Beyond FOXP3:a 20-year journey unravelling human regulatory T-cell heterogeneity

The initial idea of a distinct group of T-cells responsible for suppressing immune responses was first postulated half a century ago. However, it is only in the last three decades that we have identified what we now term regulatory T-cells (Tregs), and subsequently elucidated and crystallized our understanding of them. Human Tregs have emerged as essential to immune tolerance and the prevention of autoimmune diseases and are typically contemporaneously characterized by their CD3+CD4+CD25high CD127lowFOXP3+ phenotype. It is important to note that FOXP3+ Tregs exhibit substantial diversity in their origin, phenotypic characteristics, and function. Identifying reliable markers is crucial to the accurate identification, quantification, and assessment of Tregs in health and disease, as well as the enrichment and expansion of viable cells for adoptive cell therapy. In our comprehensive review, we address the contributions of various markers identified in the last two decades since the master transcriptional factor FOXP3 was identified in establishing and enriching purity, lineage stability, tissue homing and suppressive proficiency in CD4+ Tregs. Additionally, our review delves into recent breakthroughs in innovative Treg-based therapies, underscoring the significance of distinct markers in their therapeutic utilization. Understanding Treg subsets holds the key to effectively harnessing human Tregs for immunotherapeutic approaches

EGF Stimulates Rab35 Activation and Gastric Cancer Cell Migration by Regulating DENND1A-Grb2 Complex Formation

Aims: The aim of this study was to reveal the specific molecular mechanisms by which DENND1A accepts EGF signaling and activates Rab35 in gastric cancer.Methods: The expression of proteins related to DENND1A was examined by western blot analysis. Activation of Rab35 was assessed by GST-pulldown. The interaction of DENND1A and Grb2 was assessed by GST-pulldown and co-immunoprecipitation assays. The relationship between DENND1A and cell migration and invasion was detected using wound healing and transwell by gene overexpression and RNA interference.Results: EGF stimulation significantly promoted cell migration, whereas transfection with siRab35 partially inhibited EGF-promoted cell migration. DENND1A is also involved in these processes and active Rab35. Moreover, DENND1A binds to the N-terminal and C-terminal SH3 domains of Grb2 through PRD. Of special interest is the observation that EGFR can recruit Grb2-DENND1A complex under EGF stimulation. Further results reveal that the higher the expression of DENND1A, the shorter progression-free survival of gastric cancer patients.Conclusion: In summary, we confirmed that EGF-Grb2-DENND1A-Rab35 signaling pathway with the interaction of DENND1A and Grb2 as a regulatory center could regulate gastric cancer cell migration and invasion. Ultimately, the expression level of DENND1A predicts the survival status of gastric cancer patients and may become one of the important targets for the treatment of gastric cancer

Application of Solubility Parameter Theory to Organosolv Extraction of Lignin from Enzymatically Hydrolyzed Cornstalks

The Hildebrand solubility parameter (delta-value) was applied to explain the effect of organic solvent concentration on lignin removal during organosolv extraction of lignin from enzymatically hydrolyzed cornstalks under atmospheric pressure and low temperature (≤ 75 °C) without additional catalyst. The -value of lignin, calculated using the group-contribution method, was 13.70 (cal/cm3)1/2. The proximity of the delta-value between organic solvent-water and lignin explained the delignification capacity of the organic solvent-water. The concentration of organic solvent in the aqueous mixture that led to the highest delignification (i.e., 34.5%, 41.8%, and 53.7% delignification for ethanol-water, 1,4-dioxane-water, and tetrahydrofuran-water, respectively) was around 65 to 75% vol., which was in keeping with the prediction by the solubility parameter theory

Does Video Content Facilitate or Impair Comprehension of Documentaries?The Effect of Cognitive Abilities and Eye Movement Strategy

It remains unclear whether multimedia facilitates or impairsknowledge acquisition. Here we examined whether subtitlesand video content facilitate comprehension of documentariesconsisting of statements of facts and whether thecomprehension depends on participants’ cognitive abilitiesand eye movement strategies during video watching. Wefound that subtitles facilitated comprehension regardless ofparticipants’ cognitive abilities or eye movement strategiesfor video watching. In contrast, with video content but notsubtitles, comprehension depended on participants’ auditoryworking memory, task switching ability, and eye movementstrategy. Through the Eye Movement analysis with HiddenMarkov Models (EMHMM) method, we found that acentralized (looking mainly at the screen center) eyemovement strategy predicted better comprehension asopposed to a distributed strategy (with distributed regions ofinterest) after contributions from cognitive abilities werecontrolled. Thus, whether video content facilitatescomprehension of documentaries depends on the viewers’ eyemovement strategy in addition to cognitive abilities

The Growth-Promoting and Colonization of the Pine Endophytic <i>Pseudomonas abietaniphila</i> for Pine Wilt Disease Control

