Structural impacts of two disease-linked ADAR1 mutants: a molecular dynamics study.

Adenosine deaminases acting on RNA (ADARs) are pivotal RNA-editing enzymes responsible for converting adenosine to inosine within double-stranded RNA (dsRNA). Dysregulation of ADAR1 editing activity, often arising from genetic mutations, has been linked to elevated interferon levels and the onset of autoinflammatory diseases. However, understanding the molecular underpinnings of this dysregulation is impeded by the lack of an experimentally determined structure for the ADAR1 deaminase domain. In this computational study, we utilized homology modeling and the AlphaFold2 to construct structural models of the ADAR1 deaminase domain in wild-type and two pathogenic variants, R892H and Y1112F, to decipher the structural impact on the reduced deaminase activity. Our findings illuminate the critical role of structural complementarity between the ADAR1 deaminase domain and dsRNA in enzyme-substrate recognition. That is, the relative position of E1008 and K1120 must be maintained so that they can insert into the minor and major grooves of the substrate dsRNA, respectively, facilitating the flipping-out of adenosine to be accommodated within a cavity surrounding E912. Both amino acid replacements studied, R892H at the orthosteric site and Y1112F at the allosteric site, alter K1120 position and ultimately hinder substrate RNA binding.

Therapeutic targeting of hepatocellular carcinoma cells with antrocinol, a novel, dual-specificity, small-molecule inhibitor of the KRAS and ERK oncogenic signaling pathways.

Until recently, sorafenib has been the only treatment approved by the U.S. Food and Drug Administration for patients with advanced hepatocellular carcinoma (HCC). Some patients, however, exhibit resistance to this treatment and subsequently experience cancer progression, recurrence, or death. Therefore, identifying a new alternative treatment for patients with little or no response to sorafenib treatment is vital. In this study, we explored the therapeutic potential and underlying molecular mechanism of antrocinol ((3aS,4R,6aS,10aR)-4-(hydroxymethyl)-7,7-dimethyldecahydro-1H-naphtho[1,8a-c]furan-1-one) in patients with HCC. The results indicated that antrocinol was more therapeutically effective than antrocin, Stivarga, and sorafenib against HCC cell lines. Antrocinol also substantially suppressed the expression of KRAS-GTP, p-MEK1/2, p-ERK1/2, and p-AKT in the Huh7 cell line. Additionally, antrocinol-induced apoptosis in the Huh7 cell line, inhibited the formation of tumorspheres, and suppressed the expression of cancer stem cell markers CD133, KLF4, CD44, OCT4, SOX2, and c-Myc. Animal studies revealed that antrocinol alone considerably suppressed tumor growth in nonobese diabetic/severe combined immunodeficient mice inoculated with Huh7 tumorspheres. It also synergistically enhanced the anticancer effect of sorafenib, resulting in enhanced suppression of tumor growth (p < 0.001) and tumorsphere formation (p < 0.001). In tumor samples resected from mice treated with antrocinol alone or in combination with sorafenib, immunohistochemical analysis revealed an increase in BAX expression and a decrease in ERK and AKT protein expression. To the best of our knowledge, this is the first report of the anti-HCC activity of antrocinol. With its higher therapeutic efficacy than that of sorafenib, antrocinol is a candidate drug for patients with HCC who demonstrate little or no response to sorafenib treatment.

Ovatodiolide and antrocin synergistically inhibit the stemness and metastatic potential of hepatocellular carcinoma via impairing ribosome biogenesis and modulating ERK/Akt-mTOR signaling axis.

