Cancer-associated fibroblasts potentiate colorectal cancer progression by crosstalk of the IGF2-IGF1R and Hippo-YAP1 signaling pathways.

Colorectal cancer (CRC) is one of the most common cancers worldwide. The tumor microenvironment exerts crucial effects in driving CRC progression. Cancer-associated fibroblasts (CAFs) serve as one of the most important tumor microenvironment components promoting CRC progression. This study aimed to elucidate the novel molecular mechanisms of CAF-secreted insulin-like growth factor (IGF) 2 in colorectal carcinogenesis. Our results indicated that IGF2 was a prominent factor upregulated in CAFs compared with normal fibroblasts. CAF-derived conditioned media (CM) promoted tumor growth, migration, and invasion of HCT 116 and DLD-1 cells. IGF1R expression is significantly increased in CRC, serving as a potent receptor in response to IGF2 stimulation and predicting unfavorable outcomes for CRC patients. Apart from the PI3K-AKT pathway, RNA-seq analysis revealed that the YAP1-target signature serves as a prominent downstream effector to mediate the oncogenic signaling of IGF2-IGF1R. By single-cell RNA sequencing (scRNA-seq) and immunohistochemical validation, IGF2 was found to be predominantly secreted by CAFs, whereas IGF1R was expressed mainly by cancer cells. IGF2 triggers the nuclear accumulation of YAP1 and upregulates YAP1 target signatures; however, these effects were abolished by either IGF1R knockdown or inhibition with picropodophyllin (PPP), an IGF1R inhibitor. Using CRC organoid and in vivo studies, we found that cotargeting IGF1R and YAP1 with PPP and verteporfin (VP), a YAP1 inhibitor, enhanced antitumor effects compared with PPP treatment alone. In conclusion, this study revealed a novel molecular mechanism by which CAFs promote CRC progression. The findings highlight the translational potential of the IGF2-IGF1R-YAP1 axis as a prognostic biomarker and therapeutic target for CRC. © 2022 The Pathological Society of Great Britain and Ireland.

Specific targeting of point mutations in EGFR L858R-positive lung cancer by CRISPR/Cas9.

Cancer cells are defined genetically by the mutations they harbor, commonly single nucleotide substitutions. Therapeutic approaches which specifically target cancer cells by recognizing these defining genetic aberrations are expected to exhibit minimal side-effects. However, current protein-based targeted therapy is greatly limited by the range of genes that can be targeted, as well as by acquired resistance. We hypothesized that a therapeutic oligonucleotide-based strategy may address this need of specific cancer targeting. We used CRISPR/Cas9 system to target a commonly occurring EGFR point mutation, L858R, with an oligonucleotide guide that recognizes L858R as the suitable protospacer-adjacent motif (PAM) sequence for DNA cleavage. We found that this strategy, which utilized PAM to differentiate cancer mutation from normal, afforded high specificity to the extent of a single nucleotide substitution. The anti-L858R vehicle resulted in selective genome cleavage only in L858R mutant cells, as detected by Sanger sequencing and T7 Endonuclease I assay. Wild-type cells were unaffected by the same treatment. Digital PCR revealed 37.9 ± 8.57% of L858R gene copies were targeted in mutant. Only treated mutant cells, but not wild-type cells, showed reduction in EGFR expression and decreased cell proliferation. Treated mutant cells also formed smaller tumor load in vivo. This targeting approach is expected to be able to target a significant subset of the 15-35% cancer mutations with C > G, A > G, and T > G point mutations. Thus, this strategy may serve as a useful approach to target cancer-defining mutations with specificity, to the extent of differentiating the change of a single nucleotide.

Synergistic Nanotubular Copper-Doped Nickel Catalysts for Hydrogen Evolution Reactions.

