Metasurfaces on silicon photonic waveguides for simultaneous emission phase and amplitude control.

Chip-scale photonic systems that manipulate free-space emission have recently attracted attention for applications such as free-space optical communications and solid-state LiDAR. Silicon photonics, as a leading platform for chip-scale integration, needs to offer more versatile control of free-space emission. Here we integrate metasurfaces on silicon photonic waveguides to generate free-space emission with controlled phase and amplitude profiles. We demonstrate experimentally structured beams, including a focused Gaussian beam and a Hermite-Gaussian TEM10 beam, as well as holographic image projections. Our approach is monolithic and CMOS-compatible. The simultaneous phase and amplitude control enable more faithful generation of structured beams and speckle-reduced projection of holographic images.

WITHDRAWN: lncRNA Linc00173 modulates glucose metabolism and multidrug chemoresistance in SCLC: Potential molecular panel for targeted therapy.

This article has been withdrawn at the request of the editor-in-chief. Following publication of this article, the editor-in-chief discovered evidence of image duplication in Figures 1I, 1J, 3F, S5B, and S6B. Given the duplication of several western blots representing several gene products, the editor-in-chief has lost faith in the findings presented in this article. The authors maintain that these image duplications were the result of errors in file management and do not affect the conclusions of the study. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

Plasmonic semiconductor photocatalyst: Non-stoichiometric tungsten oxide.

Semiconductor photocatalysis has attracted increasing attention due to its potential application in solving the problems related to energy crisis and environmental pollution. As a typical plasmonic semiconductor, non-stoichiometric tungsten oxide (WO3-X) has invoked significant interest for its unique property and excellent photocatalytic performance. In this review, we briefly introduce the fundamental properties of the WO3-x, and then summarize the synthesis methods such as solvothermal reaction, solid phase reduction and exfoliation treatment, together with the modification strategies such as doping and constructing homo-/hetero-junctions. Additionally, we emphasize the practical applications of WO3-x in hydrogen evolution, nitrogen fixation, carbon dioxide reduction, and pollutant degradation. Finally, comprehensive conclusions and perspectives on the fabrication of WO3-x photocatalyst leading to satisfactory performance are given as well.

FGFRL1 affects chemoresistance of small-cell lung cancer by modulating the PI3K/Akt pathway via ENO1.

Fibroblast growth factor receptor-like 1 (FGFRL1), a member of the FGFR family, has been demonstrated to play important roles in various cancers. However, the role of FGFRL1 in small-cell lung cancer (SCLC) remains unclear. Our study aimed to investigate the role of FGFRL1 in chemoresistance of SCLC and elucidate the possible molecular mechanism. We found that FGFRL1 levels are significantly up-regulated in multidrug-resistant SCLC cells (H69AR and H446DDP) compared with the sensitive parental cells (H69 and H446). In addition, clinical samples showed that FGFRL1 was overexpressed in SCLC tissues, and high FGFRL1 expression was associated with the clinical stage, chemotherapy response and survival time of SCLC patients. Knockdown of FGFRL1 in chemoresistant SCLC cells increased chemosensitivity by increasing cell apoptosis and cell cycle arrest, whereas overexpression of FGFRL1 in chemosensitive SCLC cells produced the opposite results. Mechanistic investigations showed that FGFRL1 interacts with ENO1, and FGFRL1 was found to regulate the expression of ENO1 and its downstream signalling pathway (the PI3K/Akt pathway) in SCLC cells. In brief, our study demonstrated that FGFRL1 modulates chemoresistance of SCLC by regulating the ENO1-PI3K/Akt pathway. FGFRL1 may be a predictor and a potential therapeutic target for chemoresistance in SCLC.

Highly flexible organic-inorganic hybrid perovskite light-emitting devices based on an ultrathin Au electrode.

