Unexpected different chemoselectivity in the aerobic oxidation of methylated planar catechin and bent epicatechin derivatives catalysed by the Trametes villosa laccase/1-hydroxybenzotriazole system

Unreported methylated catechin and epicatechin derivatives 5 and 6 were synthesized by an oxa-Pictet- Spengler reaction. Catechin 5 shows the B and C rings coplanar because of the formation of a trans junction between the C ring and the newly generated six-term cycle D, in turn condensed to ring B. In contrast, epicatechin 6 presents a bent geometry due to the establishment of a cis junction between the C ring and the newly formed cycle D. The oxidation of compounds 5 and 6 in the presence of the Trametes villosa laccase/1-hydroxybenzotriazole (HBT) system was investigated under aerobic conditions in both a biphasic system and a reverse micelle. The unexpected different chemoselective oxidation at the benzylic position of catechin and epicatechin derivatives 5 and 6 has been rationalized using a molecular modelling approach. These results demonstrate that the Trametes villosa laccase/HBT system represents a useful tool to functionalize the C-2 or C-4 position of phenolic compounds depending on the structural features

Genomics and Immunomics in the Treatment of Urothelial Carcinoma

Urothelial carcinoma is a complex cancer with genomic immunomic drivers that have prognostic and predictive treatment implications. Identifying potential targetable alterations via next-generation sequencing and RNA sequencing may allow for elucidation of such targets and exploitation with targeted therapeutics. The role of immunotherapy in treating urothelial carcinoma has shown benefit, but it is unclear in which patients immunotherapeutics have the highest yield. Continuing efforts into better identifying which patients may benefit most from targeted therapies, immunotherapies, and combination therapies may ultimately lead to improved outcomes for patients with this disease

Pixantrone can be activated by formaldehyde to generate a potent DNA adduct forming agent

Mitoxantrone is an anti-cancer agent used in the treatment of breast and prostate cancers. It is classified as a topoisomerase II poison, however can also be activated by formaldehyde to generate drug–DNA adducts. Despite identification of this novel form of mitoxantrone–DNA interaction, excessively high, biologically irrelevant drug concentrations are necessary to generate adducts. A search for mitoxantrone analogues that could potentially undergo this reaction with DNA more efficiently identified Pixantrone as an ideal candidate. An in vitro crosslinking assay demonstrated that Pixantrone is efficiently activated by formaldehyde to generate covalent drug–DNA adducts capable of stabilizing double-stranded DNA in denaturing conditions. Pixantrone–DNA adduct formation is both concentration and time dependent and the reaction exhibits an absolute requirement for formaldehyde. In a direct comparison with mitoxantrone–DNA adduct formation, Pixantrone exhibited a 10- to 100-fold greater propensity to generate adducts at equimolar formaldehyde and drug concentrations. Pixantrone–DNA adducts are thermally and temporally labile, yet they exhibit a greater thermal midpoint temperature and an extended half-life at 37°C when compared to mitoxantrone–DNA adducts. Unlike mitoxantrone, this enhanced stability, coupled with a greater propensity to form covalent drug–DNA adducts, may endow formaldehyde-activated Pixantrone with the attributes required for Pixantrone–DNA adducts to be biologically active

Human adipose tissue–derived mesenchymal stromal cells promote B-cell motility and chemoattraction

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Soil communities: who responds and how quickly to a change in agricultural system?

The use of conservation and sustainable practices could restore the abundance and richness of soil organisms in agroecosystems. Fitting in this context, this study aimed to highlight whether and how different soil living communities reacted to the conversion from an integrated to an organic orchard. The metataxonomic approach for fungi and bacteria and the determination of biological forms of diatoms and microarthropods were applied. Soil analyses were carried out in order to evaluate the effect of soil chemical features on four major soil living communities. Our results showed that the different taxa reacted with different speeds to the management changes. Fungi responded quickly to the changes, suggesting that modification in agricultural practices had a greater impact on fungal communities. Bacteria and microarthropods were more affected by abiotic parameters and less by the management. The diatom composition seemed to be affected by seasonality but the highest H’ (Shannon index) value was measured in the organic system. Fungi, but also diatoms, seemed to be promising for monitoring changes in the soil since they were sensitive to both the soil features and the anthropic impact. Our study showed that soil biodiversity could be affected by the conversion to sustainable management practices from the early years of an orchard onwards. Therefore, better ecological orchard management may strengthen soil sustainability and resilience in historically agricultural region

Soil communities: Who responds and how quickly to a change in agricultural system?

