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However, it also presents a formidable challenge confronting Western societies, given that ageing is intricately linked to heightened vulnerability to a spectrum of disease, including cardiovascular diseases (CVDs), cancer, type 2 diabetes, and Alzheimer's disease (AD). The global population is experiencing an increase in ageing and life expectancy. As societies grapple with the complexities of an ageing demographic, a comprehensive grasp of the determinants of healthy ageing and the promotion of successful ageing is integral to devising strategies that mitigate the burdens posed by age-associated diseases [[2]]. Even though the hallmarks of ageing are relatively well understood [[2]], the genetic and epigenetic factors of longevity warrant heightened attention within the realm of ageing research. [Extracted from the article]

Different applications of spent Agaricus bisporus substrate (SAS), a widespread agro-industrial waste, were investigated with respect to the remediation of a historically polluted soil with Polycyclic Aromatic Hydrocarbons (PAH). In one treatment, the waste was sterilized (SSAS) prior to its application in order to assess its ability to biostimulate, as an organic amendment, the resident soil microbiota and ensuing contaminant degradation. For the other treatments, two bioaugmentation approaches were investigated; the first involved the use of the waste itself and thus implied the application of A. bisporus and the inherent microbiota of the waste. In the second treatment, SAS was sterilized and inoculated again with the fungus to assess its ability to act as a fungal carrier. All these treatments were compared with natural attenuation in terms of their impact on soil heterotrophic and PAH-degrading bacteria, fungal growth, biodiversity of soil microbiota and ability to affect PAH bioavailability and ensuing degradation and detoxification. Results clearly showed that historically PAH contaminated soil was not amenable to natural attenuation. Conversely, the addition of sterilized spent A. bisporus substrate to the soil stimulated resident soil bacteria with ensuing high removals of 3-ring PAH. Both augmentation treatments were more effective in removing highly condensed PAH, some of which known to possess a significant carcinogenic activity. Regardless of the mode of application, the present results strongly support the adequacy of SAS for environmental remediation purposes and open the way to an attractive recycling option of this waste. [ABSTRACT FROM AUTHOR]

The present work was aimed at isolating and identifying the main members of the mycobiota of a clay soil historically contaminated by mid- and long-chain aliphatic hydrocarbons (AH) and to subsequently assess their hydrocarbon-degrading ability. All the isolates were Ascomycetes and, among them, the most interesting was Pseudoallescheria sp. 18A, which displayed both the ability to use AH as the sole carbon source and to profusely colonize a wheat straw:poplar wood chip (70:30, w/w) lignocellulosic mixture (LM) selected as the amendment for subsequent soil remediation microcosms. After a 60 d mycoaugmentation with Pseudoallescheria sp. of the aforementioned soil, mixed with the sterile LM (5:1 mass ratio), a 79.7% AH reduction and a significant detoxification, inferred by a drop in mortality of Folsomia candida from 90 to 24%, were observed. However, similar degradation and detoxification outcomes were found in the non-inoculated incubation control soil that had been amended with the sterile LM. This was due to the biostimulation exerted by the amendment on the resident microbiota, fungi in particular, the activity and density of which were low, instead, in the non-amended incubation control soil. [ABSTRACT FROM AUTHOR]

Abstract: Vascular ageing can be envisioned as the consequence of the accumulation of reactive oxygen species (ROS) associated with generalized endothelial dysfunction. Oxidative stress arises when the balance between production and removal of ROS favours the pro-oxidation arm. Therefore, ROS have been traditionally considered to be only a toxic by-product of aerobic metabolism. However, it has become apparent that ROS might control many different physiological processes, such as stress response, pathogen defence and systemic signalling. This has lead to the hypothesis that a certain level of ROS is needed physiologically, so much so that an overly increased antioxidant potential might be deleterious for health. Recent evidence has strengthened this notion by correlating cellular response with oxidants and the mechanisms that regulate longevity. Here, we overview current literature on this topic and we will try to convince the reader of the importance of balanced oxidative stress for vascular integrity and healthy ageing. [Copyright &y& Elsevier]

Abstract: The low moisture content of the dry olive mill residue (DOR), solid waste from the two-phase olive oil extraction process, enables its long-term storage and its ready reconstitution with water thus leading to a candidate liquid growth medium for the microbial production of enzymes of commercial interest. To test this hypothesis, two white-rot fungi (WRF), namely Lentinus tigrinus CBS 577.79 and Phlebia sp. DABAC 9, were grown in shaken cultures on non-supplemented aqueous extracts of the dry olive mill residue (ADOR) and compared for their ability to grow therein and produce Mn-dependent peroxidase (MnP). Then, in order to assess the feasibility of scale transfer to the reactor level, the two fungi were grown in a 3-L bubble-column reactor on 25% (w/v) ADOR at 28°C and an aeration rate of 0.3vvm. Under these conditions, L. tigrinus and Phlebia sp. produced 42.60±1.74 and 38.88±1.68 nkatal mL−1 MnP with respective mean volumetric productivities of 222.9 and 324.1nkatalL−1 h−1. These results clearly show that the use of non-supplemented ADOR as a production medium enables a significant MnP production thus representing an excellent basis for process optimization. [Copyright &y& Elsevier]

Glioblastoma (GBM) is the most common primary brain cancer with the median age at diagnosis around 64 years, thus pointing to aging as an important risk factor. Indeed, aging, by increasing the senescence burden, is configured as a negative prognostic factor for GBM stage. Furthermore, several anti-GBM therapies exist, such as temozolomide (TMZ) and etoposide (ETP), that unfortunately trigger senescence and the secretion of proinflammatory senescence-associated secretory phenotype (SASP) factors that are responsible for the improper burst of (i) tumorigenesis, (ii) cancer metastasis, (iii) immunosuppression, and (iv) tissue dysfunction. Thus, adjuvant therapies that limit senescence are urgently needed. The longevity-associated variant (LAV) of the bactericidal/permeability-increasing fold-containing family B member 4 (BPIFB4) gene previously demonstrated a modulatory activity in restoring age-related immune dysfunction and in balancing the low-grade inflammatory status of elderly people. Based on the above findings, we tested LAV-BPIFB4 senotherapeutic effects on senescent glioblastoma U87-MG cells and on T cells from GBM patients. We interrogated SA-β-gal and HLA-E senescence markers, SASP factors, and proliferation and apoptosis assays. The results highlighted a LAV-BPIFB4 remodeling of the senescent phenotype of GBM cells, enhancement of their sensitivity to temozolomide and a selective reduction of the T cells' senescence from GBM patients. Overall, these findings candidate LAV-BPIFB4 as an adjuvant therapy for GBM. [ABSTRACT FROM AUTHOR]

Abstract: The ability to survive to an extremely old age is a consequence of complex interactions among genes, environment, lifestyle and luck. In the last two centuries, life expectancy in western countries has doubled, increasing from 40 to 81 years (79 for males and 82 for females). The candidate factors to determine such mortality reduction are reduced exposure to infections and the subsequent reduction in inflammatory responses, and to some extent, improvement in diet and nutrition. Among the people born at the beginning of the previous century, a small portion of individuals (1 in 10,000 born) have reached 100 years, surviving approximately 20 years more than the general population. The successful longevity of these individuals shows a familial component, possibly genetic, as underlined by the centenarian sibling''s increased chance of reaching 100 years of age compared to the general population. Genetic studies on long living individuals have led to the discovery of potential genetic causes of extreme longevity. These discoveries have highlighted the role of lipid metabolism as a potential key player in the ability to survive to extreme old age. Additional studies on the longevity phenotype have confirmed the role of lipids and lipid-associated cell activities in the predisposition to longevity, from lower eukaryotes to humans. The main focus of this review is the appreciation of demographic survival data and changes in recent diet with the above mentioned genetic and phenotypic biomarkers of longevity, in order to elucidate hypotheses on mechanisms of slow aging and disease resistance. [Copyright &y& Elsevier]

