Digital liver biopsy:Bio-imaging of fatty liver for translational and clinical research

The rapidly growing field of functional, molecular and structural bio-imaging is providing an extraordinary new opportunity to overcome the limits of invasive liver biopsy and introduce a "digital biopsy" for in vivo study of liver pathophysiology. To foster the application of bio-imaging in clinical and translational research, there is a need to standardize the methods of both acquisition and the storage of the bio-images of the liver. It can be hoped that the combination of digital, liquid and histologic liver biopsies will provide an innovative synergistic tri-dimensional approach to identifying new aetiologies, diagnostic and prognostic biomarkers and therapeutic targets for the optimization of personalized therapy of liver diseases and liver cancer. A group of experts of different disciplines(Special Interest Group for Personalized Hepatology of the Italian Association for the Study of the Liver, Institute for Biostructures and Bio-imaging of the National Research Council and Bio-banking and Biomolecular Resources Research Infrastructure) discussed criteria, methods and guidelines for facilitating the requisite application of data collection. This manuscript provides a multi-Author review of the issue with special focus on fatty liver.

Bioengineered materials with selective antimicrobial toxicity in biomedicine

Fungi and bacteria afflict humans with innumerous pathogen-related infections and ailments.Most of the commonly employed microbicidal agents target commensal and pathogenic microorganisms without discrimination.To distinguish and fight the pathogenic species out of the microflora,novel antimicrobials have been developed that selectively target specific bacteria and fungi.The cell wall features and antimicrobial mechanisms that these microorganisms involved in are highlighted in the present review.This is followed by reviewing the design of antimicrobials that selectively combat a specific community of microbes including Gram-positive and Gram-negative bacterial strains as well as fungi.Finally,recent advances in the antimicrobial immunomodulation strategy that enables treating microorganism infections with high specificity are reviewed.These basic tenets will enable the avid reader to design novel approaches and compounds for antibacterial and antifungal applications.

Characterization of volatile organic compounds in grafted tomato plants upon potyvirus necrotic infection

A headspace solid-phase microextraction-gas chromatography-mass spectrometry(HS-SPME/GC-MS)method was used to study the volatile organic compounds(VOCs)associated with the differential immune response of tomato plants infected with the recombinant strain of potato virus Y(PVY^(C)-to),necrogenic to tomato.Analysis was carried out in UC82(UC),a virus susceptible tomato variety,comparing the same UC plants grafted or not onto a virus tolerant tomato ecotype,Manduria(Ma);the three types of samples used for the GC-MS analysis were mock-inoculated UC/Ma plants,UC/Ma+PVY^(C)-to and UC+PVY^(C)-to plants;the VOCs obtained were 111.Results from symptomatic PVY^(C)-to-infected UC plants showed a VOCs composition enriched in alcohols,fatty acid derivates,benzenoids,and salicylic acid derivatives,while in mock-inoculated UC/Ma plants VOCs were mainly characterized by methyl ester compounds.The VOC profile was in line with RNAseq data analyses,denoting that PVY^(C)-to viral RNA accumulation and disease symptoms induce the specific transcriptional activation of genes involved in VOCs biosynthesis.Furthermore,principal component analysis highlighted that VOCs of PVY^(C)-to-infected and mock-inoculated grafted plants were much closer each other than that of symptomatic PVY^(C)-to-infected non-grafted UC plants.These results suggest that VOCs profiles of tomato plants are related to the viral RNA accumulation,disease intensity and graft-derived tolerance to PVY^(C)-to infection.

Intranasal nerve growth factor bypasses the blood-brain barrier and affects spinal cord neurons in spinal cord injury

The purpose of this work was to investigate whether, by intranasal administration, the nerve growth factor bypasses the blood-brain barrier and turns over the spinal cord neurons and if such therapeutic approach could be of value in the treatment of spinal cord injury. Adult Sprague-Dawley rats with intact and injured spinal cord received daily intranasal nerve growth factor administration in both nostrils for 1 day or for 3 consecutive weeks. We found an in-creased content of nerve growth factor and enhanced expression of nerve growth factor receptor in the spinal cord 24 hours after a single intranasal administration of nerve growth factor in healthy rats, while daily treatment for 3 weeks in a model of spinal cord injury improved the deifcits in locomotor behaviour and increased spinal content of both nerve growth factor and nerve growth factor receptors. These outcomes suggest that the intranasal nerve growth factor bypasses blood-brain barrier and affects spinal cord neurons in spinal cord injury. They also suggest exploiting the possible therapeutic role of intranasally delivered nerve growth factor for the neuroprotection of damaged spinal nerve cells.

