RIT1 regulates mitosis and promotes proliferation by interacting with SMC3 and PDS5 in hepatocellular carcinoma.

BACKGROUND: As a small G protein of Ras family, Ras-like-without-CAAX-1 (RIT1) plays a critical role in various tumors. Our previous study has demonstrated the involvement of RIT1 in promoting malignant progression of hepatocellular carcinoma (HCC). However, its underlying mechanism remains unclear. METHODS: Gene set enrichment analysis (GSEA) was conducted in the TCGA LIHC cohort to investigate the underlying biological mechanism of RIT1. Live cell imaging, immunofluorescence (IF) and flow cytometry assays were used to verify biological function of RIT1 in HCC mitosis. Subcutaneous xenografting of human HCC cells in BALB/c nude mice was utilized to assess tumor proliferation in vivo. RNA-seq, co-immunoprecipitation (Co-IP), mass spectrometry analyses, western blot and IF assays were employed to elucidate the mechanisms by which RIT1 regulates mitosis and promotes proliferation in HCC. RESULTS: Our findings demonstrate that RIT1 plays a crucial role in regulating mitosis in HCC. Knockdown of RIT1 disrupts cell division, leading to G2/M phase arrest, mitotic catastrophe, and apoptosis in HCC cells. SMC3 is found to interact with RIT1 and knockdown of SMC3 attenuates the proliferative effects mediated by RIT1 both in vitro and in vivo. Mechanistically, RIT1 protects and maintains SMC3 acetylation by binding to SMC3 and PDS5 during mitosis, thereby promoting rapid cell division and proliferation in HCC. Notably, we have observed an upregulation of SMC3 expression in HCC tissues, which is associated with poor patient survival and promotion of HCC cell proliferation. Furthermore, there is a significant positive correlation between the expression levels of RIT1, SMC3, and PDS5. Importantly, HCC patients with high expression of both RIT1 and SMC3 exhibit worse prognosis compared to those with high RIT1 but low SMC3 expression. CONCLUSIONS: Our findings underscore the crucial role of RIT1 in regulating mitosis in HCC and further demonstrate its potential as a promising therapeutic target for HCC treatment.

Drug Repurposing Flubendazole to Suppress Tumorigenicity via PCSK9-dependent Inhibition and Potentiate Lenvatinib Therapy for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most lethal malignant cancers across the world. It has a poor prognosis and lacks effective therapies, especially for patients with advanced-stage cancer, indicating an urgent need for new therapies and novel therapeutic targets. Here, by screening the U.S. Food and Drug Administration drug library against HCC cell lines, we identified that flubendazole, a traditional anthelmintic drug, could prominently suppress HCC cells in vivo and in vitro. RNA sequence analysis and cellular thermal shift assays showed that flubendazole reduced the expression of PCSK9 protein by direct targeting. The increased expression of PCSK9 in HCC tissues was demonstrated to be correlated with poor prognosis, and the inhibitory ability of flubendazole was selectively dependent on PCSK9 expression. PCSK9 knockdown abolished the antitumor effects of flubendazole in HCC. Mechanistically, flubendazole inhibited the Hedgehog signaling pathway induced by PCSK9, resulting in the downregulation of smoothened (SMO) and GLI Family Zinc Finger 1 (Gli1). Moreover, combining flubendazole with lenvatinib was found more effective than administering lenvatinib only for HCC treatment in vivo and in vitro. These findings reveal the therapeutic potential of flubendazole against HCC and provide clues on new repurposed drugs and targets for cancer treatment.

Surface Reconstruction of CsPbBr3 Nanocrystals by the Ligand Engineering Approach for Achieving High Quantum Yield and Improved Stability.