Developing highly active electrocatalysts with low cost and high efficiency for hydrogen evolution reactions (HERs) is of great significance for industrial water electrolysis. Herein, a 3D hierarchically structured nanotubular copper-doped nickel catalyst on nickel foam (NF) for HER is reported, denoted as Ni(Cu), via facile electrodeposition and selective electrochemical dealloying. The as-prepared Ni(Cu)/NF electrode holds superlarge electrochemical active surface area and exhibits Pt-like electrocatalytic activity for HER, displaying an overpotential of merely 27 mV to achieve a current density of 10 mA cm-2 and an extremely small Tafel slope of 33.3 mV dec-1 in 1 m KOH solution. The Ni(Cu)/NF electrode also shows excellent durability and robustness in both continuous and intermittent bulk water electrolysis. Density functional theory calculations suggest that Cu substitution and the formation of NiO on the surface leads to more optimal free energy for hydrogen adsorption. The lattice distortion of Ni caused by Cu substitution, the increased interfacial activity induced by surface oxidation of nanoporous Ni, and numerous active sites at Ni atom offered by the 3D hierarchical porous structure, all contribute to the dramatically enhanced catalytic performance. Benefiting from the facile, scalable preparation method, this highly efficient and robust Ni(Cu)/NF electrocatalyst holds great promise for industrial water-alkali electrolysis.

FOXP3 promotes tumor growth and metastasis by activating Wnt/ß-catenin signaling pathway and EMT in non-small cell lung cancer.

BACKGROUND: The role of cancer cell FOXP3 in tumorigenesis is conflicting. We aimed to study FOXP3 expression and regulation, function and clinical implication in human non-small cell lung cancer (NSCLC). METHODS: One hundred and six patients with histologically-confirmed NSCLC who underwent surgery were recruited for the study. Tumor samples and NSCLC cell lines were used to examine FOXP3 and its related molecules. Various cell functions related to tumorigenesis were performed. In vivo mouse tumor xenograft was used to confirm the in vitro results. RESULTS: NSCLC patients with the high level of FOXP3 had a significant decrease in overall survival and recurrence-free survival. FOXP3 overexpression significantly induced cell proliferation, migration, and invasion, whereas its inhibition impaired its oncogenic function. In vivo studies confirmed that FOXP3 promoted tumor growth and metastasis. The ectopic expression of FOXP3 induced epithelial-mesenchymal transition (EMT) with downregulation of E-cadherin and upregulation of N-cadherin, vimentin, snail, slug, and MMP9. The oncogenic effects by FOXP3 could be attributed to FOX3-mediated activation of Wnt/ß-catenin signaling, as FOXP3 increased luciferase activity of Topflash reporter and upregulated Wnt signaling target genes including c-Myc and Cyclin D1 in NSCLC cells. Co-immunoprecipitation results further indicated that FOXP3 could physically interacted with ß-catenin and TCF4 to enhance the functions of ß-catenin and TCF4, inducing transcription of Wnt target genes to promote cell proliferation, invasion and EMT induction. CONCLUSIONS: FOXP3 can act as a co-activator to facilitate the Wnt-b-catenin signaling pathway, inducing EMT and tumor growth and metastasis in NSCLC.

IGF2BP3 functions as a potential oncogene and is a crucial target of miR-34a in gastric carcinogenesis.

BACKGROUND: Gastric cancer (GC) is one of the frequent causes of cancer-related death in eastern Asian population. IGF2BP2 lists in the top rank up-regulated genes in GC, but its functional role is unclear. METHOD: The expression of IGF2BP3 in GC cell lines and primary samples was examined by qRT-PCR and Western blot. The biological role of IGF2BP3 was revealed by a series of functional in vitro studies. Its regulation by microRNAs (miRNAs) was predicted by TargetScan and confirmed by luciferase assays and rescue experiments. RESULTS: IGF2BP3 ranked the No.1 of the up-regulated genes by expression microarray analysis in GC cell lines. The expression level of IGF2BP3 was observed in GC tissues comparing with non-tumorous gastric epitheliums. The up-regulated IGF2BP3 expression was associated with poor disease specific survival. IGF2BP3 knockdown significantly inhibited cell proliferation and invasion. Apart from copy number gain, IGF2BP3 has been confirmed to be negatively regulated by tumor-suppressive miRNA, namely miR-34a. The expression of miR-34a showed negative correlation with IGF2BP3 mRNA expression in primary GC samples and more importantly, re-overexpression of IGF2BP3 rescued the inhibitory effect of miR-34a. CONCLUSION: We compressively revealed the oncogenic role of IGF2BP3 in gastric tumorigenesis and confirmed its activation is partly due to the silence of miR-34a. Our findings identified useful prognostic biomarker and provided clinical translational potential.

miR-508-3p concordantly silences NFKB1 and RELA to inactivate canonical NF-κB signaling in gastric carcinogenesis.