Organic-inorganic hybrid perovskite materials have received much attention in light-emitting applications during the past several years. The commonly used indium tin oxide (ITO) electrodes in perovskite light-emitting devices (PeLEDs) have unavoidable drawbacks of increasing cost and incompatibility with flexible devices, which limit the development of PeLEDs. Here, high-performance and ITO-free flexible PeLEDs utilizing ultrathin Au electrodes have been achieved and exhibited high brightness (>10,000 cdm-2). By introducing a MoO3/SU-8 modification layer, the ultrathin Au film with a thickness of 7 nm exhibits excellent surface morphology with a root-mean-square roughness value of 0.307 nm. Meanwhile, the ultrathin Au film demonstrates an outstanding optical property with transparency of 83% at the wavelength of 550 nm. Simultaneously, favorable conductivity with a sheet resistance of 13 Ω sq-1 has been achieved. High mechanical robustness and flexibility have been obtained for the flexible PeLEDs by surviving 1000 bending cycles. The flexible PeLEDs reported here exhibit tremendous potential for commercial applications.

Long non-coding RNA TUG1 is involved in cell growth and chemoresistance of small cell lung cancer by regulating LIMK2b via EZH2.

BACKGROUND: Taurine upregulated gene1 (TUG1) as a 7.1-kb lncRNA, has been shown to play an oncogenic role in various cancers. However, the biological functions of lncRNA TUG1 in small cell lung cancer (SCLC) remain unknown. The aim of this study is to explore the roles of TUG1 in cell growth and chemoresistance of SCLC and its possible molecular mechanism. METHODS: The expression of TUG1 in thirty-three cases of SCLC tissues and SCLC cell line were examined by quantitative RT-PCR (qRT-PCR). The functional roles of TUG1 in SCLC were demonstrated by CCK8 assay, colony formation assay, wound healing assay and transwell assay, flow cytometry analysis and in vivo study through siRNA or shRNA mediated knockdown. Western blot assays were used to evaluate gene and protein expression in cell lines. Chromatin immunoprecipitation (ChIP) and RNA binding protein immunoprecipitation (RIP) were performed to confirm the molecular mechanism of TUG1 involved in cell growth and chemoresistance of small cell lung cancer. RESULTS: We found that TUG1 was overexpressed in SCLC tissues, and its expression was correlated with the clinical stage and the shorter survival time of SCLC patients. Moreover, downregulation of TUG1 expression could impair cell proliferation and increased cell sensitivity to anticancer drugs both in vitro and in vivo. We also discovered that TUG1 knockdown significantly promoted cell apoptosis and cell cycle arrest, and inhibited cell migration and invasion in vitro . We further demonstrated that TUG1 can regulate the expression of LIMK2b (a splice variant of LIM-kinase 2) via binding with enhancer of zeste homolog 2 (EZH2), and then promoted cell growth and chemoresistance of SCLC. CONCLUSIONS: Together, these results suggested that TUG1 mediates cell growth and chemoresistance of SCLC by regulating LIMK2b via EZH2.

Identification of DJ-1 as a contributor to multidrug resistance in human small-cell lung cancer using proteomic analysis.

Proteomic approaches have been proven to provide an important tool in identifying drug resistance-associated proteins. The aim of this study was to investigate the protein profiling of drug resistance-related proteins in small-cell lung cancer (SCLC) by proteomic analysis. The proteomic profiling was performed by two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) coupled with MALDI-TOF-TOF of SCLC in the multidrug-resistant cell line H69AR and its parental cell line H69. A total of 11 proteins were identified to be >2-fold up-or downregulated between the two cell lines. DJ-1, one of the differently expressed proteins identified by proteomics, was further examined by immunohistochemistry staining in 116 cases of SCLC tissues. Immunohistochemical results demonstrated that DJ-1 was expressed in 51.7% (60/116) of SCLC. DJ-1 expression was correlated significantly with survival time of SCLC patients (P < 0.05), but not with other clinical parameters such as gender, age and clinical stage (P > 0.05). Downregulation of DJ-1 using DJ-1-siRNA in H69AR cells sensitized cancer cells to chemotherapeutic drugs through increasing drug-induced cell apoptosis accompanied with G0-G1 phase arrest. These findings suggest DJ-1 may serve as a potential biomarker for chemoresistance and prognostic factor for patients with SCLC.