Abstract: The present study mainly investigated the ability of solid-state cultures of the non-pathogenic Fusarium oxysporum strain BAFC 738 to transform aromatic components to reduce the phytotoxicity in olive-mill dry residue (DOR), the waste from the two-phase manufacturing process. Lignin, hemicellulose, fats and water-soluble extractives contents of DOR colonized by the fungus for 20 weeks were reduced by 16%, 25%, 71% and 13%, respectively, while the cellulose content increased by 25%. In addition, the ethyl acetate-extractable phenolic fraction of the waste was reduced by 65%. However, mass-balance ultra-filtration and size-exclusion chromatography experiments suggested that the apparent removal of that fraction, mainly including 2-(3,4-dihydroxyphenyl)ethyl alcohol and 2-(4-hydroxyphenyl)ethyl alcohol, was due to polymerization. Mn-peroxidase and Mn-independent peroxidase activities were found in F. oxysporum solid-state cultures, while laccase and aryl alcohol oxidase activities were not detected. Tests performed with seedlings of tomato (Lycopersicum esculentum L.), soybean (Glycine maximum Merr.), and alfalfa (Medicago sativa L.) grown on soils containing 6% (w/w) of bioconverted DOR (kg soil)−1 showed that the waste’s phytotoxicity was removed by 20 weeks-old fungal cultures. By contrast, the same material exhibited a high residual toxicity towards lettuce (Lactuca sativa L.). [Copyright &y& Elsevier]

Contaminated soil from a historical industrial site and containing sulfide ore ashes and aromatic hydrocarbons underwent sequential leaching by 0.5 M citrate and microbial treatments. Heavy metals leaching was with the following efficiency scale: Cu (58.7%) > Pb (55.1%) > Zn (44.5%) > Cd (42.9%) > Cr (26.4%) > Ni (17.7%) > Co (14.0%) > As (12.4%) > Fe (5.3%) > Hg (1.1%) and was accompanied by concomitant removal of organic contaminants (about 13%). Leached metals were concentrated into an iron gel, produced during ferric citrate fermentation by the metal-resistant strain BAS-10 of Klebsiella oxytoca. Concomitantly, the acidic leached soil was bioaugmented with Allescheriella sp. DABAC 1, Stachybotrys sp. DABAC 3, Phlebia sp. DABAC 9, Pleurotus pulmonarius CBS 664.97, and Botryosphaeria rhodina DABAC P82. B. rhodina was most effective, leading to a significant depletion of the most abundant contaminants, including 7-H-benz[DE]anthracene-7-one, 9,10-anthracene dione and dichloroaniline isomers, and to a marked detoxification as assessed by the mortality test with the Collembola Folsomia candida Willem. The overall degradation activities of B. rhodina and P. pulmonarius appeared to be significantly enhanced by the preliminary metal removal. [ABSTRACT FROM AUTHOR]

Abstract: The phytotoxicity of olive-mill wastewater (OMW) has been suggested to be mainly due to its phenolic components. This study investigated the impact of three different low-cost dephenolization treatments on the wastewater phytotoxicity. To this aim, germinability of maize (Zea mays L.) seeds sown on a sandy–loamy soil which had been spread with different volumes (from 40 to 160m3 ha−1) of either biologically-treated OMW or relative incubation control was determined. Biological treatments included either Panus tigrinus liquid cultures or incubation with commercial laccase (1UIml−1) or an innovative sequential combination of laccase and P. tigrinus cultures. All treatments markedly reduced phytotoxicity and promising results were obtained with commercial laccase. In fact, germinability and mean germination times in soil spread with laccase-treated OMW, did not significantly differ from those observed in soil irrigated with tap water (control) up to OMW volumes of 120m3 ha−1. Although the highest phenol reduction (ca. 81%) was obtained by the sequential use of laccase and P. tigrinus, the feasibility of the enzyme treatment is undoubtedly more convincing under the technological point of view. [Copyright &y& Elsevier]

Abstract: The present study investigated the valorization of olive-mill wastewater (OMW) by its use as a possible growth medium for the microbial production of extra-cellular lipase. To this end, strains of Geotrichum candidum (NRRL Y-552 and Y-553), Rhizopus arrhizus (NRRL 2286 and ISRIM 383), Rhizopus oryzae (NRRL 6431), Aspergillus oryzae (NRRL 1988 and 495), Aspergillus niger (NRRL 334), Candida cylindracea (NRRL Y-17506) and Penicillium citrinum (NRRL 1841 and 3754, ISRIM 118) were screened. All strains were able to grow on the undiluted OMW, producing extra-cellular lipase activity. C. cylindracea NRRL Y-17506 showed the highest lipase activity on all the typologies of OMW used. Its lipase production on OMW was markedly affected by the type of nitrogen source and was induced by the addition of olive oil. The highest activity (9.23IUml−1) of the yeast was obtained on OMW supplemented with NH4Cl (2.4gl−1) and olive oil (3.0gl−1). [Copyright &y& Elsevier]

Abstract: This study investigated the efficiency of four different immobilised laccase preparations in the mediator-assisted oxidation of a non-phenolic lignin model compound. To this aim, Trametes villosa laccase was either covalently bound onto Eupergit® C or activated carbon, or entrapped within copper or calcium alginate. The benchmark reaction, consisting in the side-chain oxidation of 4-methoxybenzyl alcohol (4-MBA) to 4-methoxybenzaldehyde, was taken as the criterion to compare the efficiency of the immobilised laccases, and to assess the possible advantages of their use in alternative to the native enzyme. For each laccase preparation, four mediators (including HBT, HPI, VLA and TEMPO) were comparatively investigated. Comparisons were made by using the same amount of activity (i.e. 10U) for each laccase preparation, and showed that the native enzyme generally led to higher p-anisaldehyde yields than the immobilised laccases. The only exception was observed with Cu-alginate-laccase, which led to a 85% conversion of 4-MBA in the presence of HBT as the mediator. When testing the reusability of this immobilised system, a significant catalytic efficiency was maintained along three consecutive reaction cycles. [Copyright &y& Elsevier]

Abstract: The white-rot fungus Panus tigrinus CBS 577.79 was cultivated both in mechanical (stirred tank, STR) and pneumatically (bubble column, BCB) agitated bioreactors and investigated for its ability to reduce the polluting load of olive-mill wastewater (OMW). Both aeration and agitation strongly influenced treatment efficiency. Best pollutants biodegradation performances were achieved in the bubble column bioreactor. Using this bioreactor, COD reduction, dephenolization and decoloration were 60.9, 97.2 and 75%, respectively. In contrast, lower depollution efficiency was generally observed in STR due to the possible occurrence of shear stress. [Copyright &y& Elsevier]

This study was aimed at assessing the potential of the white-rot fungus Panus tigrinus CBS 577.79 in removing organic load, color and toxic phenols from agro-industrial effluent olive-mill wastewater (OMW). The influence of wastewater composition on P. tigrinus degradative capability was investigated in shaken cultures using two different OMWs. The initial soluble COD of 85 000 mg l-1 led to a delay in removal of color, organic load and phenol by the fungus. This was associated with delayed onset of laccase and Mn-dependent peroxidase. On the other hand, P. tigrinus, when grown on OMW with an initial soluble COD content of 43 000 mg l-1, promptly and efficiently removed the aforementioned components. Chromatographic analyses showed that 4-hydroxy-substituted simple phenols were predominantly removed. The polymeric aromatic fraction underwent simultaneous polymerization and depolymerization. This study is a contribution to the understanding of the degradative specificity of P. tigrinus on OMW aromatic components and provides good indications for possible future applications of the fungus. [Copyright &y& Elsevier]