BACKGROUND: NF-κB signaling pathway plays an important role in gastric carcinogenesis. The basic expression and functional role of NFKB1 and RELA (components of canonical NF-κB pathway) in gastric cancer (GC) have not been well elucidated. In this study, the role of NFKB1 and RELA in gastric tumorigenesis will be investigated and their regulation by microRNAs (miRNAs) will be deeply explored. METHODS: The mRNA and protein expression of NFKB1 and RELA were investigated by qRT-PCR and Western blot in GC cell lines and primary tumors. The functional roles of NFKB1 and RELA in GC were demonstrated by MTT proliferation assay, monolayer colony formation, cell invasion and migration, cell cycle analysis and in vivo study through siRNA mediated knockdown. Identification of NFKB1 as a direct target of tumor suppressor miRNA miR-508-3p was achieved by expression regulation assays together with dual luciferase activity experiments. RESULTS: NFKB1 and RELA were up-regulated in GC cell lines and primary tumors compared with normal gastric epithelium cells and their upregulation correlation with poor survival in GC. siRNA mediated knockdown of NFKB1 or RELA exhibited anti-oncogenic effect both in vitro and in vivo. NFKB1 was further revealed to be a direct target of miR-508-3p in gastric tumorigenesis and their expression showed negative correlation in primary GC samples. miR-508-3p was down-regulated in GC cells compared with normal gastric epithelium samples and its ectopic expression in GC cell lines also exerts tumor suppressor function. NFKB1 re-expression was found to partly abolish the tumor-suppressive effect of miR-508-3p in GC. CONCLUSION: All these findings supports that canonical NF-κB signaling pathway is activated in GC at least by the inactivation of miR-508-3p and this might have therapeutic potential in GC treatment.

Targeting of YAP1 by microRNA-15a and microRNA-16-1 exerts tumor suppressor function in gastric adenocarcinoma.

BACKGROUND: MicroRNAs (miRNAs) have been reported to play an important role in tumorigenesis. In this study, the role of miR-15a and miR-16-1 in gastric adenocarcinoma (GAC) was investigated. METHODS: The expression of miR-15a and miR-16-1 in cell lines and primary tumors was examined by miRNA qRT-PCR. Proliferative assays, colony formation, cell invasion and migration, flow cytometry analysis and in vivo study were performed by ectopic expression of miR-15a and miR-16-1. The putative target genes of miR-15a and miR-16-1 were explored by TargetScan and further validated. RESULTS: We found that miR-15a and miR-16-1 were down-regulated in GAC cell lines and primary tumor samples compared with normal gastric epithelium. Functional study demonstrated that ectopic expression of miR-15a and miR-16-1 suppressed cell proliferation, monolayer colony formation, invasion and migration, and xenograft formation in vivo. In addition, miR-15a and miR-16-1 induced G0/G1 cell cycle arrest which was further confirmed by Western blot and qRT-PCR of related cell cycle regulators. YAP1 was confirmed to be a functional target of miR-15a and miR-16-1 in GAC. YAP1 re-expression partly abrogated the inhibitory effect of miR-15a and miR-16-1 in GAC cells. In clinical samples, YAP1 protein expression shows negative correlation with miR-15a and miR-16-1 expression. CONCLUSION: In conclusion, targeting YAP1 by tumor suppressor miRNA miR-15a and miR-16-1 plays inhibitory effect and this might have a therapeutic potential in GAC.

Odd-skipped related 1 is a novel tumour suppressor gene and a potential prognostic biomarker in gastric cancer.

