Development and characterization of 3D-printed electroconductive pHEMA-co-MAA NP-laden hydrogels for tissue engineering

Tissue engineering(TE)continues to be widely explored as a potential solution to meet critical clinical needs for diseased tissue replacement and tissue regeneration.In this study,we developed a poly(2-hydroxyethyl methacrylate-co-methacrylic acid)(pHEMA-co-MAA)based hydrogel loaded with newly synthesized conductive poly(3,4-ethylene-dioxythiophene)(PEDOT)and polypyrrole(PPy)nanoparticles(NPs),and subsequently processed these hydrogels into tissue engineered constructs via three-dimensional(3D)printing.The presence of the NPs was critical as they altered the rheological properties during printing.However,all samples exhibited suitable shear thinning properties,allowing for the development of an optimized processing window for 3D printing.Samples were 3D printed into pre-determined disk-shaped configurations of 2 and 10 mm in height and diameter,respectively.We observed that the NPs disrupted the gel crosslinking efficiencies,leading to shorter degradation times and compressive mechanical properties ranging between 450 and 550 kPa.The conductivity of the printed hydrogels increased along with the NP concentration to(5.10±0.37)×10^(−7)S/cm.In vitro studies with cortical astrocyte cell cultures demonstrated that exposure to the pHEMA-co-MAA NP hydrogels yielded high cellular viability and proliferation rates.Finally,hydrogel antimicrobial studies with staphylococcus epidermidis bacteria revealed that the developed hydrogels affected bacterial growth.Taken together,these materials show promise for various TE strategies.

Ultrasound unveiling:Decoding venous congestion in heart failure for precision management of fluid status

This editorial discusses the manuscript by Di Maria et al,published in the recent issue of the World Journal of Cardiology.We here focus on the still elusive pathophysiological mechanisms underlying cardio-renal syndrome(CRS),despite its high prevalence and the substantial worsening of both kidney function and heart failure.While the measure of right atrial pressure through right cardiac catheterization remains the most accurate albeit invasive and costly procedure,integrating bedside ultrasound into diagnostic protocols may substantially enhance the staging of venous congestion and guide therapeutic decisions.In particular,with the assessment of Doppler patterns across multiple venous districts,the Venous Excess Ultrasound(VExUS)score improves the management of fluid overload and provides insight into the underlying factors contributing to cardio-renal interactions.Integrating specific echocardiographic parameters,particularly those concerning the right heart,may thus improve the VExUS score sensitivity,offering perspective into the nuanced comprehension of cardio-renal dynamics.A multidisciplinary approach that consistently incorporates the use of ultrasound is emerging as a promising advance in the understanding and management of CRS.

Inflammation as a cause of acute myocardial infarction in patients with myeloproliferative neoplasm

Myeloproliferative neoplasms(MPN)are a group of diseases characterized by the clonal proliferation of hematopoietic progenitor or stem cells.They are clinically classifiable into four main diseases:chronic myeloid leukemia,essential thrombocythemia,polycythemia vera,and primary myelofibrosis.These pathologies are closely related to cardio-and cerebrovascular diseases due to the increased risk of arterial thrombosis,the most common underlying cause of acute myocardial infarction.Recent evidence shows that the classical Virchow triad(hypercoagulability,blood stasis,endothelial injury)might offer an explanation for such association.Indeed,patients with MPN might have a higher number and more reactive circulating platelets and leukocytes,a tendency toward blood stasis because of a high number of circulating red blood cells,endothelial injury or overactivation as a consequence of sustained inflammation caused by the neoplastic clonal cell.These abnormal cancer cells,especially when associated with the JAK2V617F mutation,tend to proliferate and secrete several inflammatory cytokines.This sustains a pro-inflammatory state throughout the body.The direct consequence is the induction of a pro-thrombotic state that acts as a determinant in favoring both venous and arterial thrombus formation.Clinically,MPN patients need to be carefully evaluated to be treated not only with cytoreductive treatments but also with cardiovascular protective strategies.