Discogenic low back pain (LBP) is a significant clinical condition arising from degeneration of the intervertebral disc, a common yet complex cause of chronic pain, defined by fissuring in the annulus fibrosus resulting in vascularization of growing granulation tissue and growth of nociceptive nerve fibers along the laceration area. This paper delves into the anatomical and pathophysiological underpinnings of discogenic LBP, emphasizing the role of intervertebral disc degeneration in the onset of pain. The pathogenesis is multifactorial, involving processes like mitochondrial dysfunction, accumulation of advanced glycation end products, and pyroptosis, all contributing to disc degeneration and subsequent pain. Despite its prevalence, diagnosing discogenic LBP is challenging due to the overlapping symptoms with other forms of LBP and the absence of definitive diagnostic criteria. Current diagnostic approaches include clinical evaluations, imaging techniques, and the exploration of potential biomarkers. Treatment strategies range from conservative management, such as physical therapy and pharmacological interventions, to more invasive procedures such as spinal injections and surgery. Emerging therapies targeting molecular pathways involved in disc degeneration are under investigation and hold potential for future clinical application. This paper highlights the necessity of a multidisciplinary approach combining clinical, imaging, and molecular data to enhance the accuracy of diagnosis and the effectiveness of treatment for discogenic LBP, ultimately aiming to improve patient outcomes. [ABSTRACT FROM AUTHOR]

FAs in older people are driven by immunosenescence, as well as the cell ageing and tissue modifications that characterize advanced age. The deepening of this knowledge could allow modulating the ageing rate by providing valuable information on how to achieve healthy ageing. Hallmarks of Ageing Some aspects fighting three hallmarks of ageing, i.e., characteristic features considered to contribute to the ageing process, hence determining the ageing phenotype [[23]], are instead treated in the last four papers. Taken together, their findings suggest that changes in the makeup of circulating exosomal miRNAs with age not only can be considered as a potential predictor of age but also may contribute to ageing via several key signaling pathways that regulate ageing and lifespan. [Extracted from the article]

Orange peel waste (OPW), the primary byproduct of the juice extraction process, is annually generated in massive amounts (21 Mton), and its aqueous extraction in biorefining operations yields a liquid fraction, referred to as orange peel extract (OPE). Although OPE contains significant amounts of easily assimilable carbohydrates, such as fructose, glucose, and sucrose, no investigations have been conducted yet to assess its possible use in biodiesel production by oleaginous yeasts. Consequently, the objective of the present study was to assess whether OPE might act as the basis of a liquid medium for microbial lipid production. A screening conducted with 18 strains of oleaginous yeasts in shaken flask on the OPE-based medium showed that Rhodosporidium toruloides NRRL 1091 and Cryptococcus laurentii UCD 68-201 gave the best results in terms of lipid production (5.8 and 4.5 g L−1, respectively) and accumulation (77 and 47% on a dry matter basis, respectively). The subsequent scale transfer of the process to a 3-L STR operated in batch mode halved the time required to reach the lipid peak with the ensuing increase in volumetric productivities in R. toruloides NRRL 1091 (3646 mg L−1 day−1) and C. laurentii UCD 68-201 (2970.7 mg L−1 day−1). The biodiesel yields from the lipids of the former and the latter strain were 36.9 and 31.9%, respectively. Based on multivariate analysis of fatty acid methyl ester compositions, the lipids from the former and the latter strain were highly resembling those of Jatropha and palm oils, two commonly used feedstocks for biodiesel manufacturing. [ABSTRACT FROM AUTHOR]

Soil contamination constitutes a significant threat to the health of soil ecosystems in terms of complexity, toxicity, and recalcitrance. Among all contaminants, aliphatic petroleum hydrocarbons (APH) are of particular concern due to their abundance and persistence in the environment and the need of remediation technologies to ensure their removal in an environmentally, socially, and economically sustainable way. Soil remediation technologies presently available on the market to tackle soil contamination by petroleum hydrocarbons (PH) include landfilling, physical treatments (e.g., thermal desorption), chemical treatments (e.g., oxidation), and conventional bioremediation. The first two solutions are costly and energy-intensive approaches. Conversely, bioremediation of on-site excavated soil arranged in biopiles is a more sustainable procedure. Biopiles are engineered heaps able to stimulate microbial activity and enhance biodegradation, thus ensuring the removal of organic pollutants. This soil remediation technology is currently the most environmentally friendly solution available on the market, as it is less energy-intensive and has no detrimental impact on biological soil functions. However, its major limitation is its low removal efficiency, especially for long-chain hydrocarbons (LCH), compared to thermal desorption. Nevertheless, the use of fungi for remediation of environmental contaminants retains the benefits of bioremediation treatments, including low economic, social, and environmental costs, while attaining removal efficiencies similar to thermal desorption. Mycoremediation is a widely studied technology at lab scale, but there are few experiences at pilot scale. Several factors may reduce the overall efficiency of on-site mycoremediation biopiles (mycopiles), and the efficiency detected in the bench scale. These factors include the bioavailability of hydrocarbons, the selection of fungal species and bulking agents and their application rate, the interaction between the inoculated fungi and the indigenous microbiota, soil properties and nutrients, and other environmental factors (e.g., humidity, oxygen, and temperature). The identification of these factors at an early stage of biotreatability experiments would allow the application of this on-site technology to be refined and fine-tuned. This review brings together all mycoremediation work applied to aliphatic petroleum hydrocarbons (APH) and identifies the key factors in making mycoremediation effective. It also includes technological advances that reduce the effect of these factors, such as the structure of mycopiles, the application of surfactants, and the control of environmental factors. [ABSTRACT FROM AUTHOR]

Microbial oils are regarded as a sustainable alternative to vegetable oils for biodiesel manufacturing. However, in order to develop a cost-effective process, high-lipid producer microorganisms should be combined with low-cost renewable growth substrates. For this reason, the objective of the present study was to assess comparatively the oil-producing performance of 9 oleaginous fungi belonging to the Aspergillus, Mucor, Mortierella and Cunninghamella genera on three relevant and widespread waste, such as glycerol, orange peel extract (OPE) and ricotta cheese whey (RCW). This screening was performed at the shaken flask level and, among the strains under study, Mortierella isabellina NRRL 1757 turned out to be the most efficient and versatile and its lipid profile was found to be highly compatible with biodiesel production. Process transfer of M. isabellina lipid production to the lab-scale Stirred Tank Reactor on all the three waste-based media, was shown to be feasible, achieving a lipid productivity of 0.46, 1.24 and 0.91 g/(L d) on glycerol, OPE and RCW, respectively. Noteworthy, the fatty acid analysis of the oils produced, confirmed their suitability for biodiesel manufacturing, exhibiting a high similarity to palm and Jatropha oils commonly used as feedstock for this production. [ABSTRACT FROM AUTHOR]

• Lipid production capacity of fungal strains compared on three waste-based media. • M. isabellina (Mi) was highly versatile in terms of growth and lipid production. • Mi lipid production was successfully transferred to lab-scale STR. • Mi lipid profiles resembled those of two commonly used oils (Jatropha and palm oil). Microbial oils are regarded as a sustainable alternative to vegetable oils for biodiesel manufacturing. However, in order to develop a cost-effective process, high-lipid producer microorganisms should be combined with low-cost renewable growth substrates. For this reason, the objective of the present study was to assess comparatively the oil-producing performance of 9 oleaginous fungi belonging to the Aspergillus , Mucor , Mortierella and Cunninghamella genera on three relevant and widespread waste, such as glycerol, orange peel extract (OPE) and ricotta cheese whey (RCW). This screening was performed at the shaken flask level and, among the strains under study, Mortierella isabellina NRRL 1757 turned out to be the most efficient and versatile and its lipid profile was found to be highly compatible with biodiesel production. Process transfer of M. isabellina lipid production to the lab-scale Stirred Tank Reactor on all the three waste-based media, was shown to be feasible, achieving a lipid productivity of 0.46, 1.24 and 0.91 g/(L d) on glycerol, OPE and RCW, respectively. Noteworthy, the fatty acid analysis of the oils produced, confirmed their suitability for biodiesel manufacturing, exhibiting a high similarity to palm and Jatropha oils commonly used as feedstock for this production. [ABSTRACT FROM AUTHOR]

