Use of a novel microbiome modulator improves anticancer immunity in a murine model of malignant pleural mesothelioma.

Objective: Malignant pleural mesothelioma is a fatal disease and a clinical challenge, as few effective treatment modalities are available. Previous evidence links the gut microbiome to the host immunoreactivity to tumors. We thus evaluated the impact of a novel microbiome modulator compound (MMC) on the gut microbiota composition, tumor immune microenvironment, and cancer control in a model of malignant pleural mesothelioma. Methods: Age- and weight-matched immunocompetent (n = 23) or athymic BALB/c mice (n = 15) were randomly assigned to MMC or no treatment (control) groups. MMC (31 ppm) was administered through the drinking water 14 days before AB12 malignant mesothelioma cell inoculation into the pleural cavity. The impact of MMC on tumor growth, animal survival, tumor-infiltrating leucocytes, gut microbiome, and fecal metabolome was evaluated and compared with those of control animals. Results: The MMC delayed tumor growth and significantly prolonged the survival of immunocompetent animals (P = .0015) but not that of athymic mice. The improved tumor control in immunocompetent mice correlated with increased infiltration of CD3+CD8+GRZB+ cytotoxic T lymphocytes in tumors. Gut microbiota analyses indicated an enrichment in producers of short chain fatty acids in MMC-treated animals. Finally, we observed a positive correlation between the level of fecal short chain fatty acids and abundance of tumor-infiltrating cytotoxic T cells in malignant pleural mesothelioma. Conclusions: MMC administration boosts antitumor immunity, which correlates with a change in gut microbiome and metabolome. MMC may represent a valuable treatment option to combine with immunotherapy in patients with cancer.

Upcycling of Cereal Byproducts: A Sustainable Opportunity to Valorize Wasted Nutrients and Derive Bioactive Compounds for Humans and Animals Nutrition and Health.

With the global population projected to reach close to 10 billion by 2050, the escalating demand for cereals such as wheat, rice, corn, oat, and barley places significant pressure on production systems. These systems are increasingly vulnerable to the adverse impacts of climate change, threatening global food security. This article emphasizes the critical need to address these challenges and explores strategies for sustainable foodproduction, focusing on the opportunities that the upcycling of cereal byproducts offers for human and animal nutrition and health.

Effect of thermo-chemical pretreatment on the saccharification and enzymatic digestibility of olive mill stones and their bioconversion towards alcohols.

The present study investigated the effect of thermo-chemical pretreatment on the enhancement of enzymatic digestibility of olive mill stones (OMS), as well as its possible valorisation via bioconversion of the generated free sugars to alcohols. Specifically, the influence of parameters such as reaction time, temperature, type and concentration of dilute acids and/or bases, was assessed during the thermo-chemical pretreatment. The hydrolysates and the solids remaining after pretreatment, as well as the whole pretreated slurries, were further evaluated as potential substrates for the simultaneous production of ethanol and xylitol via fermentation with the yeast Pachysolen tannophilus. The digestibility and overall saccharification of OMS were considerably enhanced in all cases, with the maximum enzymatic digestibility observed for dilute sodium hydroxide (almost 4-fold) which also yielded the highest total saccharification yield (91% of the total OMS carbohydrates). Ethanol and xylitol yields from the untreated OMS were 28 g/kg OMS and 25 g/kg OMS, respectively, and were both significantly enhanced by pretreatment. The highest ethanol yield was 79 g/kg OMS and was achieved by the alkali pretreatment and separate fermentation of hydrolysates and solids, whereas the highest xylitol yield was 49 g/kg OMS and was obtained by pretreatment with sulphuric acid and separate fermentation of hydrolysates and solids.

A Century's Breakthrough in Upcycling Lignocellulosic Biomass: Embion Technologies, Hard-tech Spin-off of the EPFL, Disrupts Nutrition Innovation with Sophisticated, Complex-prebiotics for Immunity.

Embion Technologies SA is a hard-tech spin-off of the EPFL, with a disruptive and novel platform technology that aims to enable the global transition to zero waste via the circular bioeconomy. Embion's initial focus is on transforming low-value food and agricultural industry byproduct streams to affordable next-generation prebiotics - nutrition for human and animal microbiome. We demonstrate here that the company's proprietary technology is simple and flexible and can be applied to a wide variety of feedstocks to extract tailored products with specific fingerprints. Embion's technology unlocks the natural hidden value of fibers, fats, proteins, minerals, and polyphenols within these byproduct streams to bring different functional food ingredients to the food, feed, and beverage market.

Efficient cleavage of aryl ether C-O linkages by Rh-Ni and Ru-Ni nanoscale catalysts operating in water.

Bimetallic Ru-Ni and Rh-Ni nanocatalysts coated with a phase transfer agent efficiently cleave aryl ether C-O linkages in water in the presence of hydrogen. For dimeric substrates with weaker C-O linkages, i.e. α-O-4 and ß-O-4 bonds, low loadings of the precious metal (Rh or Ru) in the nanocatalysts quantitatively afford monomers, whereas for the stronger 4-O-5 linkage higher amounts of the precious metal are required to achieve complete conversion. Under the optimized, relatively mild operating conditions, the C-O bonds in a range of substituted ether compounds are efficiently cleaved, and mechanistic insights into the reaction pathways are provided. This work paves the way to sustainable approaches for the hydrogenolysis of C-O bonds.

Influence of the Anion on the Oxidation of 5-Hydroxymethylfurfural by Using Ionic-Polymer-Supported Platinum Nanoparticle Catalysts.

