BaTiO 3 / SrTiO 3 superlattices are found to have a critical periodicity of 30 SrTiO3 unit cells, below which the room-temperature symmetry is mm2 orthorhombic. The orthorhombic-tetragonal phase-transition temperature is shifted upward from the bulk value (<3 K and normally not observed at finite temperature) of the quantum paraelectric pure strontium titanate to temperatures above ambient (599 K for 30/30-unit-cell superlattices). Antidipole patterns appear in superlattices with unit cells below 10/10. A model is presented that accounts quantitatively for the change in second-harmonic generation intensity with superlattice periodicity from 4 unit cells to 50.

Adenosquamous carcinoma of the lung (ASC), a relatively rare subtype of non-small-cell lung cancer, is defined as a malignancy containing components of lung adenocarcinoma (ADC) and lung squamous cell carcinoma (SCC). Although ASC has biological characteristics of ADC and SCC, it is not by any means a simple hybrid of two components above. It is extremely difficult to diagnose preoperatively; pathology of surgically resected gross specimen is the most effective means for adequate diagnosis of ASC. Platinum-based postoperative adjuvant chemotherapy for at least four cycles can significantly improve the survival in stage III patients with ASC. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) such as erlotinib and gefitinib can be the effective therapeutic strategies for advanced EGFR-mutant ASC. The studies of crizotinib in the treatment of patients with ASC are very limited. Immune checkpoint blockade therapy may be a potential treatment choice for ASC patients.

Heterotopic ossification (HO), acquired or hereditary, endochondral or intramembranous, is the formation of true bone outside the normal skeleton. Since perivascular Gli1+ progenitors contribute to injury induced organ fibrosis, and CD133 is expressed by a variety of populations of adult stem cells, this study utilized Cre-lox based genetic lineage tracing to test the contribution to endochondral HO of adult stem/progenitor cells that expressed either Gli1 or CD133. We found that both lineages contributed broadly to different normal tissues with distinct patterns, but that only Gli1-creERT labeled stem/progenitor cells contributed to all stages of endochondral HO in a BMP dependent, injury induced, transgenic mouse model. Hedgehog (Hh) signaling was abnormal at endochondral HO lesion sites with increased signaling surrounding the lesion but diminished signaling within it. Thus, local dysregulation of Hh signaling participates in the pathophysiology of endochondral HO. However, unlike a previous report of intramembranous HO, systemic inhibition of Hh signaling was insufficient to prevent the initiation of the endochondral HO process or to treat the existing endochondral HO, suggesting that Hh participates in, but is not essential for endochondral HO in this model. This could potentially reflect the underlying difference between intramembranous and endochondral HO. Nevertheless, identification of this novel stem/precursor cell population as a HO-contributing cell population provides a potential drugable target.

Currently, studies assessing combined small-cell lung carcinoma (C-SCLC) are relatively scarce and limited. Indeed the clinicopathological features, treatment, and prognosis of patients with C-SCLC have not been fully determined. The incidence of C-SCLC ranges from 5%–28% in different studies, which is related to the specimen types used. The clinical features of C-SCLC are characterized by the higher proportion of peripheral locations, earlier stage, and more opportunity to experience surgery. Surgery is more important for earlier stage C-SCLC. There have been no recent changes in the chemotherapy of C-SCLC, which is recommended by the treatment guidelines for SCLC, neither showing survival benefit from the 3-agent regimen. Meanwhile, the efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in EGFR-mutated C-SCLC patients remains inconclusive. This review focuses on clinical and pathologic features, prognostic factors, and optimized treatment model in C-SCLC.

It has been suggested by several authors that SrTiO 3 layers in SrTiO 3 -BaTiO 3 superlattices should be tetragonal and ferroelectric at ambient temperatures, like the BaTiO 3 layers, rather than cubic, as in bulk SrTiO 3 , and that freeenergy minimization requires continuity of the polarization direction. A recent ab initio calculation constrained solutions to this structure. Surprisingly, our x-ray study shows that the SrTiO 3 layers are orthorhombic with 0.03% in-plane strain, with the BaTiO 3 c-axis matching the SrTiO 3 a-and b-axis better than the c-axis; strain energy overcomes the cost in electrostatic energy.