Targeted radionuclide therapy for lung cancer with iodine-131-labeled peptide in a nude-mouse model.

Integrin α3ß1 has been shown to be a novel candidate target for the imaging and specific therapy of non-small-cell lung cancer. We have previously reported on a peptide containing a novel motif of NGXG that specifically binds to the integrin α3 receptor on lung cancer cells using a one-bead one-peptide combinatorial library. In this study, we developed the peptide cNGEGQQc-based therapeutic agent labeling with radionuclide iodine-131 (I) and evaluated its characteristics including stability, biodistribution, antitumor activity, and safety. The results showed that I-cNGEGQQc was stable in serum. Furthermore, the biodistribution of I-cNGEGQQc was determined in normal mice and rabbits. In-vivo biodistribution studies showed that radiolabeled peptide in the kidney was significantly higher than that in other organs. Nude mice bearing lung cancer cell xenografts (H1975 and L78) were used as an in-vivo model for tumor-inhibition efficacy studies with I-cNGEGQQc. The tumor growth decreased significantly in mice receiving I-labeled peptide compared with the controls and the effect of I-labeled peptide can be blocked by unlabeled cNGEGQQc. Safety studies showed that I-cNGEGQQc was relatively safe for animals without significant toxicity. Our data suggest that I-cNGEGQQc has potential as a targeted radiotherapeutic agent for non-small-cell lung cancer.

Hippocampal CysLT1R knockdown or blockade represses LPS-induced depressive behaviors and neuroinflammatory response in mice.

Evidence suggests that neuroinflammation is involved in depression and that the cysteinyl leukotriene receptor 1 (CysLT1R) plays a potential pathophysiological role in several types of CNS disorders. Our previous study has shown that knockdown of hippocampal CysLT1R in mice prevents the depressive-like phenotype and neuroinflammation induced by chronic mild stress (CMS). Here, we examined the effects of hippocampal CysLT1R knockdown and CysLT1R blockade on LPS-induced depressive-like behavior in mice. We found that injection of LPS (0.5 mg/kg, ip) caused marked increase in hippocampal CysLT1R expression, which was reversed by pretreatment with fluoxetine (20 mg·kg-1·d-1 for 7 d, ig). Knockdown of hippocampal CysLT1R or blockade of CysLT1R by pretreatment with pranlukast (0.5 mg/kg, ip) significantly suppressed LPS-induced depressive behaviors, as evidenced by decreases in mouse immobility time in the forced swimming test (FST) and tail suspension test (TST) and latency to feed in the novelty-suppressed feeding (NSF) test. Moreover, both CysLT1R knockdown and CysLT1R blockade markedly prevented LPS-induced neuroinflammation, as shown by the suppressed activation of microglia and NF-κB signaling as well as the hippocampal levels of TNF-α and IL-1ß in mice. Our results suggest that CysLT1R may be involved in LPS-induced depressive-like behaviors and neuroinflammation, and that downregulation of CysLT1R could be a novel and potential therapeutic strategy for the treatment of depression, at least partially due to its role in neuroinflammation.

Long noncoding RNA-HOTAIR affects chemoresistance by regulating HOXA1 methylation in small cell lung cancer cells.

Homeobox (HOX) transcript antisense RNA (HOTAIR), a long intergenic noncoding RNA (lincRNA), has been reported to play an oncogenic role in various cancers including small cell lung cancer (SCLC). However, it is not known whether HOTAIR can modulate chemoresistance in SCLC. The aim of this study is to investigate the roles of HOTAIR in chemoresistance of SCLC and its possible molecular mechanism. Knockdown of HOTAIR was carried out in SCLC multidrug-resistant cell lines (H69AR and H446AR) and the parental cell lines (H69 and H446) to assess its influence on chemoresistance. The results showed that downregulation of HOTAIR increased cell sensitivity to anticancer drugs through increasing cell apoptosis and cell cycle arrest, and suppressed tumor growth in vivo. Moreover, HOXA1 methylation increased in the resistant cells using bisulfite sequencing PCR. Depletion of HOTAIR reduced HOXA1 methylation by decreasing DNMT1 and DNMT3b expression. The interaction between HOTAIR and HOXA1 was validated by RNA immunoprecipitation. Taken together, our study suggested that HOTAIR mediates chemoresistance of SCLC by regulating HOXA1 methylation and could be utilized as a potential target for new adjuvant therapies against chemoresistance.

