Cell metabolism-based optimization strategy of CAR-T cell function in cancer therapy

Adoptive cell therapy (ACT) using chimeric antigen receptor (CAR)-modified T cells has revolutionized the field of immune-oncology, showing remarkable efficacy against hematological malignancies. However, its success in solid tumors is limited by factors such as easy recurrence and poor efficacy. The effector function and persistence of CAR-T cells are critical to the success of therapy and are modulated by metabolic and nutrient-sensing mechanisms. Moreover, the immunosuppressive tumor microenvironment (TME), characterized by acidity, hypoxia, nutrient depletion, and metabolite accumulation caused by the high metabolic demands of tumor cells, can lead to T cell “exhaustion” and compromise the efficacy of CAR-T cells. In this review, we outline the metabolic characteristics of T cells at different stages of differentiation and summarize how these metabolic programs may be disrupted in the TME. We also discuss potential metabolic approaches to improve the efficacy and persistence of CAR-T cells, providing a new strategy for the clinical application of CAR-T cell therapy

Regulatory controls of duplicated gene expression during fiber development in allotetraploid cotton.

Polyploidy complicates transcriptional regulation and increases phenotypic diversity in organisms. The dynamics of genetic regulation of gene expression between coresident subgenomes in polyploids remains to be understood. Here we document the genetic regulation of fiber development in allotetraploid cotton Gossypium hirsutum by sequencing 376 genomes and 2,215 time-series transcriptomes. We characterize 1,258 genes comprising 36 genetic modules that control staged fiber development and uncover genetic components governing their partitioned expression relative to subgenomic duplicated genes (homoeologs). Only about 30% of fiber quality-related homoeologs show phenotypically favorable allele aggregation in cultivars, highlighting the potential for subgenome additivity in fiber improvement. We envision a genome-enabled breeding strategy, with particular attention to 48 favorable alleles related to fiber phenotypes that have been subjected to purifying selection during domestication. Our work delineates the dynamics of gene regulation during fiber development and highlights the potential of subgenomic coordination underpinning phenotypes in polyploid plants. [Abstract copyright: © 2023. The Author(s).

Оптимізація техніко-технологічних показників кефіру з додаванням знежиреного кунжутного борошна та рисових висівок

Defatted sesame cake and rice bran are all by-products of agricultural processing. The aim of the study was to optimize the recipes of kefir added with defatted sesame flour and rice bran. The previous study has yielded some results including dietary fiber content, pH values and sensory evaluation values of kefir samples added with 0, 2 %, 4 %, 6 %, 8 % DSC and 0, 0.1 %, 0.3 %, 0.5 %, 0.7 % RB, but made no optimization of kefir products. Based on these data, formulation optimization was done using a mathematical model. Two central composite designs for the two-factor analysis (x1x2 and x1x3, respectively) and one three-factor design (x1x2x3) were drawn up to predict the optimal formulation and reduce the number of future experiments. After studying the results of mathematical modeling, the optimal prescription composition corresponds to the 2 % DSC or 0.1 % rice bran content or 2 % DSC and 0.4 % RB content in the recipe. Through mathematical optimization, products with high dietary fiber content, suitable acidity and excellent sensory quality can be obtained. The products meet the current social demand for healthy food and have very good research value. In practical use, three kinds of kefir can be developed: 1. DSC should be ground separately before used, 2 % DSC was introduced into cow milk (m/v), fermented at 28°C for 22 h until pH reached 4.7, then stored at 4 °C; 2. RB should be ground before used, 0.4 % RB was introduced into cow milk (m/v), fermented at 28°C for 22 h until pH reached 4.7, then stored at 4°C;  3. DSC and RB should be ground before used, 2 % DSC and 0.4 % RB were introduced into cow milk (m/v), fermented at 28 °C for 22 h until pH reached 4.7, then stored at 4 °CЗнежирена кунжутна макуха та рисові висівки є продуктами переробки сільськогосподарської сировини. Метою дослідження була оптимізація рецептур кефіру з додаванням знежиреного кунжутного борошна і рисових висівок. У попередньому дослідженні дані деякі результати, включаючи вміст харчових волокон, значення рН і показники органолептичної оцінки зразків кефіру з додаванням 0, 2 %, 4 %, 6 %, 8 % ЗКМ та 0, 0.1 %, 0.3 %, 0.5 %, 0.7 % РВ, але не проводилася оптимізація кефірних продуктів. На основі цих даних була проведена оптимізація рецептур з використанням математичної моделі. Для визначення оптимальної рецептури та скорочення кількості експериментів у майбутньому були складені два центральні композиційні плани для двофакторного аналізу (x1x2 і x1x3 відповідно) та один трифакторний план (x1x2x3). Після вивчення результатів математичного моделювання оптимальний рецептурний склад відповідає вмісту 2 % ЗКМ або 0,1 % РВ, або 2 % ЗКМ і 0,4 % РВ. Завдяки математичній оптимізації можна отримати продукти з високим вмістом харчових волокон, відповідною кислотністю та відмінними смаковими якостями. Продукти відповідають поточному суспільному попиту на здорове харчування та мають високу дослідницьку цінність. При практичному використанні можна отримати три види кефіру: 1. перед використанням ЗКМ слід окремо подрібнити, 2% ЗКМ вводять у коров'яче молоко (m/v), ферментують при температурі 28 °C протягом 22 год до досягнення рН 4,7, потім зберігають при 4 °C; 2. перед використанням РВ слід подрібнити, 0,4% РВ вводять у коров'яче молоко (m/v), ферментують при температурі 28 °C протягом 22 год до досягнення pH 4,7, потім зберігають при 4 °C; 3. перед використанням ЗКМ і РВ слід подрібнити, 2% ЗКМ і 0,4 % РВ вводять у коров'яче молоко (m/v), ферментують при температурі 28 °C протягом 22 год до досягнення pH 4,7, потім зберігають при 4 °

