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Abstract Hepatitis B virus (HBV) may integrate into the genome of infected cells and contribute to hepatocarcinogenesis. However, the role of HBV integration in hepatocellular carcinoma (HCC) development remains unclear. In this study, we apply a high-throughput HBV integration sequencing approach that allows sensitive identification of HBV integration sites and enumeration of integration clones. We identify 3339 HBV integration sites in paired tumour and non-tumour tissue samples from 7 patients with HCC. We detect 2107 clonally expanded integrations (1817 in tumour and 290 in non-tumour tissues), and a significant enrichment of clonal HBV integrations in mitochondrial DNA (mtDNA) preferentially occurring in the oxidative phosphorylation genes (OXPHOS) and D-loop region. We also find that HBV RNA sequences are imported into the mitochondria of hepatoma cells with the involvement of polynucleotide phosphorylase (PNPASE), and that HBV RNA might have a role in the process of HBV integration into mtDNA. Our results suggest a potential mechanism by which HBV integration may contribute to HCC development.

Mitochondria are subcellular organelles known for their central role in several energetic processes. Accumulating evidence supports a key role for mitochondria in the physiological response to both acute and chronic stress exposure, and, ultimately, the biological embedding of adversity in health and psychological functioning that increases the interest of these organelles in several medical conditions typical of older people. At the same time, Mediterranean diet (MedDiet) seems to affect the function of mitochondria further justifying the role of this diet in lowering the risk of negative health outcomes. In this review, we have elucidated the role of mitochondria in human diseases including the fundamental role in stress, aging, and neuropsychiatric and metabolic disorders. Overall, MedDiet can limit the production of free radicals, being rich in polyphenols. Moreover, MedDiet reduced mitochondrial reactive oxygen species (mtROS) production and ameliorated mitochondrial damage and apoptosis. Similarly, whole grains can maintain the mitochondrial respiration and membrane potential, finally improving mitochondrial function. Other components of MedDiet can have anti-inflammatory effects, again modulating mitochondrial function. For example, delphinidin (a flavonoid present in red wine and berries) restored the elevated level of mitochondrial respiration, mtDNA content, and complex IV activity; similarly, resveratrol and lycopene, present in grapefruits and tomatoes, exerted an anti-inflammatory effect modulating mitochondrial enzymes. Altogether, these findings support the notion that several positive effects of MedDiet can be mediated by a modulation in mitochondrial function indicating the necessity of further studies in human beings for finally confirming these findings.

In recent years, the issue related to electronic waste production has been gaining prominence. One of the approaches considered to limit the impact of e-waste on the environment involves the development of biodegradable electronic devices or devices that dissolve in the environment at the end of their life cycle. In this study, we present the preliminary results related to the creation of a sensor that could meet both criteria. The device was constructed using a composite material obtained by impregnating a membrane of polycaprolactone (a biodegradable polymer) with 1-Ethyl-3-Methylimidazolium tetrafluoroborate (a water-soluble ionic liquid), which was coated with a conductive silver-based varnish. Leveraging the piezoionic effect, the device has been proven to function as a vibration sensor with a sensitivity of approximately 1.9 × 10−5 V/mm and a resolution of about 0.15 mm.

Cognitive Rehabilitation (CR) is a therapeutic approach designed to improve cognitive functioning after a brain injury, including stroke. Two major categories of techniques, namely traditional and advanced (including virtual reality—VR), are widely used in CR for patients with various neurological disorders. More objective outcome measures are needed to better investigate cognitive recovery after a stroke. In the last ten years, the application of electroencephalography (EEG) as a non-invasive and portable neuroimaging method has been explored to extract the hallmarks of neuroplasticity induced by VR rehabilitation approaches, particularly within the chronic stroke population. The aim of this study is to investigate the neurophysiological effects of CR conducted in a virtual environment using the VRRS device. Thirty patients with moderate-to-severe ischemic stroke in the chronic phase (at least 6 months after the event), with a mean age of 58.13 (±8.33) for the experimental group and 57.33 (±11.06) for the control group, were enrolled. They were divided into two groups: an experimental group and a control group, receiving neurocognitive stimulation using VR and the same amount of conventional neurorehabilitation, respectively. To study neuroplasticity changes after the training, we focused on the power band spectra of theta, alpha, and beta EEG rhythms in both groups. We observed that when VR technology was employed to amplify the effects of treatments on cognitive recovery, significant EEG-related neural improvements were detected in the primary motor circuit in terms of power spectral density and time-frequency domains. Indeed, EEG analysis suggested that VR resulted in a significant increase in both the alpha band power in the occipital areas and the beta band power in the frontal areas, while no significant variations were observed in the theta band power. Our data suggest the potential effectiveness of a VR-based rehabilitation approach in promoting neuroplastic changes even in the chronic phase of ischemic stroke.

