This pilot study aims to investigate the role of microRNAs (miRNAs) as early diagnostic biomarkers for asbestos-related respiratory diseases. We conducted a pilot study to explore the plasma miRNA profile in 28 subjects, including 9 unexposed population controls, 9 ILD-free subjects formerly exposed to asbestos, and 10 cases of asbestos-related interstitial lung disease (ILD). Current smokers or subjects with other lung diseases were excluded. We used the receiver operator characteristic (ROC) area under the curve (AUC) to estimate the potential diagnostic accuracy of miRNAs. We also conducted a meta-analysis to estimate the pooled quantitative diagnostic accuracy of the differentially expressed miRNAs, based on their AUC and related 95

Ovarian reserve and reproductive life are closely linked concepts in female reproductive biology. The ovarian reserve consists of primordial follicles and refers to the number and quality of oocytes (eggs) remaining in the ovaries at any given time. Follicular dynamics shape a woman’s reproductive lifespan, ultimately leading to menopause. Elucidating the underlying genetic and molecular pathways of follicle maturation and depletion is thus crucial for understanding menopausal onset and progression, both in normal and pathophysiological contexts, such as primary ovarian insufficiency, defined as menopause before the age of 40. A key factor in ovarian differentiation and fertility maintenance is FOXL2, a forkhead family transcription factor that plays a crucial role in follicle formation and development, ovarian maintenance, and sex determination. By employing a ChIP-Seq approach in mice, we identified a previously unreported binding of FOXL2 to a Tsc1 regulatory region. Our data, along with a thorough literature review, support the hypothesis that FOXL2-mediated activation of Tsc1 in granulosa cells can help maintain primordial follicles in a dormant state by suppressing mTORC1 signalling. Understanding the mechanisms behind ovarian reserve may lay the foundation for developing novel fertility preservation strategies, improving fertility treatment protocols and promoting in vitro activation of cryopreserved ovarian tissue to support folliculogenesis.

BACKGROUND:MicroRNAs (miRNAs) have been proposed as diagnostic biomarkers of asbestos-related cancers, but their role in asbestos-related interstitial lung diseases (ILDs) is unknown. RESEARCH DESIGN AND METHODS:We conducted a pilot study in 30 subjects: 11 unexposed population controls, 8 ILD-free asbestos-exposed subjects, and 11 asbestos-related ILD cases. We used the Receiver Operator Characteristic (ROC) Area Under the Curve (AUC) to estimate the diagnostic accuracy of miRNAs, and volcano plots to assess their differential expression between the study groups. RESULTS:miR-548h-5p was over-expressed in ILD-free asbestos-exposed subjects and demonstrated a 90% accuracy (95% CI: 0.75-1.00) in discriminating them from unexposed subjects, as well as a 96% diagnostic accuracy (95% CI: 0.88-1.00) in differentiating asbestos-related ILD cases from ILD-free asbestos-exposed subjects. miR-6127-3p was over-expressed and showed an accuracy of 85% (95% CI: 0.66-1.00) in discriminating asbestos-related ILD cases from unexposed subjects in plasma. let-7f-5p was over-expressed in the exhaled breath condensate (EBC) of ILD-free asbestos-exposed subjects and showed a 90% accuracy (95% CI: 0.76-1.00) in discriminating them from unexposed subjects. CONCLUSIONS:Our results suggest that the plasma and EBC miRNA profile might serve as a diagnostic biomarker of asbestos-related ILDs.

The COVID-19 crisis has defined the need of novel approaches for a straightforward management of pandemic and epidemic conditions. Here, an approach based on electronic sensing of viral RNA is proposed for both virus detection and variant tracking. The sensing strategy of the Organic Charge-Modulated Field-Effect Transistor (OCMFET) is employed for the development of a multi-sensing platform, capable of parallel evaluation of control references and investigated samples. PCR-free detection of viral genomic RNA is demonstrated at different target concentrations, with optimal discrimination with respect to negative control. Moreover, the same approach is feasible for virus variant tracking, as a screening strategy for mutation detection in PCR-amplified samples: the approach can be used for a rationalization of RNA sequencing procedures, which are difficult to perform in the acute phases of pandemics, but are fundamental for an effective pandemic management. The results pave the way for novel strategies to enhance cost-effectiveness, easiness-of-use in combination with selectivity and sensitivity in virus detection during severe pandemic conditions, and a more effective variant tracking by optimizing the access to sequencing resources even during the acute phases of pandemic.

