RESUMO
Rationale: The heterogeneity of tumor cells within the glioblastoma (GBM) microenvironment presents a complex challenge in curbing GBM progression. Understanding the specific mechanisms of interaction between different GBM cell subclusters and non-tumor cells is crucial. Methods: In this study, we utilized a comprehensive approach integrating glioma single-cell and spatial transcriptomics. This allowed us to examine the molecular interactions and spatial localization within GBM, focusing on a specific tumor cell subcluster, GBM subcluster 6, and M2-type tumor-associated macrophages (M2 TAMs). Results: Our analysis revealed a significant correlation between a specific tumor cell subcluster, GBM cluster 6, and M2-type TAMs. Further in vitro and in vivo experiments demonstrated the specific regulatory role of the CEBPB transcriptional network in GBM subcluster 6, which governs its tumorigenicity, recruitment of M2 TAMs, and polarization. This regulation involves molecules such as MCP1 for macrophage recruitment and the SPP1-Integrin αvß1-Akt signaling pathway for M2 polarization. Conclusion: Our findings not only deepen our understanding of the formation of M2 TAMs, particularly highlighting the differential roles played by heterogeneous cells within GBM in this process, but also provided new insights for effectively controlling the malignant progression of GBM.
Assuntos
Proteína beta Intensificadora de Ligação a CCAAT , Glioblastoma , Microambiente Tumoral , Macrófagos Associados a Tumor , Glioblastoma/patologia , Glioblastoma/metabolismo , Glioblastoma/genética , Humanos , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Proteína beta Intensificadora de Ligação a CCAAT/genética , Animais , Macrófagos Associados a Tumor/metabolismo , Macrófagos Associados a Tumor/imunologia , Camundongos , Linhagem Celular Tumoral , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/genética , Regulação Neoplásica da Expressão Gênica , Transdução de Sinais , Macrófagos/metabolismoRESUMO
OBJECTIVE: Colorectal cancer (CRC) is a prevalent malignant tumor with a high fatality rate. CircPDIA4 has been shown to have a vital role in cancer development by acting as a facilitator. Nevertheless, the impact of the circPDIA4/miR-9-5p/SP1 axis on development of CRC has not been studied. METHODS: Western blot, immunohistochemistry, and reverse transcription-quantitative polymerase chain reaction assays were used to analyze gene expression. The CCK-8 assay was used to assess cell growth. The Transwell assay was used to detect invasion and migration of cells. The luciferase reporter and RNA immunoprecipitation tests were used to determine if miR-9-5p and circPDIA4 (or SP1) bind to one another. An in vivo assay was used to measure tumor growth. RESULTS: It was shown that circPDIA4 expression was greater in CRC cell lines and tissues than healthy cell lines and tissues. CircPDIA4 knockdown prevented the invasion, migration, and proliferation of cells in CRC. Additionally, the combination of circPDIA4 and miR-9-5p was confirmed, as well as miR-9-5p binding to SP1. Rescue experiments also showed that the circPDIA4/miR-9-5p/SP1 axis accelerated the development of CRC. In addition, SP1 combined with the promoter region of circPDIA4 and induced circPDIA4 transcription. CircPDIA4 was shown to facilitate tumor growth in an in vivo assay. CONCLUSIONS: The circPDIA4/miR-9-5p/SP1 feedback loop was shown to aggravate CRC progression. This finding suggests that the ceRNA axis may be a promising biomarker for CRC patient treatment.
RESUMO
Cervical cancer, significantly affecting women worldwide, often involves treatment with bleomycin, an anticancer agent targeting breast, ovarian, and cervical cancers by generating reactive oxygen species (ROS) to induce cancer cell death. The Peroxiredoxin (PRDX) family, particularly PRDX1 and 2, plays a vital role in maintaining cellular balance by scavenging ROS, thus mitigating the damaging effects of bleomycin-induced mitochondrial and cellular oxidative stress. This process reduces endoplasmic reticulum (ER) stress and prevents cell apoptosis. However, reducing PRDX1 and 2 levels reverses their protective effect, increasing apoptosis. This research highlights the importance of PRDX1 and 2 in cervical cancer treatments with bleomycin, showing their potential to enhance treatment efficacy by managing ROS and ER stress and suggesting a therapeutic strategy for improving outcomes in cervical cancer treatment.