Facing ethical concerns in the age of precise gene therapy:Outlook on inherited arrhythmias

This editorial,comments on the article by Spartalis et al published in the recent issue of the World Journal of Cardiology.We here provide an outlook on potential ethical concerns related to the future application of gene therapy in the field of inherited arrhythmias.As monogenic diseases with no or few therapeutic options available through standard care,inherited arrhythmias are ideal candidates to gene therapy in their treatment.Patients with inherited arrhythmias typically have a poor quality of life,especially young people engaged in agonistic sports.While genome editing for treatment of inherited arrhythmias still has theoretical application,advances in CRISPR/Cas9 technology now allows the generation of knock-in animal models of the disease.However,clinical translation is somehow expected soon and this make consistent discussing about ethical concerns related to gene editing in inherited arrhythmias.Genomic off-target activity is a known technical issue,but its relationship with ethnical and individual genetical diversity raises concerns about an equitable accessibility.Meanwhile,the costeffectiveness may further limit an equal distribution of gene therapies.The economic burden of gene therapies on healthcare systems is is increasingly recognized as a pressing concern.A growing body of studies are reporting uncertainty in payback periods with intuitive short-term effects for insurance-based healthcare systems,but potential concerns for universal healthcare systems in the long term as well.Altogether,those aspects strongly indicate a need of regulatory entities to manage those issues.

Oil-in-water nanoemulsions loaded with lycopene extracts encapsulated by spray drying:Formulation,characterization and optimization

Lycopene is very susceptible to degradation once released from the protective chromoplast environment.In this study,oil-in-water(O/W)nanoemulsions coupled with spray drying technology were applied for the encapsulation and stabilization of lycopene extracted from tomato waste.Tomato extract was obtained by ultrasound-assisted extraction.Nanoemulsions were prepared by a high-speed rotor stator using isopropyl myristate as the oil phase and Pluronic F-127 as the emulsifier for the aqueous external phase.The effect of emulsification process parameters was investigated.Spray drying of the produced emulsions was attempted to obtain a stabilized dry powder after the addition of a coating agent.The effect of different coating agents(maltodextrin,inulin,gum arabic,pectin,whey and polyvinylpyrrolidone),drying temperature(120-170℃),and feed flow rate(3-9 ml·min^(-1))on the obtained particles was evaluated.Results revealed that the emulsion formulation of 20/80(O/W)with 1.5%(mass fraction)of Pluronic F-127 as stabilizer in the aqueous phase resulted in a stable nanoemulsion with droplet sizes in the range of 259-276 nm with a unimodal and sharp size distribution.The extract in the nanoemulsion was well protected at room temperature with a degradation rate of lycopene of about 50%during a month of storage time.The most stable emulsions were then processed by spray drying to obtain a dry powder.Spray drying was particularly successful when using maltodextrin as a coating agent,obtaining dried spherical particles with mean diameters of(4.87±0.17)μm with a smooth surface.The possibility of dissolving the spray dried powder in order to repristinate.The original emulsion was also successfully verified.

Navigating the autophagic landscape:Epigenetic modulation in gastrointestinal cancer

This editorial comments on the manuscript by Chang et al,focusing on the still elusive interplay between epigenetic regulation and autophagy in gastrointestinal diseases,particularly cancer.Autophagy,essential for cellular homeostasis,exhibits diverse functions ranging from cell survival to death,and is particularly implicated in physiological gastrointestinal cell functions.However,its role in pathological backgrounds remains intricate and context-dependent.Studies underscore the dual nature of autophagy in cancer,where its early suppressive effects in early stages are juxtaposed with its later promotion,contributing to chemoresistance.This discrepancy is attributed to the dysregulation of autophagy-related genes and their intricate involvement in cellular processes.Epigenetic modifications and regulations of gene expression,including non-coding RNAs(ncRNAs),emerge as critical players in exerting regulatory control over autophagy flux,influencing treatment responses and tumor progression.Targeting epigenetic mechanisms and improving strategies involving the inhibition or induction of autophagy through pharmacological or genetic means present potential avenues to sensitize tumor cells to chemotherapy.Additionally,nanocarrier-based delivery of ncRNAs offers innovative therapeutic approaches.Understanding the intricate interaction between autophagy and ncRNA regula-tion opens avenues for the development of targeted therapies,thereby improving the prognosis of gastrointestinal malignancies with poor outcomes.