WW domain binding protein 5 induces multidrug resistance of small cell lung cancer under the regulation of miR-335 through the Hippo pathway.

BACKGROUND: Our previous study indicated that WW domain binding protein 5 (WBP5) expression was elevated significantly in a drug-resistant cell compared with its parental cell. Nevertheless, its functional role and underlying mechanisms remain unknown. METHODS: In this study, WBP5 was examined in 62 small cell lung cancer (SCLC) patient samples by immunohistochemical technique. Stable WBP5-overexpressed and WBP5-underexpressed cells were further established to assess the role of WBP5 in drug resistance, apoptosis and tumour growth. We also conducted western blot to detect the expression of MST2 and YAP1 and their phosphorylated protein. RESULTS: The results revealed that WBP5 expression was significantly associated with the shorter survival time in SCLC patients. Upregulation of WBP5 induced multidrug resistance (MDR) and decreased apoptosis, whereas downregulation of WBP5 enhanced drug sensitivity and increased apoptosis. We also found that miR-335 negatively regulated the MDR of WBP5 by targeting its 3'UTR. Furthermore, WBP5 can lower YAP1 phosphorylation at Serine 127 and induce nuclear accumulation of YAP1. Inhibition of YAP1 by Verteporfin could blunt the MDR phenotype of WBP5. CONCLUSIONS: WW domain binding protein 5 can modulate MDR through the Hippo pathway under the regulation of miR-335. WW domain binding protein 5 may be a prognostic predictor and a potential target for interfering with MDR in SCLC.

Thiourea-Modified TiO2 Nanorods with Enhanced Photocatalytic Activity.

Semiconductor TiO2 photocatalysis has attracted much attention due to its potential application in solving the problems of environmental pollution. In this paper, thiourea (CH4N2S) modified anatase TiO2 nanorods were fabricated by calcination of the mixture of TiO2 nanorods and thiourea at 600 °C for 2 h. It was found that only N element was doped into the lattice of TiO2 nanorods. With increasing the weight ratio of thiourea to TiO2 (R) from 0 to 8, the light-harvesting ability of the photocatalyst steady increases. Both the crystallization and photocatalytic activity of TiO2 nanorods increase first and then decrease with increase in R value, and R2 sample showed the highest crystallization and photocatalytic activity in degradation of Brilliant Red X3B (X3B) and Rhodamine B (RhB) dyes under visible light irradiation (λ > 420 nm). The increased visible-light photocatalytic activity of the prepared N-doped TiO2 nanorods is due to the synergistic effects of the enhanced crystallization, improved light-harvesting ability and reduced recombination rate of photo-generated electron-hole pairs. Note that the enhanced visible photocatalytic activity of N-doped nanorods is not based on the scarification of their UV photocatalytic activity.

Zinc finger E-box-binding homeobox 2 (ZEB2) regulated by miR-200b contributes to multi-drug resistance of small cell lung cancer.

