Histocompatibility assessment in hematopoietic stem cell transplantation: recommendations from the Italian Association of Immunogenetics and Biology of Transplantation (Associazione Italiana di Immunogenetica e Biologia dei Trapianti - AIBT).

The outcome of allogeneic hematopoietic stem cell transplantation (HSCT) is significantly influenced by the degree of HLA histocompatibility between donor and recipient. To provide shared indications for required histocompatibility testing and interpretation before HSCT, the Italian Society for Immunogenetics and Transplantation Biology (Associazione Italiana di Immunogenetica e Biologia dei Trapianti [AIBT]) gathered members and created a working group to discuss and develop recommendations for histocompatibility assessment in HSCT.After a review of the literature and multiple panel discussions, AIBT developed up-to-date recommendations for the resolution levels of HLA typing, histocompatibility definitions of patients and donors, importance of anti-HLA antibodies, and significance of NK alloreactivity, which are reported in this document. These recommendations have been shared with the Italian Group for Bone Marrow Transplantation (Gruppo Italiano per il Trapianto di Midollo Osseo, cellule staminali emopoietiche e terapia cellulare [GITMO]) and the Italian National Center for Transplantation (Centro Nazionale Trapianti [CNT]). Notably, the increased use of HLA-mismatched transplantation (i.e., mismatched unrelated, haploidentical) in recent years has made these indications even more relevant for the standardization and improvement of quality of care.This document represents a useful instrument for health care workers involved in the field of HSCT, enhancing synergy with transplant physicians and enabling greater optimization of the available resources.

Eco-Friendly Catalytic Synthesis of Top Value Chemicals from Valorization of Cellulose Waste.

The total amount of cellulose from paper, wood, food, and other human activity waste produced in the EU is in the order of 900 million tons per year. This resource represents a sizable opportunity to produce renewable chemicals and energy. This paper reports, unprecedently in the literature, the usage of four different urban wastes such as cigarette butts, sanitary pant diapers, newspapers, and soybean peels as cellulose fonts to produce valuable industrial intermediates such as levulinic acid (LA), 5-acetoxymethyl-2-furaldehyde (AMF), 5-(hydroxymethyl)furfural (HMF), and furfural. The process is accomplished by the hydrothermal treatment of cellulosic waste using both Brønsted and Lewis acid catalysts such as CH3COOH (2.5-5.7 M), H3PO4 (15%), and Sc(OTf)3 (20% w:w), thus obtaining HMF (22%), AMF (38%), LA (25-46%), and furfural (22%) with good selectivity and under relatively mild conditions (T = 200 °C, time = 2 h). These final products can be employed in several chemical sectors, for example, as solvents, fuels, and for new materials as a monomer precursor. The characterization of matrices was accomplished by FTIR and LCSM analyses, demonstrating the influence of morphology on reactivity. The low e-factor values and the easy scale up render this protocol suitable for industrial applications.

Direct Synthesis of 3-Aryl Substituted Isocoumarins and Phthalides through Palladium Acetate Catalyzed C(sp2 )-H Activation in Ionic Liquids.

A novel Pd-catalysed oxidative coupling between benzoic acids and vinylarenes or acrylates to furnish isocoumarins and phthalides is reported. The reaction proceeds smoothly in molten tetrabutylammonium acetate via a selective C-H bond activation, with very low percentage of ligand-free palladium acetate as the catalyst, under atmospheric pressure of oxygen. Sub-stoichiometric amount of copper acetate is also required as a reoxidant for the palladium.

Steel slag as low-cost catalyst for artificial photosynthesis to convert CO2 and water into hydrogen and methanol.