Activation of mitogen-activated protein kinase (MAPK) and PI3K signaling confers resistance against sorafenib, a mainstay treatment for advanced hepatocellular carcinoma (HCC). Antrocin and ovatodiolide constitute as the most potent secondary metabolites isolated from Antrodia camphorata and Anisomeles indica, respectively. Both natural compounds have recently gained a lot of attention due to their putative inhibition of MAPK and PI3K signaling in various solid cancers. However, whether their combination is effective in HCC remains unknown. Here, we investigated their effect, alone or in various combinations, on MAPK and PI3K signaling pathways in HCC cells. An array of in vitro study were used to investigate anticancer and stemness effects to treat HCC, such as cytotoxicity, drug combination index, migration, invasion, colony formation, and tumor sphere formation. Drug effect in vivo was evaluated using mouse xenograft models. In this study, antrocin and ovatodiolide synergistically inhibited the SNU387, Hep3B, Mahlavu, and Huh7 cell lines. Sequential combination treatment of Huh7 and Mahlavu with ovatodiolide followed by antrocin resulted stronger cytotoxic effect than did treatment with antrocin followed by ovatodiolide, their simultaneous administration, antrocin alone, or ovatodiolide alone. In the Huh7 and Mahlavu cell lines, ovatodiolide→antrocin significantly suppressed colony formation and proliferation as well as markedly downregulated ERK1/2, Akt, and mTOR expression. Inhibition of ERK1/2 and Akt/mTOR signaling by ovatodiolide→antrocin suppressed ribosomal biogenesis, autophagy, and cancer stem cell-like phenotypes and promoted apoptosis in Huh7 and Mahlavu cells. The sorafenib-resistant clone of Huh7 was effectively inhibited by synergistic combination of both compound in vitro. Eventually, the ovatodiolide→antrocin combination synergistically suppressed the growth of HCC xenografts. Taken together, our findings suggested that ovatodiolide→antrocin combination may represent potential therapeutic approach for patients with advanced HCC.

An order-to-disorder structural switch regulates HIF-1 transcription through S247 phosphorylation in the HIF1α PAS-B domain.

Hypoxia-inducible factor 1 (HIF-1), a transcriptional activator that mediates cellular responses to hypoxic stress, is essential for tumor progression. It is a heterodimer comprising HIF1α and HIF1ß, with multiple interfaces among their PAS-A, PAS-B, and bHLH domains. HIF1ß is also known as aryl hydrocarbon receptor nuclear translocator (ARNT). Casein kinase 1δ-dependent phosphorylation of the solvent-front residue S247 on the HIF1α PAS-B domain interrupts HIF1α-ARNT complex formation and reduces HIF-1 transcription activity. However, S247 is involved in neither HIF1α-ARNT complex formation nor stabilization of the relative orientation between the HIF1α PAS-A and PAS-B domains. To uncover the underlying allosteric mechanism, we conducted Gaussian accelerated molecular dynamics simulations and identified two distinct conformations of the pS247-carrying HIF1α PAS-B domain: H291-in and H291-out. The H291-in structure can associate with the HIF1α PAS-A domain and form a V-shaped pouch to accommodate the ARNT PAS-A domain, but it cannot associate with the ARNT PAS-B domain. By contrast, the H291-out structure can bind to the ARNT PAS-B domain, but its association with the HIF1α PAS-A domain leads to an unsuitable relative orientation to accommodate the ARNT PAS-A domain. Both conformations were also collected in parallel simulations of the unphosphorylated PAS-B domain. Both structures manage to associate with the ARNT PAS-B and HIF1α PAS-A domains; thus, they are adequate for HIF1α-ARNT complex formation. The domain-domain contact pattern in a phosphorylated variant is shuffled by an order-to-disorder structural switch, triggered by the newly formed K251-pS247 interaction.

Cancer-Associated Exosomal CBFB Facilitates the Aggressive Phenotype, Evasion of Oxidative Stress, and Preferential Predisposition to Bone Prometastatic Factor of Breast Cancer Progression.

