that the intrinsic thermal properties of neat PBSA were largely preserved. Mechanical testing revealed improvements in both the elastic modulus and elongation at break for most nanocomposite samples. In particular, CNFs provided the most consistent reinforcing effect, with enhancements of approximately 40% in the elastic modulus (495.4 vs. 356.4 GPa in neat PBSA) and 52% in elongation at the break (185.1 vs. 122.0% in neat PBSA) with 5 wt% loading. Additionally, the incorporation of nanofillers did not alter the surface hydrophilicity, but it did improve the oxygen barrier performance and enhanced disintegration under composting conditions. Overall, these findings demonstrate the promising potential of PBSA-based nanocomposites for sustainable rigid packaging applications.

The dissolution behaviour of poly(styrene-co-acrylonitrile) (SAN) was examined across a broad temperature range to identify the governing thermodynamic and kinetic factors. Two high-boiling solvents with contrasting affinities for SAN, namely diethyl succinate (DS, RED = 0.69) and triethyl citrate (TC, RED = 1.37), were selected to study dissolution below and above the SAN glass transition temperature ( T g ≈ 105 °C). Isothermal mixing calorimetry (30–150 °C) showed complete SAN dissolution in DS above 45 °C, with exothermic dissolution enthalpies decreasing from 20 J g⁻¹ at 45 °C to 6 J g⁻¹ at 120 °C, the latter reflecting polymer–solvent interactions once the glassy-rubbery transition no longer contributes. In TC, SAN did not dissolve at 30 °C and was only partially dissolved up to 80 °C; complete dissolution occurred only above T g , with an enthalpy of ∼6 J g⁻¹ at 120 °C. ATR-FTIR monitoring revealed strong effects of solvent quality and temperature on induction time. SAN chains appeared in solution after 480 s in DS but after ∼5000 s in TC at 45 °C, evidencing significant segmental-relaxation limitation in TC. Above T g , induction times sharply decreased to 120 s in DS and 360 s in TC at 120 °C. Isoconversional kinetic analysis showed that dissolution in DS above T g is diffusion-controlled, with low activation energies (6–15 kJ mol⁻¹). Below T g , SAN dissolution transitions from segmental-relaxation-controlled (increasing to 41 kJ mol⁻¹) to diffusion-controlled at higher conversion. Dissolution in TC below T g exhibited even stronger relaxation control, with E a reaching 116 kJ mol⁻¹ . • Dissolution enthalpy shifts from transition-driven below T g to mixing above T g . • Induction time in the poor solvent approaches that of the good solvent above T g . • Below T g , SAN dissolution is governed by segmental relaxations and diffusion. • Above T g , SAN dissolution follows a diffusion-limited, Fickian mechanism.

of congruent colors and shapes did impact taste perception. Participants associated angular shapes and the green color with sourness. The study highlights the role of visual cues in shaping taste experiences.Whereas the previous study altered passive perception, Parra et al. 5 explored how a conversational agent, MyndFood, can actively promote mindful cooking and eating. In a study with 40 participants, those who interacted with the mindful version of the agent reported greater enjoyment and food awareness while preparing sushi compared to those who interacted with a non-mindful version. The findings suggest that conversational agents can enhance the cooking and eating experience by promoting mindfulness.Addressing the different challenge of accessibility, Welewatta et al. 6 developed SEMA, a multisensory system that uses tactile, auditory, and somatosensory cues to help visually impaired students experience and interpret paintings. Tested with 22 visually impaired participants, the system showed strong potential, with 92.6% of users preferring it, and could enhance art experiences for the visually impaired community.Finally, turning to human-machine interaction in critical settings, Evangelou et al. 7 studied how mid-air haptic technology affects user agency in gesture-based interactions, particularly in automotive settings. They found that mid-air haptics increased users' sense of agency compared to visual feedback, regardless of the meaning behind the feedback. The study involved 36 participants who completed a time perception task using gesture poses with different sensory feedback types. The results showed a positive association between mid-air haptics and user agency, trust, and usability, highlighting its potential benefits in automotive contexts.Taken together, these five articles illustrate the breadth and potential of multisensory research at the frontier of disciplines.They demonstrate how technology can both model and personalize our environments to improve cognitive performance (Bartoletti et al. 3 ), while also revealing how specific visual cues can alter our core perception of taste (Guberman et al. 4 ). These studies pave the way for concrete applications, whether by enriching daily experiences like cooking (Parra et al. 5 ) or by compensating for sensory deficits to make art accessible to the visually impaired (Welewatta et al. 6 ).Finally, they highlight the importance of sensory feedback in enhancing user agency and trust in complex interactions, such as in-car gesture controls (Evangelou et al. 7 ). These contributions, spanning cognition, perception, accessibility, and human-computer interaction, confirm that multisensory integration is a critical field for shaping future human experiences.

It remains unclear whether altered bone density may be a stability issue in stemless reverse shoulder arthroplasty (RSA). This was a retrospective multicentric study. Patients with stemless RSA with two-year postoperative shoulder X-ray and clinical data were included. Measurement of proximal humeral cortical bone thickness (CBT avg) on postoperative radiography was used to assess bone density. 68 patients (mean age, 67.0 years) were included. CBT avg < 6mm (osteoporosis) at two years was reported in 22.2% (2/9) of patients with humeral loosening and 35.6% (21/59) without humeral loosening (p = 0.7073). After adjustment for age and body mass index (BMI), CBT avg < 6mm was not significantly associated with humeral loosening at two years (OR 0.37; 95% CI 0.04-2.21). Factors associated with humeral loosening vs. no humeral loosening at two years were BMI (24.2 vs. 27.9kg/m2; p = 0.0131), cervico-diaphyseal angle < 140° at two years (66.7% vs. 16.9%; p = 0.0039) and lateralization of polyethylene (100% vs. 59.3%; p = 0.0217). These results suggest that radiological evaluation of bone density does not predict early migration of stemless RSA implants. Some clinical factors such as BMI or implant configuration were associated to early implant migration, but never led to implant removal.