Overview of hepatitis B virus mutations and theirimplications in the management of infection

Hepatitis B virus(HBV)affects approximately two billion people worldwide and more than 240 million people in the world are currently chronic carrier that could develop serious complications in the future,like liver cirrhosis and hepatocellular carcinoma.Although an extended HBV immunization program is being carried out since the early‘80s,representing effective preventive measure,leading to a dramatic reduction of HBV hepatitis incidence,globally HBV infection still represents a major public health problem.The HBV virus is a DNA virus belongs to the Hepadnaviridae family.The HBV-DNA is a circular,partial double strand genome.All coding information is on the minus DNA strand and it is organized into four open reading frames.Despite hepatitis B virus is a DNA virus,it has a high mutation rate due to its replicative strategy,that leads to the production of many nonidentical variants at each cycle of replication.In fact,it contains a polymerase without the proofreading activity,and uses an RNA intermediate(pg RNA)during its replication,so error frequencies are comparable to those seen in retroviruses and other RNA viruses rather than in more stable DNA viruses.Due to the low fidelity of the polymerase,the high replication rate and the overlapping reading frames,mutations occur throughout the genome and they have been identified both in the structural and not structural gene.The arise of mutations being to develop of a whole of viral variants called"quasi-species"and the prevalent population,which favors virus replication,was selected by viral fitness,host’s immune pressure and external pressure,i.e.,vaccination or antiviral therapy.Naturally occurring mutations were found both in acute and chronic subjects.In the present review we examine and discuss the most recent available data about HBV genetic variability and its significance.

Role of cytokines and chemokines in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) includes a variety of histological conditions (ranging from liver steatosis and steatohepatitis, to fibrosis and hepatocarcinoma) that are characterized by an increased fat content within the liver. The accumulation/deposition of fat within the liver is essential for diagnosis of NAFLD and might be associated with alterations in the hepatic and systemic inflammatory state. Although it is still unclear if each histological entity represents a different disease or rather steps of the same disease, inflammatory processes in NAFLD might influence its pathophysiology and prognosis. In particular, non-alcoholic steatohepatitis (the most inflamed condition in NAFLDs, which more frequently evolves towards chronic and serious liver diseases) is characterized by a marked activation of inflammatory cells and the upregulation of several soluble inflammatory mediators. Among several mediators, cytokines and chemokines might play a pivotal active role in NAFLD and are considered as potential therapeutic targets. In this review, we will update evidence from both basic research and clinical studies on the potential role of cytokines and chemokines in the pathophysiology of NAFLD.

Laparoscopic resection vs laparoscopic radiofrequency ablation for the treatment of small hepatocellular carcinomas: A single-center analysis

AIMTo compare survival and recurrence after laparoscopic liver resection (LLR) and laparoscopic radiofrequency ablation (LRFA) for the treatment of small hepatocellular carcinoma (HCC).METHODSBetween June 1, 2005 and November 30, 2010, 46 patients (62.26 ± 8.55 years old; female/male: 12/34) treated for small HCC were enrolled following strict criteria. Patients with better liver function and larger tumors were referred for LLR (n = 24), while those with poorer liver function and multiple tumors were referred for LRFA (n = 22), and they were then followed for similar durations (44.74 ± 21.3 mo for LLR vs 40.27 ± 30.8 mo for LRFA).RESULTSThe LLR and LRFA groups were homogeneous with regard to age, sex, etiology of liver cirrhosis, and AFP levels. The overall survival (OS) and disease-free survival (DFS) probability was 0.354 and 0.260, respectively. A significantly higher OS was observed in the LLR group (LLR: 0.442; LRFA: 0.261; P = 0.048), whereas no statistical difference was found for DFS (LLR: 0.206; LRFA: 0.286; P = 0.205). In the LRFA group was treated a greater number of nodules (LLR: 1.41 ± 0.77; LRFA: 2.72 ± 1.54; P < 0.001). Cox regression analysis found the number of intraoperative HCC nodules as the unique variable statistically significant for OS (hazard ratio: 2.225; P < 0.001). The rank-hazard plot showed a steeper increase of relative hazard for intraoperative nodules > 2.CONCLUSIONOur preliminary results confirm the superiority of hepatic resection on thermoablation in the treatment of small HCC in selected patients, when both approaches are made laparoscopically. LLR showed better results compared to LRFA in terms of OS. These data need to be confirmed by further studies on a larger number of patients.

Hepatitis C virus in the new era:Perspectives in epidemiology,prevention,diagnostics and predictors of response to therapy

Despite the great successes achieved in the fields of virology and diagnostics,several difficulties affect improvements in hepatitis C virus(HCV)infection control and eradication in the new era.New HCV infections still occur,especially in some of the poorest regions of the world,where HCV is endemic and long-term sequelae have a growing economic and health burden.An HCV vaccine is still no available,despite years of researches and discoveries about the natural history of infection and host-virus interactions:several HCV vaccine candidates have been developed in the last years,targeting different HCV antigens or using alternative delivery systems,but viral variability and adaption ability constitute major challenges for vaccine development.Many new antiviral drugs for HCV therapy are in preclinical or early clinical development,but different limitations affect treatment validity.Treatment predictors are important tools,as they provide some guidance for the management of therapy in patients with chronic HCV infection:in particular,the role of host genomics in HCV infection outcomes in the new era of direct-acting antivirals may evolve for new therapeutic targets,representing a chance for modulated and personalized treatment management,when also very potent therapies will be available.In the present review we discuss the most recent data about HCV epidemiology,the new perspectives for the prevention of HCV infection and the most recent evidence regarding HCV diagnosis,therapy and predictors of response to it.

