Translation and Psychometric Evaluation of a Chinese Version of the Behavioral Regulation in Sport Questionnaire (BRSQ) with University Sport Athletes.

Our aim in this study was to translate and psychometrically evaluate a Chinese version of the Behavioral Regulation in Sport Questionnaire (BRSQ). Participants were Chinese collegiate athletes (N = 361) who were competitive in their respective sports. We examined the construct validity of the Chinese BRSQ using alternative structural equation models and evaluated convergent validity, factor score reliability, and measurement invariance of the optimal model. Due to insufficient score reliability for some subscales, our initial Chinese BRSQ was deemed problematic. A modified version of the questionnaire with a four-factor structure (amotivation, external regulation, introjected regulation, and autonomous motivation) demonstrated excellent construct validity, convergent validity, and score reliability. There was measurement invariance across athlete level and sex. This tool provides a valuable resource for practitioners and sport psychology researchers for assessing sport motivation among competitive university athletes in China.

The deubiquitylating enzyme USP35 restricts regulated cell death to promote survival of renal clear cell carcinoma.

The ubiquitin-proteasome system governs a wide spectrum of cellular events and offers therapeutic opportunities for pharmacological intervention in cancer treatment. Renal clear cell carcinoma represents the predominant histological subtype and accounts for the majority of cancer death related to kidney malignancies. Through a systematic survey in the association of human ubiquitin-specific proteases with patient prognosis of renal clear cell carcinoma and subsequent phenotypic validation, we uncovered the tumor-promoting role of USP35. Biochemical characterizations confirmed the stabilizing effects of USP35 towards multiple members of the IAP family in an enzymatic activity-dependent manner. USP35 silencing led to reduced expression levels of IAP proteins, which were accompanied with increased cellular apoptosis. Further transcriptomic analysis revealed that USP35 knockdown affected the expression levels of NRF2 downstream transcripts, which were conferred by compromised NRF2 abundance. USP35 functions to maintain NRF2 levels by catalyzing its deubiquitylation and thus antagonizing degradation. NRF2 reduction imposed by USP35 silencing rendered renal clear cell carcinoma cells increased sensitivity to ferroptosis induction. Finally, induced USP35 knockdown markedly attenuated xenograft formation of renal clear cell carcinoma in nude mice. Hence, our findings reveal a number of USP35 substrates and uncover the protecting roles of USP35 against both apoptosis and ferroptosis in renal clear cell carcinoma.

Pharmacological inhibition of the ubiquitin-specific protease 8 effectively suppresses glioblastoma cell growth.

Glioblastoma (GBM) is a malignant brain tumor. The purpose of this study is to estimate the potential effects and underlying mechanisms of a ubiquitin-specific protease 8 (USP8) small-molecule inhibitor on the phenotypic characteristics of GBM cells. The growth, migration, invasion, and stemness of GBM LN229 and T98G cells were evaluated by conducting cell proliferation, colony formation, wound healing, transwell, Ki-67 staining, spheroid formation, and ionizing radiation assays, and the results collectively showed the suppressive effects of USP8 inhibition on GBM cells. Furthermore, transcriptomic profiling of GBM cells treated with the USP8 inhibitor deubiquitinase (DUB)-IN-1 revealed significantly altered mRNA expression induced by pharmacological USP8 inhibition, from which we confirmed downregulated Aurora kinase A (AURKA) protein levels using immunoblotting assays. Our findings indicated that the proliferation, invasion, and stemness of LN229 and T98G cells were markedly suppressed by USP8 inhibition. Pharmacological USP8 suppression elicits multiple tumor-inhibitory effects, likely through dysregulating various mRNA expression events, including that of the key cell cycle regulator and oncogenic protein AURKA. Therefore, our observations corroborate the GBM-supportive roles of USP8 and suggest pharmacological USP8 inhibition is a viable therapeutic approach to target GBM. The purpose of this study was to investigate the effect and mechanism of action of the USP8 inhibitor DUB-IN-1 on GBM.

The ubiquitin-specific protease 8 antagonizes melatonin-induced endocytic degradation of MT1 receptor to promote lung adenocarcinoma growth.