We report that the odd-skipped related 1 (OSR1) gene encoding a zinc-finger transcription factor was preferentially methylated in gastric cancer by genome-wide methylation screening. OSR1 expression was frequently silenced or down-regulated in gastric cancer cell lines. OSR1 expression was also significantly down-regulated at both mRNA and protein levels in primary gastric cancer tissues compared with adjacent normal tissues. The silencing or down-regulation of OSR1 was closely associated with promoter hypermethylation. Overexpression of OSR1 significantly inhibited cell growth, arrested the cell cycle, and induced apoptosis in the gastric cancer cell lines AGS, MKN28, and MGC803. Conversely, knockdown of OSR1 by OSR1-short hairpin RNA significantly enhanced cell growth, promoted the cell cycle, and inhibited apoptosis in the normal gastric epithelial cell line GES1. The dual-luciferase reporter assay revealed that OSR1 activated p53 transcription and repressed the T-cell factor (TCF)/lymphoid enhancer factor (LEF). Complementary DNA expression array and western blotting showed that OSR1 increased the expression of nuclear p53, p21, Fas, and death receptor-5, and suppressed the expression of cyclin D1 and cyclin-dependent kinase 4 in the p53 signalling pathway. In addition, OSR1 suppressed the expression of cytoplasmic ß-catenin, TCF-1, and LEF1 in the Wnt/ß-catenin signalling pathway. OSR1 methylation was detected in 51.8% of primary gastric cancer patients (85 of 164) by bisulphite genomic sequencing. Multivariate Cox regression analysis showed that OSR1 methylation was an independent predictor of poor survival. Kaplan-Meier survival curves revealed that OSR1 methylation was associated with shortened survival in TNM stage I-III patients. In conclusion, OSR1 acts as a functional tumour suppressor through the transcriptional activation of p53 and repression of TCF/LEF in gastric cancer. Detection of OSR1 methylation may serve as a potential biomarker of the early stage of gastric cancer.

Detection of miRNA as non-invasive biomarkers of colorectal cancer.

Colorectal Cancer (CRC) is one of the deadliest cancers-ranking as the fourth most common cause of cancer-related deaths in the world. It is such a deadly disease because it is largely asymptomatic until the latter stages-oftentimes when the cancer has metastasized. Thus, a huge emphasis of cancer treatment is placed on early detection. Currently, there is a lack of a noninvasive, reliable, and cost-effective screening method for CRC. In recent years, microRNA (miRNA) diagnostic markers have been suggested as a viable new screening method for CRC. miRNAs play an important role in carcinogenesis, and has been observed to be dysregulated in many cancers including CRC. This review examines the diagnostic potential of circulatory and fecal miRNA markers in relation to CRC, as well as current techniques to detect them.

[Rapid Identification of Chemical Components in Polygonum multiflorum Formula Granules by UPLC/Q-TOF MS].

OBJECTIVE: To establish a simple and reliable method for rapid separation and identification of chemical components in Polygonum multiflorum Formula Granules. METHODS: An ultra-performance liquid chromatography tandem quadrupole time-of-flight mass spectrometric method( UPLC/Q-TOF MS) was used. The separation was performed on an Agilent Eclipse Plus C18 RRHD(100 mm x 2.1 mm, 1.8 µm) column with a mobile phase of water and acetonitrile in a gradient elution mode. The flow rate was 0.4 mL/min and the column temperature was maintained at 25 degrees C. TOF MS was applied for qualitative analysis under positive ion mode. RESULTS: Five compounds were identified by the time of flight mass spectrometry and literature data. CONCLUSION: This method is accurate, rapid and sensitive, it can provide reference for the quality control of Polygonum multiflorum Formula Granules.

microRNA-139-5p exerts tumor suppressor function by targeting NOTCH1 in colorectal cancer.

BACKGROUND: miR-139-5p was identified to be significantly down-regulated in colon tumor tissues by miRNA array. We aimed to clarify its biological function, molecular mechanisms and direct target gene in colorectal cancer (CRC). METHODS: The biological function of miR-139-5p was examined by cell growth, cell cycle and apoptosis analysis in vitro and in vivo. miR-139-5p target gene and signaling pathway was identified by luciferase activity assay and western blot. RESULTS: miR-139-5p was significantly down-regulated in primary tumor tissues (P < 0.0001). Ectopic expression of miR-139-5p in colon cancer cell lines significantly suppressed cell growth as evidenced by cell viability assay (P < 0.001) and colony formation assay (P < 0.01) and in xenograft tumor growth in nude mice (P < 0.01). miR-139-5p induced apoptosis (P < 0.01), concomitantly with up-regulation of key apoptosis genes including cleaved caspase-8, caspase-3, caspase-7 and PARP. miR-139-5p also caused cell cycle arrest in G0/G1 phase (P < 0.01), with upregulation of key G0/G1 phase regulators p21Cip1/Waf1 and p27Kip1. Moreover, miR-139-5p inhibited cellular migration (P < 0.001) and invasiveness (P < 0.001) through the inhibition of matrix metalloproteinases (MMP)7 and MMP9. Oncogene NOTCH1 was revealed to be a putative target of miR-139-5p, which was inversely correlated with miR-139-5p expression (r = -0.3862, P = 0.0002). CONCLUSIONS: miR-139-5p plays a pivotal role in colon cancer through inhibiting cell proliferation, metastasis, and promoting apoptosis and cell cycle arrest by targeting oncogenic NOTCH1.

