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Molecular heterogeneity of hepatobiliary tumor including intertumoral and intratumoral disparity always leads to drug resistance. Here, seven hepatobiliary tumor organoids are generated to explore heterogeneity and evolution via single-cell RNA sequencing. HCC272 with high status of epithelia-mesenchymal transition proves broad-spectrum drug resistance. By examining the expression pattern of cancer stem cells markers (e.g., PROM1, CD44, and EPCAM), it is found that CD44 positive population may render drug resistance in HCC272. UMAP and pseudo-time analysis identify the intratumoral heterogeneity and distinct evolutionary trajectories, of which catenin beta-1 (CTNNB1), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and nuclear paraspeckle assembly transcript 1 (NEAT1) advantage expression clusters are commonly shared across hepatobiliary organoids. CellphoneDB analysis further implies that metabolism advantage organoids with enrichment of hypoxia signal upregulate NEAT1 expression in CD44 subgroup and mediate drug resistance that relies on Jak-STAT pathway. Moreover, metabolism advantage clusters shared in several organoids have similar characteristic genes (GAPDH, NDRG1 (N-Myc downstream regulated 1), ALDOA, and CA9). The combination of GAPDH and NDRG1 is an independent risk factor and predictor for patient survival. This study delineates heterogeneity of hepatobiliary tumor organoids and proposes that the collaboration of intratumoral heterogenic subpopulations renders malignant phenotypes and drug resistance.Extracellular glutamine represents an important energy source for many cancer cells and its metabolism is intimately involved in maintaining redox homeostasis. The heightened metabolic activity within tumor tissues can result in glutamine deficiency, necessitating metabolic reprogramming responses. Here, dual mechanisms involving the stress-responsive transcription factor DDIT3 (DNA damage induced transcript 3) that establishes an interrelationship between glycolysis and mitochondrial respiration are revealed. DDIT3 is induced during glutamine deprivation to promote glycolysis and adenosine triphosphate production via suppression of the negative glycolytic regulator TIGAR. In concert, a proportion of the DDIT3 pool translocates to the mitochondria and suppresses oxidative phosphorylation through LONP1-mediated down-regulation of COQ9 and COX4. This in turn dampens the sustained levels of reactive oxygen species that follow glutamine withdrawal. Together these mechanisms constitute an adaptive survival mechanism permitting tumor cells to survive metabolic stress induced by glutamine starvation.A general polymer-assisted spinodal decomposition strategy is used to prepare hierarchically porous sodium super ionic conductor (NASICON)-structured polyanion-type materials (e.g., Na3 V2 (PO4 )3 , Li3 V2 (PO4 )3 , K3 V2 (PO4 )3 , Na4 MnV(PO4 )3 , and Na2 TiV(PO4 )3 ) in a tetrahydrofuran/ethanol/H2 O synthesis system. Depending on the boiling point of solvents, the selective evaporation of the solvents induces both macrophase separation via spinodal decomposition and mesophase separation via self-assembly of inorganic precursors and amphiphilic block copolymers, leading to the formation of hierarchically porous structures. The resulting hierarchically porous Na3 V2 (PO4 )3 possessing large specific surface area (≈77 m2 g-1 ) and pore volume (≈0.272 cm3 g-1 ) shows a high specific capacity of 117.6 mAh g-1 at 0.1 C achieving the theoretical value and a long cycling life with 77% capacity retention over 1000 cycles at 5 C. This method presented here can open a facile avenue to synthesize other hierarchically porous polyanion-type materials.There has been tremendous interest in the development of different innovative wear-resistant materials, which can help to reduce energy losses resulted from friction and wear by ≈40% over the next 10-15 years. This paper provides a comprehensive review of the recent progress on designs, properties, and applications of wear-resistant materials, starting with an introduction of various advanced technologies for the fabrication of wear-resistant materials and anti-wear structures with their wear mechanisms. Typical strategies of surface engineering and matrix strengthening for the development of wear-resistant materials are then analyzed, focusing on the development of coatings, surface texturing, surface hardening, architecture, and the exploration of matrix compositions, microstructures, and reinforcements. Afterward, the relationship between the wear resistance of a material and its intrinsic properties including hardness, stiffness, strength, and cyclic plasticity is discussed with underlying mechanisms, such as the lattice distortion effect, bonding strength effect, grain size effect, precipitation effect, grain boundary effect, dislocation or twinning effect. A wide range of fundamental applications, specifically in aerospace components, automobile parts, wind turbines, micro-/nano-electromechanical systems, atomic force microscopes, and biomedical devices are highlighted. This review is concluded with prospects on challenges and future directions in this critical field.Bio-nano interfaces are integral to all applications of nanomaterials in biomedicine. In addition to peptide-ligand-functionalized nanomaterials, passivation on 2D nanomaterials has emerged as a new regulatory factor for integrin activation. However, the mechanisms underlying such ligand-independent processes are poorly understood. Here, using graphene oxide passivated with polyethylene glycol (GO-PEG) as a test bed, a ternary simulation model is constructed that also includes a membrane and both subunits of integrin αv β8 to characterize GO-PEG-mediated integrin activation on the cell membrane in a ligand-independent manner. Combined with the experimental findings, production simulations of the ternary model show a three-phase mechanotransduction process in the vertical interaction mode. Specifically, GO-PEG first induces lipid aggregation-mediated integrin proximity, followed by transmembrane domain rotation and separation, leading to the extension and activation of extracellular domains. Docetaxel Thus, this study presents a complete picture of the interaction between passivated 2D nanomaterials and cell membranes to mediate integrin activation, and provides insights into the potential de novo design and rational use of novel desirable nanomaterials at diverse bio-nano interfaces.
Website: https://www.selleckchem.com/products/Docetaxel(Taxotere).html
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