Gene co-expression network analysis enables identification of biologically meaningful clusters of co-regulated genes (modules) in an unsupervised manner. We present here the largest study conducted thus far of co-expression networks in white blood cells (WBC) based on RNA-seq data from 624 individuals. We identify 41 modules, 13 of them related to specific immune-related functions and cell types (e.g. neutrophils, B and T cells, NK cells, and plasmacytoid dendritic cells); we highlight biologically relevant lncRNAs for each annotated module of co-expressed genes. We further characterize with unprecedented resolution the modules in T cell sub-types, through the availability of 95 immune phenotypes obtained by flow cytometry in the same individuals. This study provides novel insights into the transcriptional architecture of human leukocytes, showing how network analysis can advance our understanding of coding and non-coding gene interactions in immune system cells.

Background: Italy has been the first European Country dealing with SARS-CoV-2, whose diffusion on the territory has not been homogeneous. Among Italian regions, Sardinia represented one of the lowest incidence areas, likely due to its insular nature. Despite this, the impact of insularity on SARS-CoV-2 genetic diversity has not been comprehensively described. Methods: In the present study, we performed the high throughput sequencing of 888 SARS-CoV-2 genomes collected in Sardinia during the first 23 months of pandemics. In addition, 1439 high-coverage SARS-CoV-2 genomes circulating in Sardinia along three years (December 2019 – January 2023) were downloaded from GISAID, for a total of 2327 viral sequences that were characterized in terms of phylogeny and genomic diversity. Results: Overall, COVID-19 pandemic in Sardinia showed substantial differences with respect to the national panorama, with additional peaks of infections and uncommon lineages that reflects the national and regional policies of re-opening and the subsequent touristic arrivals. Sardinia has been interested by the circulation of at least 87 SARS-CoV-2 lineages, including some that were poorly represented at national and European level, likely linked to multiple importation events. The relative frequency of Sardinian SARS-CoV-2 lineages has been compared to other Mediterranean Islands, revealing a unique composition. Conclusions: The genomic diversity of SARS-CoV-2 in Sardinia has been shaped by a complex interplay of insular geography, low population density, and touristic arrivals, leading on the one side to the importation of lineages remaining rare at the national level, and resulting on the other side in the delayed entry of otherwise common variants.

Systemic rheumatic diseases, including conditions such as rheumatoid arthritis, Sjögren’s syndrome, systemic sclerosis, and systemic lupus erythematosus, represent a complex array of autoimmune disorders characterized by chronic inflammation and diverse clinical manifestations. This study focuses on unraveling the genetic underpinnings of these diseases by examining polymorphisms in key genes related to their pathology. Utilizing a comprehensive genetic analysis, we have documented the involvement of these genetic variations in the pathogenesis of rheumatic diseases. Our study has identified several key polymorphisms with notable implications in rheumatic diseases. Polymorphism at chr11_112020916 within the IL-18 gene was prevalent across various conditions with a potential protective effect. Concurrently, the same IL18R1 gene polymorphism located at chr2_103010912, coding for the IL-18 receptor, was observed in most rheumatic conditions, reinforcing its potential protective role. Additionally, a further polymorphism in IL18R1 at chr2_103013408 seems to have a protective influence against the rheumatic diseases under investigation. In the context of emerging genes involved in rheumatic diseases, like PARK2, a significant polymorphism at chr6_161990516 was consistently identified across different conditions, exhibiting protective characteristics in these pathological contexts. The findings underscore the complexity of the genetic landscape in rheumatic autoimmune disorders and pave the way for a deeper understanding of their etiology and the possible development of more targeted and effective therapeutic strategies.