Non invasive tools for the diagnosis of liver cirrhosis

Liver cirrhosis(LC),the end stage of many forms of chronic hepatitis of different etiologies is a diffuse process characterized by fibrosis and the conversion of normal liver architecture into structurally abnormal nodules surrounded by annular fibrosis.This chronic progressive clinical condition,leads to liver cell failure and portal hypertension,which can favour the onset of hepatocellular carcinoma.Defining the phase of the natural history is crucial for therapeutic choice and prognosis.Liver biopsy is currently considered the best available standard of reference but it has some limits,so alternative tools have been developed to substitute liver biopsy when assessing liver fibrosis.Serum markers offer a cost-effective alternative to liver biopsy being less invasive and theoretically without complications.They can be classified into direct and indirect markers which may be used alone or in combination to produce composite scores.Diagnostic imaging includes a number of instruments and techniques to estimate liver fibrosis and cirrhosis like ultrasound(US),US Doppler,contrast enhanced US andElastography.US could be used for the diagnosis of advanced LC while is not able to evaluate progression of fibrosis,in this case Elastography is more reliable.This review aims to revise the most recent data from the literature about non invasive methods useful in defining liver fibrosis.

Nanotechnology applications for the therapy of liver fibrosis

Chronic liver diseases represent a major global health problem both for their high prevalence worldwide and,in the more advanced stages,for the limited available curative treatment options.In fact,when lesions of different etiologies chronically affect the liver,triggering the fibrogenesis mechanisms,damage has already occurred and the progression of fibrosis will have a major clinical impact entailing severe complications,expensive treatments and death in end-stage liver disease.Despite significant advances in the understanding of the mechanisms of liver fibrinogenesis,the drugs used in liver fibrosis treatment still have a limited therapeutic effect.Many drugs showing potent antifibrotic activities in vitro often exhibit only minor effects in vivo because insufficient concentrations accumulate around the target cell and adverse effects result as other non-target cells are affected.Hepatic stellate cells play a critical role in liver fibrogenesis,thus they are the target cells of antifibrotic therapy.The application of nanoparticles has emerged as a rapidly evolving area for the safe delivery of various therapeutic agents(including drugs and nucleic acid)in the treatment of various pathologies,including liver disease.In this review,we give an overview of the various nanotechnology approaches used in the treatment of liver fibrosis.

Defective autophagy and Alzheimer’s disease: is calcium the key?

Presenilins and autophagy: Presenilin 1 (PS1) and presenilin 2 (PS2) are homologous, multi-pass transmembrane proteins endowed with pleiotropic functions, ranging from the regulation of membrane trafficking to cell differentiation. Their catalytic activity within the γ-secretase complex, an aspartyl-protease responsible for the intramembrane cleavage of several different type I transmembrane proteins, has been intensively studied in the context of Alzheimer’s disease (AD). Indeed, tens of autosomal dominant mutations in the PSEN1 and PSEN2 genes (encoding PS1 and PS2, respectively) have been associated with the rare familial forms of AD (FAD).

Surface and transport properties of Cu-Sn-Ti liquid alloys

The lack of experimental data and / or limited experimental information concerning both surface and transport properties of liquid alloys often require the prediction of these quantities. An attempt has been made to link the thermophysical properties of a ternary Cu-Sn-Ti system and its binary Cu-Sn, Cu-Ti and SnoTi subsystems with the bulk through the study of the concentration dependence of various thermodynamic, structural, surface and dynamic properties in the frame of the statistical mechanical theory in conjunction with the quasi-lattice theory （QLT）. This formalism provides valuable qualitative insight into mixing processes that occur in molten alloys.