Background: Despite therapeutic advancements, metastasis remains a major cause in breast cancer-specific mortality. Breast cancer cells are susceptible to oxidative damage and exhibit high levels of oxidative stress, including protein damage, DNA damage, and lipid peroxidation. Some breast cancer risk factors may change the level of endogenous oxidative stress. Circulating exosomes play critical roles in tumorigenesis, distant metastasis, and poor prognosis in patients with breast cancer. Methods: We used an online database to analyze the expression and prognostic value of core binding factor subunit ß (CBFB) and oxidative stress-related targets in patients with breast cancer. Serum from healthy controls and patients with primary breast cancer or bone metastatic breast cancer in the bone was collected. Exosomes were isolated from the sera or cell culture media. We used an MDA-MB-436-innoculated tumor xenograft mouse model for silencing CBFB. Results: Circulating exosomes from patients with breast cancer metastasis to the bone were rich in CBFB. The human mammary fibroblast cells HMF3A and fibroblasts derived from patient samples cocultured with exosomes had increased α-SMA and vimentin expression and IL-6 and OPN secretion. Similarly, nonmetastatic breast cancer cells cocultured with exosomes exhibited increased levels of certain markers, including vimentin, snail1, CXCR4, and Runx2, and the exosomes had high CBFB expression. Silencing CBFB in metastatic MDA-MB-436 and MDA-MB-157 cells resulted in suppressed migration and invasion and downregulation of vimentin, CXCR4, snail1, Runx2, CD44, and OPN. Conversely, CBFB overexpression resulted in upregulation of Runx2, vimentin, snail1, CD44, and OPN in nonmetastatic T47D and MCF12A cells. The CBFB-rich exosomes derived from MDA-MB-436 cells induced enhanced metastatic phenotypes in the low-metastatic T47D and MCF12A cell lines. Conclusion: Our results revealed that CBFB may promote bone metastasis in patients with breast cancer. Of therapeutic relevance, targeting CBFB resulted in decreased tumor burden and bone metastasis, downregulation of bone metastasis markers, and impaired regulation of oxidative stress-related proteins NAE1 and NOS1.

Targeting the SREBP-1/Hsa-Mir-497/SCAP/FASN Oncometabolic Axis Inhibits the Cancer Stem-like and Chemoresistant Phenotype of Non-Small Cell Lung Carcinoma Cells.

BACKGROUND: Lung cancer remains a leading cause of cancer-related death, with an annual global mortality rate of 18.4%. Despite advances in diagnostic and therapeutic technologies, non-small cell lung carcinoma (NSCLC) continues to be characterized by a poor prognosis. This may be associated with the enrichment of cancer stem cells (CSCs) and the development of chemoresistance-a double-edged challenge that continues to impede the improvement of long-term outcomes. Metabolic reprogramming is a new hallmark of cancer. Sterol regulatory element-binding proteins (SREBPs) play crucial regulatory roles in the synthesis and uptake of cholesterol, fatty acids, and phospholipids. Recent evidence has demonstrated that SREBP-1 is upregulated in several cancer types. However, its role in lung cancer remains unclear. OBJECTIVE: This study investigated the role of SREBP-1 in NSCLC biology, progression, and therapeutic response and explored the therapeutic exploitability of SREBP-1 and SREBP-1-dependent oncometabolic signaling and miRNA epigenetic regulation. METHODS: We analyzed SREBP-1 levels and biological functions in clinical samples and the human NSCLC cell lines H441 and A549 through shRNA-based knock down of SREBP function, cisplatin-resistant clone generation, immunohistochemical staining of clinical samples, and cell viability, sphere-formation, Western blot, and quantitative PCR assays. We conducted in-silico analysis of miRNA expression in NSCLC samples by using the Gene Expression Omnibus (GSE102286) database. RESULTS: We demonstrated that SREBP-1 and SCAP are highly expressed in NSCLC and are positively correlated with the aggressive phenotypes of NSCLC cells. In addition, downregulation of the expression of tumor-suppressing hsa-miR-497-5p, which predictively targets SREBP-1, was observed. We also demonstrated that SREBP-1/SCAP/FASN lipogenic signaling plays a key role in CSCs-like and chemoresistant NSCLC phenotypes, especially because the fatostatin or shRNA targeting of SREBP-1 significantly suppressed the viability, cisplatin resistance, and cancer stemness of NSCLC cells and because treatment induced the expression of hsa-miR-497. CONCLUSION: Targeting the SREBP-1/hsa-miR-497 signaling axis is a potentially effective anticancer therapeutic strategy for NSCLC.

Role of GDF15/MAPK14 Axis in Chondrocyte Senescence as a Novel Senomorphic Agent in Osteoarthritis.

