Synthesis of 1-Hexanol/Hexyl hexanoate Mixtures from Grape Pomace: Insights on Diesel Engine Performances at High Bio-Blendstock Loadings

The production of oxygenated bio-additives for traditional fuels represents a key challenge due to their depletion in the near-future and their positive contribution to the reduction in environmental pollution. The present study considers the synthesis of 1-hexanol/hexyl hexanoate mixtures, two oxygenated Diesel bio-additives produced through the hydrogenation of hexanoic acid, obtainable from the fermentation of a wide variety of waste biomasses. In our case, crude hexanoic acid was produced through the fermentation of grape pomace, an abundant Italian agrifood waste. Commercial 5 wt% Re/γ-Al2O3 was adopted for the catalytic hydrogenation of crude hexanoic acid, and the support acidity allowed the tuning of the reaction selectivity toward the formation of hexyl hexanoate, instead of 1-hexanol, reaching yields of 40 and 25 mol%, respectively. The effects of each bio-additive on Diesel engine performance and exhaust emissions (soot, nitrogen oxides, carbon monoxide, unburned hydrocarbons) were evaluated, highlighting noteworthy positive effects especially on the reduction in carbon monoxide and soot emissions, if compared with those of Diesel fuel alone. Similar promising performances were achieved by employing Diesel blend mixtures of 1-hexanol/hexyl hexanoate, mimicking typical compositions of the rhenium-catalyzed post-hydrogenation mixtures. Even in such cases, 1-hexanol/hexyl hexanoate mixtures can be blended with commercial Diesel fuel, up to high loadings currently not yet investigated (20 vol%), without altering the engine performances and, again, significantly lowering soot and carbon monoxide emissions by more than 40%. This work highlights the possibility of obtaining such oxygenated bio-additives starting from waste through to a fully sustainable process and proves their beneficial effects on the reduction in exhaust emissions with no changes in engine performance

Innovative biorefinery process for the fractionation and conversion of giant reed to carotenoids and triglycerides

Innovative biorefinery process for the fractionation and conversion of giant reed to carotenoids and triglyceride

Biomass ethanolysis: process optimization and performances of ethyl levulinate as diesel blendstock

Biomass represents a key asset for renewable energy production in the context of the more and more pressing energetic transition. Moreover, at the present, the issue of how to store a convenient amount of energy on board of electric vehicles is still a challenge and electric vehicles perspectives are limited to passenger cars and very small-range trucks, significant amount of time being necessary to define the eventual appropriate electric storage system to be employed in heavy transport, as well in aviation and shipping. In this context alkyl levulinates represent a concrete perspective for partial replacement of fossil fuel with renewable blendstocks. In particular, ethyl levulinate (EL) production by direct acid-catalyzed biomass ethanolysis was studied in order to investigate and optimize this one-step process which involves only renewable starting materials (biomass and bioethanol). In this perspective, the role of the main reaction parameters as the substrate nature and loading, type of the acid catalyst and its concentration, reaction temperature and duration were studied. EL was tested up to high concentrations in a mixture with diesel fuel in a small single-cylinder air-cooled diesel engine, to verify the engine and emission performances of the different blend compositions respect to those ascertained with a conventional diesel fuel

Blockade of EIF5A hypusination limits colorectal cancer growth by inhibiting MYC elongation

Eukaryotic Translation Initiation Factor 5A (EIF5A) is a translation factor regulated by hypusination, a unique posttranslational modification catalyzed by deoxyhypusine synthetase (DHPS) and deoxyhypusine hydroxylase (DOHH) starting from the polyamine spermidine. Emerging data are showing that hypusinated EIF5A regulates key cellular processes such as autophagy, senescence, polyamine homeostasis, energy metabolism, and plays a role in cancer. However, the effects of EIF5A inhibition in preclinical cancer models, the mechanism of action, and specific translational targets are still poorly understood. We show here that hypusinated EIF5A promotes growth of colorectal cancer (CRC) cells by directly regulating MYC biosynthesis at specific pausing motifs. Inhibition of EIF5A hypusination with the DHPS inhibitor GC7 or through lentiviral-mediated knockdown of DHPS or EIF5A reduces the growth of various CRC cells. Multiplex gene expression analysis reveals that inhibition of hypusination impairs the expression of transcripts regulated by MYC, suggesting the involvement of this oncogene in the observed effect. Indeed, we demonstrate that EIF5A regulates MYC elongation without affecting its mRNA content or protein stability, by alleviating ribosome stalling at five distinct pausing motifs in MYC CDS. Of note, we show that blockade of the hypusination axis elicits a remarkable growth inhibitory effect in preclinical models of CRC and significantly reduces the size of polyps in APCMin/+ mice, a model of human familial adenomatous polyposis (FAP). Together, these data illustrate an unprecedented mechanism, whereby the tumor-promoting properties of hypusinated EIF5A are linked to its ability to regulate MYC elongation and provide a rationale for the use of DHPS/EIF5A inhibitors in CRC therapy

GZMKhigh CD8+ T effector memory cells are associated with CD15high neutrophil abundance in non-metastatic colorectal tumors and predict poor clinical outcome.