Associations between cardiac arrhythmia,incident disability in activities of daily living and physical performance:the ILSA study

Background Cardiac arrhythmias are common conditions in older people.Unfortunately,there is limited literature on associations between cardiac arrhythmias and physical performance or disability.We therefore aimed to prospectively investigate associations between cardiac arrhythmias and changes in disability and physical performance during 8 years of follow-up,using data from the Italian Longitudinal Study on Aging(ILSA).Methods Cardiac arrhythmias diagnosis was posed through a screening phase,confirmed by a physician.The onset of disability in activities of daily living(ADL)and the changes in several physical performance tests during follow-up were considered as outcomes.Fully-adjusted and propensity-score Cox Proportional Hazard models and mixed models were used for exploring associations between cardiac arrhythmia and the outcomes of interest.Results The prevalence of cardiac arrhythmia at baseline was 23.3%.People reporting cardiac arrhythmia at the baseline were significantly older,more frequently male,smokers and reported a higher presence of all medical conditions investigated(hypertension,heart failure,angina,myocardial infarction,diabetes,stroke),but no difference in dementia,Parkinsonism,cognitive or mood disorder.Cardiac arrhythmia at baseline was significantly associated with the incidence of disability in ADL(HR=1.23;95%:CI:1.01–1.50;P=0.0478 in propensity score analyses;HR=1.28;95%CI:1.01–1.61;P=0.0401 in fully adjusted models).Cardiac arrhythmia at baseline was also associated with a significant worsening in balance test(P=0.0436).Conclusions The presence of cardiac arrhythmia at baseline was associated with a significant higher risk of disability and of worsening in some physical performance tests,particularly those relating to balance.Screening and frequently assessing physical performance in older people affected by cardiac arrhythmia can be important to prevent a loss of physical performance,with further,potential,complications of medical management.

A novel expressed prostatic secretion(EPS)-urine metabolomic signature for the diagnosis of clinically significant prostate cancer

Objective:Significant efforts are currently being made to identify novel biomarkers for the diagnosis and risk stratification of prostate cancer(PCa).Metabolomics can be a very useful approach in biomarker discovery because metabolites are an important read-out of the disease when characterized in biological samples.We aimed to determine a metabolomic signature which can accurately distinguish men with clinically significant PCa from those affected by benign prostatic hyperplasia(BPH).Methods:We first performed untargeted metabolomics using ultrahigh-performance liquid chromatography tandem mass spectrometry on expressed prostatic secretion urine(EPS-urine)from 25 patients affected by BPH and 25 men with clinically significant PCa(defined as Gleason score≥3+4).Diagnosis was histologically confirmed after surgical treatment.The EPS-urine metabolomic approach was then applied to a larger,prospective cohort of 92 consecutive patients undergoing multiparametric magnetic resonance imaging for clinical suspicion of PCa prior to biopsy.Results:We established a novel metabolomic signature capable of accurately distinguishing PCa from benign tissue.A metabolomic signature was associated with clinically significant PCa in all subgroups of the Prostate Imaging Reporting and Data System(PI-RADS)classification(100%and 89.13%of accuracy when the PI-RADS was in range of 1–2 and 4–5,respectively,and 87.50%in the more critical cases when the PI-RADS was 3).Conclusions:A combination of metabolites and clinical variables can effectively help in identifying PCa patients that might be overlooked by current imaging technologies.Metabolites from EPS-urine should help in defining the diagnostic pathway of PCa,thus improving PCa detection and decreasing the number of unnecessary prostate biopsies.

Diagnostic and therapeutic potential of exosomal miRNAs in Alzheimer’s disease

Alzheimer’s disease(AD)is a primary cause of dementia.AD is a neurodegenerative disorder,characterized by synapses loss,extracellular amyloid plaques composed of the amyloid-βpeptide(Aβ)and intracellular aggregates of hyperphosphorylated tau protein.AD is a complex disease linked to multiple interacting factors,both environmental and genetic,which can contribute to the onset and severity of the disease.Longitudinal studies have highlighted several cardiovascular risk factors that can increase the risk of AD.The genetic landscape of AD has changed dramatically in recent decades.Early studies identified mutations in the amyloid precursor protein gene(APP)as well as proteins that are involved in the enzymatic cleavage of APP to toxicβ-amyloid(Aβ),namely presenilin-1 and presnilin-2.However,these mutations were found in familial cases of early-onset AD,while the causes of sporadic late-onset AD are still unknown.The latest advances in Genomewide Association Studies(GWAS),sequencing,and bioinformatics have begun to unravel the complex genetic architecture of the sporadic form of AD.GWAS were able to uncover common variants with high frequency in the population that individually carried low risk(Robinson et al.,2017).The advent of next-generation and thirdgeneration sequencing platforms shows great promise in further unravelling the genetics of AD.