Influence of Sesame Flour on Physicochemical Properties of Sour Milk Drinks

This study aimed to investigate the technological properties of kefir fortified with defatted sesame flour (DSF). We have developed a recipe for producing kefir with the addition of 0, 2, 4, 6, 8 % DSF. The physicochemical parameters (pH, titratable acidity) and rheological properties (water-holding capacity, viscosity) of the samples within 28 days of storage were studied. All the samples were stored at a temperature of 4 °C. Nuclear magnetic resonance and chromatographic analysis were performed to determine the optimal shelf life of the product. It was found that fermentation ends on the seventh day of storage, while a low content of free water is observed. The recommended optimal storage time for kefir enriched with DSF is within 14 days. The introduction of 2 % DSF in kefir increases the content of vitamin E by three times (from 0.32 to 0.93 mg/100 g) and the content of proteins – by 1 % (from 3.36 to 4.3 %). The result showed that the pH value decreases with the introduction of DSF and is within the normal range during the entire storage period of the product (from 4.38 to 4.07). In this case, the total titratable acidity increases from 112.07 to 163.52 °T. An increase in viscosity (by 3 Pa∙s) and water-holding capacity (by almost 6 %) is observed with the addition of 2 % additive. Due to the high water-holding capacity and viscosity, dietary fiber content (up to 0.68 %), kefir supplemented with DSF showed high storage stability. The addition of 2 % DSF to kefir can increase the nutritional value and improve the structural stability of the product. DSF is a waste product with a bright prospect for use in the manufacture of fermented milk drink

The complete mitochondrial genome of Priotyrannus closteroides Thomson, 1877 (Coleoptera: Cerambycidae)

Priotyrannus closteroides Thomson, 1877 (Coleoptera: Cerambycidae) is the trunk borer of orange trees. In this study, we sequenced and annotated the whole mitochondrial genome of P. closteroides. The results showed that the length of the complete mitochondrial genome is 15,854 bp with an overall GC content of 32.11%. The genome encodes 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), and two ribosomal RNA genes (rRNAs). The relevant phylogenetic tree distinctly showed that P. closteroides is clustered with Dorysthenes paradoxus and Dorysthenes granulosus. This study provides a piece of valuable genomic information for the population genetics, evolution, and classification of P. closteroides

Influence of Sesame Flour on Physicochemical Properties of Sour Milk Drinks

This study aimed to investigate the technological properties of kefir fortified with defatted sesame flour (DSF). We have developed a recipe for producing kefir with the addition of 0, 2, 4, 6, 8 % DSF. The physicochemical parameters (pH, titratable acidity) and rheological properties (water-holding capacity, viscosity) of the samples within 28 days of storage were studied. All the samples were stored at a temperature of 4 °C. Nuclear magnetic resonance and chromatographic analysis were performed to determine the optimal shelf life of the product. It was found that fermentation ends on the seventh day of storage, while a low content of free water is observed. The recommended optimal storage time for kefir enriched with DSF is within 14 days. The introduction of 2 % DSF in kefir increases the content of vitamin E by three times (from 0.32 to 0.93 mg/100 g) and the content of proteins – by 1 % (from 3.36 to 4.3 %). The result showed that the pH value decreases with the introduction of DSF and is within the normal range during the entire storage period of the product (from 4.38 to 4.07). In this case, the total titratable acidity increases from 112.07 to 163.52 °T. An increase in viscosity (by 3 Pa∙s) and water-holding capacity (by almost 6 %) is observed with the addition of 2 % additive. Due to the high water-holding capacity and viscosity, dietary fiber content (up to 0.68 %), kefir supplemented with DSF showed high storage stability. The addition of 2 % DSF to kefir can increase the nutritional value and improve the structural stability of the product. DSF is a waste product with a bright prospect for use in the manufacture of fermented milk drink