RESUMO
The family Sisoridae is one of the largest and most diverse Asiatic catfish families, with most species occurring in the water systems of the Qinhai-Tibetan Plateau and East Himalayas. At present, the phylogenetic relationship of the Sisoridae is relatively chaotic. In this study, the mitochondrial genomes (mitogenomes) of three species Creteuchiloglanis kamengensis, Glaridoglanis andersonii, and Exostoma sp. were systematically investigated, the phylogenetic relationships of the family were reconstructed and to determine the phylogenetic position of Exostoma sp. within Sisoridae. The lengths of the mitogenomes' sequences of C. kamengensis, G. andersonii, and Exostoma sp. were 16,589 bp, 16,531 bp, and 16,529 bp, respectively. They all contained one identical control region (D-loop), two ribosomal RNAs (rRNAs), 13 protein-coding genes (PCGs) and 22 transfer RNA (tRNA) genes. We applied two approaches, Bayesian Inference (BI) and Maximum Likelihood (ML), to construct phylogenetic trees. Our findings revealed that the topological structure of both ML and BI trees exhibited significant congruence. Specifically, the phylogenetic tree strongly supports the monophyly of Sisorinae and Glyptosternoids and provides new molecular biological data to support the reconstruction of phylogenetic relationships with Sisoridae. This study is of great scientific value for phylogenetic and genetic variation studies of the Sisoridae.
RESUMO
Precise regulation of the active site structure is an important means to enhance the activity and selectivity of catalysts in CO2 electroreduction. Here, we creatively introduce anionic groups, which can not only stabilize metal sites with strong coordination ability but also have rich interactions with protons at active sites to modify the electronic structure and proton transfer process of catalysts. This strategy helps to convert CO2 into fuel chemicals at low overpotentials. As a typical example, a composite catalyst, CuO/Cu-NSO4/CN, with highly dispersed Cu(II)-SO4 sites has been reported, in which CO2 electroreduction to formate occurs at a low overpotential with a high Faradaic efficiency (-0.5â V vs. RHE, FEformate=87.4 %). Pure HCOOH is produced with an energy conversion efficiency of 44.3 % at a cell voltage of 2.8â V. Theoretical modeling demonstrates that sulfate promotes CO2 transformation into a carboxyl intermediate followed by HCOOH generation, whose mechanism is significantly different from that of the traditional process via a formate intermediate for HCOOH production.
RESUMO
The nature of the active sites and their structure sensitivity are the keys to rational design of efficient catalysts but have been debated for almost one century in heterogeneous catalysis. Though the Brønsted-Evans-Polanyi (BEP) relationship along with linear scaling relation has long been used to study the reactivity, explicit geometry, and composition properties are absent in this relationship, a fact that prevents its exploration in structure sensitivity of supported catalysts. In this work, based on interpretable multitask symbolic regression and a comprehensive first-principles data set, we discovered a structure descriptor, the topological under-coordinated number mediated by number of valence electrons and the lattice constant, to successfully address the structure sensitivity of metal catalysts. The database used for training, testing, and transferability investigation includes bond-breaking barriers of 20 distinct chemical bonds over 10 transition metals, two metal crystallographic phases, and 17 different facets. The resulting 2D descriptor composing the structure term and the reaction energy term shows great accuracy to predict the reaction barriers and generalizability over the data set with diverse chemical bonds in symmetry, bond order, and steric hindrance. The theory is physical and concise, providing a constructive strategy not only to understand the structure sensitivity but also to decipher the entangled geometric and electronic effects of metal catalysts. The insights revealed are valuable for the rational design of the site-specific metal catalysts.