Introduction: Exhaled breath condensate (EBC) sampling has been suggested as a less-invasive and cost-effective method to detect biological macromolecules, including miRNA. To explore the feasibility of its use as a biomarker of early effects of asbestos exposure, we conducted a preliminary test on male volunteers by comparing the miRNA profile in the EBC and the plasma using 2 different sequencing platforms. Methods: Six male volunteers, all retired and unexposed to dust or fumes, participated in the test. RNA was extracted from 200 μL EBC samples and same-size plasma samples. Sample aliquots were processed in 2 laboratories using 2 different sequencing platforms: a MiSeq Illumina® platform and a more performing HiSeq Illumina® platform. Results: The HiSeq3000® sequencing platform identified twice as many unique molecular indexes (UMI)-validated miRNA as the MiSeq® platform. The Spearman’s correlation coefficient between EBC counts and plasma counts was significant in 5/6 subjects with either platform (MiSeq® = 0.128-0.508, P = .026-<.001; HiSeq® = 0.156-0.412, P = .001-<.001). The intraclass correlation coefficient confirmed the consistency of the miRNA profile over the 6 participants with both biospecimens. Exploring the agreement between the EBC and plasma samples with Bland-Altman plots showed that using the HiSeq3000® platform substantially improved the EBC miRNA detection rate. Conclusion: Our preliminary study confirms that, when using the HiSeq® sequencing platform, EBC sampling is a suitable, non-invasive method to detect the miRNA profile in healthy subjects.

Introduction Currently, the health surveillance of past exposure to asbestos conveys scarce hope of improving life expectancy and quality. To uplift the screening capability, we validated our retrospective exposure assessment techniques and explored the feasibility of using the miRNA profile in the exhaled breath condensate (EBC) as a biomarker. Material and Methods We first classified lung fibrosis in the chest HRCT scans of 115 workers formerly exposed to asbestos and retrospectively estimated their exposure. We also assessed past exposure to asbestos and its correlation with the fibre count in the autoptic lung of 24 subjects who died from asbestos-related diseases. Finally, we used an NGS platform to detect miRNAs previously linked to lung cancer and pleural mesothelioma in the EBC of six subjects with no history of past exposure to respiratory hazards. Results The risk of lung fibrosis increased linearly with time-weighted average (TWA, p = 0.0045) and cumulative exposure to asbestos (p = 0.009). An estimated cumulative exposure ≥ 10 fibre/ml-year conveyed an almost 11-fold (95% CI 1.54–75.7) excess risk of lung fibrosis. Cumulative exposure to asbestos correlated well with the fibre count in the autoptic lung (p = <0.0001). There was a good agreement between the miRNA detection rate in the EBC and plasma samples. The Spearman's correlation between EBC and plasma miRNA counts was significant in 5/6 subjects (p = 0.001 – <0.001). The miRNA profile was consistent among the six participants. Conclusions Retrospective exposure estimates can reliably reflect past exposure to asbestos. Parenchymal lung alterations show up in relation to estimates of past asbestos exposure much lower than previously thought. EBC sampling is a non-invasive, easily repeatable method to monitor the miRNA profile. It might be profitably used to detect early treatable effects even in subjects with low-level exposure to asbestos.

The immune system plays a critical role in modulating cancer development and progression. Polymorphisms in key genes involved in immune responses are known to affect susceptibility to cancer. Here, we analyzed 35 genes to evaluate the association between variants of genes involved in immune responses and prostate cancer risk. Thirty-five genes were analyzed in 47 patients with prostate cancer and 43 healthy controls using next-generation sequencing. Allelic and genotype frequencies were calculated in both cohorts, and a generalized linear mixed model was applied to test the relationship between prostate cancer risk and nucleotide substitution. Odds ratios were calculated to describe the association between each single nucleotide polymorphism (SNP) and prostate cancer risk. Significant changes in allelic and genotypic distributions were observed for IL4R, IL12RB1, IL12RB2, IL6, TMPRSS2, and ACE2. Furthermore, a generalized linear mixed model identified statistically significant associations between prostate cancer risk and SNPs in IL12RB2, IL13, IL17A, IL4R, MAPT, and TFNRS1B. Finally, a statistically significant association was observed between IL2RA and TNFRSF1B and Gleason scores, and between SLC11A1, TNFRSF1B and PSA values. We identified SNPs in inflammation and two prostate cancer-associated genes. Our results provide new insights into the immunogenetic landscape of prostate cancer and the impact that SNPs on immune genes may have on affecting the susceptibility to prostate cancer.