Osteoarthritis (OA) is most prevalent in older individuals and exerts a heavy social and economic burden. However, an effective and noninvasive approach to OA treatment is currently not available. Chondrocyte senescence has recently been proposed as a key pathogenic mechanism in the etiology of OA. Furthermore, senescent chondrocytes (SnCCs) can release various proinflammatory cytokines, proteolytic enzymes, and other substances known as the senescence-associated secretory phenotype (SASP), allowing them to connect with surrounding cells and induce senesce. Studies have shown that the pharmacological elimination of SnCCs slows the progression of OA and promotes regeneration. Growth differentiation factor 15 (GDF15), a member of the tumor growth factor (TGF) superfamily, has recently been identified as a possible aging biomarker and has been linked to a variety of clinical conditions, including coronary artery disease, diabetes, and multiple cancer types. Thus, we obtained data from a publicly available single-cell sequencing RNA database and observed that GDF15, a critical protein in cellular senescence, is highly expressed in early OA. In addition, GDF15 is implicated in the senescence and modulation of MAPK14 in OA. Tissue and synovial fluid samples obtained from OA patients showed overexpression of GDF15. Next, we treated C20A4 cell lines with interleukin (IL)-1ß with or without shGDF15 then removed the conditioned medium, and cultured C20A4 and HUVEC cell lines with the aforementioned media. We observed that C20A4 cells treated with IL-1ß exhibited increased GDF15 secretion and that chondrocytes cultured with media derived from IL-1ß-treated C20A4 exhibited senescence. HUVEC cell migration and tube formation were enhanced after culturing with IL-1ß-treated chondrocyte media; however, decreased HUVEC cell migration and tube formation were noted in HUVEC cells cultured with GDF15-loss media. We tested the potential of inhibiting GDF15 by using a GDF15 neutralizing antibody, GDF15-nAb. GDF15-nAb exerted a similar effect, resulting in the molecular silencing of GDF15 in vivo and in vitro. Our results reveal that GDF15 is a driver of SnCCs and can contribute to OA progression by inducing angiogenesis.

High-sensitivity of initial SrO growth on the residual resistivity in epitaxial thin films of SrRuO[Formula: see text] on SrTiO[Formula: see text] (001).

The growth of SrRuO[Formula: see text] (SRO) thin film with high-crystallinity and low residual resistivity (RR) is essential to explore its intrinsic properties. Here, utilizing the adsorption-controlled growth technique, the growth condition of initial SrO layer on TiO[Formula: see text]-terminated SrTiO[Formula: see text] (STO) (001) substrate was found to be crucial for achieving a low RR in the resulting SRO film grown afterward. The optimized initial SrO layer shows a c(2 [Formula: see text] 2) superstructure that was characterized by electron diffraction, and a series of SRO films with different thicknesses (ts) were then grown. The resulting SRO films exhibit excellent crystallinity with orthorhombic-phase down to [Formula: see text] 4.3 nm, which was confirmed by high resolution X-ray measurements. From X-ray azimuthal scan across SRO orthorhombic (02 ± 1) reflections, we uncover four structural domains with a dominant domain of orthorhombic SRO [001] along cubic STO [010] direction. The dominant domain population depends on t, STO miscut angle ([Formula: see text]), and miscut direction ([Formula: see text]), giving a volume fraction of about 92 [Formula: see text] for [Formula: see text] 26.6 nm and [Formula: see text] (0.14[Formula: see text], 5[Formula: see text]). On the other hand, metallic and ferromagnetic properties were well preserved down to t [Formula: see text] 1.2 nm. Residual resistivity ratio (RRR = [Formula: see text]/[Formula: see text]) reduces from 77.1 for t [Formula: see text] 28.5 nm to 2.5 for t [Formula: see text] 1.2 nm, while [Formula: see text] increases from 2.5 [Formula: see text]cm for t [Formula: see text] 28.5 nm to 131.0 [Formula: see text]cm for t [Formula: see text] 1.2 nm. The ferromagnetic onset temperature ([Formula: see text]) of around 151 K remains nearly unchanged down to t [Formula: see text] 9.0 nm and decreases to 90 K for t [Formula: see text] 1.2 nm. Our finding thus provides a practical guideline to achieve high crystallinity and low RR in ultra-thin SRO films by simply adjusting the growth of initial SrO layer.

Risk Values of Weight and Body Mass Index for Chest Wall Thickness in Patients Requiring Needle Thoracostomy Decompression.

