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Maturing immunometabolic research empowers immune regulation novel approaches. Progressive metabolic adaptation of tumor cells permits a thriving tumor microenvironment (TME) in which immune cells always lose the initial killing capacity, which remains an unsolved dilemma even with the development of immune checkpoint therapies. In recent years, many studies on tumor immunometabolism have been reported. The development of immunometabolism may facilitate anti-tumor immunotherapy from the recurrent crosstalk between metabolism and immunity. Here, we discuss clinical studies of the core signaling pathways of immunometabolism and their inhibitors or agonists, as well as the specific functions of these pathways in regulating immunity and metabolism, and discuss some of the identified immunometabolic checkpoints. Understanding the comprehensive advances in immunometabolism helps to revise the status quo of cancer treatment. An overview of the new landscape of immunometabolism. The PI3K pathway promotes anabolism and inhibits catabolism. The LKB1 pathway inhibits anabolism and promotes catabolism. Overactivation of PI3K/AKT/mTOR pathway and IDO, IL4I1, ACAT, Sirt2, and MTHFD2 promote immunosuppression of TME formation, as evidenced by increased Treg and decreased T-cell proliferation. The LKBI-AMPK pathway promotes the differentiation of naive T cells to effector T cells and memory T cells and promotes anti-tumor immunity in DCs.
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BACKGROUND: The production of succinic acid (SA) from biomass has attracted worldwide interest. Saccharomyces cerevisiae is preferred for SA production due to its strong tolerance to low pH conditions, ease of genetic manipulation, and extensive application in industrial processes. However, when compared with bacterial producers, the SA titers and productivities achieved by engineered S. cerevisiae strains were relatively low. To develop efficient SA-producing strains, it's necessary to clearly understand how S. cerevisiae cells respond to SA. RESULTS: In this study, we cultivated five S. cerevisiae strains with different genetic backgrounds under different concentrations of SA. Among them, KF7 and NBRC1958 demonstrated high tolerance to SA, whereas NBRC2018 displayed the least tolerance. Therefore, these three strains were chosen to study how S. cerevisiae responds to SA. Under a concentration of 20 g/L SA, only a few differentially expressed genes were observed in three strains. At the higher concentration of 60 g/L SA, the response mechanisms of the three strains diverged notably. For KF7, genes involved in the glyoxylate cycle were significantly downregulated, whereas genes involved in gluconeogenesis, the pentose phosphate pathway, protein folding, and meiosis were significantly upregulated. For NBRC1958, genes related to the biosynthesis of vitamin B6, thiamin, and purine were significantly downregulated, whereas genes related to protein folding, toxin efflux, and cell wall remodeling were significantly upregulated. For NBRC2018, there was a significant upregulation of genes connected to the pentose phosphate pathway, gluconeogenesis, fatty acid utilization, and protein folding, except for the small heat shock protein gene HSP26. Overexpression of HSP26 and HSP42 notably enhanced the cell growth of NBRC1958 both in the presence and absence of SA. CONCLUSIONS: The inherent activities of small heat shock proteins, the levels of acetyl-CoA and the strains' potential capacity to consume SA all seem to affect the responses and tolerances of S. cerevisiae strains to SA. These factors should be taken into consideration when choosing host strains for SA production. This study provides a theoretical basis and identifies potential host strains for the development of robust and efficient SA-producing strains.