The major histocompatibility complex (MHC) loci, the most polymorphic regions within the human genome, encode protein complexes responsible for antigen presentation and CD4+ and CD8+ cell activation. In prostate cancer (PCa), the second most diagnosed cancer in the male population, MHC loci undergo significant changes in their expression patterns, which affect the ability of the immune system to attack and eliminate malignant cells. The purpose of this study was to explore the genetic diversity of human leukocyte antigen (HLA)-A and HLA-B in patients with PCa and healthy controls (HCs) by performing HLA genotyping using NGS technology. The analysis highlighted statistically significant differences (p < 0.05) in the prevalence of three alleles (A*11:01, A*24:02, and B*18:01). Among the HCs analyzed, 14.89% had A*11:01, 20.21% had A*24:02, and 30.61% had B*18:01; while 5.21% of patients with PCa presented A*11:01, 9.38% presented A*24:02, 18.08% presented B*18:01. Odds ratio (OR) calculations underlined a negative association between the three alleles and the risk of PCa (OR < 1). The results presented in this study suggest a protective role of A*11:01, A*24:02, and B*18:01 in PCa.

The immunomodulatory effects of HLA-G expression and its role in cancers, human liver infections and liver transplantation are well documented, but so far, there are only a few reports addressing autoimmune liver diseases, particularly autoimmune hepatitis (AIH).Method and materialsWe analyzed the genetic and phenotypic characteristics of HLA-G in 205 type 1 AIH patients (AIH-1) and a population of 210 healthy controls from Sardinia (Italy).ResultsAnalysis of the HLA-G locus showed no substantial differences in allele frequencies between patients and the healthy control population. The HLA-G UTR-1 haplotype was the most prevalent in both AIH-1 patients and controls (40.24% and 34.29%). Strong linkage was found between the HLA-G UTR-1 haplotype and HLA-DRB1*03:01 in AIH-1 patients but not controls (D’ = 0.92 vs D’ = 0.50 respectively; P = 1.3x10-8). Soluble HLA-G (sHLA-G) levels were significantly lower in AIH-1 patients compared to controls [13.9 (11.6 – 17.4) U/mL vs 21.3 (16.5 – 27.8) U/mL; P = 0.011]. Twenty-four patients with mild or moderate inflammatory involvement, as assessed from liver biopsy, showed much higher sHLA-G levels compared to the 28 patients with severe liver inflammation [33.5 (23.6 – 44.8) U/mL vs 8.8 (6.1 – 14.5) U/mL; P = 0.003]. Finally, immunohistochemistry analysis of 52 liver biopsies from AIH-1 patients did not show expression of HLA-G molecules in the liver parenchyma. However, a percentage of 69.2% (36/52) revealed widespread expression of HLA-G both in the cytoplasm and the membrane of plasma cells labeled with anti-HLA-G monoclonal antibodies.ConclusionThis study highlights the positive immunomodulatory effect of HLA-G molecules on the clinical course of AIH-1 and how this improvement closely correlates with plasma levels of sHLA-G. However, our results open the debate on the ambiguous role of HLA-G molecules expressed by plasma cells, which are pathognomonic features of AIH-1.