Oleylamine/oleic acid (OAm/OA) as the commonly used ligand is indispensable in the synthesis of perovskite nanocrystals (PNCs). Unfortunately, poor colloidal stability and unsatisfactory photoluminescence quantum yield (PLQY) are observed, resulting from a highly dynamic binding nature between ligands. Herein, we adopt a facile hybrid ligand (DDAB/ZnBr2) passivation strategy to reconstruct the surface chemistry of CsPbBr3 NCs. The hybrid ligand can detach the native surface ligand, in which the acid-base reactions between ligands are suppressed effectively. Also, they can substitute the loose capping ligand, anchor to the surface firmly, and supply sufficient halogens to passivate the surface trap, realizing an exceptional PLQY of 95% and an enhanced tolerance toward ambient storage, UV irradiation, anti-solvents, and thermal treatment. Besides, the as-fabricated white light-emitting diode (WLED) utilizing the PNCs as the green-emitting phosphor has a luminous efficiency around 73 lm/W; the color gamut covers 125% of the NTSC standard.

Self-assembly formation of CuI hybrid micron phosphors with tunable emission for multifunctional applications.

Low-cost and eco-friendly CuI hybrid compounds with various structures have recently attracted increasing attention due to their excellent optical properties and promising phosphor applications. However, the poor solubility and solution processability of bulk powders with agglomerated particle limited their practical applications greatly. In this work, we reported the self-assembly formation of CuI hybrid micron phosphors via the aqueous PVP micelle-assisted assembly route. Seven CuI hybrid micron phosphors with the emission from blue 450 nm to red 636 nm have been successfully synthesized. Among them, CuI-pyridine hybrid micron phosphors can be obtained via the reaction of CuI with various pyridines. PVP limits the size growth of the phosphors efficiently and it also plays an important role in controlling the distinct crystal phase formation. Whereas, micron phosphors based on bidentate ligands including 2-propylpyrazine, 5-bromopyrimidine or 4,4'-bipyridine need to be prepared via ligand exchange reaction. The micron phosphors present excellent stability in water and can be dispersed in the aqueous solution of PVP or PVA to form homogenous luminescent composites. The luminescent composites based on PVP are easy to use for fabricating anti-counterfeiting patterns via brush-painting or screen-printing. On the other hand, PVA composites can be applied for preparing free standing monochromatic or multichromatic emitting films as color convertor for display backlight. The PVA composites also exhibit the promising phosphor application for light-emitting diode (LED). Especially, the white LED can be directly realized via optimizing the mixing ratio of blue and orange phosphors.

In Situ Formed Core-Shell LiZnxMn2-xO4@ZnMn2O4 as Cathode for Li-Ion Batteries.

Elemental doping and surface modification are commonly used strategies for improving the electrochemical performance of LiMn2O4, such as the rated capacity and cycling stability. In this study, in situ formed core-shell LiZnxMn2-xO4@ZnMn2O4 cathodes are prepared by tuning the Zn-doping content. Through comprehensive microstructural analyses by the spherical aberration-corrected scanning transmission microscopy (Cs-STEM) technique, we shed light on the correlation between the microstructural configuration and the electrochemical performance of Zn-doped LiMn2O4. We demonstrate that part of Zn2+ ions dope into the spinel to form LiZnxMn2-xO4 in bulk and other Zn2+ ions occupy the 8a sites of the spinel to form the ZnMn2O4 shell on the outermost surface. This in situ formed core-shell LiZnxMn2-xO4@ZnMn2O4 contributes to better structural stabilization, presenting a superior capacity retention ratio of 95.8% after 700 cycles at 5 C at 25 °C for the optimized sample (LiZn0.02Mn1.98O4), with an initial value of 80 mAh g-1. Our investigations not only provide an effective way toward high-performance LIBs but also shed light on the fundamental interplay between the microstructural configuration and the electrochemical performance of Zn-doped spinel LiMn2O4.