let-7b/g silencing activates AKT signaling to promote gastric carcinogenesis.

BACKGROUND: Aberrant AKT activation contributes to gastric cancer cell survival and chemotherapy resistance, however its regulation is poorly understood. microRNAs have been established to be important regulators in gastric carcinogenesis. Here, we showed the functional role and putative target of let-7b and let-7g (let-7b/g) in gastric carcinogenesis. METHODS: The expression of let-7b/g in gastric cancer cell lines and primary tumors were evaluated by miRNA qRT-PCR. The putative target gene of let-7b/g was explored by TargetScan followed by further validation. Functional analyses including MTT proliferation, monolayer colony formation, cell invasion assays and in vivo study were performed in both ectopic expression and knockdown approaches. RESULTS: let-7b/g was found down-regulated in gastric cancer and its downregulation was associated with poor survival and correlated with lymph node metastasis. let-7b/g inhibited AKT2 expression by directly binding to its 3'UTR, reduced p-AKT (S473) activation and suppressed expression of the downstream effector pS6. AKT2 mRNA expression showed negative correlation with the expression of let-7b/g in primary tumors. Short interfering RNA (siRNA) mediated knockdown of AKT2 phenocopied the tumor-suppressive effects of let-7b/g. Moreover, AKT2 re-expression partly abrogated the growth-inhibitory effect of let-7b/g. CONCLUSION: In conclusion, our findings reveal decreased let-7b/g contributes to aberrant AKT activation in gastric tumorigenesis and provide a potential therapeutic strategy for gastric cancer.

Yin Yang 1 contributes to gastric carcinogenesis and its nuclear expression correlates with shorter survival in patients with early stage gastric adenocarcinoma.

BACKGROUND: Yin Yang 1 (YY1) is a transcription factor that regulates diverse biological processes and increasing recognized to have important roles in carcinogenesis. The function and clinical significance of YY1 in gastric adenocarcinoma (GAC) have not been elucidated. METHODS: In this study, the functional role of YY1 in gastric cancer was investigated by MTT proliferation assays, monolayer colony formation, cell cycle analysis, signaling pathway analysis, Western blot analysis and in vivo study through YY1 knockdown or overexpression. Immunohistochemical study with YY1 antibody was performed on tissue microarray consisting of 247 clinical GAC samples. The clinical correlation and prognosis significance were evaluated. RESULTS: YY1 expression was up-regulated in gastric cancer cell lines and primary gastric cancers. Knocking down YY1 by siYY1 inhibited cell growth, inducing G1 phase accumulation and apoptosis. Ectopic YY1 expression enhanced cell proliferation in vitro and in vivo. Knocking down YY1 in gastric cancer cells suppressed proliferation by inhibiting Wnt/ß-catenin pathway, whereas its overexpression exerted oncogenic property by activating Wnt/ß-catenin pathway. In primary GAC samples, YY1 nuclear expression correlated with shorter survival and predicted poor prognosis in early stage GACs. CONCLUSION: Our data demonstrated that YY1 contributes to gastric carcinogenesis in gastric cancer. In early stage GACs YY1 might serve as a poor prognostic marker and possibly as a potential therapeutic target.

[Establishing quantitative model of naringin in citrus Grandis Exocarpium by near infrared spectroscopy].