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Regulação Fúngica da Expressão Gênica , Saccharomyces cerevisiae , Ácido Succínico , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Ácido Succínico/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , FermentaçãoRESUMO
The intestinal bacteria of longhorn beetles would be ideal targets for pest control and lignocellulosic resources by destroying or exploiting their cellulose-degrading function. This article aims to investigate the diversity and community structure of intestinal bacteria the oligophagous longhorn beetle Glenea cantor. Additionally, it seeks to identify the presence of lignocellulose-degrading bacteria in the gut, and explore their role in consuming host kapok trees Bombax malabaricum. In this study, the bacterial community from G. cantor was examined by Illumina sequencing of 16S ribosomal RNA (rRNA) targeting the V3 and V4 regions. A total of 563,201 valid sequences and 814 OTUs were obtained. The dominant phyla were Proteobacteria, and the dominant genera were Acinetobacter and Lactococcus. The analysis of microbial diversity revealed a high bacterial diversity in the samples, with the gut bacteria playing a crucial role in the physiological activities of the host, particularly, 9 genera of intestinal bacteria with cellulose degradation function were found, highlighting their vital role in cellulose degradation. Five strains of cellulose-degrading bacteria, belonging to the genus Pseudomonas, were obtained from the intestinal tract of G. cantor larvae using traditional isolation and culture techniques as well as 16S rDNA sequencing. Among these strains, A4 exhibited a cellulase activity of 94.42 ± 0.42 U/mL, while A5 displayed the highest filter paper enzyme activity of 127.46 ± 3.54 U/mL. These results offered valuable insights into potential targets for pest control through internal attack digestion and cellulose-degrading bacteria in longhorn beetles.
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Tumor-associated macrophage (TAM) affects the intrinsic properties of tumor cells and the tumor microenvironment (TME), which can stimulate tumor cell proliferation, migration, and genetic instability, and macrophage diversity includes the diversity of tumors with different functional characteristics. Macrophages are now a central drug target in various diseases, especially in the TME, which, as "tumor promoters" and "immunosuppressors", have different responsibilities during tumor development and accompany by significant dynamic alterations in various subpopulations. Remodelling immunosuppression of TME and promotion of pre-existing antitumor immune responses is critical by altering TAM polarization, which is relevant to the efficacy of immunotherapy, and uncovering the exact mechanism of action of TAMs and identifying their specific targets is vital to optimizing current immunotherapies. Hence, this review aims to reveal the triadic interactions of macrophages with programmed death and oncotherapy, and to integrate certain relationships in cancer treatment.
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Traditionally, the formation of amorphous shear bands in crystalline materials has been undesirable, because shear bands can nucleate voids and act as precursors to fracture. They also form as a final stage of accumulated damage. Only recently were shear bands found to form in undefected crystals, where they serve as the primary driver of plasticity without nucleating voids. Here we have discovered trends in materials properties that determine when amorphous shear bands will form and whether they will drive plasticity or lead to fracture. We have identified the materials systems that exhibit shear-band deformation, and by varying the composition, we were able to switch from ductile to brittle behaviour. Our findings are based on a combination of experimental characterization and atomistic simulations, and they provide a potential strategy for increasing the toughness of nominally brittle materials.
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Neuropeptides and neuropeptide receptors are crucial regulators to insect physiological processes. The 21.0 Gb bases were obtained from Illumina sequencing of two libraries representing the female and male heads of Phauda flammans (Walker) (Lepidoptera: Phaudidae), which is a diurnal defoliator of ficus plants and usually outbreaks in the south and south-east Asia, to identify differentially expressed genes, neuropeptides and neuropeptide receptor whose tissue expressions were also evaluated. In total, 99,386 unigenes were obtained, in which 156 up-regulated and 61 down-regulated genes were detected. Fifteen neuropeptides (i.e., F1b, Ast, NP1, IMF, Y, BbA1, CAP2b, NPLP1, SIF, CCH2, NP28, NP3, PDP3, ARF2 and SNPF) and 66 neuropeptide receptor genes (e.g., A2-1, FRL2, A32-1, A32-2, FRL3, etc.) were identified and well-clustered with other lepidopteron. This is the first sequencing, identification neuropeptides and neuropeptide receptor genes from P. flammans which provides valuable information regarding the molecular basis of P. flammans.