Photoreduction of CO2 with sunlight to produce solar fuels, also named artificial photosynthesis, is considered one of the most attractive strategies to face the challenge of reducing greenhouse gases and achieving climate neutrality. Following an approach in line with the principles of the circular economy, the low-cost catalytic system (1) based on an industrial by-product such as steel slag was assessed, which was properly modified with nanostructured palladium on its surface in order to make it capable of promoting the conversion of CO2 into methanol and hydrogen through a two-stage process of photoreduction and thermal conversion having formic acid as the intermediate. Notably, for the first time in the literature steel slag is used as photoreduction catalyst.

Phase I/II Multicenter Trial of a Novel Therapeutic Cancer Vaccine, HepaVac-101, for Hepatocellular Carcinoma.

PURPOSE: Immunotherapy for hepatocellular carcinoma (HCC) shows considerable promise in improving clinical outcomes. HepaVac-101 represents a single-arm, first-in-human phase I/II multicenter cancer vaccine trial for HCC (NCT03203005). It combines multipeptide antigens (IMA970A) with the TLR7/8/RIG I agonist CV8102. IMA970A includes 5 HLA-A*24 and 7 HLA-A*02 as well as 4 HLA-DR restricted peptides selected after mass spectrometric identification in human HCC tissues or cell lines. CV8102 is an RNA-based immunostimulator inducing a balanced Th1/Th2 immune response. PATIENTS AND METHODS: A total of 82 patients with very early- to intermediate-stage HCCs were enrolled and screened for suitable HLA haplotypes and 22 put on study treatment. This consisted in a single infusion of low-dose cyclophosphamide followed by nine intradermal coadministrations of IMA970A and CV8102. Only patients with no disease relapse after standard-of-care treatments were vaccinated. The primary endpoints of the HepaVac-101 clinical trial were safety, tolerability, and antigen-specific T-cell responses. Secondary or exploratory endpoints included additional immunologic parameters and survival endpoints. RESULTS: The vaccination showed a good safety profile. Transient mild-to-moderate injection-site reactions were the most frequent IMA970A/CV8102-related side effects. Immune responses against ≥1 vaccinated HLA class I tumor-associated peptide (TAA) and ≥1 vaccinated HLA class II TAA were respectively induced in 37% and 53% of the vaccinees. CONCLUSIONS: Immunotherapy may provide a great improvement in treatment options for HCC. HepaVac-101 is a first-in-human clinical vaccine trial with multiple novel HLA class I- and class II-restricted TAAs against HCC. The results are initial evidence for the safety and immunogenicity of the vaccine. Further clinical evaluations are warranted.

Valorization of cigarette butts for synthesis of levulinic acid as top value-added chemicals.

Unprecedented in the literature, levulinic acid (LA), one of the top value-added intermediates of chemical industry, is obtained from cigarette butts as cellulose feedstock by means of a one-pot hydrothermal process carried out at 200 °C for 2 h and catalysed by phosphoric acid. The protocol avoids the use of more aggressive and toxic H2SO4 and HCl, that are generally employed on several cellulose sources (e.g. sludge paper), thus minimizing corrosion phenomena of plants. Neither chemical pre-treatment of butts nor specific purification procedure of LA are required. Notably, by simply modifying acid catalyst (e.g. using CH3COOH), another top value-added fine chemical such as 5-hydroxymethylfuraldehyde (HMF) is obtained, thus widening the scope of the method. Being cigarette filters a waste available in quantities of megatonnes per year, they represent an unlimited at no cost source of cellulose, thus enabling the up-scale to an industrial level of LA production.

Concerning Synthesis of New Biobased Polycarbonates with Curcumin in Replacement of Bisphenol A and Recycled Diphenyl Carbonate as Example of Circular Economy.