The use of conservation and sustainable practices could restore the abundance and richness of soil organisms in agroecosystems. Fitting in this context, this study aimed to highlight whether and how different soil living communities reacted to the conversion from an integrated to an organic orchard. The metataxonomic approach for fungi and bacteria and the determination of biological forms of diatoms and microarthropods were applied. Soil analyses were carried out in order to evaluate the effect of soil chemical features on four major soil living communities. Our results showed that the different taxa reacted with different speeds to the management changes. Fungi responded quickly to the changes, suggesting that modification in agricultural practices had a greater impact on fungal communities. Bacteria and microarthropods were more affected by abiotic parameters and less by the management. The diatom composition seemed to be affected by seasonality but the highest H’ (Shannon index) value was measured in the organic system. Fungi, but also diatoms, seemed to be promising for monitoring changes in the soil since they were sensitive to both the soil features and the anthropic impact. Our study showed that soil biodiversity could be affected by the conversion to sustainable management practices from the early years of an orchard onwards. Therefore, better ecological orchard management may strengthen soil sustainability and resilience in historically agricultural regions

Lightweight Model for Session-Based Recommender Systems with Seasonality Information in the Fashion Domain

This paper presents the solution designed by the team "Boston Team Party"for the ACM RecSys Challenge 2022. The competition was organized by Dressipi and was framed under the session-based fashion recommendations domain. Particularly, the task was to predict the purchased item at the end of each anonymous session. Our proposed two-stage solution is effective, lightweight, and scalable. First, it leverages the expertise of several strong recommendation models to produce a pool of candidate items. Then, a Gradient-Boosting Decision Tree model aggregates these candidates alongside several hand-crafted features to produce the final ranking. Our model achieved a score of 0.18800 in the public leaderboard. To aid in the reproducibility of our findings, we open-source our materials

Agronomical valorization of eluates from the industrial production of microorganisms: Chemical, microbiological, and ecotoxicological assessment of a novel putative biostimulant

Plant Biostimulants (BSs) are a valid supplement to be considered for the integration of conventional fertilization practices. Research in the BS field keeps providing alternative products of various origin, which can be employed in organic and conventional agriculture. In this study, we investigated the biostimulant activity of the eluate obtained as a by-product from the industrial production of lactic acid bacteria on bare agricultural soil. Eluates utilization is in line with the circular economy principle, creating economical value for an industrial waste product. The research focused on the study of physical, chemical, biochemical, and microbiological changes occurring in agricultural soil treated with the biowaste eluate, applied at three different dosages. The final aim was to demonstrate if, and to what extent, the application of the eluate improved soil quality parameters and enhanced the presence of beneficial soil-borne microbial communities. Results indicate that a single application at the two lower dosages does not have a pronounced effect on the soil chemical parameters tested, and neither on the biochemical proprieties. Only the higher dosage applied reported an improvement in the enzymatic activities of β-glucosidase and urease and in the chemical composition, showing a higher content of total, nitric and ammonia N, total K, and higher humification rate. On the other hand, microbial communities were strongly influenced at all dosages, showing a decrease in the bacterial biodiversity and an increase in the fungal biodiversity. Bioinformatic analysis revealed that some Operative Taxonomic Units (OTUs) promoted by the eluate application, belong to known plant growth promoting microbes. Some other OTUs, negatively influenced were attributed to known plant pathogens, mainly Fusarium spp. Finally, the ecotoxicological parameters were also determined and allowed to establish that no toxic effect occurred upon eluate applications onto soil

Heat Stress During the Transition Period is Associated with Impaired Production, Reproduction, and Survival in Dairy Cows

The objectives of this retrospective cohort study were to determine the association of heat stress exposure during the transition period with production, health, reproduction, and survival during the first 90 days postpartum in dairy cows. A total of 5,722 Holstein cows (2,324 heifers and 3,397 cows) were categorized into environmental condition (EC) groups based on average temperature humidity index (THI) exposure as thermoneutral (TN) or heat stress (HS) during the pre (Pre) and early postpartum (Post) periods into TN-TN, TN-HS, HS-TN, and HS-HS. In heifers, exposure to HS during the Pre, Post, or Pre and Post was associated with a 3.7-lb/d reduction in milk yield compared with TN-TN. Postpartum HS was associated with increases of 4.4-percentage points in incidence of retained placenta, 18.1-percentage points in incidence of metritis, and 2.0-percentage points in incidence of mastitis, and a reduction in 5.3-percentage points in pregnancy at first AI, and an increase in 4.5-percentage points in pregnancy loss compared with Post TN. In cows, exposure to HS during the Pre, Post, or Pre and Post was associated with a 5.3-lb/d reduction in milk yield when compared with TN-TN. Post HS was associated with an increased incidence of retained placenta of 5.8-percentage points within Pre HS cows, whereas no difference was found within Pre TN cows. Metritis was increased by 6.3-percentage points in Post HS cows. For pregnancy per AI, Post HS was associated with reduced pregnancy of 10.6-percentage points within Pre TN cows, whereas no difference was found within Pre HS cows. Removal from the herd increased in cows exposed to HS during the Pre or Post, or Pre and Post. These data suggest that early postpartum HS is associated with performance losses to a greater extent than prepartum HS and that heifers and cows are vulnerable to losses associated with exposure to HS during the transition period