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Lepidópteros , Neuropeptídeos , Animais , Feminino , Lepidópteros/genética , Lepidópteros/metabolismo , Masculino , Neuropeptídeos/genética , Neuropeptídeos/metabolismo , Receptores de Neuropeptídeos/genética , Receptores de Neuropeptídeos/metabolismoRESUMO
Glenea cantor Fabricius (Cerambycidae: Lamiinae) is a pest that devastates urban landscapes and causes ecological loss in southern China and Southeast Asian countries where its main host kapok trees are planted. The olfactory system plays a vital role in mating, foraging, and spawning in G. cantor as an ideal target for pest control. However, the olfactory mechanism of G. cantor is poorly understood at the molecular level. In this study, we first established the antennal transcriptome of G. cantor and identified 76 olfactory-related genes, including 29 odorant binding proteins (OBPs), 14 chemosensory proteins (CSPs), 13 odorant receptors (ORs), 18 ionotropic receptors (IRs) and 2 sensory neuron membrane proteins (SNMPs). Furthermore, the phylogenetic trees of olfactory genes were constructed to study the homology with other species of insects. We also verified the reliability of transcriptome differential genes by qRT-PCR, which indicated the reliability of the transcriptome. Based on the relative expression of 30 d adults, GcanOBP22 and GcanOBP25 were highly expressed not only in the antennae, but also in the wings and legs. In addition, GcanCSP4 was the highest expression on the female antennae at 12 d. These findings laid the foundation for further research on the mechanism of G. cantor olfactory mechanism at the molecular level.
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BACKGROUND: Strong multiple stress-tolerance is a desirable characteristic for Saccharomyces cerevisiae when different feedstocks are used for economical industrial ethanol production. Random mutagenesis or genome shuffling has been applied for improving multiple stress-tolerance, however, these techniques are generally time-consuming and labor cost-intensive and their molecular mechanisms are unclear. Genetic engineering, as an efficient technology, is poorly applied to construct multiple stress-tolerant industrial S. cerevisiae due to lack of clear genetic targets. Therefore, constructing multiple stress-tolerant industrial S. cerevisiae is challenging. In this study, some target genes were mined by comparative transcriptomics analysis and applied for the construction of multiple stress-tolerant industrial S. cerevisiae strains with prominent bioethanol production. RESULTS: Twenty-eight shared differentially expressed genes (DEGs) were identified by comparative analysis of the transcriptomes of a multiple stress-tolerant strain E-158 and its original strain KF-7 under five stress conditions (high ethanol, high temperature, high glucose, high salt, etc.). Six of the shared DEGs which may have strong relationship with multiple stresses, including functional genes (ASP3, ENA5), genes of unknown function (YOL162W, YOR012W), and transcription factors (Crz1p, Tos8p), were selected by a comprehensive strategy from multiple aspects. Through genetic editing based on the CRISPR/Case9 technology, it was demonstrated that expression regulation of each of these six DEGs improved the multiple stress-tolerance and ethanol production of strain KF-7. In particular, the overexpression of ENA5 significantly enhanced the multiple stress-tolerance of not only KF-7 but also E-158. The resulting engineered strain, E-158-ENA5, achieved higher accumulation of ethanol. The ethanol concentrations were 101.67% and 27.31% higher than those of the E-158 when YPD media and industrial feedstocks (straw, molasses, cassava) were fermented, respectively, under stress conditions. CONCLUSION: Six genes that could be used as the gene targets to improve multiple stress-tolerance and ethanol production capacities of S. cerevisiae were identified for the first time. Compared to the other five DEGs, ENA5 has a more vital function in regulating the multiple stress-tolerance of S. cerevisiae. These findings provide novel insights into the efficient construction of multiple stress-tolerant industrial S. cerevisiae suitable for the fermentation of different raw materials.