Sperm associated antigen 4 promotes SREBP1-mediated de novo lipogenesis via interaction with lamin A/C and contributes to tumor progression in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a highly malignant tumor and its progression is associated with altered lipid metabolism in precancerous lesions, such as non-alcoholic fatty liver disease. Here, we identified sperm associated antigen 4 (SPAG4), and explored its oncogenic role in HCC progression. Database analysis and immunohistochemistry indicated increased level of SPAG4 in HCC tissues which was of prognostic value. Gain/loss-of-function experiments showed that SPAG4 exerted oncogenic roles in HCC growth both in vitro and in vivo. RNA sequencing revealed activation of a lipogenic state and SREBP1-mediated pathway following SPAG4 overexpression. Mechanistically, the N-terminal region of SPAG4 bound to lamin A/C, which increased SREBP1 expression, nuclear translocation, and transcriptional activity. Treatment with orlistat, a lipid synthesis inhibitor, reversed SPAG4-mediated oncogenic effects, and its efficacy varied with SPAG4 level. The effect of orlistat was further amplified when combined with sorafenib in tumor xenograft mouse models. Our study provides evidence that SPAG4 mediates HCC progression by affecting lipid metabolism. Administration of orlistat combined with sorafenib reverses SPAG4-mediated oncogenesis in HCC cells and ectopic xenograft tumors in mice, suggesting that this pathway represents a potential target for HCC treatment.

Thermoinduced structural-transformation and luminescent conversion in hybrid manganese halides.

We report here the synthesis of hybrid manganese halide crystals, (C4H7N2)MnCl3· H2O and (C4H7N2)2MnCl4, by using the same organic ligand 2-methylimidazole. Upon heating treatment, the red-emissive (C4H7N2)MnCl3· H2O crystal is structurally transformed into green-emissive (C4H7N2)2MnCl4crystalin situ. The crystal structural analysis reveals that the [MnCl5· H2O]3-octahedra chains decompose into mono [MnCl4]2-tetrahedra, accompanied by the departure of H2O molecules. Upon cooling in air or water vapor, the crystal structure and luminescence of (C4H7N2)2MnCl4are transformed to those of (C4H7N2)MnCl3· H2O. Thein situconversion of luminescence between (C4H7N2)MnCl3· H2O and (C4H7N2)2MnCl4provides new insight into the potential application of hybrid manganese halides.

High-efficiency synthesis of Cu superfine particles via reducing cuprous and cupric oxides with monoethanolamine and their antimicrobial potentials.

Cuprous oxide (Cu2O) and cupric oxide (CuO) are widely available and low cost raw materials. Their applications as precursors for wet chemical synthesis of metallic Cu materials are greatly limited due to their insoluble in water and most organic solvents. In this work, copper superfine particles (Cu SPs) are synthesized using Cu2O and CuO as precursors via a heating process in monoethanoamine (MEA). Due to the strong coordinating character, Cu2O and CuO can be partially dissolved in MEA. The dissolved copper source is reduced by MEA at elevated temperature with the drastically releasing of NH3. As the dissolved copper source is reduced, more oxide will be dissolved and finally leads to the full reduction of Cu2O and CuO to produce the Cu SPs. The advantage of this synthesis method is that MEA acts as both the solvent and the reducing agent. The antimicrobial properties are investigated to find that the obtained Cu SPs depress the growth of Escherichia coli (E. coli) and Staphylococcus aureus (St. aureus) efficiently. More interesting, the composites produced via curing Cu2O and CuO with a small amount of MEA also exhibit excellent antimicrobial activity, indicating the MEA curing method is high-efficiency. The synthesis is low cost, high-efficiency, high atom-economy and up-scale synthesizing easily, which will benefit the wide applications of Cu SPs.

Understanding the Effect of Al Doping on the Electrochemical Performance Improvement of the LiMn2O4 Cathode Material.

It is well known that the electrochemical performance of spinel LiMn2O4 can be improved by Al doping. Herein, combining X-ray diffraction, Raman spectroscopy, X-ray photoelectron spectroscopy, and spherical aberration-corrected scanning transmission electron microscopy (Cs-STEM) with in situ electron-beam (E-beam) irradiation techniques, the influence of Al doping on the structural evolution and stability improvement of the LiMn2O4 cathode material is revealed. It is revealed that an appropriate concentration of Al3+ ions could dope into the spinel structure to form a more stable LiAlxMn2-xO4 phase framework, which can effectively stabilize the surface and bulk structure by inhibiting the dissolution of Mn ions during cycling. The optimized LiAl0.05Mn1.95O4 sample exhibits a superior capacity retention ratio of 80% after 1000 cycles at 10 C (1 C = 148 mA h g-1) in the voltage range of 3.0-4.5 V, which possesses an initial discharge capacity of 90.3 mA h g-1. Compared with the undoped LiMn2O4 sample, the Al-doped sample also shows superior rate performance, especially the capacity recovery performance.