Zinc finger E-box-binding homeobox 2 (ZEB2) was closely related to the oncogenesis, development and response to chemotherapy of cancer. However, its biological functions in small cell lung cancer (SCLC) remain unknown. The aim of this study is to investigate the roles of ZEB2 in chemoresistance of SCLC and its possible molecular mechanism. Expression of ZEB2 was examined in sixty-eight cases of SCLC tissues by immunohistochemistry. Knockdown of ZEB2 was carried out in SCLC multidrug resistant cells (H69AR) to assess its influence on chemoresistance. The results showed that ZEB2 was expressed in 23.5% (16/68) of SCLC. Overexpression of ZEB2 was associated with the poor pathologic stage of SCLC (P < 0.001 by the Fisher's Exact Test) and the shorter survival time (by the Kaplan-Meier method). Inhibition of ZEB2 expression using small interfering RNA in H69AR cells sensitized cancer cells to chemotherapeutic drugs through increasing drug-induced cell apoptosis accompanied with S phase arrest. In silico analysis demonstrated that there are complementary binding sites between miR-200b and ZEB2 3'-UTR, and identified miR-200b as a potential regulator of ZEB2. We found that miR-200b was down-regulated in the resistant cells and enforced expression of miR-200b by miRNA mimics increased cell sensitivity. Overexpression of miR-200b led to the downregulation of ZEB2 at protein level. Luciferase reporter gene assay showed that 3'UTR ZEB2 activity was regulated by miR-200b. Our results suggest that ZEB2 modulates drug resistance and is regulated by miR-200b. All findings provide insight into the ZEB2 signaling mechanism and ZEB2 may be a potentially novel target for multi-drug resistance in SCLC.

Tryptophan fuels MYC-dependent liver tumorigenesis through indole 3-pyruvate synthesis.

Cancer cells exhibit distinct metabolic activities and nutritional dependencies compared to normal cells. Thus, characterization of nutrient demands by individual tumor types may identify specific vulnerabilities that can be manipulated to target the destruction of cancer cells. We find that MYC-driven liver tumors rely on augmented tryptophan (Trp) uptake, yet Trp utilization to generate metabolites in the kynurenine (Kyn) pathway is reduced. Depriving MYC-driven tumors of Trp through a No-Trp diet not only prevents tumor growth but also restores the transcriptional profile of normal liver cells. Despite Trp starvation, protein synthesis remains unhindered in liver cancer cells. We define a crucial role for the Trp-derived metabolite indole 3-pyruvate (I3P) in liver tumor growth. I3P supplementation effectively restores the growth of liver cancer cells starved of Trp. These findings suggest that I3P is a potential therapeutic target in MYC-driven cancers. Developing methods to target this metabolite represents a potential avenue for liver cancer treatment.

Synthesis of heparin oligosaccharides and their interaction with eosinophil-derived neurotoxin.

A convenient route for the synthesis of heparin oligosaccharides involving regioselective protection of D-glucosamine and a concise preparation of rare L-ido sugars from diacetone α-D-glucose is described. Stereoselective coupling of a D-glucosamine-derived trichloroacetimidate with a 1,6-anhydro-ß-L-idopyranosyl 4-alcohol gave the desired α-linked disaccharide, which was used as repeating unit for dual chain elongation and termination. Stepwise assembly from the reducing to the non-reducing end with a D-glucosamine-derived monosaccharide as starting unit furnished the oligosaccharide skeletons having different chain lengths. A series of functional group transformations afforded the expected heparin oligosaccharides with 3, 5 and 7 sugar units. Interaction of these oligosaccharides with eosinophil-derived neurotoxin (EDN), a cationic ribonuclease and a mediator produced by human eosinophils, was further investigated. The results revealed that at 5 µg mL(-1), the heptasaccharide has sufficiently strong interference to block EDN binding to Beas-2B cells. The tri- and pentasaccharides have moderate inhibitory properties at 50 µg mL(-1) concentration, but no inhibition has been observed at 10 µg mL(-1). The IC(50) values of the tri-, penta- and heptasaccharides are 69.4, 47.2 and 0.225 µg mL(-1), respectively.

circRNA_010383 Acts as a Sponge for miR-135a, and Its Downregulated Expression Contributes to Renal Fibrosis in Diabetic Nephropathy.