Overlap of functional heartburn and gastroesophageal reflux disease with irritable bowel syndrome

Several studies indicate a significant degree of overlap between irritable bowel syndrome(IBS)and gastroesophageal reflux disease(GERD).Likewise,both functional heartburn(FH)and IBS are functional digestive disorders that may occur in the same patients.However,data establishing a solid link between FH and IBS are lacking,mainly because the clinical definition of FH has undergone substantial changes over the years.The available literature on the overlap between GERD or FH and IBS highlights considerable heterogeneity in terms of the criteria and diagnostic procedures used to assess heartburn and IBS.In particular,several epidemiological studies included patients with concomitant IBS and GERD without any attempt to distinguish FH(as defined by the RomeⅢcriteria)from GERD via pathophysiological investigations.Independent of these critical issues,there is preliminary evidence supporting a significantdegree of FH-IBS overlap.This underscores the need for studies based on updated diagnostic criteria and accurate pathophysiological classifications,particularly to distinguish FH from GERD.This distinction would represent an essential starting point to achieving a better understanding of pathophysiology in the subclasses of patients with GERD and FH and properly assessing the different degrees of overlap between IBS and the subcategories of heartburn.The present review article intends to appraise and critically discuss current evidence supporting a possible concomitance of GERD or FH with IBS in the same patients and to highlight the pathophysiological relationships between these disorders.

Alcohol and hepatocellular carcinoma:A review and a point of view

It is well recognized that one cause of chronic liver disease and hepatocellular carcinoma(HCC)is alcohol consumption.Research in Italy and the United States concludes that the most common cause of HCC(responsible for 32%to 45%of HCC)is alcohol.It has recently been shown that a significant relationship between alcohol intake,metabolic changes,and hepatitis virus infection does exist.Alcohol may be a factor in the development of HCC via direct(genotoxic)and indirect mechanisms(cirrhosis).There is only one way of diagnosing HCC,which is early identification through surveillance,when curative treatments become possible.After stopping alcohol intake the risk of liver cancer decreases by 6%to 7%a year,and an estimated time period of 23 years is also needed.Therefore,surveillance is also important in former drinkers and,in our opinion,independently from the presence of compensated cirrhosis.In cases of very early stage(VES)and early stage with portal hypertension,liver transplantation is the optimal option;and in cases of associated disease,percutaneous ethanol injections,radiofrequency and microwave ablation are the ideal treatments.Despite the possibility of detecting microvascular invasion with HR,several studies and some randomized controlled trials revealed that overall survival and DSF rates in patients with VES HCC are much the same after ablation and HR.Therefore,ablation can be regarded as a firstline choice for patients with VES HCC.It is important to emphasize that the choice of treatment should be weighed carefully in the context of a multidisciplinary cancer team.

Therapeutic potential of curcumin in digestive diseases

Curcumin is a low-molecular-weight hydrophobic polyphenol that is extracted from turmeric,which possesses a wide range of biological properties including anti-inflammatory,anti-oxidant,anti-proliferative and anti-microbial activities.Despite its diverse targets and substantial safety,clinical applications of this molecule for digestive disorders have been largely limited to case series or small clinical trials.The poor bioavailability of curcumin is likely the major hurdle for its more widespread use in humans.However,complexation of curcumin into phytosomes has recently helped to bypass this problem,as it has been demonstrated that this new lecithin formulation enables increased absorption to a level 29-fold higher than that of traditional curcuminoid products.This allows us to achieve much greater tissue substance delivery using significantly lower doses of curcumin than have been used in past clinical studies.As curcumin has already been shown to provide good therapeutic results in some small studies of both inflammatory and neoplastic bowel disorders,it is reasonable to anticipate an even greater efficacy with the advent of this new technology,which remarkably improves its bioavailability.These features are very promising and may represent a novel and effective therapeutic approach to both functional and organic digestive diseases.