Modulation of Cyclodextrin Particle Amphiphilic Properties to Stabilize Pickering Emulsion

Cyclodextrins have been proven to form complexes with linear oil molecules and stabilize emulsions. Amphiphilic properties of cyclodextrin particles were modulated through esterification reaction between β-cyclodextrin (β-CD) and octadecenyl succinic anhydride (ODSA) under alkaline conditions. ODS-β-CD particles with degree of substitution (DS) of 0.003, 0.011, and 0.019 were obtained. The introduced hydrophobic long chain that was linked within β-CD cavity led to the change of ODS-β-CD in terms of morphological structure, surface charge density, size, and contact angle, upon which the properties and stability of the emulsions stabilized by ODS-β-CD were highly dependent. The average diameter of ODS-β-CD particles ranged from 449 to 1484 nm. With the DS increased from 0.003 to 0.019, the contact angle and absolute zeta potential value of these ODS-β-CD particles improved from 25.7° to 47.3° and 48.1 to 62.8 mV, respectively. The cage structure of β-CD crystals was transformed to channel structure, then further to amorphous structure after introduction of the octadecenyl succinylation chain. ODS-β-CD particles exhibited higher emulsifying ability compared to β-CD. The resulting Pickering emulsions formed by ODS-β-CD particles were more stable during storage. This study investigates the ability of these ODS-β-CD particles to stabilize oil-in-water emulsions with respect to their amphiphilic character and structural properties

Reconstruction of Fluorophore Concentration Variation in Dynamic Fluorescence Molecular Tomography

Dynamic fluorescence molecular tomography (DFMT) is a potential approach for drug delivery, tumor detection, diagnosis, and staging. The purpose of DFMT is to quantify the changes of fluorescent agents in the bodies, which offer important information about the underlying physiological processes. However, the conventional method requires that the fluorophore concentrations to be reconstructed are stationary during the data collection period. As thus, it cannot offer the dynamic information of fluorophore concentration variation within the data collection period. In this paper, a method is proposed to reconstruct the fluorophore concentration variation instead of the fluorophore concentration through a linear approximation. The fluorophore concentration variation rate is introduced by the linear approximation as a new unknown term to be reconstructed and is used to obtain the time courses of fluorophore concentration. Simulation and phantom studies are performed to validate the proposed method. The results show that the method is able to reconstruct the fluorophore concentration variation rates and the time courses of fluorophore concentration with relative errors less than 0.0218

DataSheet_1_Molecular identification and functional characterization of two glycosyltransferases genes from Fallopia multiflora.pdf

The traditional Chinese medicine plant Fallopia multiflora (Thunb.) Harald. contains various pharmacodynamically active glycosides, such as stilbene glycosides, anthraquinone (AQ) glycosides, and flavonoid glycosides. Glycosylation is an important reaction in plant metabolism that is generally completed by glycosyltransferase in the last step of the secondary metabolite biosynthesis pathway, and it can improve the beneficial properties of many natural products. In this study, based on the transcriptome data of F. multiflora, we cloned two Uridine-diphosphate-dependent glycosyltransferases (UGTs) from the cDNA of F. multiflora (FmUGT1 and FmUGT2). Their full-length sequences were 1602 and 1449 bp, encoding 533 and 482 amino acids, respectively. In vitro enzymatic reaction results showed that FmUGT1 and FmUGT2 were promiscuous and could catalyze the glycosylation of 12 compounds, including stilbenes, anthraquinones, flavonoids, phloretin, and curcumin, and we also obtained and structurally identified 13 glycosylated products from both of them. Further experiments on the in vivo function of FmUGT1 and FmUGT2 showed that 2, 3, 5, 4’- tetrahydroxy stilbene-2-O-β-d-glucoside (THSG) content in hairy roots was elevated significantly when FmUGT1 and FmUGT2 were overexpressed and decreased accordingly in the RNA interference (RNAi) groups. These results indicate that FmUGT1 and FmUGT2 were able to glycosylate a total of 12 structurally diverse types of acceptors and to generate O-glycosides. In addition, FmUGT1 and FmUGT2 efficiently catalyzed the biosynthesis of THSG, and promoted the production of AQs in transgenic hairy roots.</p