The increasing demand of plant oils for biodiesel production has highlighted the need for alternative strategies based either on non-food crops or agro-industrial wastes that do not compete with food and feed production. In this context, the combined use of wastewater and oleaginous microorganisms could be a valuable production option. Ricotta cheese whey (RCW), one of the major byproducts of the dairy industry, is produced in very high and steadily increasing amounts and, due to its high organic load, its disposal is cost-prohibitive. In the present study, in order to assess the adequacy of RCW as a growth medium for lipid production, 18 strains of oleaginous yeasts were investigated in shaken flask for their growth and lipid-producing capabilities on this substrate. Among them, Cryptococcus curvatus NRRL Y-1511 and Cryptococcus laurentii UCD 68-201 adequately grew therein producing substantial amounts of lipids (6.8 and 5.1 g L − 1 , respectively). A high similarity between the percent fatty acid methyl esters (FAME) composition of lipids from the former and the latter strain was found with a predominance of oleic acid (52.8 vs. 48.7%) and of total saturated fatty acids (37.9 vs. 40.8%). The subsequent scale transfer of the C. laurentii UCD 68-201 lipid production process on RCW to a 3-L STR led to significantly improved biomass and total lipid productions (14.4 and 9.9 g L − 1 , respectively) with the biodiesel yield amounting to 32.6%. Although the C. laurentii FAME profile was modified upon process transfer, it resembled that of the Jatropha oil, a well established feedstock for biodiesel production. In conclusion, C. laurentii UCD 68-201, for which there is very limited amount of available information, turned out to be a very promising candidate for biodiesel production and wide margins of process improvement might be envisaged. [ABSTRACT FROM AUTHOR]

The homozygous genotype of the Longevity-Associated Variant (LAV) in Bactericidal/Permeability-Increasing Fold-Containing Family B member 4 (BPIFB4) is enriched in long-living individuals of three independent populations and its genetic transfer in C57BL/6J mice showed a delay in frailty progression and improvement of several biomarkers of aging and multiple aspects of health. The C57BL/6J strain is a suitable model for studying therapies aimed at extending healthy aging and longevity due to its relatively short lifespan and the availability of aging biomarkers. Epigenetic clocks based on DNA methylation profiles are reliable molecular biomarkers of aging, while frailty measurement tools are used to evaluate overall health during aging. In this study, we show that the systemic gene transfer of LAV-BPIFB4 in aged C57BL/6J mice was associated with a significant reduction in the epigenetic clock-based biological age, as measured by a three CpG clock method. Furthermore, LAV-BPIFB4 gene transfer resulted in an improvement of the Vitality Score with a reduction in the Frailty Index. These findings further support the use of LAV-BPIFB4 gene therapy to induce beneficial effects on epigenetic mechanisms associated with aging and frailty in aged mice, with potential implications for future therapies to prevent frailty in humans. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 infection causes a considerable inflammatory response coupled with impaired platelet reactivity, which can lead to platelet disorders recognized as negative prognostic factors in COVID-19 patients. The virus may cause thrombocytopenia or thrombocytosis during the different disease stages by destroying or activating platelets and influencing platelet production. While it is known that several viruses can impair megakaryopoiesis by generating an improper production and activation of platelets, the potential involvement of SARS-CoV-2 in affecting megakaryopoiesis is poorly understood. To this purpose, we explored, in vitro, the impact of SARS-CoV-2 stimulation in the MEG-01 cell line, a human megakaryoblastic leukemia cell line, considering its spontaneous capacity of releasing platelet-like particles (PLPs). We interrogated the effect of heat-inactivated SARS-CoV-2 lysate in the release of PLPs and activation from MEG-01, the signaling pathway influenced by SARS-CoV-2, and the functional effect on macrophagic skewing. The results highlight the potential influence of SARS-CoV-2 in the early stages of megakaryopoiesis by enhancing the production and activation of platelets, very likely due to the impairment of STATs signaling and AMPK activity. Overall, these findings provide new insight into the role of SARS-CoV-2 in affecting megakaryocyte–platelet compartment, possibly unlocking another avenue by which SARS-CoV-2 moves. [ABSTRACT FROM AUTHOR]

Huntington's disease (HD) is caused by the production of mutant Huntingtin (mHTT), characterized by long polyglutamine repeats with toxic effects. There are currently no clinically validated therapeutic agents that slow or halt HD progression, resulting in a significant clinical unmet need. The striatum-derived STHdh cell line, generated from mHTT knock-in mouse embryos (STHdhQ111/Q111), represents a useful model to study mechanisms behind pathogenesis of HD and to investigate potential new therapeutic targets. Indeed, these cells show susceptibility to nucleolar stress, activated DNA damage response and apoptotic signals, and elevated levels of H3K9me3 that all together concur in the progressive HD pathogenesis. We have previously shown that the adeno-associated viral vector-mediated delivery of the longevity-associated variant (LAV) of BPIFB4 prevents HD progression in a mouse model of HD. Here, we show that LAV-BPIFB4 stably infected in STHdhQ111/Q111 cells reduces (i) nucleolar stress and DNA damage through the improvement of DNA repair machinery, (ii) apoptosis, through the inhibition of the caspase 3 death signaling, and (iii) the levels of H3K9me3, by accelerating the histone clearance, via the ubiquitin–proteasome pathway. These findings pave the way to propose LAV-BPIFB4 as a promising target for innovative therapeutic strategies in HD. [ABSTRACT FROM AUTHOR]

The removal of aged hydrophobic contaminants from fine-textured soils is a challenging issue in remediation. The objective of this study was to compare the efficacy of augmentation treatments to that of biostimulation in terms of total aliphatic hydrocarbon (TAH) and toxicity removal from a historically contaminated clay soil and to assess their impact on the resident microbial community. To this aim, Pleurotus ostreatus , Botryosphaeria rhodina and a combination of both were used as the inoculants while the addition of a sterilized lignocellulose mixture to soil (1:5, w / w ) was used as a biostimulation approach. As opposed to the non-amended control soil, where no changes in TAH concentration and residual toxicity were observed after 60 days, the activation of specialized bacteria was found in the biostimulated microcosms resulting in significant TAH removal (79.8%). The bacterial community structure in B. rhodina -augmented microcosms did not differ from the biostimulated microcosms due to the inability of the fungus to be retained within the resident microbiota. Best TAH removals were observed in microcosms inoculated with P. ostreatus alone ( Po ) and in binary consortium with B. rhodina (BC) (86.8 and 88.2%, respectively). In these microcosms, contaminant degradation exceeded their bioavailability thresholds determined by sequential supercritical CO 2 extraction. Illumina metabarcoding of 16S rRNA gene showed that the augmentation with Po and BC led to lower relative abundances of Gram(+) taxa, Actinobacteria in particular, than those in biostimulated microcosms. Best detoxification, with respect to the non-amended incubation control, was found in Po microcosms where a drop in collembola mortality (from 90 to 22%) occurred. At the end of incubation, in both Po and BC, the relative abundances of P. ostreatus sequences were higher than 60% thus showing the suitability of this fungus in bioaugmentation-based remediation applications. [ABSTRACT FROM AUTHOR]