CSE1L, as a novel prognostic marker, promotes pancreatic cancer proliferation by regulating the AKT/mTOR signaling pathway.

Pancreatic cancer is one of the most aggressive tumors with poor prognosis and new targetable therapies are urgently required. CSE1L (chromosome segregation 1 like) is thought to play an important role in tumorigenesis and acts as a cancer therapeutic target. However, the biological function and the underlying mechanism of CSE1L in pancreatic cancer are still not fully explicit. In the present study, we found that high CSE1L expression was related to a worse prognosis in patients with pancreatic cancer according to data from the Cancer Genome Atlas (TCGA) database. Additionally, we found that CSE1L knockdown inhibited the proliferation of pancreatic cancer cells and promoted apoptosis, while CSE1L overexpression demonstrated the opposite phenomenon. Furthermore, we discovered that CSE1L might regulate pancreatic cancer proliferation through AKT signaling pathway. In summary, we reveal that CSE1L plays a crucial role in tumor growth and may serve as a potential prognostic and therapeutic target for pancreatic cancer.

Highly Stable Waterborne Luminescent Inks Based on MAPbBr3@PbBr(OH) Nanocrystals for LEDs and Anticounterfeit Applications.

Waterborne polymers are advantageous in terms of cost, convenience, sustainability, and environmental friendliness. As lead halide perovskite (LHP) nanocrystals suffer from fast degradation in the presence of water, it is challenging to encapsulate LHP nanocrystals in waterborne polymers. In this work, luminescent MAPbBr3@PbBr(OH) nanocrystals were synthesized via the aqueous grinding process in the presence of 2-methyl-imidazole (2-MIM) and oleylamime (OAm). 2-MIM triggers the formation of the PbBr(OH) matrix, and OAm acts as a size-control ligand to control the size of MAPbBr3@PbBrOH particles in the nanoscale range. Highly stable waterborne luminescent inks were successfully prepared by blending MAPbBr3@PbBr(OH) nanocrystals with waterborne polymers, including poly(vinylpyrrolidone), poly(vinyl acetate), and acrylate resins. Owning to the dual protection of the polymer matrix and PbBr(OH) to LHP quantum dots (QDs), the luminescent films exhibit excellent stability to the environment under thermal and light irradiation. The ink can be used as a phosphor to fabricate down-converting green and white light-emitting diodes (LEDs). Waterborne anticounterfeiting inks suitable for screen printing were prepared via formula tuning for the anticounterfeit purpose. The anticounterfeiting luminescent patterns can be screen printed on paper, cloth, and poly(ethylene terephthalate) (PET), with encryption and decryption of information being accurately and conveniently realized by switching UV irradiation.

Atomic Insights into Ti Doping on the Stability Enhancement of Truncated Octahedron LiMn2O4 Nanoparticles.

Ti-doped truncated octahedron LiTixMn2-xO4 nanocomposites were synthesized through a facile hydrothermal treatment and calcination process. By using spherical aberration-corrected scanning transmission electron microscopy (Cs-STEM), the effects of Ti-doping on the structure evolution and stability enhancement of LiMn2O4 are revealed. It is found that truncated octahedrons are easily formed in Ti doping LiMn2O4 material. Structural characterizations reveal that most of the Ti4+ ions are composed into the spinel to form a more stable spinel LiTixMn2-xO4 phase framework in bulk. However, a portion of Ti4+ ions occupy 8a sites around the {001} plane surface to form a new TiMn2O4-like structure. The combination of LiTixMn2-xO4 frameworks in bulk and the TiMn2O4-like structure at the surface may enhance the stability of the spinel LiMn2O4. Our findings demonstrate the critical role of Ti doping in the surface chemical and structural evolution of LiMn2O4 and may guide the design principle for viable electrode materials.

A new risk model comprising genes highly correlated with CD133 identifies different tumor-immune microenvironment subtypes impacting prognosis in hepatocellular carcinoma.