Curcumin (CM) is a natural polyphenol wellknown for its antioxidant and pharmaceutical properties, that can represent a renewable alternative to bisphenol A (BPA) for the synthesis of biobased polycarbonates (PC). In the presented strategy, preparation of the CMbased PC was coupled with chemical recycling of the fossilbased BPA polycarbonate (BPAPC) conducting a twosteps transpolymerization that replaces BPA monomer with CM or its tetrahydrogenated colorless product (THCM). In the first step of synthetic strategy, depolymerization of commercial BPAPC was carried out with phenol as nucleophile, according to our previous procedure based on zinc derivatives and ionic liquids as catalysts, thus producing quantitatively diphenyl carbonate (DPC) e BPA. In the second step, DPC underwent a melt transesterification with CM or THCM monomers affording the corresponding biobased polycarbonates, CMPC and THCMPC, respectively. THCM was prepared by reducing natural bisphenol with cyclohexene as a hydrogen donor and characterized by 1H-NMR and MS techniques. Polymerization reactions were monitored by infrared spectroscopy and average molecular weights and dispersity of the two biobased polymers THCMPC and CMPC were determined by means of gel permeation chromatography (GPC). Optical properties of the prepared polymers were also measured.

Expression profile of HLA-B*38:55Q allele.

The identification of null or questionably expressed HLA allelic variants is a major issue in HLA diagnostics, because the mistyping of the aberrant expression of such alleles can have a major impact on the outcome of both hematopoietic stem cell transplantation (HSCT) and solid organ transplants. It is debated how questionable (Q) alleles, because of their unknown expression profile, should be considered in an allogenic HSCT setting. The HLA-B*38:55Q allele was detected as an HLA-B blank specificity; DNA sequencing identified a single polymorphism at position 373 in exon 3 (TGC > CGC), which results in the replacement of cysteine 101 with an arginine in the HLA-B heavy chain, thus, impairing disulfide bridge formation in the alpha-2 domain, essential for the normal expression of the HLA molecules. In order to determine the RNA and protein expression profile of this allelic variant, we analyzed antigenic expression at different levels, transcriptional and transductional, using a combination of cellular methods, such as serological testing and flow cytometric analysis, polymerase chain reaction (PCR) sequence-specific primer (SSP) cDNA group-specific amplification and immunocytochemical assay, demonstrating the prevalent cytoplasmatic distribution of the HLA-B*38:55Q protein. Our findings suggest that in matching process the HLA-B*38:55Q allele needs to be considered as a low expressed allele, able to elicit an allogenic T-cell response in vivo and impair the transplant outcome.

Preparation of Biowax Esters in Continuous Flow Conditions.

Biowaxes synthesized from vegetable fatty acids are an alternative to petrochemical paraffins. A simple way of access to these compounds involves Fisher-type esterification of long-chain acids and alcohols under acidic conditions, but long reaction times and harsh conditions are commonly required. In this study, for the first time in the literature, biowax esters are prepared under flow conditions cutting dramatically both reaction times (from 12 h to 30 min) and temperature conditions, with respect to batch procedures (from 90-120 °C to 55 °C). This approach brings substantial improvements to the biowax synthesis process from an economic and environmental point of view, thus making the method up-scalable to the industrial level.

Continued Progress towards Efficient Functionalization of Natural and Non-natural Targets under Mild Conditions: Oxygenation by C-H Bond Activation with Dioxirane.

The successful isolation and characterization of a dioxirane species in 1988 opened up one of the most attractive methods for the efficient oxidation of simple and/or structurally complex molecules. Dioxirane today rank among the most powerful tools in organic chemistry, with numerous applications in commercially important processes. They were quickly recognized as efficient oxygen transfer agents, especially for epoxidations and for a wide range of O-insertion reactions into C-H bonds. Dioxirane possess catalytic activity and appear as highly (chemo-, regio-, and stereo-) selective oxidants, despite their reactivity under mild and strictly neutral conditions being controlled by a combination of steric and electronic factors. In this review, we discuss some of the most recent and significant developments in the selective homogeneous and heterogeneous oxyfunctionalization of non-activated C-H bonds in hydrocarbons of natural and non-natural targets by using isolated dioxirane or, more generally, by using the ketones (i.e., the dioxirane precursors) as organocatalysts.

Epoxidation of Carbon Nanocapsules: Decoration of Single-Walled Carbon Nanotubes Filled with Metal Halides.