RESUMO
To maintain, develop and rationally utilize marine organisms, understanding their genetic structure and habitat adaptation pattern is necessary. Konosirus punctatus, which is a commercial fish species inhabiting the Indo-west Pacific Ocean, has shown an obvious annual global capture and aquaculture production decline due to climate changes and human activities. In the present study, restriction-site associated DNA sequencing (RAD-seq) was used to describe its genome-wide single nucleotide polymorphisms panel (SNPs). Among 146 individuals collected at nine locations scattered in China, Korea and Japan, a set of 632,090 SNPs were identified. Population genetic analysis showed that K. punctatus individuals were divided into two significant genetic clusters. Meanwhile, potential genetic differentiation between northern and southern population of K. punctatus was found. Treemix results indicated that gene flow existed among sampling locations of K. punctatus, especially from southern Japan to others. Moreover, candidate genes associated with habitat adaptations of K. punctatus were identified, which are involved in diverse physiological processes of K. punctatus including growth and development (e.g., KIDINS220, PAN3), substance metabolism (e.g., PGM5) and immune response (e.g., VAV3, CCT7, HSPA12B). Our findings may aid in understanding the possible mechanisms for the population genetic structure and local adaptation of K. punctatus, which is beneficial to establish the management and conservation units of K. punctatus, guiding the rational use of resources, with reference significance for a profound understanding of the adaptative mechanisms of other marine organisms to the environment. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-024-00216-2.
RESUMO
The performance of a chemical reaction is critically dependent on the electronic and/or geometric structures of a material in heterogeneous catalysis. Over the past century, the Sabatier principle has already provided a conceptual framework for optimal catalyst design by adjusting the electronic structure of the catalytic material via a change in composition. Beyond composition, it is essential to recognize that the geometric atomic structures of a catalyst, encompassing terraces, edges, steps, kinks, and corners, have a substantial impact on the activity and selectivity of a chemical reaction. Crystal-phase engineering has the capacity to bring about substantial alterations in the electronic and geometric configurations of a catalyst, enabling control over coordination numbers, morphological features, and the arrangement of surface atoms. Modulating the crystallographic phase is therefore an important strategy for improving the stability, activity, and selectivity of catalytic materials. Nonetheless, a complete understanding of how the performance depends on the crystal phase of a catalyst remains elusive, primarily due to the absence of a molecular-level view of active sites across various crystal phases. In this review, we primarily focus on assessing the dependence of catalytic performance on crystal phases to elucidate the challenges and complexities inherent in heterogeneous catalysis, ultimately aiming for improved catalyst design.
RESUMO
In high-altitude (4500 m) freshwater lakes, Daphnia is the apex species and the dominant zooplankton. It frequently dwells in the same lake as the Gammarid. Branchiopoda, a class of Arthropoda, Crustacea, is a relatively primitive group in the subphylum Crustacea, which originated in the Cambrian period of the Paleozoic. The complete mitogenome sequence of Daphnia sp. (Branchiopoda: Cladocera) was sequenced and annotated in this study and deposited in GenBank. The sequence structure of this species was studied by comparing the original sequences with BLAST. In addition, we have also researched the mechanisms of their mitochondrial gene rearrangement by establishing a model. We have used the Bayesian inference [BI] and maximum likelihood [ML] methods to proceed with phylogenetic analysis inference, which generates identical phylogenetic topology that reveals the phylogenetic state of Daphnia. The complete mitogenome of Daphnia sp. shows that it was 15,254 bp in length and included two control regions (CRs) and 37 genes (13 protein-coding genes, 22 tRNAs and two ribosomal RNAs [16S and 12S]). In addition to tRNA-Ser (GCT), other tRNAs have a typical cloverleaf secondary structure. Meanwhile, the mitogenome of Daphnia sp. was clearly rearranged when compared to the mitogenome of typical Daphnia. In a word, we report a newly sequenced mitogenome of Daphnia sp. with a unique rearrangement phenomenon. These results will be helpful for further phylogenetic research and provide a foundation for future studies on the characteristics of the mitochondrial gene arrangement process in Daphnia.