INTRODUCTION: The human genome encodes two melatonin receptors (MT1 and MT2) that relay melatonin signals to cellular interior. Accumulating evidence has linked melatonin to multiple health benefits, among which its anticancer effects have become well-established. However, the implications of its receptors in lung adenocarcinoma have so far remained incompletely understood. OBJECTIVES: This study aims to investigate the response of the MT1 receptor to melatonin treatment and its dynamic regulation by ubiquitin-specific protease 8 (USP8) in lung adenocarcinoma. METHODS: The mRNA levels of MT1 and MT2 receptors were analyzed with sequencing data. The expression and localization of the MT1 receptor with melatonin treatment were investigated by immunoblotting, immunofluorescence and confocal microscopy assays. Endocytic deubiquitylases were screened to identify MT1 association. The effects of USP8 were assessed with shRNA-mediated knockdown and small molecule inhibitor. The combined efficacy of melatonin and USP8 suppression was also evaluated using xenograft animal models. RESULTS: Bioinformatic analysis revealed increased expression of the MT1 receptor in lung adenocarcinoma tissues. Melatonin treatment leads to the downregulation of the MT1 receptor in lung adenocarcinoma cells, which is attributed to receptor endocytosis and lysosomal degradation via the canonical endo-lysosomal route. USP8 negatively regulates the endocytic degradation of the MT1 receptor incurred by melatonin exposure and thus protects lung adenocarcinoma cell growth. USP8 suppression by knockdown or pharmacological inhibition effectively deters cancer cell proliferation and sensitizes lung adenocarcinoma cells to melatonin in vitro. Furthermore, USP8 silencing significantly potentiates the anticancer effects of melatonin in xenograft tumor models. CONCLUSION: The MT1 receptor responds to melatonin treatment and is endocytosed for lysosomal degradation that is counteracted by USP8. The inhibition of USP8 demonstrates tumor-suppressive effects and thus can be exploited as potential therapeutic strategy either as monotherapy or combined therapy with melatonin.

MIM waveguide system with independently tunable double resonances and its application for two-parameter detection.

A metal-insulator-metal (MIM) waveguide system consisting of a MIM waveguide, a ring cavity, and a semi-ring cavity is proposed. Using the finite element method, the transmission characteristics of the MIM waveguide system are discussed under the different geometry parameters. By detecting the resonance wavelength and varying the refractive index, the sensing performance of the MIM waveguide system is analyzed. The proposed structure can be used as a refractive index sensor with the maximum sensitivity of 2412 nm/RIU. Due to isolating the ring cavity and semi-ring cavity, the independent tuning of double resonances can be realized by changing the refractive index of the insulator in the ring cavity or the semi-ring cavity. Benefiting from two independent refractive index sensing modes, the structure with two isolated resonators can realize the simultaneous measurement of glucose solution concentration and blood plasma concentration. The sensitivity of glucose solution sensing in the ring cavity is 0.13133 nm/(g/L). Meanwhile, the blood plasma concentration detection in the semi-ring cavity is realized with the sensitivity of 0.358 nm/(g/L). The system with two isolated cavities has the potential to be used as an efficient nano sensor, which can achieve simultaneous measurement of two parameters.

PKC signal amplification suppresses non-small cell lung cancer growth by promoting p21 expression and phosphorylation.

Protein kinase C (PKC) activation was previously associated with oncogenic features. However, small molecule inhibitors targeting PKC have so far proved ineffective in a number of clinical trials for cancer treatment. Recent progresses have revealed that most PKC mutations detected in diverse cancers actually lead to loss-of-function, thus suggesting the tumor-suppressive roles of PKC proteins. Unfortunately, the development of chemicals to enhance PKC activity is lagging behind relative to its small molecular inhibitors. Here, we report that a bisindolylmaleimide derivative (3,4-bis(1-(prop-2-ynyl)-1H-indol-3-yl)-1 H-pyrrole-2,5-dione, BD-15) significantly inhibited cell growth in non-small cell lung cancer (NSCLC). Mechanistically, BD-15 treatment resulted in markedly enhanced phosphorylation of PKC substrates and led to cell cycle arrest in G2/M. Further, BD-15 treatment upregulated p21 protein levels and enhanced p21 phosphorylation. BD-15 also promoted caspase3 cleavage and triggered cellular apoptosis. In xenograft mouse models, BD-15 exerted anti-tumor effects to suppress in vivo tumor formation. Collectively, our findings revealed the tumor-suppressive roles of BD-15 through enhancing PKC signaling and thus leading to upregulation of p21 expression and phosphorylation.

Proteasomal deubiquitylase activity enhances cell surface recycling of the epidermal growth factor receptor in non-small cell lung cancer.

