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Tissues derive ATP from two pathways-glycolysis and the tricarboxylic acid (TCA) cycle coupled to the electron transport chain. Most energy in mammals is produced via TCA metabolism1. In tumours, however, the absolute rates of these pathways remain unclear. Here we optimize tracer infusion approaches to measure the rates of glycolysis and the TCA cycle in healthy mouse tissues, Kras-mutant solid tumours, metastases and leukaemia. Then, given the rates of these two pathways, we calculate total ATP synthesis rates. We find that TCA cycle flux is suppressed in all five primary solid tumour models examined and is increased in lung metastases of breast cancer relative to primary orthotopic tumours. As expected, glycolysis flux is increased in tumours compared with healthy tissues (the Warburg effect2,3), but this increase is insufficient to compensate for low TCA flux in terms of ATP production. Thus, instead of being hypermetabolic, as commonly assumed, solid tumours generally produce ATP at a slower than normal rate. In mouse pancreatic cancer, this is accommodated by the downregulation of protein synthesis, one of this tissue's major energy costs. We propose that, as solid tumours develop, cancer cells shed energetically expensive tissue-specific functions, enabling uncontrolled growth despite a limited ability to produce ATP.

ObjectiveTo study the effects of Hericium erinaceus polysaccharide on the microstructure， cytokine secretion， antioxidant function， cell proliferation and apoptosis of thymus and spleen in mice with immune stress induced by lipopolysaccharide （LPS）， so as to provide reference for the application of Hericium erinaceus polysaccharide in relieving stress.MethodsFifty male Kunming mice of 12-week old were randomly divided into control group， model group and experimental group I - III （n = 10）. In addition to the control group， the other four groups were intraperitoneally injected with 0.6 mL/kg/d LPS （once a day） three days before the end of the experiment. The experimental groups I， II and III were given 80， 160 and 320 mg/kg Hericium erinaceus polysaccharide by gavage for 2 weeks.ResultsCompared with the control group， the levels of interleukin-1 β （IL-1β）， interleukin-4 （IL-4） and interferon γ （IFN- γ） in thymus and spleen of mice in the model group were significantly increased （P

Signaling pathways are responsible for transmitting information between cells and regulating cell growth, differentiation, and death. Proteins in cells form complexes by interacting with each other through specific structural domains, playing a crucial role in various biological functions and cell signaling pathways. Protein–protein interactions (PPIs) within cell signaling pathways are essential for signal transmission and regulation. The spatiotemporal features of PPIs in signaling pathways are crucial for comprehending the regulatory mechanisms of signal transduction. Bimolecular fluorescence complementation (BiFC) is one kind of imaging tool for the direct visualization of PPIs in living cells and has been widely utilized to uncover novel PPIs in various organisms. BiFC demonstrates significant potential for application in various areas of biological research, drug development, disease diagnosis and treatment, and other related fields. This review systematically summarizes and analyzes the technical advancement of BiFC and its utilization in elucidating PPIs within established cell signaling pathways, including TOR, PI3K/Akt, Wnt/β-catenin, NF-κB, and MAPK. Additionally, it explores the application of this technology in revealing PPIs within the plant hormone signaling pathways of ethylene, auxin, Gibberellin, and abscisic acid. Using BiFC in conjunction with CRISPR-Cas9, live-cell imaging, and ultra-high-resolution microscopy will enhance our comprehension of PPIs in cell signaling pathways. [ABSTRACT FROM AUTHOR]

Heterotopic ossification (HO) is pathological bone formation characterized by ossification within muscle, tendons, or other soft tissues. However, the cells of origin and mechanisms involved in the pathogenesis of HO remain elusive. Here we show that deletion of suppressor of fused (Sufu) in cathepsin K-Cre-expressing (Ctsk-Cre-expressing) cells resulted in spontaneous and progressive ligament, tendon, and periarticular ossification. Lineage tracing studies and cell functional analysis demonstrated that Ctsk-Cre could label a subpopulation of tendon-derived progenitor cells (TDPCs) marked by the tendon marker Scleraxis (Scx). [Ctsk.sup.+][Scx.sup.+] TDPCs are enriched for tendon stem cell markers and show the highest self-renewal capacity and differentiation potential. Sufu deficiency caused enhanced chondrogenic and osteogenic differentiation of Ctsk-Cre-expressing tendon-derived cells via upregulation of Hedgehog (Hh) signaling. Furthermore, pharmacological intervention in Hh signaling using JQ1 suppressed the development of HO. Thus, our results show that Ctsk-Cre labels a subpopulation of TDPCs contributing to HO and that their cell-fate changes are driven by activation of Hh signaling., Introduction Heterotopic ossification (HO) is a pathological process in which ectopic bone forms within muscles, tendons, or other soft tissues (1). HO currently develops after trauma induced by deep burns, [...]