In December 2019, a novel coronavirus emerged in Wuhan, China, rapidly spreading into a global pandemic. Italy was the first European country to experience SARS-CoV-2 epidemic, and one of the most severely affected during the first wave of diffusion. In contrast to the general restriction of people movements in Europe, the number of migrants arriving at Italian borders via the Mediterranean Sea route in the summer of 2020 had increased dramatically, representing a possible, uncontrolled source for the introduction of novel SARS-CoV-2 variants. Importantly, most of the migrants came from African countries showing limited SARS-CoV-2 epidemiological surveillance. In this study, we characterized the SARS-CoV-2 genome isolated from an asymptomatic migrant arrived in Sardinia via the Mediterranean route in September 2020, in comparison with SARS-CoV-2 isolates arrived in Sicily through the Libyan migration route; with SARS-CoV-2 isolates circulating in Sardinia during 2020; and with viral genomes reported in African countries during the same summer. Results showed that our sequence is not phylogenetically related to isolates from migrants arriving in Sicily, nor to isolates circulating in Sardinia territory, having greater similarity to SARS-CoV-2 genomes reported in countries known for being sites of migrant embarkation to Italy. This is in line with the hypothesis that most SARS-CoV-2 infections among migrants have been acquired prior to embarking to Italy, possibly during the travel to or the stay in crowded Libyan immigrant camps. Overall, these observations underline the importance of dedicated SARS-CoV-2 surveillance of migrants arriving in Italy and in Europe through the Mediterranean routes.

Background Thyroid hormones (THs) inhibit hepatocellular carcinoma (HCC) through different mechanisms. However, whether microRNAs play a role in the antitumorigenic effect of THs remains unknown. Methods By next generation sequencing (NGS) we performed a comprehensive comparative miRNomic and transcriptomic analysis of rat hepatic preneoplastic lesions exposed or not to a short-term treatment with triiodothyronine (T3). The expression of the most deregulated miRs was also investigated in rat HCCs, and in human hepatoma cell lines, treated or not with T3. Results Among miRs down-regulated in preneoplastic nodules following T3, co-expression networks revealed those targeting thyroid hormone receptor-β (Thrβ) and deiodinase1, and Oxidative Phosphorylation. On the other hand, miRs targeting members of the Nrf2 Oxidative Pathway, Glycolysis, Pentose Phosphate Pathway and Proline biosynthesis – all involved in the metabolic reprogramming displayed by preneoplastic lesions– were up-regulated. Notably, while the expression of most miRs deregulated in preneoplastic lesions was not altered in HCC or in hepatoma cells, miR-182, a miR known to target Dio1 and mitochondrial complexes, was down-deregulated by T3 treatment at all stages of hepatocarcinogenesis and in hepatocarcinoma cell lines. In support to the possible critical role of miR-182 in hepatocarcinogenesis, exogenous expression of this miR significantly impaired the inhibitory effect of T3 on the clonogenic growth capacity of human HCC cells. Conclusions This work identified several miRNAs, so far never associated to T3. In addition, the precise definition of the miRNA-mRNA networks elicited by T3 treatment gained in this study may provide a better understanding of the key regulatory events underlying the inhibitory effect of T3 on HCC development. In this context, T3-induced down-regulation of miR-182 appears as a promising tool.