In this study, we focused on evaluating the impact of Pseudomonas abietaniphila BHJ04 on the growth of Pinus massoniana seedlings and its biocontrol efficacy against pine wilt disease (PWD). Additionally, the colonization dynamics of P. abietaniphila BHJ04 on P. massoniana were examined. The growth promotion experiment showed that P. abietaniphila BHJ04 significantly promoted the growth of the branches and roots of P. massoniana. Pot control experiments indicated that strain BHJ04 significantly inhibited the spread of PWD. There were significant changes in the expression of several genes related to pine wood nematode defense in P. massoniana, including chitinase, nicotinamide synthetase, and triangular tetrapeptide-like superfamily protein isoform 9. Furthermore, our results revealed significant upregulation of genes associated with the water stress response (dehydration-responsive proteins), genetic material replication (DNA/RNA polymerase superfamily proteins), cell wall hydrolase, and detoxification (cytochrome P450 and cytochrome P450 monooxygenase superfamily genes) in the self-regulation of P. massoniana. Colonization experiments demonstrated that strain BHJ04 can colonize the roots, shoots, and leaves of P. massoniana, and the colonization amount on the leaves was the greatest, reaching 160,000 on the 15th day. However, colonization of the stems lasted longer, with the highest level of colonization observed after 45 d. This study provides a preliminary exploration of the growth-promoting and disease-preventing mechanisms of P. abietaniphila BHJ04 and its ability to colonize pines, thus providing a new biocontrol microbial resource for the biological control of plant diseases

Uridine and its role in metabolic diseases, tumors, and neurodegenerative diseases

Uridine is a pyrimidine nucleoside found in plasma and cerebrospinal fluid with a concentration higher than the other nucleosides. As a simple metabolite, uridine plays a pivotal role in various biological processes. In addition to nucleic acid synthesis, uridine is critical to glycogen synthesis through the formation of uridine diphosphate glucose in which promotes the production of UDP-GlcNAc in the hexosamine biosynthetic pathway and supplies UDP-GlcNAc for O-GlcNAcylation. This process can regulate protein modification and affect its function. Moreover, Uridine has an effect on body temperature and circadian rhythms, which can regulate the metabolic rate and the expression of metabolic genes. Abnormal levels of blood uridine have been found in people with diabetes and obesity, suggesting a link of uridine dysregulation and metabolic disorders. At present, the role of uridine in glucose metabolism and lipid metabolism is controversial, and the mechanism is not clear, but it shows the trend of long-term damage and short-term benefit. Therefore, maintaining uridine homeostasis is essential for maintaining basic functions and normal metabolism. This article summarizes the latest findings about the metabolic effects of uridine and the potential of uridine metabolism as therapeutic target in treatment of metabolic disorders

Identification and Conservation Analysis of <i>Cis</i>-Regulatory Elements in Pig Liver

The liver plays a key role in metabolism and affects pig production. However, the functional annotation of noncoding regions of the pig liver remains poorly understood. We revealed the landscape of cis-regulatory elements and their functional characterization in pig liver. We identified 102,373 cis-regulatory elements in the pig liver, including enhancers, promoters, super-enhancers, and broad H3K4me3 domains, and highlighted 26 core transcription regulatory factors in the pig liver as well. We found similarity of cis-regulatory elements among those of pigs, humans, and cattle. Despite the low proportion of functionally conserved enhancers (~30%) between pig and human liver tissue, ~78% of the pig liver enhancer orthologues sequence could play an enhancer role in other human tissues. Additionally, we observed that the ratio of consistent super-enhancer-associated genes was significantly higher than the ratio of functionally conserved super-enhancers. Approximately 54% of the core regulation factors driven by super-enhancers were consistent across the liver from these three species. Our pig liver annotation and functional characterization studies provide a system and resource for noncoding annotation for future gene regulatory studies in pigs. Furthermore, our study also showed the high level functional conservation of cis-regulatory elements in mammals; it also improved our understanding of regulation function of mammal cis-regulatory elements

Regulating interfacial ion migration with pillar effect in layer-by-layer inter-embedded MoS2/Ti3C2 for high-performance zinc-ion batteries

Two-dimensional (2D) layered materials have promising prospects for Zn-storage due to their flexible and adjustable interlayer architecture. The strong electrostatic interaction and high diffusion energy barrier, however, lead to slow diffusion kinetics of Zn-ions between the 2D interfaces, limiting its widespread application. Herein, Ti3C2 MXene is introduced into the MoS2 interlayer by the pillar effect to assemble a layer-by-layer inter-embedded structure (L-MoS2/Ti3C2), which provides sufficient diffusion channels for Zn-ions. DFT computations and GITT confirm that the L-MoS2/Ti3C2 exhibits superior Zn-ions migration kinetics. Therefore, L-MoS2/Ti3C2 shows excellent long-term cycling stability (75.6% capacity retention after 7000 cycles at 15 A g-1) and glorious high-rate capability (107 mAh g-1 at 20 A g-1). In addition, the practical application of this material is demonstrated by evaluating the performance of L-MoS2/Ti3C2 in flexible quasi-solid-state aqueous zinc ion batteries under various extreme bending conditions, which exhibits good stability under 180° during the 4000 cycles with a capacity retention of 80.5% at 2.0 A g-1