INTRODUCTION: Emergency decompression is needed in patients with tension pneumothorax, a life-threatening condition. The catheter-based needle thoracostomy was suggested using a 5 cm catheter inserted into the 2nd intercostal space (ICS) and 5th ICS according to the ninth and tenth editions of Advanced Trauma Life Support, respectively. A catheter of suitable length may not be available immediately or the muscle structure of the chest wall may be modified in pneumothorax. Furthermore, alternative sites for needle thoracostomy and reference values of chest wall thickness (CWT) should be explored and warranted. METHOD: CT scan data and medical data of 650 eligible patients from October 2016 to December 2016 were reviewed. CWT values at four ICSs as well as four variables, namely, age, weight, height, and body mass index (BMI) for both men and women were compared using a nonparametric method, namely, the Wilcoxon signed-rank test. The associations between CWT and the four variables were assessed using the Pearson correlation coefficient. The overall performance of BMI, weight, and height in predicting CWT > 5 cm was evaluated using the receiver-operating characteristic (ROC) curve. Finally, the prediction models were built by using the bootstrap method. RESULTS: Four variables, namely, age, height, weight, and BMI, were compared between the men and women groups. All four variables differed significantly between the two groups, and CWTs at all ICSs, except for the 3rd ICS, differed significantly between the two groups. Among the women, the area under the ROC curve (AUROC) of BMI for predicting CWT > 5 cm at 2nd ICS was larger than the AUROC of weight and height. Among the men, the AUROC of weight for predicting CWT > 5 cm at 2nd ICS was larger than that of BMI and height. The reference value tables were provided for five proposed models for women and men, respectively. Under emergencies, the variable, BMI, or even weight itself, could be used for predicting a failure performance of the needle decompression. For women, CWT at 5th ICS was predicted over 5 cm at BMI over 25.9 kg/m2 or weight over 103.1 kg. For men, CWT at 5th ICS was predicted over 5 cm at BMI over 25.5 kg/m2 or weight over 157.4 kg. CONCLUSION: Needle thoracostomy is the preferred first technique for many emergency providers for decompression. Therefore, a reference table for safe needle thoracostomy decompression at four usual sites, namely, 2nd ICS, 3rd CIS, 4th ICS, and 5th ICS, was recommended, which will enable paramedics and emergency specialists to rapidly determine CWT at the appropriate ICSs during emergencies.

Epitaxy from a Periodic Y-O Monolayer: Growth of Single-Crystal Hexagonal YAlO3 Perovskite.

The role of an atomic-layer thick periodic Y-O array in inducing the epitaxial growth of single-crystal hexagonal YAlO3 perovskite (H-YAP) films was studied using high-angle annular dark-field and annular bright-field scanning transmission electron microscopy in conjunction with a spherical aberration-corrected probe and in situ reflection high-energy electron diffraction. We observed the Y-O array at the interface of amorphous atomic layer deposition (ALD) sub-nano-laminated (snl) Al2O3/Y2O3 multilayers and GaAs(111)A, with the first film deposition being three cycles of ALD-Y2O3. This thin array was a seed layer for growing the H-YAP from the ALD snl multilayers with 900 °C rapid thermal annealing (RTA). The annealed film only contained H-YAP with an excellent crystallinity and an atomically sharp interface with the substrate. The initial Y-O array became the bottom layer of H-YAP, bonding with Ga, the top layer of GaAs. Using a similar ALD snl multilayer, but with the first film deposition of three ALD-Al2O3 cycles, there was no observation of a periodic atomic array at the interface. RTA of the sample to 900 °C resulted in a non-uniform film, mixing amorphous regions and island-like H-YAP domains. The results indicate that the epitaxial H-YAP was induced from the atomic-layer thick periodic Y-O array, rather than from GaAs(111)A.

Structure-Dependent Photoluminescence in Low-Dimensional Ethylammonium, Propylammonium, and Butylammonium Lead Iodide Perovskites.