Purpose: Leptomeningeal metastasis (LM) is a detrimental complication of non-small cell lung cancer (NSCLC) and associated with poor prognosis. However, the underlying mechanisms of the metastasis process are still poorly understood.Experimental Design: We performed next-generation panel sequencing of primary tumor tissue, cerebrospinal fluid (CSF), and matched normal controls from epidermal growth factor receptor (EGFR) mutation-positive NSCLC patients with LM.Results: The status of EGFR-activating mutations was highly concordant between primary tumor and CSF. PIK3CA aberrations were high in these patients, implicating an association with LM risk. Intriguingly, low overlapping of somatic protein-changing variants was observed between paired CSF and primary lesions, exhibiting tumor heterogeneity and genetic divergence. Moreover, genes with CSF-recurrent genomic alterations were predominantly involved in cell-cycle regulation and DNA-damage response (DDR), suggesting a role of the pathway in LM development.Conclusions: Our study has shed light on the genomic variations of NSCLC-LM, demonstrated genetic heterogeneity and divergence, uncovered involvement of cell-cycle and DDR pathway, and paved the way for potential therapeutic approaches to this unmet medical need.

To investigate the optical properties of metallic nanocluster/oxide composite films, Ag nanocluster/BaTiO3 composite films were synthesized on MgO (100) substrates by co-depositing the Ag and BaTiO3 targets using pulsed laser deposition. The x-ray diffraction results demonstrated that the Ag and BaTiO3 were well crystallized. The x-ray photoelectron spectroscopy analysis indicated that the samples were composed of nano-metal Ag embedded in the BaTiO3 matrices. The optical absorption properties were measured from 300 to 800 nm, and the absorption peaks due to the surface plasmon resonance of Ag particles were observed. With increasing the Ag concentration, the peak absorption increased and shifted to longer wavelength (redshift). Furthermore, the z-scan results showed that the films exhibited large optical nonlinearities and the signs of the nonlinear absorption (β) and nonlinear refractive index (n2) changed with increasing the Ag concentration.

BackgroundHeterotopic ossification (HO), either acquired (aHO) or hereditary, such as fibrodysplasia ossificans progressiva (FOP), is a serious condition without effective treatment. Understanding of the core process of injury-induced HO is still severely limited.MethodsDouble-pulse thymidine analog labeling was used to explore the distinctive domains evolved in injury-induced lesions in an animal model of HO (Nse-BMP4). Histological studies were performed to see whether a similar zonal pattern is also consistently found in biopsies from patients with aHO and FOP. In vivo clonal analysis with Rainbow mice, genetic loss-of-function studies with diphtheria toxin A (DTA)-mediated depletion and lineage tracing with Zsgreen reporter mice were used to obtain further evidence that Tie2-cre-, Gli1-creERT-, and Glast-creERT-labeled cells contribute to HO as niche-dwelling progenitor/stem cells. Immunohistochemistry was used to test whether vasculature, neurites, macrophages, and mast cells are closely associated with the proposed niche and thus are possible candidate niche supportive cells. Similar methods also were employed to further understand the signaling pathways that regulate the niche and the resultant HO.ResultsWe found that distinctive domains evolved in injury-induced lesions, including, from outside-in, a mesenchymal stem cell (MSC) niche, a transient domain and an inner differentiated core in an animal model of HO (Nse-BMP4). A similar zonal structure was found in patients with aHO and FOP. In vivo clonal analysis with Rainbow mice and genetic loss-of-function studies with DTA provided evidence that Tie2-cre-, Gli1-creERT-, and Glast-creERT-labeled cells contribute to HO as niche-dwelling progenitor/stem cells; consistently, vasculature, neurites, macrophages, and mast cells are closely associated with the proposed niche and thus are possible candidate niche supportive cells. Further mechanistic study found that BMP and hedgehog (Hh) signaling co-regulate the niche and the resultant HO.ConclusionsAvailable data provide evidence of a potential core mechanism in which multiple disease-specific cellular and extracellular molecular elements form a unique local microenvironment, i.e., an injury-induced stem cell niche, which regulates the proliferation and osteogenic differentiation of mesenchymal stem cells (MSCs). The implication for HO is that therapeutic approaches must consider several different disease specific factors as parts of a functional unit, instead of treating one factor at a time.Electronic supplementary materialThe online version of this article (10.1186/s13287-018-1107-7) contains supplementary material, which is available to authorized users.