The combination of nontrivial band topology and symmetry-breaking phases gives rise to novel quantum states and phenomena such as topological superconductivity, quantum anomalous Hall effect, and ...axion electrodynamics. Evidence of intertwined charge density wave (CDW) and superconducting order parameters has recently been observed in a novel kagome material AV_{3}Sb_{5} (A=K, Rb, Cs) that features a Z_{2} topological invariant in the electronic structure. However, the origin of the CDW and its intricate interplay with the topological state has yet to be determined. Here, using hard-x-ray scattering, we demonstrate a three-dimensional CDW with 2×2×2 superstructure in (Rb,Cs)V_{3}Sb_{5}. Unexpectedly, we find that the CDW fails to induce acoustic phonon anomalies at the CDW wave vector but yields a novel Raman mode that quickly damps into a broad continuum below the CDW transition temperature. Our observations exclude strong electron-phonon-coupling-driven CDW in AV_{3}Sb_{5} and support an unconventional CDW that was proposed in the kagome lattice at van Hove filling.
As an emergent electronic material and model system for condensed-matter physics, graphene and its electrical transport properties have become a subject of intense focus. By performing ...low-temperature transport spectroscopy on single-layer and bilayer graphene, we observe ballistic propagation and quantum interference of multiply reflected waves of charges from normal electrodes and multiple Andreev reflections from superconducting electrodes, thereby realizing quantum billiards in which scattering only occurs at the boundaries. In contrast to the conductivity of conventional two-dimensional materials, graphene's conductivity at the Dirac point is geometry-dependent because of conduction via evanescent modes, approaching the theoretical value 4e²/πh (where e is the electron charge and h is Planck's constant) only for short and wide devices. These distinctive transport properties have important implications for understanding chaotic quantum systems and implementing nanoelectronic devices, such as ballistic transistors.
Nanoparticle based delivery formulations have become a leading delivery strategy for cancer imaging and therapy. The success of nanoparticle-based therapy relies heavily on their ability to utilize ...the enhanced permeability and retention (EPR) effect and active targeting moieties to their advantage. However, these methods often fail to enable a uniform NP distribution across the tumor, and lead to insufficient local concentrations of drug. Oftentimes, this heterogeneous drug distribution is one of the primary reasons for suboptimal treatment efficacy in NP delivery platforms. Herein, we seek to examine the biophysical causes of heterogeneous NP distribution in stroma-rich desmoplastic tumors; namely the abnormal tumor vasculature, deregulated extracellular matrix and high interstitial hypertension associated with these tumors. It is suggested that these factors help explain the discrepancy between promising outlooks for many NP formulations in preclinical studies, but suboptimal clinical outcomes for most FDA approved nanoformulations. Furthermore, examination into the role of the physicochemical properties of NPs on successful drug delivery was conducted in this review. In light of the many formidable barriers against successful NP drug delivery, we provided possible approaches to mitigate delivery issues from the perspective of stromal remodeling and NP design. In all, this review seeks to provide guidelines for optimizing nanoparticle-based cancer drug delivery through both modified nanoparticle design and alleviation of biological barriers to successful therapy.
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Several recent studies have showed that mouse and human fibroblasts can be directly reprogrammed into induced neuronal (iN) cells, bypassing a pluripotent intermediate state. However, fibroblasts ...represent heterogeneous mesenchymal progenitor cells that potentially contain neural crest lineages, and the cell of origin remained undefined. This raises the fundamental question of whether lineage reprogramming is possible between cell types derived from different germ layers. Here, we demonstrate that terminally differentiated hepatocytes can be directly converted into functional iN cells. Importantly, single-cell and genome-wide expression analyses showed that fibroblast- and hepatocyte-derived iN cells not only induced a neuronal transcriptional program, but also silenced their donor transcriptome. The remaining donor signature decreased over time and could not support functional hepatocyte properties. Thus, the reprogramming factors lead to a binary lineage switch decision rather than an induction of hybrid phenotypes, but iN cells retain a small but detectable epigenetic memory of their donor cells.
► Direct lineage reprogramming is possible across different defined germ layers ► Terminally differentiated endodermal cells can be directly converted to neurons ► Reprogramming factors induce silencing of the donor-specific transcriptional program ► Induced neuronal cells retain a small but detectable epigenetic memory
Significance Here we report a fundamental and previously unknown role for the receptor tyrosine kinase AXL as a direct hypoxia-inducible transcription factor target driving the aggressive phenotype ...in renal clear cell carcinoma through the regulation of the SRC proto-oncogene nonreceptor tyrosine kinase and the MET proto-oncogene receptor tyrosine kinase. Of therapeutic relevance, we demonstrate that inactivation of growth arrest-specific 6 (GAS6)/AXL signaling using a soluble AXL decoy receptor reversed the invasive and metastatic phenotype of clear cell renal cell carcinoma (ccRCC) cells. Furthermore, we define a pathway by which GAS6/AXL signaling utilizes lateral activation of MET through SRC to maximize cellular invasion. Our data provide an alternative model for SRC and MET activation by GAS6 in ccRCC and identify AXL as a therapeutic target driving the aggressive phenotype in renal clear cell carcinoma.
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