Methyl(trifluoromethyl)dioxirane (TFDO) can be used for the oxyfunctionalization of SWCNTs filled with NaI and LuCl3 under mild conditions. The chosen metal halides are of interest for theranostics, both for imaging and therapy when in their radioactive form. The applied functionalization methodology does not require metal catalyst, preserves the integrity of the nanotubes during treatment, avoiding the release of the filling material. In this way, epoxidation can be considered as an efficient methodology for the functionalization of carbon nanocapsules, where the traditional harsh oxidation conditions by acids are not applicable.

Catalytic Activity of Silicon Nanowires Decorated with Gold and Copper Nanoparticles Deposited by Pulsed Laser Ablation.

Silicon nanowires (SiNWs) decorated by pulsed laser ablation with gold or copper nanoparticles (labeled as AuNPs@SiNWs and CuNPs@SiNWs) were investigated for their catalytic properties. Results demonstrated high catalytic performances in the Caryl-N couplings and subsequent carbonylations for gold and copper catalysts, respectively, that have no precedents in the literature. The excellent activity, attested by the very high turn over number (TON) values, was due both to the uniform coverage along the NW length and to the absence of the chemical shell surrounding the metal nanoparticles (MeNPs). A high recyclability was also observed and can be ascribed to the strong covalent interaction at the Me-Si interface by virtue of metal "silicides" formation.

TiO2@PEI-Grafted-MWCNTs Hybrids Nanocomposites Catalysts for CO2 Photoreduction.

Anatase (TiO2) and multiwalled carbon nanotubes bearing polyethylenimine (PEI) anchored on their surface were hybridized in different proportions according to a sol-gel method. The resulting nanocomposites (TiO2@PEI-MWCNTs), characterized by BET, XRD, XPS, SEM, and UV techniques, were found efficient catalysts for CO2 photoreduction into formic and acetic acids in water suspension and under visible light irradiation. PEI-grafted nanotubes co-catalysts are believed to act as CO2 activators by forming a carbamate intermediate allowing to accomplish the first example in the literature of polyamines/nanotubes/TiO2 mediated CO2 photoreduction to carboxylic acids.

Heterogenization of Ketone Catalyst for Epoxidation by Low Pressure Plasma Fluorination of Silica Gel Supports.

Low pressure plasma was used for preparing heterogeneous organocatalysts 2-(A)-(C) suitable for dioxirane-mediated epoxidations. Heterogenization was accomplished by adsorption of the methyl perfluoroheptyl ketone (2) on fluorinated supports (A)-(C) deriving from the treatment of commercial C8-silica gel in low pressure plasma fed with fluorocarbons. Catalyst 2-(C) proved to be the most efficient one, promoting epoxidation of an array of alkenes, including unsaturated fatty esters like methyl oleate (10) and the triglyceride soybean oil (11), with the cheap potassium peroxymonosulfate KHSO5 (caroate) as a green oxidant. Notably, the perfluorinated matrix gives rise to the activation of caroate, generating singlet oxygen. Materials were characterized by infrared Attenuated Total Reflectance spectroscopy (ATR-FTIR), X-ray Photoelectron Spectroscopy (XPS ) and Emission Scanning Electron Microscope (FESEM).

Preparation and Characterization of Soybean Oil-Based Polyurethanes for Digital Doming Applications.

Polyurethane-resin doming is currently one of the fastest growing markets in the field of industrial graphics and product identification. Semi-rigid bio-based polyurethanes were prepared deriving from soybean oil as a valuable alternative to fossil materials for digital doming and applied to digital mosaic technology. Bio-resins produced can favorably compete with the analogous fossil polymers, giving high-quality surface coatings (ascertained by SEM analyses). In addition, polyurethane synthesis was accomplished by using a mercury- and tin-free catalyst (the commercially available zinc derivative K22) bringing significant benefits in terms of cost efficiency and eco-sustainability.