The existence of cancer stem cells (CSCs), marked by CD133, is the primary cause of death in hepatocellular carcinoma (HCC). Here, we generated a new risk model comprising the signatures of four genes highly correlated with CD133 (CD133(hi)) that help improve survival in HCC. Three datasets were used to identify the differential CD133(hi) genes by comparing sorted CD133+ liver CSCs and CD133- differentiated counterparts. Univariate analysis was used to screen significantly differential CD133(hi) genes associated with overall survival in the training dataset, which were used for risk model construction. High-risk patients were strongly associated with poor survival by Kaplan-Meier survival analysis in both the training and validation datasets. Clinical stratification analyses further demonstrated that the risk factors acted as independent factors and that high-risk patients were characterized by more aggressive cancer features. Functional enrichment analyses performed by gene set enrichment analysis (GSEA) and the Database for Annotation, Visualization and Integrated Discovery (DAVID) revealed that high-risk patients showed the disturbance of immune hepatic homeostasis involving aberrant immune cells, including macrophages and T and B cells, and an abnormal inflammatory response including the IL6/Jak/STAT3 pathway and TNF signaling pathway. In conclusion, our constructed CD133(hi) gene risk model provides a resource for understanding the role of CD133+ CSCs in the progression of HCC in terms of tumor-immune interactions.

Synergistic effect of cobalt boride nanoparticles on MoS2 nanoflowers for a highly efficient hydrogen evolution reaction in alkaline media.

The development of efficient, stable and low-cost electrocatalysts for the alkaline hydrogen evolution reaction (HER) is critical for large-scale, economically viable water splitting. In this work, we successfully prepared non-precious metal CoB@MoS2 hybrid electrocatalysts for the HER in alkaline media by the reductive growth of cobalt boride nanoparticles (CoB NPs) on the surface of MoS2 nanoflowers (MoS2 NFs). The CoB@MoS2-0.5-300 hybrid showed an HER overpotential of only 146 mV at a current density of 10 mA cm-2 and a Tafel slope of 80.9 mV dec-1 in 1.0 M KOH solution. The significantly enhanced HER activity of the hybrid is primarily attributable to the ability of CoB to drive the OER in alkaline solution and improved electrical conductivity of the hybrid electrocatalyst relative to the pristine MoS2. Furthermore, the synthetic strategy used to prepare the CoB@MoS2 electrocatalyst was successfully applied to prepare NiB@MoS2 and FeB@MoS2 hybrid electrocatalysts, which similarly showed very good HER activity in 1.0 M KOH solution. Thus, this work conclusively demonstrates that the introduction of transition metal borides is an effective approach for enhancing the HER performance of MoS2 in alkaline media.

TBX2 Identified as a Potential Predictor of Bone Metastasis in Lung Adenocarcinoma via Integrated Bioinformatics Analyses and Verification of Functional Assay.

Objective: Bone metastasis from patients with advanced lung adenocarcinoma (LAC) is a very serious complication. To better understand the molecular mechanism, our current study sheds light on identification of hub genes mediating bone metastatic spread by combining bioinformatic analysis with functional verification. Methods: First, we downloaded a lung adenocarcinoma dataset (GSE76194) from Gene Expression Omnibus, analyzed differentially expressed genes (DEGs) through Limma package in R software and constructed a protein-protein interaction network. Based on that preliminary data, we further performed modular and topological analysis using Cystoscope to obtain biological connected genes. Through literature searching and performing mRNA expression analysis on the other independent public dataset (GSE10799), we finally focused on TBX2. Functional effects of TBX2 were performed in tumorigenicity assays including migration and invasion assays, cell proliferation assay, and cell cycle assay. In addition, mechanically, we found enriched pathways related to bone metastasis using Gene Set Enrichment Analysis (GSEA) and validated our results by western blot. Result: A total of 1132 significant genes were sorted initially. We selected common significant genes (log FC>2; p<0.01) from both the biological network data and microarray data. In total, 44 such genes were identified. we found TBX2, along with 10 other genes, to be reported with relevance to bone metastasis in other cancer types. Moreover, TBX2 showed significantly higher expression levels in patients that were found positive for metastasis to bone marrow compared to patients that did not exhibit this type of metastasis in the other separated cohort (GSE10799). Thus, we finally focused on TBX2. We found that TBX2 had detectable expression in LAC cell lines and silencing endogenous TBX2 expression in A549 and H1299 cell lines markedly suppressed migration and invasion, cell proliferation and arrested cell-cycle. Pathway enrichment analyses suggested that TBX2 drove LAC oncogenesis and metastasis through various pathways with epithelial mesenchymal transition (EMT) figuring prominently in the bone metastatic group, which was evidenced by western blot. Conclusion: Collectively, TBX2 plays as a potential predictor of bone metastasis from LAC, yielding a better promise view towards "driver" gene responsible for bone metastasis.

