Institute of Biomedical Technologies

Tissue-level phase transitions are emerging as a crucial mechanism in tumour development and metastasis. When becoming invasive, epithelial tumours undergo a transition from a solid-like state to a more fluid-like one. Although the contributions of cell adhesions, traction forces and cell migration for such behaviour are known, the exact biophysical and molecular mechanisms controlling these transitions are not fully understood. Here we show that breast cancer cell fluidity is regulated by IRSp53, a protein linking plasma membranes to the cytoskeleton. In both two-dimensional monolayers and three-dimensional spheroids, the depletion of IRSp53 increases fluidity and active wetting of the substrate due to a decrease in intercellular friction and enhanced local cell rearrangements. Molecularly, IRSp53 interacts with the junctional protein Afadin to control global tensile state and active wetting, establishing these proteins as key regulators of epithelial collectives' viscosity in breast cancer tumouroids. In breast cancer patient samples, low IRSp53 expression levels and aberrant localization correlate with worse clinical outcomes. These findings support the broader relevance of IRSp53-regulated mechanics in epithelia and their potential prognostic value in cancer.

Antarctic microorganisms have developed extraordinary strategies for adaptation. They have also demonstrated the ability to produce various biopolymers in response to environmental stress. The demand for biopolymers is constantly increasing and is expected to grow further. Among emerging biomaterials, bacterial cellulose (BC) is generating significant interest due to its unique characteristics that distinguish it from plant-based cellulose. BC exhibits higher purity, water-holding capacity, and tensile strength compared to its plant-based counterpart. Furthermore, BC can be obtained through environmentally friendly protocols. Several bacterial strains have already been identified as cellulose producers, including Komagataeibacter xylinus. In this study, a marine bacterial strain named Pseudomonas sp. ef1, isolated from a consortium associated with the Antarctic ciliate Euplotes focardii, was tested for cellulose production. We found that this Antarctic Pseudomonas can produce BC in conditions that appear unique to this bacterial strain. Furthermore, the final BC product is structurally different from that obtained from the well-known BC producer Komagataeibacter xylinus. Additionally, a putative cellulose synthase was identified from the Pseudomonas sp. ef1 genome, exhibiting unique characteristics that may account for the unique BC production capability of this Antarctic marine Pseudomonas. The versatility of BC opens numerous applications, including in papermaking, food, pharmaceutical, and biomedical sectors.

The vaginal microbiota (VMB), predominantly shaped by Lactobacillus species, plays a crucial role in maintaining vaginal health and preventing infections. However, its delicate balance is increasingly challenged by the widespread use of antibiotics and the consequent rise in antibiotic resistance genes (ARGs). While the VMB has been recognized as a potential reservoir for ARGs, limited research has explored how microbial composition, antibiotic exposure, and individual behavioral factors converge to shape the vaginal resistome. In this cross-sectional study, vaginal swabs were collected from 105 reproductive-age Caucasian women. The VMB composition was characterized and classified into Community State Types (CSTs), by sequencing the hypervariable V3-V4 regions of the bacterial 16S rRNA gene. In order to highlight common patterns of abundance among taxa, a co-abundance groups (CAGs) analysis was performed. We assessed the distribution of 14 ARGs conferring resistance to macrolides, tetracyclines, beta-lactams, and quinolones along with two associated transposons by means of PCR. An overall composite ARGs score was also calculated. Participants completed detailed questionnaires assessing demographics and behavioral factors, with a particular focus on both health- and antibiotic-related behaviors. Statistical analyses examined associations between ARG prevalence, vaginal microbiome composition and relevant exposures. CSTs I and III were the most prevalent, with the most frequently detected ARGs being erm(F), tet(M), erm(B), erm(A), and tet(W), each present in over 65% of participants. ARG presence was positively correlated with a higher vaginal microbiome alpha-diversity. Moreover, BV-associated bacterial taxa showed strong associations with ARGs, while Lactobacillus species generally exhibited negative correlations. Smoking, a higher body mass index (BMI), presence of Candida spp. and a history of antibiotic use were significantly associated with increased ARG prevalence, whereas oral contraceptive use and higher diet quality scores were negatively associated. Correlating together the relative abundances of the microbial CAGs and the presence/absence of specific ARGs, we found a positive association between several genes related to macrolide and tetracycline resistance and the Gardnerella-Prevotella CAG. Additionally, the Gardnerella-Prevotella, and the Streptococcus CAGs were positively correlated to the total ARG score, whereas the L. crispatus/jenesenii/gasseri CAG was negatively correlated. These findings underscore the role of the VMB as a dynamic reservoir of ARGs and highlight the influence of individual lifestyle and antibiotic-related behaviors on ARG dissemination in the vaginal niche. This supports the need for integrated public health strategies that combine antibiotic stewardship with targeted lifestyle and behavioral interventions, as well as the development of individualized therapeutic approaches.