PURPOSE: The epidermal growth factor receptor (EGFR) represents a top therapeutic target in the treatment of non-small cell lung cancer. EGFR expression is intricately modulated by receptor endocytosis, during which EGFR ubiquitylation and deubiquitylation play fundamental roles to govern receptor fate. This study aims to uncover novel aspects of the endocytic regulation of EGFR trafficking by deubiquitylases. METHODS: The expression and ubiquitylation of EGFR in non-small cell lung cancer cells treated with deubiquitylase inhibitors were assessed by immunoblotting, immunoprecipitation and mass spectrometry analyses. The intracellular EGFR distribution was investigated using immunofluorescence and confocal microscopy assays, and colocalizations with endocytic compartments were examined using GFP-tagged Rab proteins as markers. The influence of the proteasomal deubiquitylase inhibitor b-AP15 on EGF- and HSP90 inhibitor-induced EGFR downregulation was evaluated by immunoblotting. The anticancer effects of b-AP15 were assessed by cell proliferation, colony formation and flow cytometry assays, as well as xenograft animal models. RESULTS: We found that b-AP15 caused a dramatically enhanced ubiquitylation of EGFR in lung cancer cells. Treatment with b-AP15 decreased cell surface EGFR levels and accumulated EGFR on recycling endosomes marked with Rab4A and Rab11A. b-AP15 effectively repressed EGF- and HSP90 inhibitor-induced EGFR degradation. Lung cancer cells exposed to b-AP15 showed markedly reduced cell propagation and significantly increased cell apoptosis. Furthermore, b-AP15 effectively inhibited tumor xenograft growth in nude mice. CONCLUSION: Proteasomal USP14 and UCHL5 act collectively to promote cell surface recovery of EGFR. Inhibition of proteasomal deubiquitylase activity induces increased EGFR ubiquitylation and retention on recycling endosomes. The USP14 and UCHL5 dual inhibitor b-AP15 elicits potent tumor-suppressive effects to deter cell proliferation and induce apoptotic cell death in lung cancer.

Distributed Intelligent Learning and Decision Model Based on Logic Predictive Control.

By the method of documentation and logical analysis, based on the data, based on logic and based on the knowledge of three kinds of artificial intelligence in the sports education, the intelligent learning system feedback delay are studied, combined with mobile communication which led to the artificial intelligence online sports games teaching, pattern recognition, and virtual technology combined with innovative teaching interaction and experience. Promoting the development of green PE teaching machine learning can identify the types of PE activities and realize efficient PE learning diagnosis. Intelligent decision support system can identify sports talents and improve the effect of personalized PE teaching evaluation. From the perspective of psychological development and education, the key problems to be solved in the integration of artificial intelligence and physical education are examined. Then, the consistent model predictive control for feedback delay of nonlinear sports learning multiagent system with network induced delay and random communication protocol is studied. Under the communication waiting mechanism designed, each agent has a certain tolerance of delay, and this tolerance can be determined by ensuring the stability of the system. At the same time, a random communication protocol is designed to ensure the ordered communication of the multiagent system. Finally, the effectiveness of the proposed algorithm is verified by numerical simulation. To solve the channel competition access problem of the sports intelligent learning system with special structure feedback delay model predictive control, a dual channel awareness scheduling strategy under the model predictive control framework was proposed, and the distributed threshold strategy of sensors and the priority threshold strategy of controllers were designed. It is proved that the sensor will eventually work at Nash equilibrium point under the policy updating mechanism, and the priority threshold strategy of the controller is better than the traditional independent and identically distributed access strategy. By avoiding the data transmission when the channel status is poor, the channel access of the system is efficient and saves energy.

Tunable dual-channel slow light in a graphene grating plasmonic waveguide.

We propose a plasmonic waveguide comprising a single-layer graphene, a silica dielectric layer, and a silicon grating substrate to realize dual-channel slow surface plasmon polaritons. The dual-channel results from the introduction of two kinds of periodic structures with defects in the waveguide. According to the Bragg equation, we match the appropriate structure parameters to ensure the slow light dual-channel working around λ1=9369.1nm (32 THz) and λ2=7138.2nm (42 THz). The influence of the structure parameters on the slow light effect is discussed, and the largest value of the normalized delay bandwidth product (NDBP) is up to 7.38. Then, by shifting the gate voltage, obvious linear blueshift of the dual-channel is achieved. In this process, the slow light performance of the dual-channel exhibits good stability, and the average values of the NDBP are 4.5 and 4.4. Due to the flexible tunability, the waveguide may pave the way for the design of slow light devices.

USP42 drives nuclear speckle mRNA splicing via directing dynamic phase separation to promote tumorigenesis.