Validation of an Emission Model for a Marine Diesel Engine with Data from Sea Operations

In this study,a model is developed to simulate the dynamics of an internal combustion engine,and it is calibrated and validated against reliable experimental data,making it a tool that can effectively be adopted to conduct emission predictions.In this work,the Ricardo WAVE software is applied to the simulation of a particular marine diesel engine,a four-stroke engine used in the maritime field.Results from the bench tests are used for the calibration of the model.Finally,the calibration of the model and its validation with full-scale data measured at sea are presented.The prediction includes not only the classic engine operating parameters for a comparison with surveys but also an estimate of nitrogen oxide emissions,which are compared with similar results obtained with emission factors.The calibration of the model made it possible to obtain an overlap between the simulation results and real data with an average error of approximately 7%on power,torque,and consumption.The model provides encouraging results,suggesting further applications,such as in the study on transient conditions,coupling of the engine model with the ship model for a complete simulation of the operating conditions,and optimization studies on consumption and emissions.The availability of the emission data during the sea trial and validated simulation results are the strengths and novelties of this work.

Effect of Cambering on the Aerodynamic Performance of Heaving Airfoils

In the present work,a parametric numerical study is conducted in order to assess the effect of airfoil cambering on the aerodynamic performance of rigid heaving airfoils.The incompressible Navier-Stokes equations are solved in their velocity-pressure formulation using a second-order accurate in space and time finite-difference scheme.To tackle the problem of moving boundaries,the governing equations are solved on overlapping structured grids.The numerical simulations are performed at a Reynolds number of Re=1100 and at different values of Strouhal number and reduced frequency.The results obtained show that the airfoil cambering geometric parameter has a strong influence on the average lift coefficient,while it has a smaller impact on the average thrust coefficient and propulsive efficiency of heaving airfoils.

The Impact of Delay in Software-Defined Integrated Terrestrial-Satellite Networks

Satellite communication networks have been evolving from standalone networks with ad-hoc infrastructures to possibly interconnected portions of a wider Future Internet architecture. Experts belonging to the fifth-generation(5 G) standardization committees are considering satellites as a technology to integrate in the 5 G environment. Software Defined Networking(SDN) is one of the paradigms of the next generation of mobile and fixed communications. It can be employed to perform different control functionalities, such as routing, because it allows traffic flow identification based on different parameters and traffic flow management in a centralized way. A centralized set of controllers makes the decisions and sends the corresponding forwarding rules for each traffic flow to the involved intermediate nodes that practically forward data up to the destination. The time to perform this process in integrated terrestrial-satellite networks could be not negligible due to satellite link delays. The aim of this paper is to introduce an SDN-based terrestrial satellite network architecture and to estimate the mean time to deliver the data of a new traffic flow from the source to the destination including the time required to transfer SDN control actions. The practical effect is to identify the maximum performance than can be expected.

Cambro-Silurian magmatisms at the northern Gondwana margin(Penninic basement of the Ligurian Alps)

The Early Paleozoic evolution of the northern margin of Gondwana is characterized by several episodes of bimodal magmatism intruded or outpoured within thick sedimentary basins. These processes are well recorded in the Variscan blocks incorporated in the Ligurian Alps because they experienced low temperature Alpine metamorphism. During the Paleozoic, these blocks, together with the other Alpine basements, were placed between the Corsica-Sardinia and the Bohemian Massif along the northern margin of Gondwana. In this framework, they host several a variegated lithostratigraphy forming two main complexes(Complexs I and II) that can be distinguished by both the protoliths and their crosscutting relationships, which indicate that the acidic and mafic intrusives of Complex II cut an already folded sequence made of sediments, basalts and granitoids of Complex I. Both complexes were involved in the Variscan orogenic phases as highlighted by the pervasive eclogite-amphibolite facies schistosity(foliation II). However, rare relicts of a metamorphic foliation at amphibolite facies conditions(foliation I)is locally preserved only in the rocks of Complex I. It is debatable if this schistosity was produced during the early folding event e occurred between the emplacement of Complex I and II e rather than during an early stage of the Variscan metamorphic cycle.New SHRIMP and LA ICP-MS Ue Pb zircon dating integrated with literature data, provide emplacement ages of the several volcanic or intrusive bodies of both complexes. The igneous activity of Complex I is dated between 507 ± 15 Ma and 494 ± 5 Ma, while Complex II between 467 ± 12 Ma and 445.5 ± 12 Ma.The folding event recorded only by the Complex I should therefore have occurred between 494 ± 5 Ma and 467 ± 12 Ma. The Variscan eclogite-amphibolite facies metamorphism is instead constrained between ~420 Ma and ~300 Ma. These ages and the geochemical signature of these rocks allow constraining the Early Paleozoic tectono-magmatic evolution of the Ligurian blocks, from a middleeupper Cambrian rifting stage, through the formation of an Early Ordovician volcanic arc during the Rheic Ocean subduction, until a Late Ordovician extension related to the arc collapse and subsequent rifting of the PaleoThetys. Furthermore, the ~420-350 Ma ages from zircon rims testify to thermal perturbations that may be associated with the Silurian rifting-related magmatism, followed by the subduction-collisional phases of the Variscan orogeny.