OBJECTIVE: To establish the quantitative model of naringin in Citrus Grandis Exocarpium by near infrared reflectance spectroscopy(NIRS). METHODS: NIRSs of 54 Citrus Grandis Exocarpium samples were collected and pretreated by TQ Analyst 8.0 software with first derivative + Norris filter. The wavebands in 10,000-4000 cm(-1) were collected and 9 numbers of factors were used. The calibration model was built with partial least squares (PLS). RESULTS: The quantitative calibration model had good correlation coefficients (r = 0.9927) and low root mean square error of calibration (RMSEC = 0.0746). Root mean square error of prediction (RMSEP) was 0.282. The average rate of recovery of validation was 101.65% (n = 9). CONCLUSION: The quantitative calibration model is trustworthy and it can be used to predict naringin in Citrus Grandis Exocarpium accurately. This simple, fast and non-destructive advantages of NIRS can be used for quality control and exploitation of Citrus Grandis Exocarpium.

MicroRNA-218 inhibits cell cycle progression and promotes apoptosis in colon cancer by downregulating BMI1 polycomb ring finger oncogene.

Deregulated miRNAs participate in colorectal carcinogenesis. In this study, miR-218 was found to be downregulated in human colorectal cancer (CRC) by miRNA profile assay. miR-218 was silenced or downregulated in all five colon cancer cells (Caco2, HT29, SW620, HCT116 and LoVo) relative to normal colon tissues. miR-218 expression was significantly lower in 46 CRC tumor tissues compared with their adjacent normal tissues (P < 0.001). Potential target genes of miR-218 were predicted and BMI1 polycomb ring finger oncogene (BMI-1), a polycomb ring finger oncogene, was identified as one of the potential targets. Upregulation of BMI-1 was detected in CRC tumors compared with adjacent normal tissues (P < 0.001) and in all five colon cancer cell lines. Transfection of miR-218 in colon cancer cell lines (HCT116, HT29) significantly reduced luciferase activity of the wild-type construct of BMI-1 3' untranslated region (3'UTR) (P < 0.001), whereas this effect was not seen in the construct with mutant BMI-1 3'UTR, indicating a direct and specific interaction of miR-218 with BMI-1. Ectopic expression of miR-218 in HCT116 and HT29 cells suppressed BMI-1 mRNA and protein expression. In addition, miR-218 suppressed protein expression of BMI-1 downstream targets of cyclin-dependent kinase 4, a cell cycle regulator, while upregulating protein expression of p53. We further revealed that miR-218 induced apoptosis (P < 0.01), inhibited cell proliferation (P < 0.05) and promoted cell cycle arrest in the G2 phase (P < 0.01). In conclusion, miR-218 plays a pivotal role in CRC development through inhibiting cell proliferation and cycle progression and promoting apoptosis by downregulating BMI-1.

Highly efficient rare-earth free vanadate phosphors for WLEDs.

Yellow-green emitting phosphors of vanadate Ca5Mg4(VO4)6 (CMV) doped with different concentrations of Ta5+ ions were synthesized by a solid-state reaction method. The formation of single-phase compounds with a garnet structure was verified by X-ray diffraction (XRD), Rietveld refinement calculations and energy-dispersive X-ray spectroscopy. Different luminescence properties of CMV phosphors such as spectral shift, luminescence lifetime, quantum efficiency, color coordinates and Stokes shift were measured and have been discussed in detail. PLE and PL spectra showed that CMV : xTa5+ (0 ≤ x ≤ 5%) phosphors could match well to 365 nm LED chips, and showed bright yellow-green emission in the visible range of 400-750 nm, with a peak at 544 nm, which is attributed to the charge transfer (CT) of an electron from the 2p orbital of the oxygen atom to the vacant 3d orbital of V5+ ions in the tetrahedral [VO4]3- group. Compared with the CMV host, the integrated luminescence intensity of CMV : 0.5%Ta5+ increased by 26.31%, and the quantum efficiency increased by 15.98%. The phenomenon can be ascribed to the substitution of V5+ ions by the large Ta5+ ions, which resulted in the squeezed and distorted VO4 tetrahedron. Finally, the white light emitting diode (WLED) devices prepared with UV WLED chips and the CMV : 0.5%Ta5+ phosphor exhibited excellent color temperature (4083 K) and CIE coordinates (0.3677, 0.3409). The CMV : 0.5%Ta5+ phosphor can be considered as a potential yellow-green emitting phosphor in the solid-state lighting field.

A metal-to-metal charge transfer induced green-yellow phosphor CsAlGe2O6:Bi3+ for full-spectrum LED devices.