Diabetic nephropathy (DN), a vascular complication of diabetes, is the leading cause of death in patients with diabetes. The contribution of aberrantly expressed circular RNAs (circRNAs) to DN in vivo is poorly understood. Integrated comparative circRNA microarray profiling was used to examine the expression of circRNAs in diabetic kidney of db/db mice. We found that circRNA_010383 expression was markedly downregulated in diabetic kidneys, mesangial cells, and tubular epithelial cells cultured in high-glucose conditions. circRNA_010383 colocalized with miRNA-135a (miR-135a) and inhibited miR-135a function by directly binding to miR-135a. In vitro, the knockdown of circRNA_010383 promoted the accumulation of extracellular matrix (ECM) proteins and downregulated the expression of transient receptor potential cation channel, subfamily C, member 1 (TRPC1), which is a target protein of miR-135a. Furthermore, circRNA_010383 overexpression effectively inhibited the high-glucose-induced accumulation of ECM and increased TRPC1 levels in vitro. More importantly, the kidney target of circRNA_010383 overexpression inhibited proteinuria and renal fibrosis in db/db mice. Mechanistically, we identified that a loss of circRNA_010383 promoted proteinuria and renal fibrosis in DN by acting as a sponge for miR-135a. This study reveals that circRNA_010383 may be a novel therapeutic target for DN in the future.

Hippocampal CysLT1R overexpression or activation accelerates memory deficits, synaptic dysfunction, and amyloidogenesis in young APP/PS1 transgenic mice.

BACKGROUND: Our previous studies demonstrated that cysteinyl leukotrienes receptor 1 (CysLT1R) knockout, pharmacological blockade, or hippocampus knockdown produced beneficial effects against Alzheimer's disease (AD); however, whether CysLT1R upregulation has deleterious effects on AD remains elusive. METHODS: In this study, we investigated the changes in behaviors, hippocampal amyloidogenesis, and synapse plasticity after CysLT1R overexpression by microinfusion of the lentiviral vector, containing its coding sequence of mouse (LV-CysLT1R), into the bilateral dentate gyri (DG) of the hippocampus or CysLT1R activation by repeated systemic administration of its agonist YM-17690 (0.1 mg/kg, once a day, i.p., for 28 d). RESULTS: The behavior data showed that overexpression of CysLT1R in hippocampal DG or administration of YM-17690 deteriorated behavioral performance in Morris water maze (MWM), Y-maze tests, and novel object recognition (NOR) in young APP/PS1 mice. The further studies showed that these treatments significantly destroyed synaptic function, as evidenced by impaired hippocampal long-term potentiation (LTP), decreased spine density, low number of synapses, and decreased postsynaptic protein (PSD95), and promoted the generation of amyloid ß (Aß) through increased expression of BACE1 and PS1 in the hippocampus of young APP/PS1 mice. CONCLUSIONS: Together, our results indicate that CysLT1R upregulation accelerates memory impairment in young APP/PS1 mice, which is associated with promoting synaptic dysfunction and amyloidogenesis in the hippocampus.

TNF-alpha mediates eosinophil cationic protein-induced apoptosis in BEAS-2B cells.

BACKGROUND: Eosinophilic granulocytes are important for the human immune system. Many cationic proteins with cytotoxic activities, such as eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN), are released from activated eosinophils. ECP, with low RNase activity, is widely used as a biomarker for asthma. ECP inhibits cell viability and induces apoptosis to cells. However, the specific pathway underlying the mechanisms of ECP-induced cytotoxicity remains unclear. This study investigated ECP-induced apoptosis in bronchial epithelial BEAS-2B cells and elucidated the specific pathway during apoptosis. RESULTS: To address the mechanisms involved in ECP-induced apoptosis in human BEAS-2B cells, investigation was carried out using chromatin condensation, cleavage of poly (ADP-ribose) polymerase (PARP), sub-G1 distribution in cell cycle, annexin V labeling, and general or specific caspase inhibitors. Caspase-8-dependent apoptosis was demonstrated by cleavage of caspase-8 after recombinant ECP treatment, accompanied with elevated level of tumor necrosis factor alpha (TNF-alpha). Moreover, ECP-induced apoptosis was effectively inhibited in the presence of neutralizing anti-TNF-alpha antibody. CONCLUSION: In conclusion, our results have demonstrated that ECP increased TNF-alpha production in BEAS-2B cells and triggered apoptosis by caspase-8 activation through mitochondria-independent pathway.