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Kapok is the main host of Glenea cantor (Fabricius), which causes serious damage and is difficult to control. In severe cases, it often causes the kapok trees to die continuously, which seriously affects the results of urban landscaping. To provide reference for the functional research on related genes in G. cantor, we screened the stable expression of candidate reference genes at different developmental stages (i.e., eggs, larvae, pupae, and adults), in various adult tissues (i.e., head, thorax, abdomen, feet, antennae, and wings), and sexes (i.e., male pupae, female pupae, male adults, and female adults). In this study, 12 candidate reference genes (i.e., ACTINLIKE, ACTININ, TUB, RPL36, RPL32, RPS20, TBP, GAPDH, 18S rRNA, EF1A1, EF1A2, and UBQ) were evaluated using different adult tissues, developmental stages, and sexes. RefFinder, geNorm, NormFinder, and BestKeeper were used to evaluate and comprehensively analyze the stability of the expression of the candidate reference genes. The results show that RPL32 and EF1A1 were the most suitable reference genes in the different adult tissues, and RPL36 and EF1A1 were best at the different developmental stages. RPL36 and EF1A2 were the best fit for the qRT-PCR reference genes in the different sexes, while RPL36 and EF1A1 were the most appropriate qRT-PCR reference genes in all samples. Results from geNorm showed that the optimal number of reference genes was two. We also surveyed the expression of cellulase at the different developmental stages and in the different adult tissues. Results further verified the reliability of the reference genes, and confirmed the best reference genes under the different experimental conditions. This study provides a useful tool for molecular biological studies on G. cantor.
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Besouros/genética , Genes de Insetos/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa/normas , Transcriptoma/genética , Animais , China , Perfilação da Expressão Gênica/métodos , Larva/genética , Pupa/genética , Padrões de Referência , Reprodutibilidade dos Testes , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodosRESUMO
In metallic systems, increasing the density of interfaces has been shown to be a promising strategy for annealing defects introduced during irradiation. The role of interfaces during irradiation of ceramics is more unclear because of the complex defect energy landscape that exists in these materials. Here, we report the effects of interfaces on radiation-induced phase transformation and chemical composition changes in SiC-Ti3SiC2-TiC x multilayer materials based on combined transmission electron microscopy (TEM) analysis and first-principles calculations. We found that the undesirable phase transformation of Ti3SiC2 is substantially enhanced near the SiC/Ti3SiC2 interface, and it is suppressed near the Ti3SiC2/TiC interface. The results have been explained by ab initio calculations of trends in defect segregation to the above interfaces. Our finding suggests that the phase stability of Ti3SiC2 under irradiation can be improved by adding TiC x , and it demonstrates that, in ceramics, interfaces are not necessarily beneficial to radiation resistance.
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The complete mitochondrial genome of the Megopis sinica White was sequenced. The 15,689 bp long genome has the standard metazoan complement of 38 genes. These genes contained 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes and 1 control reigion. The nucleotide composition of the M. sinica White mitogenome was A: 37.8%, C: 18.6%, G: 11.7%, T: 32.0%. The A + T was 69.8%.
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We validated and used a high-performance liquid chromatography procedure for the determination of four different amino acid neurotransmitters in cultured rat neurons and used culture medium. Samples were derivatized using 2,4-dinitrofluorobenzene and the amino acids were separated on a C18 column. The method yielded good reproducibility and sensitivity for the quantification of the four free amino acid neurotransmitters, with average recovery factors of 80.25-118.43%, an intraday precision of 0.09-0.17%, and an interday precision of 0.62-0.74%. The assay method can be readily utilized as a precise, sensitive, and highly accurate method for the determination of concentrations of the four amino acid neurotransmitters in cultured rat neurons and used culture medium. Using the described methods, we found that the aspartate, glutamic acid, glycine, and γ-aminobutyric acid concentrations (µmol/g protein) in cultured rat neurons were 25.23±0.81, 35.16±0.32, 77.56±4.51, and 62.87±3.12, respectively, whereas their concentrations (µM) in the used culture medium were 18.18±0.82, 24.27±1.01, 107.18±9.56, and 35.78±2.98, respectively.