Naturally occurring SARS-CoV-2 variants mutated in genomic regions targeted by antiviral drugs have not been extensively studied. This study investigated the potential of the RNA-dependent RNA polymerase (RdRp) complex subunits and non-structural protein (Nsp)5 of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) to accumulate natural mutations that could affect the efficacy of antiviral drugs. To this aim, SARS-CoV-2 genomic sequences isolated from 4155 drug-naive individuals from southern Italy were analyzed using the Illumina MiSeq platform. Sequencing of the 4155 samples showed the following viral variant distribution: 71.2% Delta, 22.2% Omicron, and 6.4% Alpha. In the Nsp12 sequences, we found 84 amino acid substitutions. The most common one was P323L, detected in 3777/4155 (91%) samples, with 2906/3777 (69.9%) also showing the G671S substitution in combination. Additionally, we identified 28, 14, and 24 different amino acid substitutions in the Nsp5, Nsp7, and Nsp8 genomic regions, respectively. Of note, the V186F and A191V substitutions, affecting residues adjacent to the active site of Nsp5 (the target of the antiviral drug Paxlovid), were found in 157/4155 (3.8%) and 3/4155 (0.07%) samples, respectively. In conclusion, the RdRp complex subunits and the Nsp5 genomic region exhibit susceptibility to accumulating natural mutations. This susceptibility poses a potential risk to the efficacy of antiviral drugs, as these mutations may compromise the drug ability to inhibit viral replication

Fibrosis is the strongest predictor for disease-specific mortality in non-alcoholic fatty liver diseases (NAFLD), but the need for liver biopsy limits its diagnosis. We assessed the performance of plasma ficolin-2 (FCN-2) as a biomarker of fibrosis identified by an in silico discovery strategy. Two hundred and thirty-five morbidly obese (MO) subjects with biopsy-proven NAFLD stratified by fibrosis stage (F0, n = 44; F1, n = 134; F2, n = 46; F3/F4, n = 11) and 40 cirrhotic patients were enrolled. The cohort was subdivided into discovery (n = 76) and validation groups (n = 159). The plasma level of FCN-2 and other candidate markers was determined. FCN-2 was inversely correlated with the stage of liver fibrosis (ρ = −0.49, p < 0.001) independently of steatosis (p = 0.90), inflammation (p = 0.57), and ballooning (p = 0.59). In the global cohort, FCN-2 level decreased significantly in a stepwise fashion from F0/F1 (median 4753 ng/mL) to F2–F3–F4 (2760 ng/mL) and in cirrhotic subjects (1418 ng/mL). The diagnostic performance of FCN-2 in detecting F ≥ 2 was higher than other indexes (APRI, FIB-4) (AUROC 0.82, 0.68, and 0.6, respectively). The accuracy improved when combined with APRI score and HDL values (FCNscore, AUROC 0.85). Overall, the FCN-2 plasma level can accurately discriminate liver fibrosis status (minimal vs. moderate/advanced) significantly improving the fibrosis diagnostic algorithms.

In this paper, an environmentally friendly inertial motion sensor is investigated, modelled, and characterized as an accelerometer. The sensor is obtained by using bacterial cellulose (BC) as a base biopolymer. BC is then impregnated with ionic liquids. Electrodes are realized by a conducting polymer, in a typical three-layer structure. The sensor works in a cantilever configuration and produces an open voltage signal as the result of a flexing deformation. A model is proposed for the transduction phenomenon. The composite mechano-electric transduction capability is exploited for realizing the accelerometer. Results of the chemical and transduction characterization of the accelerometer are reported. Finally, experimental evidence of the possible nature of the transduction phenomenon is given.

Entry of hepatitis C virus (HCV) into hepatocytes is a complex process that involves numerous cellular factors, including the scavenger receptor class B type 1 (SR-B1), the tetraspanin CD81, and the tight junction (TJ) proteins claudin-1 (CLDN1) and occludin (OCLN). Despite expression of all known HCV-entry factors, in vitro models based on hepatoma cell lines do not fully reproduce the in vivo susceptibility of liver cells to primary HCV isolates, implying the existence of additional host factors which are critical for HCV entry and/or replication. Likewise, HCV replication is severely impaired within hepatocellular carcinoma (HCC) tissue in vivo, but the mechanisms responsible for this restriction are presently unknown. Here, we identify tumor-associated calcium signal transducer 2 (TACSTD2), one of the most downregulated genes in primary HCC tissue, as a host factor that interacts with CLDN1 and OCLN and regulates their cellular localization. TACSTD2 gene silencing disrupts the typical linear distribution of CLDN1 and OCLN along the cellular membrane in both hepatoma cells and primary human hepatocytes, recapitulating the pattern observed in vivo in primary HCC tissue. Mechanistic studies suggest that TACSTD2 is involved in the phosphorylation of CLDN1 and OCLN, which is required for their proper cellular localization. Silencing of TACSTD2 dramatically inhibits HCV infection with a pan-genotype effect that occurs at the level of viral entry. Our study identifies TACSTD2 as a novel regulator of two major HCV-entry factors, CLDN1 and OCLN, which is strongly downregulated in malignant hepatocytes. These results provide new insights into the complex process of HCV entry into hepatocytes and may assist in the development of more efficient cellular systems for HCV propagation in vitro.