RESUMO
The black sea bass, Centropristis striata, is a potential candidate for commercial aquaculture. Due to inadequate removal of nitrogen in its breeding environment, C. striata exhibits increased nitrate concentration, which can cause acute toxicity, including energy metabolism damage and tissue damage. Therefore, RNA-seq technology was applied to characterize genes associated with toxicity tolerance under nitrate stress. The nitrate treatment caused significant changes in a total of 8920 genes, of which 2949 genes were up-regulated and 5971 genes were down-regulated. It was found that significantly enriched GO terms and KEGG were associated with blood microparticles, inhibitors of enzyme activity, and complement and coagulation cascade pathways. Furthermore, through bioinformatics analysis, it was found that these different pathways obtained in GO and KEGG enrichment analysis were mostly related to the immune and inflammatory response of fish. This study expands our understanding of the mechanism of nitrate stress affecting the liver function of C. striata.
Assuntos
Bass , Animais , Bass/genética , Bass/metabolismo , Transcriptoma , Mar Negro , Nitratos/metabolismo , Fígado/metabolismoRESUMO
Understanding the genetic structure and the factors associated with adaptive diversity has significant implications for the effective management of wild populations under threat from overfishing and climate change. The common hairfin anchovy (Setipinna tenuifilis) is an economically and ecologically important pelagic fish species, spanning a broad latitudinal gradient along marginal seas of the Northwest Pacific. In this study, we constructed the first reference genome of S. tenuifilis using PacBio long reads and high-resolution chromosome conformation capture (Hi-C) technology. The assembled genome was 798.38 Mb with a contig N50 of 1.43 Mb and a scaffold N50 of 32.42 Mb, which were anchored onto 24 pseudochromosomes. A total of 22,019 genes were functionally annotated, which accounted for 95.27% of the predicted protein-coding genes. Chromosomal collinearity analysis revealed chromosome fusion or fission events in Clupeiformes species. Three genetic groups of S. tenuifilis were revealed along the Chinese coast using restriction site-associated DNA sequencing (RADseq). We investigated the influence of four bioclimatic variables as potential drivers of adaptive divergence in S. tenuifilis, suggesting that these environmental variables, especially sea surface temperature, may play important roles as drivers of spatially varying selection for S. tenuifilis. We also identified candidate functional genes underlying adaptive mechanisms and ecological tradeoffs using redundancy analysis (RDA) and BayeScan analysis. In summary, this study sheds light on the evolution and spatial patterns of genetic variation of S. tenuifilis, providing a valuable genomic resource for further biological and genetic studies on this species and other closely related Clupeiformes.
RESUMO
BACKGROUND: Stromal cells in the tumor microenvironment play crucial roles in glioma development. Current methods for isolating tumor-associated stromal cells (such as neutrophils) are inefficient due to the conflict between tissue dissociation and cell surface protein protection, which hampers the research on patient-derived stromal cells. Our study aims to establish a novel method for isolating glioma-associated neutrophils (GANs). METHODS: To observe neutrophil-like polymorphonuclear cells, we performed Hematoxylin-Eosin staining on glioma tissues. For isolating single cells from glioma tissues, we evaluated the efficiency of tissue dissociation with FastPrep Grinder-mediated homogenization or proteases (trypsin or papain) digestion. To definite specific markers of GANs, fluorescence-activated cell sorting (FACS) and immunofluorescence staining were performed. FACS and Ficoll were performed for the separation of neutrophils from glioma tissue-derived single-cell or whole blood pool. To identify the isolated neutrophils, FACS and RT-PCR were carried out. RESULTS: Neutrophil-like cells were abundant in high-grade glioma tissues. Among the three tissue dissociation methods, papain digestion produced a 5.1-fold and 1.7-fold more living cells from glioma mass than physical trituration and trypsin digestion, respectively, and it preserved over 97% of neutrophil surface protein markers. CD66B could be adopted as a unique neutrophil surface protein marker for FACS sorting in glioma. Glioma-derived CD66B+ cells specifically expressed neutrophil marker genes. CONCLUSION: A combination of papain-mediated tissue dissociation and CD66B-mediated FACS sorting is an effective novel method for the isolation of GANs from glioma tissues.