Hematophagous female mosquitoes are important vectors of numerous devastating human diseases, posing a major public health threat. Effective prevention and control of mosquito‐borne diseases rely considerably on progress in understanding the molecular mechanisms of various life activities, and accordingly, the molecules that regulate the various life activities of mosquitoes are potential targets for implementing future vector control strategies. Many long non‐coding RNAs (lncRNAs) have been identified in mosquitoes and significant progress has been made in determining their functions. Here, we present a comprehensive overview of the research advances on mosquito lncRNAs, including their molecular identification, function, and interaction with other non‐coding RNAs, as well as their synergistic regulatory roles in mosquito life activities. We also highlight the potential roles of competitive endogenous RNAs in mosquito growth and development, as well as in insecticide resistance and virus–host interactions. Insights into the biological functions and mechanisms of lncRNAs in mosquito life activities, viral replication, pathogenesis, and transmission will contribute to the development of novel drugs and safe vaccines. [ABSTRACT FROM AUTHOR]

Bone osteogenic sarcoma has a poor prognosis, as the exact cell of origin and the signaling pathways underlying tumor formation remain undefined. Here, we report an osteogenic tumor mouse model based on the conditional knockout of liver kinase b1 (Lkb1, also known as Stk11) in Cathepsin K-Cre-expressing (Ctsk-Cre-expressing) cells. Lineage-tracing studies demonstrated that Ctsk-Cre could label a population of periosteal cells. The cells functioned as mesenchymal progenitors with regard to markers and functional properties. LKB1 deficiency increased proliferation and osteoblast differentiation of [Ctsk.sup.+] periosteal cells, while downregulation of mTORC1 activity, using a Raptor genetic mouse model or mTORC1 inhibitor treatment, ameliorated tumor progression of Ctsk-Cre [Lkb1.sup.fllfl] mice. Xenograft mouse models using human osteosarcoma cell lines also demonstrated that LKB1 deficiency promoted tumor formation, while mTOR inhibition suppressed xenograft tumor growth. In summary, we identified periosteum-derived Ctsk-Cre-expressing cells as a cell of origin for osteogenic tumor and suggested the LKB1/mTORC1 pathway as a promising target for treatment of osteogenic tumor., Introduction Osteogenic tumor is the most common primary tumor of the bone tissue, including benign bone-forming neoplasm, osteoma, osteoblastoma, and a malignant neoplasm called osteogenic sarcoma, also referred to as [...]

Objective: To investigate the effect of lncRNA SNHG15 targeting miR-153 on cell viability and apoptosis of breast cancer cells and its apoptotic mechanism. Methods: The expression of SNHG15 in breast cancer cell lines (MDA-MB-231, BT-549 and MCF-7) were detected by Real-time fluorescent quantitative PCR (qPCR). MDA-MB-231 cells were divided into control (Ctrl) group, si-NC group, si-SNHG15 group, si-SNHG15+anti-NC group and si-SNHG15+anti-miR-153 group. Cell viability and apoptosis rate were detected by MTT and Flow cytometry, respectively. The targeting relationship between SNHG15 and miR-153 was verified by Dual luciferase report gene system. Mitochondrial membrane potential fluorescent probe (JC-1) staining method was used to detect cell mitochondrial membrane potential. The expressions of mitochondrial apoptosis-related proteins (Bcl-2, Bax, caspase3, cleaved caspase3 [c-caspase3] and Cyt-C) were detected by Western blotting. Results: The expression of SNHG15 in breast cancer cells was significantly higher than that in human normal mammary epithelial MCF10A cells (P<0.01). There was a targeting relationship between SNHG15 and miR-153. Compared with the control group, the cell viability and mitochondrial membrane potential of MDA-MB-231 cells in si-SNHG15 group were decreased, while apoptosis rate was increased (all P<0.01); the expressions of Bcl-2 and caspase3 were decreased while expressions of Bax, c-caspase3 and Cyt-C were increased (all P<0.01). However, co-transfection of si-SNHG15 and anti-miR-153 significantly attenuated the effects of si-SNHG15 on cell viability, apoptosis, mitochondrial membrane potential and expressions of Bcl-2, Bax, caspase3, c-caspase3 and Cyt-C (all P<0.01). Conclusion: lncRNA SNHG15 can target miR-153 to induce apoptosis of MDA-MB-231 cells, and the mechanism may be related to the regulation of apoptosis of mitochondrial pathway. [ABSTRACT FROM AUTHOR]