Replacement Meal: Effectiveness of a Soluble Powder Rich in Fibers and at Low Glycemic Index in Overweight but Not in Obese Patients

Active lifestyle and qualitative and quantitative diets are the best way to lose weight. In our study we have assessed the effectiveness and tolerability of a soluble powder rich in fibers and at low glycemic index and used, with a portion of fresh fruit, as replacement meal (for a total calorie intake ranging from a minimum of about 130 kcal to a maximum of 260 kcal) in 52 overweight/obese subjects of the outpatient clinic of the Italian National Research Council (CNR) of Rome already in treatment with a low-fat low-carbohydrates qualitative diet. The study was a parallel, prospective trial of two randomized sample groups, “intervention” (26 subjects) and “control” (26 subjects). After 8 weeks, the treatment based on the replacement meal has improved the results obtained through the qualitative diet alone above all in the overweight subjects: 11/16, versus only 2/16 in the control group, became ranged within normal weight. On the contrary, the majority of obese subjects didn’t change their BMI classification suggesting that, in case of obesity, a controlled quantitative correction with weighing food portions could be a better strategy than low-calorie replacement meal.

Effect of thinning on above-ground biomass accumulation in a Douglas-fir plantation in southern Italy

We investigated the effects of a long-term thinning experiment on the distribution of above-ground biomass of Douglas-fir （Pseudotsuga menziesii [Mirb.] Franco var. menziesii） in a plantation in southern Italy. Allometric equations were used to estimate biomass and partitioning to stem and crown compartments. Variation in biomass stock estimated with allometric equations were evaluated according to seven thinning treatments： geo- metric-systematic （1 row every 3）, selective （light-moderate-heavy）, mixed systematic-selective （1 row every 4, 1 row every 5）, unthinned （control）. Over the experimental period of 13 years, current annual increments of carbon were lower （3.4 Mg ha^-1 year^-1） in control plots than in treated plots. At age 30, plots subjected to light selective thinning showed higher values of above-ground biomass （249.7 Mg ha^-1）. The biomass harvested with this treatment was 29.3 Mg ha^-1, and the mean annual increment of carbon over 13 years was 4.8 Mg ha^-1. Our results showed that light thinning stimulated increase in carbon stock, with a minimal loss of carbon during the treatment and a current annual increment of carbon higher than in control sub-plots and sub-plots thinned using systematic methods. This treatment yielded least carbon emissions and we affirm it has discrete global warming mitigation potential.

Almond diversity and homozygosity define structure, kinship, inbreeding, and linkage disequilibrium in cultivated germplasm, and reveal genomic associations with nut and seed weight

Almond[Prunus dulcis Miller(D.A.Webb)]is the main tree nut species worldwide.Here,genotyping-by-sequencing(GBS)was applied to 149 almond cultivars from the ex situ collections of the Italian Council for Agricultural Research(CREA)and the Spanish National Research Council(CSIC),leading to the detection of 93,119 single-nucleotide polymorphisms(SNPs).The study of population structure outlined four distinct genetic groups and highlighted diversification between the Mediterranean and Californian gene pools.Data on SNP diversity and runs of homozygosity(ROHs)allowed the definition of kinship,inbreeding,and linkage disequilibrium(LD)decay in almond cultivated germplasm.Four-year phenotypic observations,gathered on 98 cultivars of the CREA collection,were used to perform a genome-wide association study(GWAS)and,for the first time in a crop species,homozygosity mapping(HM),resulting in the identification of genomic associations with nut,shell,and seed weight.Both GWAS and HM suggested that loci controlling nut and seed weight are mostly independent.Overall,this study provides insights on the almond cultivation history and delivers information of major interest for almond genetics and breeding.In a broader perspective,our results encourage the use of ROHs in crop science to estimate inbreeding,choose parental combinations minimizing the risk of inbreeding depression,and identify genomic footprints of selection for specific traits.