RNA-binding protein KHSRP promotes tumor growth and metastasis in non-small cell lung cancer.

BACKGROUND: KH-type splicing regulatory protein (KHSRP) plays an important role in cancer invasion, but the relevant mechanism is not well known. In the present study, we investigated the function and potential molecular mechanism of KHSRP in non-small cell lung cancer (NSCLC) metastasis and elucidated its clinical significance. METHODS: Isobaric tags for relative and absolute quantitation and the SWATH™ approach were combined with nanoliquid chromatography-tandem mass spectrometry analysis to identify metastasis-associated nucleoproteins in NSCLC. Real-time PCR and Western blot were used to screen for metastasis-associated candidate molecules. Gene knockdown and overexpression were used to investigate their functions and molecular mechanisms in lung cancer cells. Coimmunoprecipitation (Co-IP) experiments were performed to identify the interactions between candidate molecules and their interacting proteins. Gene expression and its association with multiple clinicopathologic characteristics were analyzed by immunohistochemistry (IHC) and Western blot in human lung cancer specimens. RESULTS: KHSRP was identified as a metastasis-associated candidate molecule. In NSCLC cell lines, knockdown of KHSRP significantly reduced lung cancer cell proliferation, migration, and invasion in vitro and in vivo, whereas overexpression of KHSRP did the opposite. Mechanistically, the protein heterogeneous nuclear ribonucleoprotein C (C1/C2) (HNRNPC) was identified to interact with KHSRP using Co-IP experiments. In NSCLC cell lines, overexpression of HNRNPC significantly promoted lung cancer cell proliferation, migration, and invasion in vitro and in vivo. KHSRP and HNRNPC may induce human lung cancer cell invasion and metastasis by activating the IFN-α-JAK-STAT1 signaling pathway. Drastically higher expression levels of KHSRP and HNRNPC were observed in lung cancer tissues compared to those in adjacent noncancerous tissues. Increased KHSRP and HNRNPC expression was significantly associated with advanced tumor stages and metastasis (both lymph node and distant). Kaplan-Meier survival analysis showed that patients with high KHSRP and HNRNPC expression levels were predicted to have the shortest survival times and to have a poor prognosis. CONCLUSIONS: KHSRP plays an important role in NSCLC metastasis and may serve as a potential prognostic marker and novel therapeutic target for lung cancer metastasis treatment.

Facile Synthesis of 3d Transition-Metal-Doped α-Co(OH)2 Nanomaterials in Water-Methanol Mediated with Ammonia for Oxygen Evolution Reaction.

Layered cobalt hydroxides are cost-efficient electrocatalysts for oxygen evolution reaction (OER) in the field of energy conversion. Herein, we developed a facile synthesis method of 3d transition-metal-doped α-Co(OH)2 nanomaterials mediated with ammonia in water-methanol at room temperature. The doping of Cu2+ and Ni2+ leads to flower-like nanostructures similar to pure α-Co(OH)2, whereas the doping of Fe2+ produces nanoparticles with more than 2 times larger surface area in comparison with the Cu2+- and Ni2+-doped nanoflowers. The obtained dispersion with the addition of Nafion can be used directly as an electrocatalyst for OER with excellent catalytic activity, especially that the overpotential of Fe2+ doped is as low as 290 mV at 10 mA cm-2 and the turnover frequency is improved by 3 times as compared with that of α-Co(OH)2. Furthermore, the catalyst can be loaded onto foam nickel, which presents excellent durability with the current density unchanged under continuous chronoamperometry reaction for as long as 12 h and almost quantitative faradaic efficiency. The superior electrocatalytic properties combined with the simple synthesis without the tedious purification procedure is very promising for OER.