Liquid-liquid phase separation is considered a generic approach to organize membrane-less compartments, enabling the dynamic regulation of phase-separated assemblies to be investigated and pivotal roles of protein posttranslational modifications to be demonstrated. By surveying the subcellular localizations of human deubiquitylases, USP42 was identified to form nuclear punctate structures that are associated with phase separation properties. Bioinformatic analysis demonstrated that the USP42 C-terminal sequence was intrinsically disordered, which was further experimentally confirmed to confer phase separation features. USP42 is distributed to SC35-positive nuclear speckles in a positively charged C-terminal residue- and enzymatic activity-dependent manner. Notably, USP42 directs the integration of the spliceosome component PLRG1 into nuclear speckles, and its depletion interferes with the conformation of SC35 foci. Functionally, USP42 downregulation deregulates multiple mRNA splicing events and leads to deterred cancer cell growth, which is consistent with the impact of PLRG1 repression. Finally, USP42 expression is strongly correlated with that of PLRG1 in non-small-cell lung cancer samples and predicts adverse prognosis in overall survival. As a deubiquitylase capable of dynamically guiding nuclear speckle phase separation and mRNA splicing, USP42 inhibition presents a novel anticancer strategy by targeting phase separation.

The Anticancer Potential of Apigenin Via Immunoregulation.

Apigenin is an edible flavonoid widely distributed in natural plants, including most vegetables and fruits. Previous studies have revealed that apigenin possesses multiple biological functions by demonstrating antiinflammatory, anti-oxidative, anti-bacterial, anti-viral, anti-tumor and cardiovascular protective effects. Furthermore, recent progressions have disclosed a novel perspective of the anti-cancer roles of apigenin through its immunoregulatory functions. With the rapid progression of the groundbreaking strategies being developed for cancer immunotherapy, its immunoregulatory roles are being recognized as intriguing features of the multifaceted apigenin. However, the current understanding of this emerging role of apigenin still remains limited. Therefore, in the present review, recent advances on the immunoregulatory properties of apigenin in various diseases with a special focus on neoplasm, are summarized. Clinical strategies of cancer immunotherapy are briefly introduced and findings on apigenin linked to immunoregulatory roles in immunotherapy-associated aspects are brought together. The bioactivity, bioavailability, toxicity and potential of apigenin, to be considered as a therapeutic agent in anti-tumor immunotherapy, is discussed. Disclosed molecular mechanisms underlying the immunoregulatory roles of apigenin in cancer immunotherapy are also summarized. Based on findings from the literature, apigenin has the potential to serve as a prospective adjuvant for anti-cancer immunotherapy and warrants further investigations.

USP29 enhances chemotherapy-induced stemness in non-small cell lung cancer via stabilizing Snail1 in response to oxidative stress.

Chemotherapy remains an essential part of diverse treatment regimens against human malignancies. However, recent progressions have revealed a paradoxical role of chemotherapies to induce the cancer stem cell-like features that facilitate chemoresistance and tumor dissemination, with the underlying mechanisms underinvestigated. The zinc-finger transcription factor Snail1 is a central regulator during the epithelial-mesenchymal transition process and is closely implicated in cancer progression. Snail1 expression is strictly regulated at multiple layers, with its stability governed by post-translational ubiquitylation that is counterbalanced by the activities of diverse E3 ligases and deubiquitylases. Here we identify the deubiquitylase USP29 as a novel stabilizer of Snail1, which potently restricts its ubiquitylation in a catalytic activity-dependent manner. Bioinformatic analysis reveals a reverse correlation between USP29 expression and prognosis in lung adenocarcinoma patients. USP29 is unique among Snail1 deubiquitylases through exhibiting chemotherapy-induced upregulation. Mechanistically, oxidative stresses incurred by chemotherapy stimulate transcriptional activation of USP29. USP29 upregulation enhances the cancer stem cell-like characteristics in lung adenocarcinoma cells to promote tumorigenesis in athymic nude mice. Our findings uncover a novel mechanism by which chemotherapy induces cancer stemness and suggest USP29 as a potential therapeutic target to impede the development of chemoresistance and metastasis in lung adenocarcinoma.

The deubiquitylase USP2 maintains ErbB2 abundance via counteracting endocytic degradation and represents a therapeutic target in ErbB2-positive breast cancer.