INTRODUCTION Chronic Myeloid Leukemia (CML) has become a manageable and possibly curable disease due to the use of Tyrosine Kinase inhibitors (TKI). Although the immune system has been shown to be dysfunctional in newly diagnosed CML patients, TKI therapy may restore the function of the immune cells, and thus, the immune system may play a role in the leukemia control. In this complex immune interplay, the modulation and possible role of Human Endogenous Retroviruses (HERVs) expression is still poorly characterized. HERVs represent ~8% of the human genome and have been repeatedly domesticated by the host for major physiological functions, such as the development of placenta and the shaping of complex networks, including the main antiviral pathways of innate immunity. Accordingly, HERVs are still able to both modulate and be influenced by the host immune system and are thus highly investigated in several pathological contexts of immune dysregulation, such as autoimmunity and cancer. The aim of this study was to evaluate the overall HERV transcription profile in CML patients as compared to healthy controls (HC), to explore the regulatory influence of HERVs and their links to CML immune pathogenesis. METHODS The analysis included 10 HC and a total of 23 CML (11 Male, 7 Female, age range 45-84) being either at diagnosis (5 patients) or after TKI treatment (18 patients) for a minimum of 24 months and a molecular response of MR3 or deeper. Total RNA from peripheral blood cells was deep sequenced to obtain transcriptomic profiles, analyzed for the set of HERVs (~3300) and cellular genes (~60700) expression. RESULTS HERV transcriptome is significantly modulated in CML patients, clearly dividing them from HC. In addition, among CML patients, specific signatures of HERV modulation allows to distinguish actively affected patients from the ones that are in molecular remission after TKI treatment. The latter are also very different from HC in terms of HERV expression, possibly due to residual modulation by the disease and/or the prosecution of TKI therapy. Differential expression analyses allowed to identify a total of 575 and 568 deHERVs significantly modulated between CML patients at diagnosis and HC and between CML treated patients in molecular remission (MR3-MR5) and HC (padj: 3.36e-96 to 0.0098 and 8.32e-69 to 0.0099, respectively). In addition, 267 deHERVs were found comparing the same CML patients at diagnosis and during remission (padj: 5.55e-81 to 0.0099). The differential human gene expression revealed about 5800 dysregulated genes (4782 up and 1019 down, padj: 3.96e-260 to 9.5e-30) in CML pts vs HC. The top overexpressed genes were DDX17, VPS13B, PHIP, SMG1, STK10, LRRFIP1 with under-regulation of RNF213, MIR1276, ZRANB2-AS1, AC138028.4 genes, among others. Pairwise comparisons of 5 CML at diagnosis vs samples after treatment with imatinib resulted in a downregulation of ZNF831, EVL, TXK, HAPLN3, SEPTIN1, TNFRSF25 and upregulation of LTF, MPO, ABCA13, BPI, BCL2L15, ERG, MMP8, DEFA4, ANLN, SCN9A genes. CONCLUSIONS The present study provides the first high-throughput snapshot of HERV transcriptome in CML and identify specific sets of HERVs that can distinguish patients at diagnosis, patients in molecular response to TKI therapies and HC. Patient's gene expression profiles revealed that during molecular remission and under continuous treatments is present a disregulated pathway that is different from healthy individuals. Our results can give insights on the role of HERVs in the biology of CML and may add information useful to select the most effective pathways to target to maximize an advantageous immune response and promote a successful TKI discontinuation. Moreover, the following question is open: is there a potential regulatory role of HERVs in the genomic balance of CML patients? Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

This study was aimed at characterizing the gut microbiota (GM) and its functional profile in two groups of Sardinian subjects with a long healthy life expectancy, overall named Long-Lived Subjects (LLS) [17 centenarians (CENT) and 29 nonagenarians (NON)] by comparing them to 46 healthy younger controls (CTLs). In addition, the contribution of genetics and environmental factors to the GM phenotype was assessed by comparing a subgroup of seven centenarian parents (CPAR) with a paired cohort of centenarians' offspring (COFF). The analysis was performed through Next Generation Sequencing (NGS) of the V3 and V4 hypervariable region of the 16S rRNA gene on the MiSeq Illumina platform. The Verrucomicrobia phylum was identified as the main biomarker in CENT, together with its members Verrucomicrobiaceae, Akkermansia and Akkermansia muciniphila. In NON, the strongest associations concern Actinobacteria phylum, Bifidobacteriaceae and Bifidobacterium, while in CTLs were related to the Bacteroidetes phylum, Bacteroidaceae, Bacteroides and Bacteroides spp. Intestinal microbiota of CPAR and COFF did not differ significantly from each other. Significant correlations between bacterial taxa and clinical and lifestyle data, especially with Mediterranean diet adherence, were observed. We observed a harmonically balanced intestinal community structure in which the increase in taxa associated with intestinal health would limit and counteract the action of potentially pathogenic bacterial species in centenarians. The GM of long-lived individuals showed an intrinsic ability to adapt to changing environmental conditions, as confirmed by functional analysis. The GM analysis of centenarians' offspring suggest that genetics and environmental factors act synergistically as a multifactorial cause in the modulation of GM towards a phenotype similar to that of centenarians, although these findings need to be confirmed by larger study cohorts and by prospective studies.