Assuntos
Separação Celular , Glioma , Neutrófilos , Humanos , Citometria de Fluxo/métodos , Glioma/metabolismo , Neutrófilos/metabolismo , Neutrófilos/patologia , Papaína/metabolismo , Tripsina/metabolismo , Microambiente Tumoral , Separação Celular/métodosRESUMO
BACKGROUND: In this study, the complete mitogenome of Hemigrapsus sinensis was the first identified and analyzed. OBJECTIVE: The complete mitochondrial genome of Hemigrapsus sinensis (Brachyura, Grapsoidea, Varunidae) and its phylogenetic position within Grapsoidea. METHODS: The sample of Hemigrapsus sinensis was collected and DNA was extracted. After sequencing, NOVOPlasty was used for sequence assembly. Annotate sequences with MITOS WebServer, tRNAscan-SE2.0, and NCBI database. MEGA was used for sequence analysis and Phylosuite was used for phylogenetic tree construction. DnaSP was used to calculate Ka/Ks. RESULTS: This mitochondrial genome shows that it was 15,900 bp and encoded 13 PCGs, 22 tRNA genes, two rRNA genes, and one control region. The genome composition tends to A + T (74.34%) and presents a negative GC-skew (- 0.22) and AT-skew (- 0.03). The PCGs initiation codon was the typical ATN and termination codon was the typical TAN, incomplete T or missing. The ML and BI trees showed that H. sinensis was most closely related to Hemigrapsus and clustered together with the Varunidae. And our phylogenetic trees provide proof that Ocypodoidea and Grapsoidea may be of common origin. Meanwhile, in the phylogenetic tree, parallel mixing of Chiromantes and Orisarma raised doubts over the traditional classification system. Besides, Incomplete Lineage sorting (ILS) was observed in Varunidae. In the subsequent analysis of evolution rate, we found that all of the PCGs (NAD4 was not calculated) had undergone negative selections, indicating the conservation of mitochondrial genes of H. sinensis during the evolution. CONCLUSION: Therefore, researching the complete mitogenome of H. sinensis would be contributing to molecular taxonomy, phylogenetic relationship, and breeding optimization within the Grapsoidea superfamily.
Assuntos
Braquiúros , Genoma Mitocondrial , Animais , Filogenia , Braquiúros/genética , Genes Mitocondriais , RNA de Transferência/genéticaRESUMO
To meet the requirements of Angang's blast furnace smelting for sintering output, improve the double-layer sintering process, and determine the appropriate parameters for the double-layer sintering process, this article established a mathematical model and simulated the temperature field in the burden bed and the changing trends of O2 and CO2 concentrations in the sintering tail gas during the single-layer and double-layer sintering processes of the sintering machine. The simulation results show that (1) compared with the sintering time of single-layer sintering in the baseline period, the error of the single-sintering model is only about 2.5%, and the model's accuracy is high. (2) Two combustion zones of double-layer sintering increase O2 consumption, and the O2 concentration in the tail gas decreases significantly. (3) The thickness of the upper and lower feeding layers of double-layer oxygen supplement sintering is 650 + 300 mm better than that of 600 + 350 mm. (4) The optimal secondary ignition time is 15 min.
RESUMO
Considerable attention has been drawn to tune the geometric and electronic structure of interfacial catalysts via modulating strong metal-support interactions (SMSI). Herein, we report the construction of a series of TiO2-x/Ni catalysts, where disordered TiO2-x overlayers immobilized onto the surface of Ni nanoparticles (~20 nm) are successfully engineered with SMSI effect. The optimal TiO2-x/Ni catalyst shows a CO conversion of ~19.8% in Fischer-Tropsch synthesis (FTS) process under atmospheric pressure at 220 °C. More importantly, ~64.6% of the product is C2+ paraffins, which is in sharp contrast to the result of the conventional Ni catalyst with the main product being methane. A combination study of advanced electron microscopy, multiple in-situ spectroscopic characterizations, and density functional theory calculations indicates the presence of Niδ-/TiO2-x interfacial sites, which could bind carbon atom strongly, inhibit methane formation and facilitate the C-C chain propagation, lead to the production of C2+ hydrocarbon on Ni surface.