Beyond well-assessed risk factors, cardiovascular events could be also associated with the presence of epigenetic and genetic alterations, such as the methylenetetrahydrofolate-reductase (MTHFR) C677T polymorphism. This gene variant is related to increased circulating levels of homocysteine (Hcy) and cardiovascular risk. However, heterozygous carriers have an augmented risk of cardiovascular accidents independently from normal Hcy levels, suggesting the presence of additional deregulated processes in MTHFR C677T carriers. Here, we hypothesize that targeting Sirtuin 1 (SIRT1) could be an alternative mechanism to control the cardiovascular risk associated to MTHFR deficiency condition. Flow Mediated Dilatation (FMD) and light transmission aggregometry assay were performed in subjects carrying MTHFR C677T allele after administration of resveratrol, the most powerful natural clinical usable compound that owns SIRT1 activating properties. MTHFR C677T carriers with normal Hcy levels revealed endothelial dysfunction and enhanced platelet aggregation associated with SIRT1 downregulation. SIRT1 activity stimulation by resveratrol intake was able to override these abnormalities without affecting Hcy levels. Impaired endothelial function, bleeding time, and wire-induced thrombus formation were rescued in a heterozygous Mthfr-deficient (Mthfr+/–) mouse model after resveratrol treatment. Using a cell-based high-throughput multiplexed screening (HTS) assay, a novel selective synthetic SIRT1 activator, namely ISIDE11, was identified. Ex vivo and in vivo treatment of Mthfr+/– mice with ISIDE11 rescues endothelial vasorelaxation and reduces wire-induced thrombus formation, effects that were abolished by SIRT1 inhibitor. Moreover, platelets from MTHFR C677T allele carriers treated with ISIDE11 showed normalization of their typical hyper-reactivity. These results candidate SIRT1 activation as a new therapeutic strategy to contain cardio and cerebrovascular events in MTHFR carriers. [ABSTRACT FROM AUTHOR]

In the ongoing global COVID-19 pandemic, male sex is a risk factor for severe disease and death, and the reasons for these clinical discrepancies are largely unknown. The aim of this work is to study the influence of sex on the course of infection and the differences in prognostic markers between genders in COVID-19 patients. Our cohort consisted of 64 adult patients (n = 34 men and n = 30 women) with PCR-proven SARS-CoV-2 infection. Further, a group of patients was characterized by a different severity degree (n = 8 high- and n = 8 low-grade individuals for both male and female patients). As expected, the serum concentrations of LDH, fibrinogen, CRP, and leucocyte count in men were significantly higher than in females. When serum concentrations of the inflammatory cytokines, including IL-6, IL-2, IP-10 and IL-4 and chemokines like MCP-1, were measured with multiplex ELISA, no significant differences between male and female patients were found. In COVID-19 patients, we recently attributed a new prognostic value to BPIFB4, a natural defensin against dysregulation of the immune responses. Here, we clarify that BPIFB4 is inversely related to the disease degree in men but not in women. Indeed, higher levels of BPIFB4 characterized low-grade male patients compared to high-grade ones. On the contrary, no significant difference was reported between low-grade female patients and high-grade ones. In conclusion, the identification of BPIFB4 as a biomarker of mild/moderate disease and its sex-specific activity would open an interesting field for research to underpin gender-related susceptibility to the disease. [ABSTRACT FROM AUTHOR]

Fungal strains naturally occurring on the wood and leaves of the salt-excreting desert tree Tamarix were isolated and characterized for their ability to produce cellulose- and starch-degrading enzymes. Of the 100 isolates, six fungal species were identified by ITS1 sequence analysis. No significant differences were observed among taxa isolated from wood samples of different Tamarix species, while highly salt-tolerant forms related to the genus Scopulariopsis (an anamorphic ascomycete) occurred only on the phylloplane of T. aphylla. All strains had cellulase and amylase activities, but the production of these enzymes was highest in strain D, a Schizophyllum-commune-related form. This strain, when grown on pretreated Tamarix biomass, produced an enzymatic complex containing levels of filter paperase (414 ± 16 IU/ml) that were higher than those of other S. commune strains. The enzyme complex was used to hydrolyze different lignocellulosic substrates, resulting in a saccha-rification rate of pretreated milk thistle (73.5 ± 1.2 %) that was only 10 % lower than that obtained with commercial cellulases. Our results support the use of Tamarix biomass as a useful source of cellulolytic and amylolytic fungi and as a good feedstock for the economical production of commercially relevant cellulases and amylases. [ABSTRACT FROM AUTHOR]

Dry olive mill residue (DOR) is a solid waste arising from the olive oil two-phase extraction system. The objective of the present study was to investigate the impact of an aerobic treatment of DOR with selected lignin-degrading fungi on both organic matter evolution and residual phytotoxicity of the waste. To this aim, several white-rot fungi, including Phlebia radiata, Coriolopsis rigida, Phanerochaete chrysosporium, Pycnoporus cinnabarinus, Poria subvermispora and Pleurotus pulmonarius were inoculated under axenic conditions for 2 and 20 weeks. The chemical composition and phytotoxicity of DOR were scarcely affected by fungi after 2 weeks incubation. By contrast, both a significant depletion of phenolic compounds and a partial removal of phytoxicity towards Lycopersicum esculentum plants were generally obtained after 20 weeks. The most effective fungus in degrading lignin, total phenols and in removing phytotoxicity was C. rigida. A high correlation was observed between phytotoxicity and phenols added to soil with the waste. [Copyright &y& Elsevier]

This review summarizes all the research efforts that have been spent to immobilize laccase and tyrosinase for various applications, including synthetic and analytical purposes, bioremediation, wastewater treatment, and must and wine stabilization. All immobilization procedures used in these areas are discussed. Considerations on the efficacy of immobilized copper oxidases and products, in addition to their kinetic parameters are also discussed. The available data indicate that the immobilization of laccase into cationic polymer cross-linked with epichlorohydrin appears to be a promising procedure for industrial applications. The development of laccase and tyrosinase-based biosensors to monitor a wide range of compounds appears to be at a mature stage of technology. [Copyright &y& Elsevier]

Aging and comorbidities make individuals at greatest risk of COVID-19 serious illness and mortality due to senescence-related events and deleterious inflammation. Long-living individuals (LLIs) are less susceptible to inflammation and develop more resiliency to COVID-19. As demonstrated, LLIs are characterized by high circulating levels of BPIFB4, a protein involved in homeostatic response to inflammatory stimuli. Also, LLIs show enrichment of homozygous genotype for the minor alleles of a 4 missense single-nucleotide polymorphism haplotype (longevity-associated variant [LAV]) in BPIFB4, able to counteract progression of diseases in animal models. Thus, the present study was designed to assess the presence and significance of BPIFB4 level in COVID-19 patients and the potential therapeutic use of LAV-BPIFB4 in fighting COVID-19. BPIFB4 plasma concentration was found significantly higher in LLIs compared to old healthy controls while it significantly decreased in 64 COVID-19 patients. Further, the drop in BPIFB4 values correlated with disease severity. Accordingly to the LAV-BPIFB4 immunomodulatory role, while lysates of SARS-CoV-2-infected cells induced an inflammatory response in healthy peripheral blood mononuclear cells in vitro, the co-treatment with recombinant protein (rh) LAV-BPIFB4 resulted in a protective and self-limiting reaction, culminating in the downregulation of CD69 activating-marker for T cells (both TCD4+ and TCD8+) and in MCP-1 reduction. On the contrary, rhLAV-BPIFB4 induced a rapid increase in IL-18 and IL-1b levels, shown largely protective during the early stages of the virus infection. This evidence, along with the ability of rhLAV-BPIFB4 to counteract the cytotoxicity induced by SARS-CoV-2 lysate in selected target cell lines, corroborates BPIFB4 prognostic value and open new therapeutic possibilities in more vulnerable people. [ABSTRACT FROM AUTHOR]