Epoxy Thermosets with Self-Healing Ability

A hybrid epoxy resin with intrinsic self healing properties has been prepared from a bifunctional Diels-Alder (DA) adduct. The obtained network, based on conventional Diglycidyl ether of BisphenolA (DGEBA) and DA epoxy, leads to simultaneous tuning of physical-chemical properties and healing capability. The self-repairing behavior has been verified by means of scratch recovery observation and micromechanical analysis. A satisfactory morphological and mechanical recovery has been achieved by thermal stimulus, leading to very promising application in the field of adhesives and structural applications.

Air Pollution Steady-State Advection-Diffusion Equation: The General Three-Dimensional Solution

Atmospheric air pollution turbulent fluxes can be assumed to be proportional to the mean concentration gradient. This assumption, along with the equation of continuity, leads to the advection-diffusion equation. Many models simulating air pollution dispersion are based upon the solution (numerical or analytical) of the advection-diffusion equation as- suming turbulence parameterization for realistic physical scenarios. We present the general steady three-dimensional solution of the advection-diffusion equation considering a vertically inhomogeneous atmospheric boundary layer for arbitrary vertical profiles of wind and eddy-diffusion coefficients. Numerical results and comparison with experimental data are shown.

Engineering biomimetic intestinal topological features in 3D tissue models: retrospects and prospects

Conventional 2D intestinal models cannot precisely recapitulate biomimetic features in vitro and thus are unsuitable for various pharmacokinetic applications,development of disease models,and understanding the host-microbiome interactions.Thus,recently,efforts have been directed toward recreating in vitro models with intestine-associated unique 3D crypt-villus(for small intestine)or crypt-lumen(for large intestine)architectures.This review comprehensively delineates the current advancements in this research area in terms of the different microfabrication technologies(photolithography,laser ablation,and 3D bioprinting)employed and the physiological relevance of the obtained models in mimicking the features of native intestinal tissue.A major thrust of the manuscript is also on highlighting the dynamic interplay between intestinal cells(both the stem cells and differentiated ones)and different biophysical,biochemical,and mechanobiological cues along with interaction with other cell types and intestinal microbiome,providing goals for the future developments in this sphere.The article also manifests an outlook toward the application of induced pluripotent stem cells in the context of intestinal tissue models.On a concluding note,challenges and prospects for clinical translation of 3D patterned intestinal tissue models have been discussed.

An Analytical Air Pollution Model with Time Dependent Eddy Diffusivity

Air pollution transport and dispersion in the atmospheric boundary layer are modeled by the advection-diffusion equation, that is, essentially, a statement of conservation of the suspended material in an incompressible flow. Many models simulating air pollution dispersion are based upon the solution (numerical or analytical) of the advection-diffusion equation assuming turbulence parameterization for realistic physical scenarios. We present the general time dependent three-dimensional solution of the advection-diffusion equation considering a vertically inhomogeneous atmospheric boundary layer for arbitrary vertical profiles of wind and eddy-diffusion coefficients. Numerical results and comparison with experimental data are shown.

Bitumen Removal Determination on Asphalt Pavement Using Digital Imaging Processing and Spectral Analysis

This research aims to define an efficient and fast quantification of bitumen removal on the road surface by Digital Imaging Processing (DIP) and spectral analysis. The retrieval of bitumen removal is an important issue for road management and environmental studies related to asphalt wear and environmental pollution. The calculation of the Exposed Aggregate Index (EAI), based on DIP, allows to quantify in each frame the superficial removal of bitumen and the exposure of aggregates. A procedure, based on non-parametric classification process of digital images, gives a fast response of EAI. A correlation among EAI and spectral data, between 390 nm and 900 nm range, is evaluated. Results show a good correlation between spectral data at different wavelength and EAI. Finally, this work evaluates the possibility to retrieve asphalt bitumen removal through remote sensed imagery.

Granger Causality Analyses for Climatic Attribution

This review paper focuses on the application of the Granger causality technique to the study of the causes of recent global warming (a case of climatic attribution). A concise but comprehensive review is performed and particular attention is paid to the direct role of anthropogenic and natural forcings, and to the influence of patterns of natural variability. By analyzing both in-sample and out-of-sample results, clear evidences are obtained (e.g., the major role of greenhousegases radiative forcing in driving temperature, a recent causal decoupling between solar irradiance and temperature itself) together with interesting prospects of further research.