RESUMO
BACKGROUND: Glioma is the most common malignant intracranial tumor with high lethality. Despite surgery combined with chemoradiotherapy, the prognosis for patients with glioma remains poor. This is primarily due to acquired chemoradiotherapy resistance. Therefore, to improve the prognosis of glioma, further study into the mechanism of chemoradiotherapy resistance is needed. OBJECTIVE: This study aimed to (1) evaluate the prognosis of patients with glioma by using a prognostic risk score model constructed by chemoradiotherapy resistance genes, (2) provide new targets and directions for precise treatment of glioma, and (3) discuss the tumor heterogeneity of tumor cells. METHODS: According to therapy class and overall survival (OS), we identified 53 genes associated with glioma chemoradiotherapy resistance in The Cancer Genome Atlas Glioblastoma (TCGA GBM) database. Considering the important role of chemoradiotherapy resistance-related genes in the prognosis of glioma, we preliminarily screened and identified vital prognostic factors among these genes by using the Cox regression model of absolute contraction and selection operators in the TCGA GBM lower-grade glioma (TCGA GBMLGG) dataset. Next, the heterogeneity of the chemoradiotherapy resistance-associated genes in different glioma cells was revealed by single-cell sequencing in the GSE117891 cohort. RESULTS: A prognostic risk score model consisting of three genes (ARL4C, MSN, TNFAIP6) was constructed. The expression of this model was high in glioma neural progenitor cells (NPCs) and low in glioma oligodendrocytes. The OS rates were significantly lower in the high- vs. low-risk group. CONCLUSION: Our 3 gene risk score complements the current glioma diagnosis and provides a novel insight into chemoradiotherapy resistance mechanisms for the prognosis of patients with glioma.
Assuntos
Fatores de Ribosilação do ADP , Neoplasias Encefálicas , Moléculas de Adesão Celular , Glioblastoma , Glioma , Proteínas dos Microfilamentos , Fatores de Ribosilação do ADP/genética , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Moléculas de Adesão Celular/genética , Quimiorradioterapia , Resistencia a Medicamentos Antineoplásicos , Regulação Neoplásica da Expressão Gênica , Glioblastoma/tratamento farmacológico , Glioma/tratamento farmacológico , Glioma/genética , Humanos , Proteínas dos Microfilamentos/genética , Prognóstico , Tolerância a Radiação , Células-TroncoRESUMO
Synthesis of atomically dispersed catalysts with high metal loading and thermal stability is challenging but particularly valuable for industrial application in heterogeneous catalysis. Here, we report a facile synthesis of a thermally stable atomically dispersed Ir/α-MoC catalyst with metal loading as high as 4 wt%, an unusually high value for carbide supported metal catalysts. The strong interaction between Ir and the α-MoC substrate enables high dispersion of Ir on the α-MoC surface, and modulates the electronic structure of the supported Ir species. Using quinoline hydrogenation as a model reaction, we demonstrate that this atomically dispersed Ir/α-MoC catalyst exhibits remarkable reactivity, selectivity and stability, for which the presence of high-density isolated Ir atoms is the key to achieving high metal-normalized activity and mass-specific activity. We also show that the water-promoted quinoline hydrogenation mechanism is preferred over the Ir/α-MoC, and contributes to high selectivity towards 1,2,3,4-tetrahydroquinoline. The present work demonstrates a new strategy in constructing a high-loading atomically dispersed catalyst for the hydrogenation reaction.
RESUMO
[This corrects the article DOI: 10.3892/etm.2021.10664.].