• Bioremediation failed to decontaminate a chronically oil-polluted soil. • Electrokinetic remediation (EKR) was combined with bioremediation. • Bioremediation was applied downstream of the EKR. • The sequential treatment exhibited high degradation performance. • The EKR induced a partial, albeit reversible, inhibition of the microbiota. This study focused on the remediation of a chronically diesel-polluted soil by combining an electrokinetic treatment with a variety of bioremediation approaches. Priority within the sequential treatment was given to electrokinetic remediation (EKR) since the application of natural attenuation (NA), biostimulation and site-specific bio-augmentation resulted in very low degradation performance for total petroleum hydrocarbons (TPH) and polycyclic hydrocarbons (PAH). The application of 20-day EKR (1.0 V cm−1 with polarity reversal) led to 47.2 % and 46.2 % removal of TPH and PAH, respectively, and exerted a negative impact on bacterial abundance, as determined indirectly by quantitative PCR of 16S rRNA genes and community function, as investigated by community-level physiological profiling. These adverse effects were transient and, after a 50-day NA treatment applied downstream from EKR, bacterial abundance was an order of magnitude higher than that found in the initial soil and TPH and PAH removals were significantly higher than those attained by EKR (64.1 % and 56.3 %, respectively). The combination of EKR with site-specific bioaugmentation led to the greatest TPH and PAH degradation (76.0 % and 78.6 %, respectively). The results indicate that bioremediation can be successfully applied downstream from EKR and that the adverse effects exerted by this physico-chemical approach on soil microbiota are reversible. [ABSTRACT FROM AUTHOR]

One of the basis of exceptional longevity is the maintaining of the balance between inflammatory and anti-inflammatory networks. The monocyte-macrophages activation plays a major role in tuning the immune responses, by oscillating between patrolling-protective to inflammatory status. Longevity-associated variant (LAV) of bactericidal/permeability-increasing fold-containing family B member 4 (BPIFB4) activates calcium, PKC-alpha, and eNOS, rescuing endothelial dysfunction in aged mice and inducing revascularization. The BPIFB4's increment in serum of healthy long-living individuals (LLIs) compared to nonhealthy ones, its therapeutic potential in improving vascular homeostasis, which depends on immune system, together with its expression in bone marrow myeloid cells, suggests that LAV-BPIFB4 may improve immune regulation. Here we show that human monocytes exposed to LAV-BPIFB4 protein increased co-stimulatory molecules in resting state and reduced pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) after activating stimuli. Accordingly, a low percentage of CD69+ activated lymphocytes are found among LAV-BPIFB4-treated peripheral blood mononuclear cells (PBMCs). Moreover, human monocyte-derived dendritic cells (DCs) generated in presence of LAV-BPIFB4 secreted higher anti-(IL-10 and TGF-β) and lower pro-inflammatory (TNF-α and IL-1β) cytokines. Accordingly, LLIs' plasma showed higher levels of circulating IL-10 and of neutralizing IL-1 receptor antagonist (IL-1RA) compared to controls. Thus, LAV-BPIFB4 effects on myeloid compartment could represent one example of a genetic predisposition carried by LLIs to protect from immunological dysfunctions. [ABSTRACT FROM AUTHOR]

The production of seed oils from Cynara cardunculus generates huge amounts of lignocellulosic residues which can be exploited according to a cascade approach. In this paper, residual cardoon biomass (RCB) was tested as a growth substrate for the solid-state production of cellulolytic cocktails by species known to produce glucose-tolerant β-glucosidase isoenzymes. Best productions were obtained with 10- d -old Aspergillus tubingensis cultures on RCB supplemented with wheat bran (200 g kg−1) yielding β-glucosidase and endo-β-1,4-glucanase activities as high as (25 and 4) IU g−1, respectively, and 4 FPU g−1. The saccharification performance of the obtained cocktail tested on acid-catalysed steam-exploded RCB at low solid loading (25 g dm−3) was around 53% at 20 FPU g−1 cellulose. These performance were significantly enhanced by adding the xylanase-rich NS 22083 commercial formulation, reaching glucose yields higher than 80% after 72 h incubation. The use of the catalytic additive was optimized by a statistical approach, based on factorial analysis. A comparison of the performance of the A. tubingensis reinforced cocktail with the Cellic®CTec2 taken as benchmark formulation was done at the same enzyme load and performed at industrially relevant solid loadings, namely at (100 and 200) g dm−3. This comparison showed that Cellic®CTec2 led to only slightly higher glucose yields while an opposite outcome was observed for xylose yields, irrespective of the solid loading conditions. Thus, this study shows that an in-house enzyme production, based on the solid-state conversion of an industrial byproduct, able of yielding cellulolytic cocktails with substantial saccharification performance is feasible. • Residual cardoon biomass (RCB) from oil extraction needs to be exploited. • Significant levels of glycosyl hydrolases produced by A. tubingensis cultures on RCB. • Its cellulolytic cocktail leads to 53% saccharification at 20 FPU g−1 cellulose. • Saccharification performance of A. tubingensis cocktail (ATC) improved by xylanase. • ATC has similar performance on RCB compared to CTec2 commercial formulation. [ABSTRACT FROM AUTHOR]

Lignin was isolated from wood wastes comprising Iroko sawdust (IR) and mixed sawdust from Iroko and Norway spruce (IRNS), furnished by a local wood houses producer. The respective acidolysis lignin fractions were structurally characterized using pyrolysis (Py)-GCMS, two-dimensional heteronuclear single quantum correlation nuclear magnetic resonance (2D HSQC NMR), Fourier-transform infrared FTIR and ultraviolet-visible (UV-VIS) spectroscopies, size exclusion chromatography, and standard wet-chemistry methods for Klason lignin and polysaccharides determination. The isolated lignin fractions were subsequently used for the preparation of lignin nanoparticles (LNPs) using a non-solvent method. LNPs were then used for wood surface treatment using a dip-coating technique. The coated wood samples were analyzed by colorimetry and scanning electron microscopy (SEM) before and after artificial weathering experiments in a UV chamber to investigate the UV protection potential of the LNPs coatings. Wood samples dip-coated with LNPs showed promising surface modifications resembling a sort of film of fused LNPs. Coatings made from IR-LNPs and IRNS-LNPs performed significantly better in artificial weathering experiments than uncoated reference samples. [ABSTRACT FROM AUTHOR]

Highlights • A biorefinery byproduct was tested as the basis of a production medium for microbial enzymes. • Enzyme production on olive-mill wastewater high-molecular weight fraction (HMW-OMW). • Trametes ochracea produced both laccase and Mn-peroxidase (MnP) on HMW-OMW in reactor. • Mechanically mixed and pneumatically agitated reactor systems were compared. • Best performance (16,856 IU/L MnP on day 5) observed in a 3-L STR at 500 rpm and 1 vvm. • MnP productivity on HMW-OMW was the best so far reported for a wild-type fungal strain. Abstract The high-molecular weight fraction of olive mill wastewater (HMW-OMW), a byproduct of olive oil biorefinery, was used at the reactor level as the basal medium for production of laccase and Mn-dependent peroxidase (MnP) by Trametes ochracea. Three reactor systems, namely stirred tank reactors equipped with either Rushton turbines or marine impeller and draft tube (STR and STR-MD, respectively) and an air-lift reactor (ALR) were compared for this purpose. Although inocula were supplied as intact pellets, in both STR-based systems fungal growth evolved rapidly into a dispersed form while the ALR enabled the maintenance of the pellet growth mode. STR was deemed to be the most promising system since it best supported the production MnP activity on the HMW-OMW-based medium and its performance in laccase production did not differ from that observed with the STR-MD. Among the stirring regimes considered (250, 400, 500 and 600 rpm), the best production in the STR was observed at 500 rpm and 1.0 vvm for both laccase (8850 ± 270 IU L−1 on day 15) and MnP (17,027.4 ± 87.2 IU L-1 on day 13). When the inocula were supplied to the STR in homogenized form, the MnP production peak (16,856 ± 1070 IU L-1) was attained 8 days earlier than the previous condition and that of laccase was nearly doubled (14,967 ± 907 IU L-1). When compared with literature data, T. ochracea MnP production and productivity on the HMW-OMW-based medium were the highest reported for a wild-type fungal strain. [ABSTRACT FROM AUTHOR]