Hybrid organic-inorganic perovskites have attracted great attention as the next generation materials for photovoltaic and light-emitting devices. However, their environment instability issue remains as the largest challenge for practical applications. Recently emerging two-dimensional (2D) perovskites with Ruddlesden-Popper structures are found to greatly improve the stability and aging problems. Furthermore, strong confinement of excitons in these natural quantum-well structures results in the distinct and narrow light emission in the visible spectral range, enabling the development of spectrally tunable light sources. Besides the strong quasi-monochromatic emission, some 2D perovskites composed of the specific organic cations and inorganic layer structures emit a pronounced broadband emission. Herein, we report the light-emitting properties and the degradation of low-dimensional perovskites consisting of the three shortest alkylammonium spacers, mono-ethylammonium (EA), n-propylammonium (PA), and n-butylammonium (BA). While (BA)2PbI4 is known to form well-oriented 2D thin films consisting of layers of corner-sharing PbI6 octahedra separated by a bilayer of BA cations, EA with shorter alkyl chains tends to form other types of lower-dimensional structures. Nevertheless, optical absorption edges of as-prepared fresh EAPbI3, (PA)2PbI4, and (BA)2PbI4 are obviously blue-shifted to 2.4-2.5 eV compared to their 3D counterpart, methylammonium lead iodide (MAPbI3) perovskite, and they all emit narrow excitonic photoluminescence. Furthermore, by carefully optimizing deposition conditions, we have achieved a predominantly 2D structure for (PA)2PbI4. However, unlike (BA)2PbI4, upon exposure to ambient environment, (PA)2PbI4 readily transforms to a different crystal structure, exhibiting a prominently broadband light from ∼500 to 800 nm and a gradual increase in intensity as structural transformation proceeds.

Defect induced ferromagnetic ordering in epitaxial Zn0.95Mn0.05O films on sapphire (0 0 0 1).

We report the influence of Mn dopant on magnetic properties of Zn0.95Mn0.05O (ZMO)/Al2O3(0 0 0 1) hetero-epitaxial systems grown by using pulsed-laser deposition. The room temperature (RT) intrinsic ferromagnetic (FM) ordering verified by superconducting quantum interference device magnetometer and x-ray magnetic circular dichroism spectrum of Mn L 2,3 edges is ascribed to the substitutional Mn atoms in the Zn site of ZnO. Mn in ZMO has a tetrahedral local symmetry instead of the octahedral symmetry of MnO, after verifying the absence of the Mn-related impurities or clusters in ZMO epitaxial film by Mn K-edge and Zn K-edge x-ray absorption spectroscopy spectrum, as well as the analysis of long-range structural ordering on Renninger scan of forbidden (0 0 0 5) reflection in x-ray diffraction, transmission electron microscopy and Raman spectrum. Comparison of x-ray absorption spectra of ZMO with those of ZnO epilayers at O K-, Zn K-, and L 3-edges indicates that the substitution of the Zn site with Mn enhances the charge-transfer (CT) transition and the presence of Zn vacancies (VZn) also dominate the photoluminescence (PL) spectrum, implying that the formation of numerous VZn defects plays an important role in activating FM interactions. The strong CT effect and the existence of high-density VZn suggest that the intrinsic RT FM ordering of insulating ZMO is a result of the formation of the bound magnetic polarons (BMPs) that interact with each other via intermediate magnetic impurities.

Loss of function in SAGA deubiquitinating module caused by Sgf73 H93A mutation: A molecular dynamics study.

The Spt-Ada-Gcn5-acetyltransferase (SAGA) deubiquitinating module (DUBm), comprising Ubp8, Sgf11, Sus1, and Sgf73, functions as a deubiquitinase. Data from recent biomolecular experiments have indicated that the H93A mutation in Sgf73 abrogates the enzyme function without interfering with module formation. Interestingly Sgf73 H93 residue is neither involved in the active site nor near the ubiquitin substrate binding site but is capable of influencing the active site through an allosteric mechanism. In this study, molecular dynamics simulations were used to analyze the structural discrepancy between wild-type and H93A mutant of the SAGA DUBm to reveal the interprotein communication pathway linking the mutation site to the catalytic site. We concluded that H93A mutation directly impairs Sgf73's zinc finger motif and further induces a downward movement of Sgf11's N-terminal long α-helix. The structural influence gradually propagates toward Sgf11's C-terminal end and results in the rearrangement of the catalytic triad of Ubp8 protein. The repositioned catalytic Cys-His-Asn triad could no longer execute the deubiquitinating function.