CD8(+) T cells are a major prognostic determinant in solid tumors, including colorectal cancer (CRC). However, understanding how the interplay between different immune cells impacts on clinical outcome is still in its infancy. Here, we describe that the interaction of tumor infiltrating neutrophils expressing high levels of CD15 with CD8(+) T effector memory cells (T(EM)) correlates with tumor progression. Mechanistically, stromal cell-derived factor-1 (CXCL12/SDF-1) promotes the retention of neutrophils within tumors, increasing the crosstalk with CD8(+) T cells. As a consequence of the contact-mediated interaction with neutrophils, CD8(+) T cells are skewed to produce high levels of GZMK, which in turn decreases E-cadherin on the intestinal epithelium and favors tumor progression. Overall, our results highlight the emergence of GZMK(high) CD8(+) T(EM) in non-metastatic CRC tumors as a hallmark driven by the interaction with neutrophils, which could implement current patient stratification and be targeted by novel therapeutics

Impact of Chronic Lung Disease on Very Low Birth Weight infants: a collaborative study of the Italian Group of Neonatal Pneumology

Objective. To evaluate the incidence and risk factors for chronic lung disease in a population of very low birth weight infants. Methods. In a prospective multicentric trial all very low birth weight infants (< 1500 g) accepted in 36 Italian Neonatal Intensive care units were studied from February 89 to January 99. For each patient were recorded maternal history, perinatal events, respiratory disease, infections, patent ductus arteriosus, retinopathy of prematurity, intraventricular haemorrhage and final outcome. Logistic regression analysis was performed in a multivariate assessment of risk factors for chronic lung disease. Results. In the study were included 1634 patients: 1387 infants survived beyond 36 weeks and 6.9% of them still oxygen dependent. The incidence of chronic lung disease was higher among babies with a gestational age of < 28 weeks and weight \ub2 1000 g. The multivariate analysis showed that low birth weight, respiratory distress syndrome, persistent ductus arteriosus and sepsis were the main risk factors. Conclusions. In our study the incidence of chronic lung disease was relatively lo

Development of an All-in-One Lentiviral Vector System Based on the Original TetR for the Easy Generation of Tet-ON Cell Lines

Lentiviral vectors (LVs) are considered one of the most promising vehicles to efficiently deliver genetic information for basic research and gene therapy approaches. Combining LVs with drug-inducible expression systems should allow tight control of transgene expression with minimal side effect on relevant target cells. A new doxycycline-regulated system based on the original TetR repressor was developed in 1998 as an alternative to the TetR-VP16 chimeras (tTA and rtTA) to avoid secondary effects due to the expression of transactivator domains. However, previously described TetR-based systems required cell cloning and/or antibiotic selection of tetracycline-responsive cells in order to achieve good regulation. In the present manuscript we have constructed a dual Tet-ON system based on two lentiviral vectors, one expressing the TetR through the spleen focus forming virus (SFFV) promoter (STetR) and a second expressing eGFP through the regulatable CMV-TetO promoter (CTetOE). Using these vectors we have demonstrated that the TetR repressor, contrary to the reverse transactivator (rtTA), can be expressed in excess to bind and modulate a high number of TetO operons. We have also showed that this dual vector system can generate regulatable bulk cell lines (expressing high levels of TetR) that are able to modulate transgene expression either by varying doxycycline concentration and/or by varying the amount of CTetOE vector genomes per cell. Based on these results we have developed a new all-in-one lentiviral vector (CEST) driving the expression of TetR through the SFFV promoter and the expression of eGFP through the doxycycline-responsive CMV-TetO operon. This vector efficiently produced Tet-ON regulatable immortalized (293T) and primary (human mesenchymal stem cells and human primary fibroblasts) cells. Bulk doxycycline-responsive cell lines express high levels of the transgene with low amount of doxycycline and are phenotypically indistinct from its parental cells

T Helper 1–Inducing Adjuvant Protects against Experimental Paracoccidioidomycosis

Immunostimulatory therapy is a promising approach to improving the treatment of systemic fungal infections such as paracoccidioidomycosis (PCM), whose drug therapy is usually prolonged and associated with toxic side effects and relapses. The current study was undertaken to determine if the injection of a T helper (Th) 1–stimulating adjuvant in P. brasiliensis–infected mice could have a beneficial effect on the course of experimental PCM. For this purpose, mice were infected and treated with complete Freund's adjuvant (CFA), a well-established Th1 experimental inductor, or incomplete Freund's adjuvant (IFA - control group) on day 20 postinfection. Four weeks after treatment, the CFA-treated mice presented a mild infection in the lungs characterized by absence of epithelioid cell granulomas and yeast cells, whereas the control mice presented multiple sites of focal epithelioid granulomas with lymphomonocytic halos circumscribing a high number of viable and nonviable yeast cells. In addition, CFA administration induced a 2.4 log reduction (>99%) in the fungal burden when compared to the control group, and led to an improvement of immune response, reversing the immunosuppression observed in the control group. The immunotherapy with Th1-inducing adjuvant, approved to be used in humans, might be a valuable tool in the treatment of PCM and potentially useful to improve the clinical cure rate in humans

Lack of Galectin-3 Drives Response to Paracoccidioides brasiliensis toward a Th2-Biased Immunity

There is recent evidence that galectin-3 participates in immunity to infections, mostly by tuning cytokine production. We studied the balance of Th1/Th2 responses to P. brasiliensis experimental infection in the absence of galectin-3. The intermediate resistance to the fungal infection presented by C57BL/6 mice, associated with the development of a mixed type of immunity, was replaced with susceptibility to infection and a Th2-polarized immune response, in galectin-3-deficient (gal3−/−) mice. Such a response was associated with defective inflammatory and delayed type hypersensitivity (DTH) reactions, high IL-4 and GATA-3 expression and low nitric oxide production in the organs of infected animals. Gal3−/− macrophages exhibited higher TLR2 transcript levels and IL-10 production compared to wild-type macrophages after stimulation with P. brasiliensis antigens. We hypothesize that, during an in vivo P. brasiliensis infection, galectin-3 exerts its tuning role on immunity by interfering with the generation of regulatory macrophages, thus hindering the consequent Th2-polarized type of response