Lignin was isolated through mild acidolysis from local wood sources such as beech wood and chestnut wood sawdust, a high-volume side product of wood industries. The lignin fractions were characterized by pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS), Fourier-transform infrared (FTIR), ultraviolet-visible (UV-Vis) and two-dimensional heteronuclear single-quantum correlation nuclear magnetic resonance (2D HSQC NMR) spectroscopies and size exclusion chromatography (SEC). The Klason lignin (KL) content and polysaccharide composition were determined using traditional methods. Lignin nanoparticles (LNPs) were prepared via a non-solvent method involving dialysis and characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) and FTIR and UV-VIS spectroscopies. Semi-porous as well as hollow nanoparticles endowed with a spherical shape were observed. The large majority of the LNPs exhibited an average particle diameter of 90–120 nm. Dynamic light scattering (DLS) analysis showed that both distribution and frequency of dimensional classes of LNPs are clearly affected by the lignin solvent system, i.e. solvent selection governs the size distribution of LNPs. [ABSTRACT FROM AUTHOR]

Fenton-like treatment (FLT) is an ISCO technique relying on the iron-induced H 2 O 2 activation in the presence of additives aimed at increasing the oxidant lifetime and maximizing iron solubility under natural soil pH conditions. The efficacy of FLT in the clean-up of hydrocarbon-contaminated soils is well established at the field-scale. However, a better assessment of the impact of the FLT on density, diversity and activity of the indigenous soil microbiota, might provide further insights into an optimal combination between FLT and in-situ bioremediation (ISB). The aim of this work was to assess the impacts of FLT on the microbial community of a diesel-contaminated soil collected nearby a gasoline station. Different FLT conditions were tested by varying either the H 2 O 2 concentrations (2 and 6%) or the oxidant application mode (single or double dosage). The impact of these treatments on the indigenous microbial community was assessed immediately after the Fenton-like treatment and after 30, 60 and 90 d and compared with enhanced natural attenuation (ENA). After FLT, a dramatic decrease in bacterial density, diversity and functionality was evident. Although in microcosms with double dosing at 2% H 2 O 2 a delayed recovery of the indigenous microbiota was observed as compared to those subjected to single oxidant dose, after 60 d incubation the respiration rate increased from 0.036 to 0.256 μg C CO 2 g −1 soil h −1 . Irrespective of the oxidant dose, best degradation results after 90 d incubation (around 80%) were observed with combined FLT, relying on double oxidant addition, and bioremediation. [ABSTRACT FROM AUTHOR]

Background: Mutations in the gene that encodes CDGSH iron sulfur domain 2 (CISD2) are causative of Wolfram syndrome type 2 (WFS2), a rare autosomal recessive neurodegenerative disorder mainly characterized by diabetes mellitus, optic atrophy, peptic ulcer bleeding and defective platelet aggregation. Four mutations in the CISD2 gene have been reported. Among these mutations, the homozygous c.103 + 1G > A substitution was identified in the donor splice site of intron 1 in two Italian sisters and was predicted to cause a exon 1 to be skipped. Methods: Here, we employed molecular assays to characterize the c.103 + 1G > A mutation using the patient's peripheral blood mononuclear cells (PBMCs). 5'-RACE coupled with RT-PCR were used to analyse the effect of the c.103 + 1G > A mutation on mRNA splicing. Western blot analysis was used to analyse the consequences of the CISD2 mutation on the encoded protein. Results: We demonstrated that the c.103 + 1G > A mutation functionally impaired mRNA splicing, producing multiple splice variants characterized by the whole or partial absence of exon 1, which introduced amino acid changes and a premature stop. The affected mRNAs resulted in either predicted targets for nonsense mRNA decay (NMD) or non-functional isoforms. Conclusions: We concluded that the c.103 + 1G > A mutation resulted in the loss of functional CISD2 protein in the two Italian WFS2 patients. [ABSTRACT FROM AUTHOR]

Aims Ageing is associated with impairment of endothelial nitric oxide synthase (eNOS) and progressive reduction in endothelial function. A genetic study on long-living individuals--who are characterized by delays in ageing and in the onset of cardiovascular disease--previously revealed I229V (rs2070325) in bactericidal/permeability-increasing fold-containing-family-B-member-4 (BPIFB4) as a longevity-associated variant (LAV); the LAV protein enhanced endothelial NO production and vasorelaxation through a protein kinase R-like endoplasmic reticulum kinase/14-3-3/heat shock protein 90 signal. Here, we further characterize the molecular mechanisms underlying LAV-BPIFB4-dependent enhancement of vascular function. Methods and results LAV-BPIFB4 upregulated eNOS function via mobilization of Ca2+ and activation of protein kinase C alpha (PKCα). Indeed, the overexpression of LAV-BPIFB4 in human endothelial cells enhanced ATP-induced Ca2+ mobilization and the translocation of PKCα to the plasma membrane. Coherently, pharmacological inhibition of PKCα blunted the positive effect of LAV-BPIFB4 on eNOS and endothelial function. In addition, although LAV-BPIFB4 lost the ability to activate PKCa and eNOS in ex vivo vessels studied in an external Ca2+-free medium and in vessels from eNOS-/- mice, it still potentiated endothelial activity, recruiting an alternative mechanism dependent upon endothelium-derived hyperpolarizing factor (EDHF). Conclusions We have identified novel molecular determinants of the beneficial effects of LAV-BPIFB4 on endothelial function, showing the roles of Ca2+ mobilization and PKCa in eNOS activation and of EDHF when eNOS is inhibited. These results highlight the role LAV-BPIFB4 can have in restoring signals that are lost during ageing. [ABSTRACT FROM AUTHOR]

The objective of this work was to test the PCB-degrading abilities of two white-rot fungi, namely Pleurotus ostreatus and Irpex lacteus, in real contaminated soils with different chemical properties and autochthonous microflora. In addition to the efficiency in PCB removal, attention was given to other important parameters, such as changes in the toxicity and formation of PCB transformation products. Moreover, structural shifts and dynamics of both bacterial and fungal communities were monitored using next-generation sequencing and phospholipid fatty acid analysis. The best results were obtained with P. ostreatus , which resulted in PCB removals of 18.5, 41.3 and 50.5% from the bulk, top (surface) and rhizosphere, respectively, of dumpsite soils after 12 weeks of treatment. Numerous transformation products were detected (hydoxylated and methoxylated PCBs, chlorobenzoates and chlorobenzyl alcohols), which indicates that both fungi were able to oxidize and decompose the aromatic moiety of PCBs in the soils. Microbial community analysis revealed that P. ostreatus efficiently colonized the soil samples and suppressed other fungal genera. However, the same fungus substantially stimulated bacterial taxa that encompass putative PCB degraders. The results of this study finally demonstrated the feasibility of using this fungus for possible scaled-up bioremediation applications. [ABSTRACT FROM AUTHOR]

The prototype of long pentraxins, Pentraxin 3 (PTX3), is an evolutionarily conserved multifunctional, pattern-recognition protein constituted by a cyclic multimeric structure. PTX3 interacts with a variety of ligands, such as growth factors, extracellular matrix components, molecules of the complement cascade, pathogens recognition proteins, angiogenetic and adhesion molecules. PTX3 could be considered as a molecular link between innate and adaptive immunity as well as between focal and circulating responses during inflammation. In fact, it modulates the functions of resident dendritic cells and circulating lymphocytes. Recent evidence demonstrates that manipulation of PTX3 may produce even opposite effects depending on which target organ is considered and the physiopathological context. In the present review we discuss the good and bad cops of PTX3 concerning multifacted effects on inflammation, innate immunity, brain diseases and tumorigenesis. Finally, a perspective on PTX3 and autophagy is provided as a convergent pathway. [ABSTRACT FROM AUTHOR]