Time-resolved X-ray reflection phases of the nearly forbidden Si(222) reflection under laser excitation.

The covalent electron density, which makes Si(222) measurable, is subject to laser excitation. The three-wave Si(222)/(13 {\overline 1}) diffraction at 7.82 keV is used for phase measurements. It is found that laser excitation causes a relative phase change of around 4° in Si(222) in the first 100 ps of excitation and this is gradually recovered over several nanoseconds. This phase change is due to laser excitation of covalent electrons around the silicon atoms in the unit cell and makes the electron density deviate further from the centrosymmetric distribution.

Flexible Organometal-Halide Perovskite Lasers for Speckle Reduction in Imaging Projection.

Disorder is emerging as a strategy for fabricating random laser sources with very promising materials, such as perovskites, for which standard laser cavities are not effective or too expensive. We need, however, different fabrication protocols and technologies for reducing the laser threshold and controlling its emission. Here, we demonstrate an effectively solvent-engineered method for high-quality perovskite thin films on a flexible polyimide substrate. The fractal perovskite thin films exhibit excellent optical properties at room temperature and easily achieve lasing action without any laser cavity above room temperature with a low pumping threshold. The lasing action is also observed in curved perovskite thin films on flexible substrates. The lasing threshold can be further reduced by increasing the local curvature, which modifies the scattering strengths of the bent thin film. We also show that the curved perovskite lasers are extremely robust with respect to repeated deformations. Because of the low spatial coherence, these curved random laser devices are efficient and durable speckle-free light sources for applications in spectroscopy, bioimaging, and illumination.

The Association of Acquired T790M Mutation with Clinical Characteristics after Resistance to First-Line Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor in Lung Adenocarcinoma.

PURPOSE: The main objective of this study was to investigate the relationship among the clinical characteristics and the frequency of T790M mutation in advanced epidermal growth factor receptor (EGFR)‒mutant lung adenocarcinoma patients with acquired resistance after firstline EGFR‒tyrosine kinase inhibitor (TKI) treatment. MATERIALS AND METHODS: We enrolled EGFR-mutant stage IIIB-IV lung adenocarcinoma patients, who had progressed to prior EGFR-TKI therapy, and evaluated their rebiopsy EGFR mutation status. RESULTS: A total of 205 patients were enrolled for analysis. The overall T790M mutation rate of rebiopsy was 46.3%. The T790M mutation rates among patients with exon 19 deletion mutation, exon 21 L858R point mutation, and other mutations were 55.0%, 37.3%, and 27.3%, respectively. Baseline exon 19 deletion was associated with a significantly higher frequency of T790M mutation (adjusted odds ratio, 2.14; 95% confidence interval [CI], 1.20 to 3.83; p=0.010). In the exon 19 deletion subgroup, there was a greater prevalence of T790M mutation than other exon 19 deletion subtypes in patients with the Del E746-A750 mutation (61.6% vs. 40.6%; odds ratio, 2.35; 95% CI, 1.01 to 5.49; p=0.049). The progression-free survival (PFS) of first-line TKI treatment > 11 months was also associated with a higher T790M mutation rate (54.1% vs. 39.3%; adjusted odds ratio, 1.82; 95% CI, 1.02 to 3.25; p=0.044). Patients who underwent rebiopsy at metastatic sites had more chance to harbor T790M mutation (52.6% vs. 33.8%; adjusted odds ratio, 1.97; 95% CI, 1.06 to 3.67; p=0.032). CONCLUSION: PFS of first-line EGFR-TKI, rebiopsy site, EGFR exon 19 deletion and its subtype Del E746- A750 mutation are associated with the frequency of T790M mutation.

Saturation and beating of acoustic phonon oscillations excited near the exciton resonance of strained polar ZnO/Zn0.8Mg0.2O multiple quantum wells.

Saturation and beating of coherent acoustic phonon (CAP) oscillations were observed and attributed to the screening of a built-in electric field with increasing pump power using degenerate pump-probe measurements near the exciton resonance of polar ZnO/Zn0.8Mg0.2O multiple quantum wells (MQWs). After purifying the CAP signals by using an empirical mode decomposition, we found not only that the CAP amplitude follows the trend of the band gap renormalization (BGR) and shows saturation at high pump power, but also that the CAP oscillation period coincides with that of the MQWs, consistent with the XRD and TEM results. An additional low-frequency oscillation modifying the CAP signal is revealed due to the negative change in refractive index caused by BGR as the pump power increases.