One-Pot Conversion of Epoxidized Soybean Oil (ESO) into Soy-Based Polyurethanes by MoCl2O2 Catalysis.

An innovative and eco-friendly one-pot synthesis of bio-based polyurethanes is proposed via the epoxy-ring opening of epoxidized soybean oil (ESO) with methanol, followed by the reaction of methoxy bio-polyols intermediates with 2,6-tolyl-diisocyanate (TDI). Both synthetic steps, methanolysis and polyurethane linkage formation, are promoted by a unique catalyst, molybdenum(VI) dichloride dioxide (MoCl2O2), which makes this procedure an efficient, cost-effective, and environmentally safer method amenable to industrial scale-up.

Heterolytic (2 e) vs Homolytic (1 e) Oxidation Reactivity: N-H versus C-H Switch in the Oxidation of Lactams by Dioxirans.

Dioxiranes are powerful oxidants that can act via two different mechanisms: 1) homolytic (H abstraction and oxygen rebound) and 2) heterolytic (electrophilic oxidation). So far, it has been reported that the nature of the substrate dictates the reaction mode independently from the dioxirane employed. Herein, we report an unprecedented case in which the nature of the dioxirane rules the oxidation chemoselectivity. In particular, a switch from C-H to N-H oxidation is observed in the oxidation of lactams moving from dimethyl dioxirane (DDO) to methyl(trifluoromethyl)dioxirane (TFDO). A physical organic chemistry study, which combines the oxidation with two other dioxiranes methyl(fluoromethyl)dioxirane, MFDO, and methyl(difluoromethyl)dioxirane, DFDO, with computational studies, points to a diverse ability of the dioxiranes to either stabilize the homo or the heterolytic pathway.

Synthesis and Biological Evaluation of a Valinomycin Analog Bearing a Pentafluorophenyl Active Ester Moiety.

A valuable analog of the K(+)-ionophore valinomycin (1), bearing a pentafluorophenyl ester moiety, has been obtained by selective reaction between the tertiary hydroxyl moiety of analog 2 (available from valinomycin hydroxylation) and the isocyanate group of pentafluorophenyl N-carbonyl glycinate (3) catalyzed by bis(N,N-dimethylformamide)dichlorodioxomolybdenum(VI). LC-HRMS studies show that analog 4 undergoes easy derivatization under mild conditions by reaction with OH- and NH2-containing compounds. Mitochondrial depolarization assays suggest that 4 acts as a K(+)-ionophore, provided that the glycine carboxyl group is appropriately masked.

Photoreduction of carbon dioxide to formic acid in aqueous suspension: a comparison between phthalocyanine/TiO2 and porphyrin/TiO2 catalysed processes.

Composite materials prepared by loading polycrystalline TiO2 powders with lipophilic highly branched Cu(II)- and metal-free phthalocyanines or porphyrins, which have been used in the past as photocatalysts for photodegradative processes, have been successfully tested for the efficient photoreduction of carbon dioxide in aqueous suspension affording significant amounts of formic acid. The results indicated that the presence of the sensitizers is beneficial for the photoactivity, confirming the important role of Cu(II) co-ordinated in the middle of the macrocycles. A comparison between Cu(II) phthalocyanines and Cu(II) porphyrins indicated that the Cu(II)- phthalocyanine sensitizer was more efficient in the photoreduction of CO2 to formic acid, probably due to its favorable reduction potential.

Direct synthesis of ESBO derivatives-¹8O labelled with dioxirane.

This work addresses a new approach developed in our laboratory, consisting in the application of isolated dimethyldioxirane (DDO, 1a) labelled with ¹8O for synthesis of epoxidized glyceryl linoleate (Gly-LLL, 2). We expect that this work could contribute in improving analytical methods for the determination of epoxidized soybean oil (ESBO) in complex food matrices by adopting an ¹8O-labelled-epoxidized triacylglycerol as an internal standard.