Orange peel waste was converted into ethanol by consecutive acid-catalyzed steam-explosion (ACSE), enzymatic saccharification, and fermentation with Saccharomyces cerevisiae F15. With the aim of increasing the concentration of fermentable sugars in the hydrolysate and to fully recycle the spent acid liquor as the suspending medium for saccharification, the technical feasibility of increasing the solid loading in the ACSE step from 160 to 480 g L was assessed. At high solid loading in the ACSE pretreatment (HSLAP), the solubilization degrees of polysaccharides were lower while those of potential inhibitors (e.g., acetic and formic acids and phenols) were generally higher than those found at low solid loading (LSLAP). However, residual solids from both solid loadings showed similar susceptibility to enzymatic saccharification (ES) in a 7-L stirred-tank reactor (STR) (cellulase, 12 FPU g cellulose; pectinase, 25 IU g dry matter; 72 h incubation at 50 °C). Fermentation was performed in a 1-L STR along five repeated batches with the first one being used to enable yeast proliferation. By using the hydrolysates arising from the HSLAP-ES combination, it was possible to rely on a fermentation medium with a 2.5-fold higher concentration of simple sugars and to double the ethanol concentration in the final beer to be distilled of. However, the higher content of inhibitory compounds in hydrolysates from HSLAP-ES than in the LSLAP-ES ones led to a reduction in the ethanol yield per unit substrate consumed (0.49 vs. 0.41 g g, respectively) and overall productivity (3.4 vs. 2.7 g h, respectively). [ABSTRACT FROM AUTHOR]

Background: Lone atrial flutter (AFL) and atrial fibrillation (AF) are common and sometimes consequential cardiac conduction disorders with a strong heritability, as underlined by recent genome-wide association studies that identified genetic modifiers. Follow-up family-based genetic analysis also identified Mendelian transmission of disease alleles. Three affected members were exome-sequenced for the identification of potential causative mutations, which were subsequently validated by direct sequencing in the other 3 affected members. Taqman assay was then used to confirm the role of any mutation in an independent population of sporadic lone AFL/AF cases. Results: The family cluster analysis provided evidence of genetic inheritance of AFL in the family via autosomal dominant transmission. The exome-sequencing of 3 family members identified 7 potential mutations: of these, rs58238559, a rare missense genetic variant in the ATP-binding cassette sub-family B, member 4 (ABCB4) gene was carried by all affected members. Further analysis of 82 subjects with sporadic lone AF, 63 subjects with sporadic lone AFL, and 673 controls revealed that the allele frequency for this variation was significantly higher in cases than in the controls (0.05 vs. 0.01; OR = 3.73; 95% CI = 1.16-11.49; P = 0.013). Conclusions: rs58238559 in ABCB4 is a rare missense variant with a significant effect on the development of AFL/AF. [ABSTRACT FROM AUTHOR]

The adequacy of the Calgary biofilm device, often referred to as the MBEC system, as a high-throughput approach to the production and subsequent characterization of Pleurotus ostreatus biofilms was assessed. The hydroxyapatite-coating of pegs was necessary to enable biofilm attachment, and the standardization of vegetative inocula ensured a uniform distribution of P. ostreatus biofilms, which is necessary for high-throughput evaluations of several antimicrobials and exposure conditions. Scanning electron microscopy showed surface-associated growth, the occurrence of a complex aggregated growth organized in multilayers or hyphal bundles, and the encasement of hyphae within an extracellular matrix (ECM), the extent of which increased with time. Chemical analyses showed that biofilms differed from free-floating cultures for their higher contents of total sugars (TS) and ECM, with the latter being mainly composed of TS and, to a lesser extent, protein. Confocal laser scanning microscopy analysis of 4-day-old biofilms showed the presence of interspersed interstitial voids and water channels in the mycelial network, the density and compactness of which increased after a 7-day incubation, with the novel occurrence of ECM aggregates with an α-glucan moiety. In 4- and 7-day-old biofilms, tolerance to cadmium was increased by factors of 3.2 and 11.1, respectively, compared to coeval free-floating counterparts. [ABSTRACT FROM AUTHOR]

Highlights: [•] Dairy wastewater was treated in an industrial three-cascade-reactor plant. [•] The plant maintained high treatment performances over a wide range of influent loads. [•] The large majority of the organic matter depletion occurred in the first reactor. [•] At high organic loads of the influent DO and ORP were very low in the first reactor. [•] Values of the sludge volume index indicated good settling properties of the flocs. [ABSTRACT FROM AUTHOR]

Objective of this study was to assess the single or combined effect of a plant oil and a lignocellulosic waste, namely soybean oil (SO) and maize stalks (MS), respectively, on resident microbiota and bioremediation performances of a soil historically contaminated by medium to highly chlorinated PCBs. Higher concentrations of both biphenyl- and chlorobenzoate-degrading cultivable bacteria were found in the MS-amended microcosms (MSM) than the non amended or SO-amended ones after 30 d incubation at 28°C. Fungal growth, instead, was strikingly stimulated in the microcosms that had undergone concomitant MS and SO supplementation (MS-SOM). Denaturing gradient gel electrophoresis analyses of 16S and 18S rRNA genes showed that both amendments promoted a remarkable increase in both bacterial and fungal biodiversity. The abundances of biphenyl-2,3-dioxygenase (bph) and that of catechol-2,3-dioxygenase (C230) genes in the non-amended contaminated soil were constant over time. Conversely, after 60 d incubation, bph and C230 abundances increased 2.8- and 61-fold in the MSM, respectively, and, in the MS-SOM, 1.4- and 46-fold, respectively, with respect to the zero time point. Although the overall PCB removal was not positively affected by the amendments, the concomitant presence of both MS and SO led to significantly higher depletions of hexa-, hepta-, octa- and nona-chlorinated congeners than in the non-amended microcosms (i.e. 24.6, 22, 20.5 and 9.5%, versus 19.4, 16.4, 14.7 and 6.1%, respectively). In all microcosms, PCB degradation was negatively correlated with hydrophobicity, organic matter/water partition coefficient, molecular weight and extent of chlorination of the pollutants with the notable exception of the MS-SOM ones where such a relationship was less stringent. [ABSTRACT FROM AUTHOR]

Abstract: The main aim of this study was to assess the ability of producing extracellular phenoloxidases (EPO) of fungi isolated from olive brine wastewater (OBW), the effluent from the debittering process of table olives. Five out of twenty isolates displayed EPO-producing ability as assessed by selective agar plate assays and were all halotolerant. Among them, Citeromyces matritensis (syn. Candida globosa) and Aspergillus fumigatus concomitantly produced laccase and Mn-peroxidase (MnP) activities. Candida boidinii and Candida bombi, instead, only produced laccase and Candida diddensiae only released MnP. Both C. matritensis and A. fumigatus, grown in shaken cultures on OBW, maintained their EPO-producing ability and removed phenols by 52.3 and 82.3%, respectively, after 10d incubation in the non-supplemented effluent. These results might suggest the possible use of these strains in the treatment of other saline phenol-rich effluents, such as pickling and tannery wastewater. [Copyright &y& Elsevier]

Abstract: This study comparatively investigated the PAH degradation ability of Lentinus tigrinus and Irpex lacteus in a historically polluted soil and creosote-impregnated shavings. With this regard, the effect of type of inoculum carrier (i.e., wheat straw, corn cobs and commercial pellets) and contaminant bioavailability was thoroughly determined. Although degradation performances of L. tigrinus were not significantly affected by the type of the support, they were invariably better than those of I. lacteus on both the polluted soil and the creosote-impregnated shavings. Although degradation efficiencies of all fungal microcosms were highly and significantly correlated with bioavailability, certain PAHs, such as chrysene and benzo[a]pyrene, were removed by L. tigrinus from the polluted soil at amounts that exceeded about 2.3-fold their respective bioavailabilities. Degradation of PAHs was negatively correlated with their organic carbon sorption coefficients (K oc) and hydrophobicity (log P). The strength of linear association with the latter parameter, however, was not affected by the type of contaminated matrix in L. tigrinus-based microcosms while it was significantly larger in the historically polluted soil than in the creosote-impregnated shavings in I. lacteus ones. [Copyright &y& Elsevier]