Sofosbuvir/velpatasvir: A promising combination

Hepatitis C virus(HCV) affects 3% of the world population. It represents the main cause of chronic liver disease and is responsible for extra-hepatic complications, such as type 2 diabetes and cardiovascular diseases. HCV includes 7 genotypes differing in the nucleotide sequence variability, the geographic distribution, the rates of viral clearance, the risk of progression to liver fibrosis and to hepatocellular carcinoma, and the response to therapy. Last years have seen remarkable advances in the field of HCV infection with the approval of direct antiviral agents(DAAs) targeting key viral proteins involved in the HCV replication. Several oral regimens combining DAAs from different families have been developed and these regimens showed increased and sustained virological response rates to above 90% reducing the treatment duration to 12 wk or less. In particular, sofosbuvir, a nucleotide analogue nonstructural(NS)5B polymerase inhibitor, and velpatasvir, a NS5 A inhibitor, have been tested in two phase 3 trials, the ASTRAL-2(against HCV genotype 2) and the ASTRAL-3(against HCV genotype 3), demonstrating to be effective, safe, and well tolerated in patients who were 18 years of age or older and had at least a 6-mo history of HCV infection with a compensated liver disease.

Left atrial thrombosis in an anticoagulated patient after bioprosthetic valve replacement:Report of a case

We present the case of a 74 year old woman suffering from severe mitral valve incompetence and rapid atrial fibrillation. After an appropriate vitamin K antagonist(VKA) therapy, the patient underwent mitral valve replacement by bioprosthesis. Then, the patient was rehospitalized for jaundice. Suspecting hepatotoxicity, VKA was discontinued and fondaparinux was started. During this treatment, the patient developed a symptomatic atrial thrombus. After exclusion of a hepatic disease, VKA was re-established with hemodynamic and liver enzymes normalization and atrial thrombus resolution. Caution has to be used when considering fondaparinux as an alternative strategy to VKA in patients with multiple thrombotic risk factors.

U-Pb geochronology and geochemistry of late Palaeozoic volcanism in Sardinia(southern Variscides)

The latest Carboniferous to lower Permian volcanism of the southern Variscides in Sardinia developed in a regional continental transpressive and subsequent transtensile tectonic regime.Volcanism produced a wide range of intermediate-silicic magmas including medium-to high-K calc-alkaline andesites,dacites,and rhyolites.A thick late Palaeozoic succession is well exposed in the four most representative Sardinian continental basins(Nurra,Perdasdefogu,Escalaplano,and Seui-Seulo),and contains substantial stratigraphic,geochemical,and geochronological evidence of the area's complex geological evolution from the latest Carboniferous to the beginning of the Triassic.Based on major and trace element data and LA-ICP-MS U-Pb zircon dating,it is possible to reconstruct the timing of postVariscan volcanism.This volcanism records active tectonism between the latest Carboniferous and Permian,and post-dates the unroofing and erosion of nappes in this segment of the southern Variscides.In particular,igneous zircon grains from calc-alkaline silicic volcanic rocks yielded ages between299±1 and 288±3 Ma,thereby constraining the development of continental strike-slip faulting from south(Escalaplano Basin)to north(Nurra Basin).Notably,andesites emplaced in medium-grade metamorphic basement(Mt.Cobingius,Ogliastra)show a cluster of older ages at 332±12 Ma.Despite the large uncertainty,this age constrains the onset of igneous activity in the mid-crust.These new radiometric ages constitute:(1)a consistent dataset for different volcanic events;(2)a precise chronostratigraphic constraint which fits well with the biostratigraphic data and(3)insights into the plate reorganization between Laurussia and Gondwana during the late Palaeozoic evolution of the Variscan chain.