Lipodystrophy (LD) indicates a group of rare disorders, with generalized or partial loss of white adipose tissue (WAT) often associated with metabolic derangements. Heterogeneity/wide spectrum of the disease and lack of biomarkers make diagnosis often difficult. MicroRNAs are important to maintain a correct WAT function and WAT is a source of circulating miRNAs (cmiRs). miRNAs from 320 family were previously detected in the WAT and variably associated to the metabolic syndrome. Our aim was then to investigate if LD can result in altered abundance of cmiRs-320. We collected samples from a cohort of LD subjects of various subtypes and from age matched controls. Use of quantitative PCR determined that cmiRs- 320a-3p, 320b, 320c, 320e are upregulated, while 320d is downregulated in LD. CmiRs-320 power as classifiers was more powerful in the most extreme and defined forms of LD, including the generalized and the Dunnigan subtypes. cmiR-320a-3p showed significant inverse relationships with plasma leptin (P < 0.0001), typically low in LD. The hepatic enzymes gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and the marker of inflammation C-reactive protein (CRP) were inversely related to cmiR 320d (P < 0.05, for CRP and GGT; P < 0.01, for AST and ALT). Gene ontology analysis revealed cell-cell adhesion as a process regulated by 320 miRNAs targets, thus disclosing a novel route to investigate origin of WAT loss/dysfunction. In conclusion, cmiRs-320 constitute novel biomarkers of LD, abundance of miR320a-3p is inversely associated to indicators related to WAT function, while downregulation of cmiR-320d predicts an altered hepatic profile and higher inflammation.

Parkinson’s disease (PD) is a clinically heterogenic disorder characterized by distinct clinical entities. Most studies on motor deficits dichotomize PD into tremor dominant (TD) or non-tremor dominant (non-TD) with akinetic-rigid features (AR). Different pathophysiological mechanisms may affect the onset of motor manifestations. Recent studies have suggested that gut microbes may be involved in PD pathogenesis. The aim of this study was to investigate the gut microbiota and metabolome composition in PD patients in relation to TD and non-TD phenotypes. In order to address this issue, gut microbiota and the metabolome structure of PD patients were determined from faecal samples using 16S next generation sequencing and gas chromatography–mass spectrometry approaches. The results showed a reduction in the relative abundance of Lachnospiraceae, Blautia, Coprococcus, Lachnospira, and an increase in Enterobacteriaceae, Escherichia and Serratia linked to non-TD subtypes. Moreover, the levels of important molecules (i.e., nicotinic acid, cadaverine, glucuronic acid) were altered in relation to the severity of phenotype. We hypothesize that the microbiota/metabolome enterotypes associated to non-TD subtypes may favor the development of gut inflammatory environment and gastrointestinal dysfunctions and therefore a more severe α-synucleinopathy. This study adds important information to PD pathogenesis and emphasizes the potential pathophysiological link between gut microbiota/metabolites and PD motor subtypes.

RIALE (Remote Intelligent Access to Lab Experiment) is a concept designed to supplement school science laboratories. Its multifunctional platform for innovative learning applications offers a multimodal approach of science. During Lab experiments Internet of Things (IoT) devices collect data, while an Artificial Intelligence (AI) tool is trained to recognize the tools, identify procedures and protocol phases, highlight the results of quantitative observations and tag collected data in a Timeline enriched with tagged additional educational contents (videos, external links, etc.). After remotely witnessing live the Lab experiment, students will access all educational contents from the platform to go deeper into single aspects of the experiment. A second AI tool will explore students' approaches to learning, enabling us, in the long term, to obtain a user-friendly tool that will give information on students' learning styles and help adapt teaching to their learning needs and styles. The first RIALE experiment deals with bioinformatics analysis. The educational scenario deals with exome sequencing and related scientific concepts (family tree, inheritance, genes…).