BackgroundMitochondrial membrane protein–associated neurodegeneration (MPAN) from the neurodegeneration with brain iron accumulation (NBIA) family is a rare neurodegenerative disease marked by α‐synuclein aggregation, brain iron accumulation, and midbrain dopaminergic neuron degeneration.ObjectiveThe mechanisms driving neuron vulnerability remain unclear. Our study aimed to develop a patient‐derived disease model replicating key pathologies of patient brains.MethodsWe generated induced pluripotent stem cell–derived midbrain dopaminergic neurons from MPAN patients and examined ultrastructural and biochemical markers of pathology.ResultsMPAN patient neurons displayed α‐synuclein aggregation, axonal swellings, iron accumulation, and severe membrane destruction. In addition, levels of the major histocompatibility complex class I (MHC‐I), linked to cellular stress and neurodegenerative processes, were elevated in patient neurons. Treatment with acetyl‐leucine, a potentially neuroprotective compound, decreased MHC‐I.ConclusionsThis first patient‐derived neuronal model of MPAN provides a useful tool for further research aimed at unraveling the complexities of this disease and developing potential therapeutic interventions. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

IntroductionMicroRNAs (miRNAs) are emerging as promising biomarkers of neuroinflammation and may capture the influence of lifestyle and environmental exposures in people with multiple sclerosis (pwMS). The EXPOSITION study[1] aims to elucidate relationships between internal exposome markers including miRNA profiles and clinical, demographic, and lifestyle factors in pwMS. Objective(s) To assess the associations between the relative expression of five candidate miRNAs and clinical, demographic, and lifestyle variables, with a particular focus on the exposome and functional and psychological outcomes in pwMS. MethdsIn this cross-sectional analysis, we included 139 pwMS (median age 45 years [IQR: 35–56], 65% female) from the provinces of Pavia and Milan in the Lombardy region of Italy. Relative expression levels of five candidate miRNAs (mir30, mir146, mir330, mir574, mir664) were quantified and compared across clinical and lifestyle categorical variables groups using the Mann-Whitney U test (for binary variables) or the Kruskal-Wallis test (for variables with more than two categories). Spearman correlation analyses were conducted to assess the relationship between each miRNA and continuous variables, including age, BMI, EDSS, dietary inflammatory index, and quality of life scores. ResultsThere were no statistically significant differences in microRNA expression between EDSS disability groups or across most clinical or lifestyle variables. Notably, mir146 expression was significantly higher in participants with a pro-inflammatory dietary pattern compared to those with an anti-inflammatory pattern (p = 0.0187), and mir146 was positively correlated with the mental health component of the quality of life MSQoL-29 questionnaire (rho = 0.336, p = 0.0174) [Table 1]. In contrast, higher disability status (EDSS >4) was significantly associated with older age (median 51 vs. 44 years, p = 0.047), more frequent prior relapses (94% vs. 69%, p = 0.040), and lower physical (p = 0.039) and mental (p = 0.034) quality of life. Significant group differences were also observed for MS type (p = 0.008), MS stage (p = 0.034), and occupational status (p = 0.063, trend) between the two EDSS groups. No significant associations were identified between disability status and microRNA expression, diet category, physical activity, or MRI lesion status. ConclusionsIn this preliminary analysis, higher disability among pwMS was more strongly linked to clinical history, age, and quality of life than to lifestyle factors or circulating miRNA levels. Mir146 may act as a molecular intermediary between dietary inflammation, mental health, and neuroinflammatory processes in MS. These findings highlight the need for replication and longitudinal validation in larger, independent cohorts.

Digital Twin (DT) has emerged as a promising solution for channel estimation. By leveraging high-resolution 3D models of the scenario and ray-tracing simulations, DT could provide valuable site-specific prior knowledge on the channel’s space-time (ST) invariant features of the multipath environment, such as angles of arrival, angles of departure, and propagation delays. However, the real-time characterization of these features imposes computational constraints on ray-tracing simulations, hence limiting the prior knowledge of the multipath environment and corresponding ST features, and degrading estimation accuracy. In this paper, we propose and investigate, for the first time, three distinct DT-empowered low-rank methods for channel estimation, under different degrees of prior knowledge corresponding to limited number of paths provided by DT. Specifically, these methods perform modal projection onto a joint space-time, a spatial, and a temporal subspace. We compare our proposed methods with state-of-the-art techniques, and evaluate their performance in a synthetic scenario. Numerical results show that robustness, when prior knowledge is limited to few paths, is achieved when exploiting only temporal features, while estimation accuracy is attained when joint space-time features are considered.

Abstract COVID-19 Health Certificates represented a key policy in Europe during the COVID-19 pandemic and were introduced globally by the World Health Organization to strengthen pandemic preparedness. This article undertakes a comparative analysis of COVID-19 Health Certificate policies, and their underlying narratives and framings in nine European countries. Policies differed across European nations in timing, scope, and stringency of the measures entailed and were often subject to major controversies and heated public debates. By tracing their distinct policy narratives (providing emergency response, restoring social and economic activities, and incentivizing vaccination), we suggest that Certificates also served as a proxy for other, highly controversial measures (such as vaccine mandates). When this happened, they were met with intense pushbacks from citizens. Additionally, we show that scientific evidence was differently appropriated in national policy narratives, and that concerns commonly associated with novel digital health technologies (e.g. privacy) did not rise to prominence in public debates.

Alzheimer's disease (AD) is a progressive, complex, multifactorial, neurodegenerative disease and accounts for most cases of dementia. The currently approved therapy includes cholinesterase inhibitors, NMDA-receptor antagonists and monoclonal antibodies. However, these medications were gradually discovered to be ineffective in removing the root of AD pathogenesis, having only symptomatic effects. Thus, the priority remains prevention and clarifying AD etiology. A better understanding of the neuroprotective mechanisms undertaken by specific genes is crucial to guide the design of novel therapeutic agents via selective ligands and precision medicine. In this review, we present a perspective of the physiological phase of the AD spectrum, of risk factors in AD with a focus on therapeutic approaches in three categories: neurotransmitters/ion modulations, peptide deposit control and aspecific treatments, followed by a discussion of treatment limitations. An overview of innovative strategies and non-pharmaceutical ancillary support is given.