Platinum nanoparticles stabilized by an imidazolium-based cross-linked polymer (with chloride as the counteranion) efficiently catalyzed the oxidation of 5-hydroxymethylfurfural to form 2,5-furandicarboxylic acid in water under mild conditions with oxygen as the oxidant. This catalyst system is explored herein by varying the counteranion, that is, replacing chloride by BF4 - , PF6 - , bis(trifluoromethylsulfonyl)imide, hexanoate, or laurate anions, in the cationic polymer. The counteranion influences the structure of the obtained platinum nanoparticles, the surface electronic properties, and their catalytic activity. The highest reaction rates were obtained with the weakly nucleophilic bis(trifluoromethylsulfonyl)imide anion, which also favored platinum in the zero oxidation state, leading to complete conversion of the substrate and a high yield of 2,5-furandicarboxylic acid under mild conditions.

Influence of the Anion on the Oxidation of 5-Hydroxymethylfurfural by Using Ionic-Polymer-Supported Platinum Nanoparticle Catalysts.

Invited for this month's cover are the groups of Prof. Paul J. Dyson at Ecole Polytechnique Fédérale de Lausanne (EPFL), Switzerland and Prof. Ning Yan at National University of Singapore, Singapore. The cover shows the catalytic conversion of 5-hydroxymethylfurfural (5-HMF) into 2,5-furandicarboxylic acid catalyzed by platinum nanoparticles stabilized by polymeric imidazolium salts. The catalyst is represented by a nanoparticle footprint. The background represents a potential source of biomass. Read the full text of the article at 10.1002/cplu.201700344.

Direct Conversion of Mono- and Polysaccharides into 5-Hydroxymethylfurfural Using Ionic-Liquid Mixtures.

Platform chemicals are usually derived from petrochemical feedstocks. A sustainable alternative commences with lignocellulosic biomass, a renewable feedstock, but one that is highly challenging to process. Ionic liquids (ILs) are able to solubilize biomass and, in the presence of catalysts, convert the biomass into useful platform chemicals. Herein, we demonstrate that mixtures of ILs are powerful systems for the selective catalytic transformation of cellulose into 5-hydroxymethylfurfural (HMF). Combining ILs with continuous HMF extraction into methyl-isobutyl ketone or 1,2-dimethoxyethane, which form a biphase with the IL mixture, allows the online separation of HMF in high yield. This one-step process is operated under relatively mild conditions and represents a significant step forward towards sustainable HMF production.

Application of Ionic Liquids in the Downstream Processing of Lignocellulosic Biomass.

Chemical transformations of lignocellulosic substrates to valuable platform chemicals are challenging as lignin and cellulose have high thermal and chemical stabilities. However, certain ionic liquids are able to dissolve and deconstruct biomass and, in the presence of catalysts, convert the dissolved/deconstructed species into useful platform chemicals. Herein, we provide a concise overview of the role of ionic liquids in biomass processing. Using 5-hydroxymethylfurfural as an example of a renewable building block, available from cellulose, we show how ionic liquids can facilitate its production.

Quantification of Conventional and Nonconventional Charge-Assisted Hydrogen Bonds in the Condensed and Gas Phases.

Charge-assisted hydrogen bonds (CAHBs) play critical roles in many systems from biology through to materials. In none of these areas has the role and function of CAHBs been explored satisfactorily because of the lack of data on the energy of CAHBs in the condensed phases. We have, for the first time, quantified three types of CAHBs in both the condensed and gas phases for 1-(2'-hydroxylethyl)-3-methylimidazolium acetate ([C2OHmim][OAc]). The energy of conventional OH···[OAc](-) CAHBs is ∼10 kcal·mol(-1), whereas nonconventional C(sp2)H···[OAc](-) and C(sp3)H···[OAc](-) CAHBs are weaker by ∼5-7 kcal·mol(-1). In the gas phase, the strength of the nonconventional CAHBs is doubled, whereas the conventional CAHBs are strengthened by <20%. The influence of cooperativity effects on the ability of the [OAc](-) anion to deprotonate the imidazolium cation is evaluated. The ability to quantify CAHBs in the condensed phase on the basis of easier accessible gas-phase estimates is highlighted.

Potential of cycloaddition reactions to generate cytotoxic metal drugs in vitro.

Severe general toxicity issues blight many chemotherapeutics utilized in the treatment of cancers, resulting in the need for more selective drugs able to exert their biological activity at only the required location(s). Toward this aim, we report the development of an organometallic ruthenium compound, functionalized through a η(6)-bound arene ligand with a bicyclononyne derivative, able to participate in strain-promoted cycloaddition reactions with tetrazines. We show that combination of the ruthenium compound with a ditetrazine in biological media results in the in situ formation of a dinuclear molecule that is more cytotoxic toward cancer cells than the starting mononuclear ruthenium compound and tetrazine components. Such an approach may be extended to in vivo applications to construct a cytotoxic metallodrug at a tumor site, providing a novel approach toward the turn-on cytotoxicity of metallodrugs in the treatment of cancer.

Enhanced conversion of carbohydrates to the platform chemical 5-hydroxymethylfurfural using designer ionic liquids.

5-Hydroxymethylfurfural (HMF) is a key platform chemical that may be obtained from various cellulosic (biomass) derivatives. Previously, it has been shown that ionic liquids (ILs) facilitate the catalytic conversion of glucose into HMF. Herein, we demonstrate that the careful design of the IL cation leads to new ionic solvents that enhance the transformation of glucose and more complex carbohydrates into HMF significantly. In Situ NMR spectroscopy and computational modeling pinpoint the key interactions between the IL, catalyst, and substrate that account for the enhanced reactivities observed.