DCUN1D1 facilitates tumor metastasis by activating FAK signaling and up-regulates PD-L1 in non-small-cell lung cancer.

E3 ubiquitin ligases, which are key enzymes in the ubiquitin proteasome system, catalyze the ubiquitination of proteins to target them for proteasomal degradation. Emerging evidence suggests that E3 ubiquitin ligases play important roles in the development and progression of lung cancer. In our study, we characterized the gene expression landscape of lung cancer using data obtained from TCGA to explore the changes in E3 ubiquitin ligase containing the regulators of E3 ubiquitin ligase activity. Overall, most gene expression changes occurred in NSCLC tissues compared with adjacent normal ones. In total, 48 E3 ubiquitin ligases containing the regulators were up-regulated in NSCLC tissues compared with their levels in normal tissues. We analyzed the expression of up-regulated E3 ubiquitin ligases containing the regulators in two publicly available transcriptome data sets (GSE13213 and GSE30219). We found that four E3 ubiquitin ligases (UHRF1, BRCA1, TRAIP and HLTF) and one regulator of ubiquitin E3 activity DCUN1D1 that were dramatically up-regulated in cancer were significantly associated with tumor metastasis and patient's poor prognosis both in two transcriptome data sets. Next, clinical analysis indicated that the expression levels of DCUN1D1 correlated with clinical stage and lymph node metastasis in NSCLC patients as determined by quantitative reverse transcription-PCR. Furthermore, functional assays showed that DCUN1D1 promoted NSCLC cell invasion and migration as determined by transwell assay in vitro. Mechanistically, we found that the C-terminal Cullin binding domain leads to oncogenic activity and the UBA domain acts as a negative regulator of DCUN1D1 function in NSCLC. Moreover, DCUN1D1 activated the FAK oncogenic signaling pathway and up-regulated PD-L1. Taken together, our results demonstrate that DCUN1D1 is a metastasis regulator and suggest a new therapeutic option for NSCLC metastasis.

CPNE3 promotes migration and invasion in non-small cell lung cancer by interacting with RACK1 via FAK signaling activation.

Approximately 90% of patients diagnosed with non-small cell lung cancer (NSCLC) die due to distant metastases. However, the complicated molecular and cellular mechanisms involved in lung cancer metastasis remain poorly understood. Copine III (CPNE3), a member of a Ca2+-dependent phospholipid-binding protein family, was identified as a novel metastasis-associated protein in NSCLC in our previous study, however, its function in metastasis remains unclear. Here, we found that CPNE3 was expressed at high levels in NSCLC tissues and advanced TNM stages and was significantly associated with poor prognosis. In addition, CPNE3 interacted with phosphorylated erb-b2 receptor tyrosine kinase 2 (pErbB2) and receptor of activated protein C kinase 1 (RACK1) and activated the focal adhesion (FA) signaling pathway in NSCLC cells. Moreover, knockdown of RACK1 inhibited cell motility in the CPNE3-overexpressed NSCLC cells. These findings offer mechanistic insights into the oncogenic roles of CPNE3 and the pivotal effects of CPNE3 as a biomarker and therapeutic target for NSCLC metastasis.

Luminescent Nanofluids of Organometal Halide Perovskite Nanocrystals in Silicone Oils with Ultrastability.

Luminescent nanofluids are successfully prepared by directly dispersing organometal halide perovskite nanocrystals (OHP NCs) with different emission colors in silicone oils. The photoluminescence quantum yields of nanofluids with green, blue and red emission are 47, 32, and 19%, respectively. Furthermore, the nanofluids greatly enhance the stability of OHP NCs and show excellent resistance against moisture, heat and ultraviolet light. The luminescent nanofluids can be used as liquid color converter for LED. By loading them onto silica aerogel, luminescent perovskite powders were achieved. Their applications as phosphor additives for preparing luminescent PMMA composites were demonstrated.