ErbB2 overexpression identifies a subclass of breast cancer as ErbB2-positive that is frequently associated with poor prognosis. Current ErbB2-targeted therapies have profoundly improved patient outcomes, but mutations occurring in ErbB2 have been shown to confer drug resistance. Induction of ErbB2 degradation was proposed as an intriguing strategy to battle with ErbB2-positive breast cancer and reduced mutation-incurred drug resistance. Although multiple HSP90 inhibitors have been demonstrated to effectively trigger ErbB2 degradation, none succeeded in the clinical evaluations. To develop novel ErbB2-targeting strategies, we investigated the endocytic degradation and reversible ubiquitylation of ErbB2 in breast cancer. In this study, we reveal that HSP90 inhibition leads to efficient ubiquitylation and endocytic degradation of ErbB2 through the canonical endo-lysosomal route. USP2 associates with internalized ErbB2 and prevents its lysosomal sorting and degradation via exerting deubiquitylase activity. Accordingly, the USP2 inhibitor ML364 is capable of inducing ErbB2 ubiquitylation and accelerating its turnover. ML364 potentiates the pro-degradation effects of HSP90 inhibitors on ErbB2 and hence sensitizes ErbB2-positive breast cancer cells to HSP90 inhibition. The combination of USP2 and HSP90 inhibitors effectively restrains ErbB2-positive breast cancer xenograft growth in vivo. Based on these observations, we conclude that USP2 safeguards ErbB2 surface levels by antagonizing its ubiquitylation-mediated endocytic degradation, which can be exploited to design novel therapeutic strategies against ErbB2-driven malignancies as combinatorial treatment with HSP90 inhibitors.

Linker-Eliminated Nano Metal-Organic Framework Fluorescent Probe for Highly Selective and Sensitive Phosphate Ratiometric Detection in Water and Body Fluids.

Phosphate is an important anion in both the aquatic environment and biological systems. The search for a selective and sensitive phosphate ratiometric fluorescent probe to quantify the phosphate level in water samples and body fluids is of great significance for the protection of the ecological environment and human health. Here, a porphyrin-based nano metal-organic framework (NMOF), PCN-224, was successfully exploited as a simple but highly sensitive and selective single-component ratiometric fluorescent probe with accurate composition and measurable structure for the quantitative determination of phosphate, based on the interesting double-emission fluorescence of the porphyrin ligand itself. Compared with other zirconium-based NMOF probes for phosphate, the reduced number of connections for ZrO clusters with the ligand in PCN-224 obtained by a linker-elimination strategy simultaneously provides more active recognition sites for phosphate, which effectively improves the sensitivity of the zirconium-based NMOF probes. The detection limit of the probe is only 54 nM. Additionally, the accuracy of the ratiometric detection based on this probe was further proved by the detection of phosphate in human serum and drinking water.

Dynasore potentiates c-Met inhibitors against hepatocellular carcinoma through destabilizing c-Met.

c-Met receptor is frequently overexpressed in hepatocellular carcinoma and thus considered as an attractive target for pharmacological intervention with small molecule tyrosine kinase inhibitors. Albeit with the development of multiple c-Met inhibitors, none reached clinical application in the treatment of hepatoma so far. To improve the efficacy of c-Met inhibitors towards hepatocellular carcinoma, we investigated the combined effects of the dynamin inhibitor dynasore with several c-Met inhibitors, including tivantinib, PHA-665752, and JNJ-38877605. We provide several lines of evidence that dynasore enhanced the inhibitory effects of these inhibitors on hepatoma cell proliferation and migration, accompanied with increased cell cycle arrest and apoptosis. Mechanically, the combinatorial treatments decreased c-Met levels and hence markedly disrupted downstream signaling, as revealed by the dramatically declined phosphorylation of AKT and MEK. Taken together, our findings demonstrate that the candidate agent dynasore potentiated the inhibitory effects of c-Met inhibitors against hepatoma cells and will shed light on the development of novel therapeutic strategies to target c-Met in the clinical management of hepatocellular carcinoma patients.

TIGAR Promotes Tumorigenesis and Protects Tumor Cells From Oxidative and Metabolic Stresses in Gastric Cancer.