Characteristics of young lung cancer: Analysis of Taiwan's nationwide lung cancer registry focusing on epidermal growth factor receptor mutation and smoking status.

Lung cancer is relatively rare in young patients as the median age at diagnosis is 65-70 years. The main objective of this nationwide study was to investigate the characteristics of young lung cancer in Taiwan, especially the relationships among smoking behavior, epidermal growth factor receptor (EGFR) mutation, and age. The National Taiwan Lung Cancer Registry, a database contain detailed cancer statistics, was analyzed in this study for the period 2011-2012. Young lung cancer was defined as age ≦ 45 years. There were 21,536 lung cancer patients (13,187 men and 8349 women). Among these patients, 1074 (5.0%) were in the younger group, and 20,462 patients (95.0%) were in the older group. Female gender (48.8% versus 38.2%, P < 0.001), never-smokers (47.3% versus 43.8%, P = 0.015), and adenocarcinoma (70.4% versus 58.1%, P < 0.001) were more frequent in the younger group. While the EGFR mutation rate was lower in the younger group (52.5% versus 60.6%, P = 0.001), the primary site of lung cancer and stage distribution were not significantly different. If only adenocarcinoma patients were included in the analysis, female gender, older age, and never-smokers were more likely to have EGFR mutation. In conclusion, lung cancer in young patients (≦ 45 year-old) was associated with unique characteristics, with greater percentages of female patients, adenocarcinoma, and never-smokers and a lower EGFR mutation rate compared with older patients.

Structural Transitions in Nanosized Zn0.97Al0.03O Powders under High Pressure Analyzed by in Situ Angle-Dispersive X-ray Diffraction.

Nanosized aluminum-doped zinc oxide Zn1-xAlxO (AZO) powders (AZO-NPs) with x = 0.01, 0.03, 0.06, 0.09 and 0.11 were synthesized by chemical precipitation method. The thermogravimetric analysis (TGA) indicated that the precursors were converted to oxides from hydroxides near 250 °C, which were then heated to 500 °C for subsequent thermal processes to obtain preliminary powders. The obtained preliminary powders were then calcined at 500 °C for three hours. The structure and morphology of the products were measured and characterized by angle-dispersive X-ray diffraction (ADXRD) and scanning electron microscopy (SEM). ADXRD results showed that AZO-NPs with Al content less than 11% exhibited würtzite zinc oxide structure and there was no other impurity phase in the AZO-NPs, suggesting substitutional doping of Al on Zn sites. The Zn0.97Al0.03O powders (A3ZO-NPs) with grain size of about 21.4 nm were used for high-pressure measurements. The in situ ADXRD measurements revealed that, for loading run, the pressure-induced würtzite (B4)-to-rocksalt (B1) structural phase transition began at 9.0(1) GPa. Compared to the predicted phase-transition pressure of ~12.7 GPa for pristine ZnO nanocrystals of similar grain size (~21.4 nm), the transition pressure for the present A3ZO-NPs exhibited a reduction of ~3.7 GPa. The significant reduction in phase-transition pressure is attributed to the effects of highly selective site occupation, namely Zn2+ and Al3+, were mainly found in tetrahedral and octahedral sites, respectively.

Anisotropic exciton relaxation in nanostructured metal (Zn and F(16)Zn)-phthalocyanine.

We report ultrafast excited state dynamics of zinc phthalocyanine and zinc hexadecafluoro phthalocyanine thin films which have nanorod-like structures. Excitons in the singlet states undergo multi-exponential relaxation processes to the ground state and the singlet lifetime within a few tens of picoseconds is attributed to the diffusion-limited exciton annihilation process. Diffusive migration of the singlet excitons shows the anisotropic lifetimes depending on the polarization of probe beam. Similar anisotropy is observed in the X-ray diffraction data which exhibits long-range alignment of molecular columns along the long axis of nanorod, whereas disordered arrangement in lateral direction to the axis of nanorod.