With the development of solid-state lighting, full-spectrum lighting has gradually received extensive attention. Until now, Bi3+-doped narrow-band blue phosphors have been widely reported, but broadband green-yellow Bi3+-doped luminescent materials generated by metal-to-metal charge transfer have been rarely reported. In this study, a Bi3+ ion doped germanate luminescent material CsAlGe2O6:x%Bi3+ (1 ≤ x ≤ 11) is synthesized by a high-temperature sintering method. The phosphor can generate a broad green-yellow band peaking at 535 nm with a full width at half maximum of 165 nm under ultraviolet radiation. Through the analysis of the coordination environment, photoluminescence spectra and decay curves, the broadband emission spectra of Bi3+ ions are proved to be generated by the metal-to-metal charge transfer state and the 3P1 → 1S0 transition. By using theoretical research, luminescence kinetics, and Gaussian fitting, the luminescence mechanism of Bi3+ is examined. Meanwhile, the high quantum efficiency and superior thermal stability prove that the phosphor can be used as an efficient luminescent material in the field of full-spectrum LED devices.

A novel efficient red-emitting K7SrY2B15O30: Eu3+ phosphor with non-concentration quenching and robust thermal stability for white LEDs.

Inhibiting energy migration between Eu3+ ions in a fixed host to get higher doping concentration is a permanent topic. Herein, a novel non-concentration quenching red-emitting K7SrY2-2xB15O30: xEu3+ (0.1 ≤ x ≤ 1.0) phosphor was synthesized via high-temperature sintering method. XRD measurement, Rietveld refinement results, and radius percentage deviation calculation demonstrated the phase purity and the occupation preference of Eu3+ ions. With continuously increasing doping Eu3+ ions, the absence of concentration quenching could be explained by long distance between two Eu3+ (7.012 Å) and the K7SrEu2B15O30 could exhibit striking photoluminescence performance with the highest emission wavelength centered at 617 nm. Meanwhile, under the radiation of 393 nm, the high internal quantum efficiency ( âˆ¼ 78.71 %), excellent color purity ( âˆ¼ 88.32 %) and robust thermal stability whose emission intensity at 140 °C could still reach âˆ¼ 97.31 % could guarantee its potential application. When coating BaMgAl10O17: Eu2+, (Ba, Sr)2SiO4: Eu2+, and K7SrEu2B15O30 on a near-ultraviolet chip, the bright white light with a low correlated color temperature of 4211 K and CIE color coordinates of (0.3675, 0.3556) could be obtained. Taking the analytic results above, the non-concentration quenching K7SrY2B15O30: Eu3+ compound has great potential to act as a candidate for red-emitting phosphors in solid-state lighting field.

MLK4 promotes glucose metabolism in lung adenocarcinoma through CREB-mediated activation of phosphoenolpyruvate carboxykinase and is regulated by KLF5.

MLK4, a member of the mitogen-activated protein kinase kinase kinase (MAP3K) family, has been implicated in cancer progression. However, its role in lung adenocarcinoma has not been characterized. Here, we showed that MLK4 was overexpressed in a significant subset of lung adenocarcinoma, associated with a worse prognosis, and exerted an oncogenic function in vitro and in vivo. Bioinformatics analyses of clinical datasets identified phosphoenolpyruvate carboxykinase 1 (PCK1) as a novel target of MLK4. We validated that MLK4 regulated PCK1 expression at transcriptional level, by phosphorylating the transcription factor CREB, which in turn mediated PCK1 expression. We further demonstrated that PCK1 is an oncogenic factor in lung adenocarcinoma. Given the importance of PCK1 in the regulation of cellular metabolism, we next deciphered the metabolic effects of MLK4. Metabolic and mass spectrometry analyses showed that MLK4 knockdown led to significant reduction of glycolysis and decreased levels of glycolytic pathway metabolites including phosphoenolpyruvate and lactate. Finally, the promoter analysis of MLK4 unravelled a binding site of transcription factor KLF5, which in turn, positively regulated MLK4 expression in lung adenocarcinoma. In summary, we have revealed a KLF5-MLK4-PCK1 signalling pathway involved in lung tumorigenesis and established an unusual link between MAP3K signalling and cancer metabolism.