Surface TREM2 on circulating M-MDSCs as a novel prognostic factor for adults with treatment-naïve diffuse large B-cell lymphoma.

INTRODUCTION: Circulating monocytic myeloid-derived suppressive cells (M-MDSCs) are implicated as a poor prognostic factor and cause CAR T-cell failure in diffuse large B-cell lymphoma (DLBCL). Triggering receptors expressed on myeloid cells 2 (TREM2) are a transmembrane glycoprotein that polarize macrophages to anti-inflammation phenotype but have never been explored on M-MDSCs. This study aims to elucidate the expression and clinical impact of surface TREM2 on circulating M-MDSCs derived from DLBCL adults. METHODS: This prospective, observational study enrolled 100 adults with newly diagnosed and treatment-naïve DLBCL from May 2019 to October 2021. Human circulating M-MDSCs were obtained from freshly isolated peripheral blood, and each patient's surface-TREM2 level on M-MDSCs was normalized via a healthy control at the same performance of flow-cytometry analysis. Murine MDSCs derived from bone marrow (BM-MDSCs) were adopted to assess the link between Trem2 and cytotoxic T lymphocytes. RESULTS: More circulating M-MDSCs at diagnosis of DLBCL predicted worse progression-free (PFS) and overall survival (OS). Patients with higher IPI scores, bone marrow involvement, or lower absolute counts of CD4+ or CD8+ T cells in PB had significantly higher normalized TREM2 levels on M-MDSCs. Additionally, normalized TREM2 levels on M-MDSCs could be grouped into low (< 2%), medium (2-44%), or high (> 44%) levels, and a high normalized TREM2 level on M-MDSCs was proven as an independent prognostic factor for both PFS and OS via multivariate Cox regression analysis and associated with worst PFS and OS. Interestingly, normalized levels of surface TREM2 on M-MDSCs were negatively associated with absolute counts of PB CD8+ T cells and positively correlated with levels of intracellular arginase 1 (ARG1) within M-MDSCs. Wild-type BM-MDSCs had significantly higher mRNA levels of Arg1 and showed more prominent ability to suppress the proliferation of co-cultured CD8+ T cells than BM-MDSCs from Trem2 knockout mice, and the suppressive ability could be impaired by adding Arg1 inhibitors (CB1158) or supplementing L-arginine. CONCLUSION: In treatment-naïve DLBCL adults, a high surface-TREM2 level on circulating M-MDSCs is a poor prognostic factor for both PFS and OS and warrants further investigation for its potential as a novel target in immunotherapy.

Identifying sensory drivers of liking for plant-based milk coffees: Implications for product development and application.

The global plant-based product market is growing rapidly, and plant-based milks show promising potential in the coffee beverage sector. This study aimed to identify sensory drivers of liking of plant-based milk coffees for guiding the development of plant-based products with competitive advantages over dairy milk coffees. Twelve coffee samples were prepared with plant-based (oat, soy, almond, and coconut) and dairy (cow) milk. Quantitative descriptive analysis was used to generate sensory attribute terms for the 12 samples. Check-all-that-apply (CATA) questions were given to consumers to evaluate the sensory profiles and consumer acceptance of the 12 samples. Correspondence analysis and cluster analysis of the CATA results from 80 consumers showed that the oat and soy milk coffee samples were closer to what the consumers perceived as "typical" milk products, while the coconut and almond milk coffee samples were closer to the "flavored" milk products. Partial least squares regression results revealed that the attributes smooth, milky, and thick were important drivers of liking for the milk coffee samples. On the contrary, rancid oil, greasy, astringent, and rice bran were the major sensory attributes lowering the panelists' acceptance of the milk coffee samples. The majority of consumers (53.5%) were "dairy milk lovers," who specifically liked the dairy milk coffee sample and had low acceptance for the plant-based milk coffee samples. There was also a group of consumers (46.2%) classified as "plant-based milk coffee lovers." They enjoyed coffees prepared with a wide range of milks (both dairy and nondairy milks) and represent high-potential consumers for plant-based milk coffee products. PRACTICAL APPLICATION: The positive and negative drivers of liking for plant-based milk coffee samples were identified. A competitive landscape analysis method for assessing the acceptability and sensory attributes of 12 milk coffee samples (11 commercial plant-based milks and 1 dairy milk product) in the current Asian market was established. The sensory terms developed in this study can also be applied to evaluate sensory profiles of other plant-based and dairy milk coffee samples.

Removal of emerging contaminants using spent mushroom compost.

Acetaminophen and sulfonamides are emerging contaminants. Conventional wastewater treatment systems fail to degrade these compounds properly. Mycoremediation, is a form of novel bioremediation that uses extracellular enzymes of white-rot fungi to degrade pollutants in the environment. In this study, spent mushroom compost (SMC), which contains fungal extracellular enzymes, was tested for acetaminophen and sulfonamides removal. Among the SMCs of nine mushrooms tested in batch experiments, the SMC of Pleurotus eryngii exhibited the highest removal rate for acetaminophen and sulfonamides. Several fungal extracellular enzymes that might be involved in removal of acetaminophen and sulfonamides were identified by metaproteomic analysis. The bacterial classes, Betaproteobacteria and Alphaproteobacteria, were revealed by metagenomic analysis and may be assisting with acetaminophen and sulfonamide removal, respectively, in the SMC of Pleurotus eryngii. Bioreactor experiments were used to simulate the capability of Pleurotus eryngii SMC for the removal of acetaminophen and sulfonamides from wastewater. The results of this study provide a feasible solution for acetaminophen and sulfonamide removal from wastewater using the SMC of Pleurotus eryngii.

Green and efficient production of octyl hydroxyphenylpropionate using an ultrasound-assisted packed-bed bioreactor.

A solvent-free system to produce octyl hydroxyphenylpropionate (OHPP) from p-hydroxyphenylpropionic acid (HPPA) and octanol using immobilized lipase (Novozym® 435) as a catalyst in an ultrasound-assisted packed-bed bioreactor was investigated. Response-surface methodology (RSM) and a three-level-three-factor Box-Behnken design were employed to evaluate the effects of reaction temperature (x1), flow rate (x2) and ultrasonic power (x3) on the percentage of molar production of OHPP. The results indicate that the reaction temperature and flow rate were the most important variables in optimizing the production of OHPP. Based on a ridge max analysis, the optimum conditions for OHPP synthesis were predicted to consist of a reaction temperature of 65°C, a flow rate of 0.05 ml/min and an ultrasonic power of 1.74 W/cm² with a yield of 99.25%. A reaction was performed under these optimal conditions, and a yield of 99.33 ± 0.1% was obtained.

Continuous production of lipase-catalyzed biodiesel in a packed-bed reactor: optimization and enzyme reuse study.

An optimal continuous production of biodiesel by methanolysis of soybean oil in a packed-bed reactor was developed using immobilized lipase (Novozym 435) as a catalyst in a tert-butanol solvent system. Response surface methodology (RSM) and Box-Behnken design were employed to evaluate the effects of reaction temperature, flow rate, and substrate molar ratio on the molar conversion of biodiesel. The results showed that flow rate and temperature have significant effects on the percentage of molar conversion. On the basis of ridge max analysis, the optimum conditions were as follows: flow rate 0.1 mL/min, temperature 52.1°C, and substrate molar ratio 1 : 4. The predicted and experimental values of molar conversion were 83.31 ± 2.07% and 82.81 ± .98%, respectively. Furthermore, the continuous process over 30 days showed no appreciable decrease in the molar conversion. The paper demonstrates the applicability of using immobilized lipase and a packed-bed reactor for continuous biodiesel synthesis.