Cancer cells adopt glycolysis to facilitate the generation of biosynthetic substrates demanded by cell proliferation and growth, and to adapt to stress conditions such as excessive reactive oxygen species (ROS) accumulation. TIGAR (TP53-induced glycolysis and apoptosis regulator) is a fructose-2,6-bisphosphatase that is regulated by p53. TIGAR functions to inhibit glycolysis and promote antioxidative activities, which assists the generation of NADPH to maintain the levels of GSH and thus reduces intracellular ROS. However, the functions of TIGAR in gastric cancer (GC) remain unclear. TIGAR expression levels were detected by immunoblotting and immunohistochemistry in gastric cancer samples, along with four established cell lines of GC. The functions of TIGAR were determined by utilizing shRNA-mediated knockdown experiments. The NADPH/NADP+ ratio, ROS, mitochondrial ATP production, and phosphorus oxygen ratios were determined in TIGAR-depleted cells. Xenograft experiment was conducted with BALB/c nude mice. TIGAR was up-regulated compared with corresponding non-cancerous tissues in primary GCs. TIGAR knockdown significantly reduced cell proliferation and increased apoptosis. TIGAR protected cancer cells from oxidative stress-caused damages, but also glycolysis defects. TIGAR also increased the production of NADPH in gastric cancer cells. TIGAR knockdown led to increased ROS production, elevated mitochondrial ATP production, and phosphorus oxygen ratios. The prognosis of high TIGAR expression patients was significantly poorer than those with low TIGAR expression. Taken together, TIGAR exhibits oncogenic features in GC, which can be evaluated as a target for intervention in the treatment of GC.

Endocytic degradation of ErbB2 mediates the effectiveness of neratinib in the suppression of ErbB2-positive ovarian cancer.

The tyrosine kinase receptor ErbB2 is frequently found to be overexpressed in multiple cancer types. Targeted therapeutic approaches against ErbB2 have shown promising results and received FDA approvals in the treatment of breast cancer. However, this approach has not been granted in ovarian cancers till now. In order to assess the validity of ErbB2-targeted therapy in ovarian cancer, we investigated the effectiveness of two FDA-approved tyrosine kinase inhibitors of ErbB2, lapatinib and neratinib, on the growth of ovarian cancers. We observed that both lapatinib and neratinib displayed inhibitory effects towards the proliferation and migration of ErbB2-positive ovarian cancer cells in vitro, with neratinib showing stronger suppression in general. Neratinib treatment led to the reduction of ErbB2 protein levels, with concomitant attenuation of the phosphorylation of AKT, MEK, and ERK1/2. Immunofluorescence assays revealed that neratinib induced the internalization and lysosomal degradation of ErbB2, which was accompanied by its hyperubiquitylation. Lapatinib and neratinib also repressed the in vivo growth of SKOV3 cells, and neratinib downregulated ErbB2 levels in xenograft tumors to cause potent inhibition. Therefore, the ubiquitylation-mediated endocytic degradation of ErbB2 incurred by neratinib treatment conferred potent inhibition of ovarian cancer growth. Clinical investigations of neratinib in ErbB2-positive ovarian cancer are warranted.

Metal ion-assisted carboxyl-containing covalent organic frameworks for the efficient removal of Congo red.

Covalent organic frameworks (COFs) have been utilized as molecular sieves to adsorb or remove or separate a wide range of substances. Herein, a new carboxyl-containing COF (COF-COOH) is fabricated from the polymerization of 1,3,5-triformylphloroglucinol (TP) and 4,4'-diamino-[1,1'-biphenyl]-3,3'-dicarboxylic acid (DBA). COF-COOH displays good adsorption performance on Congo red (CR) through hydrogen bonds and π-π stacking interactions. Through post-modification with Ca2+/Ni2+ ions, the adsorption capacity of COF-COOCa/COF-COONi to CR is improved, which is due to the coordinated metal cations having a positive contribution to the electrostatic interactions. At 25 °C, the maximum adsorption amount of COF-COOCa and COF-COONi to CR is 704.23 mg g-1 and 781.25 mg g-1, respectively. The removal efficiency of COF-COOCa to CR is 95% and that of COF-COONi is 96%. This demonstrates that the new metal ion-assisted COFs are viable adsorbents to remove dye pollutants, which are harmful to the environment and to human health, from wastewater.

Amplification of USP13 drives non-small cell lung cancer progression mediated by AKT/MAPK signaling.

USP13 is emerging as a potential target in cancer therapy. However, the effect of USP13 on tumor progression is controversial. Here we focused on non-small cell lung cancer (NSCLC), a common cancer with high mortality, and studied the role of USP13 in tumor growth. By analysis of multi-level genetic database, we found USP13 is high expressed in heart among healthy primary tissues and is most amplified in lung cancer. Clinical samples of NSCLC showed tumor exhibited high USP13 level compared with adjacent normal tissues. We further utilized lung adenocarcinoma A549 and squamous carcinoma H226 cells as cell model and investigated USP13 effect by USP13 knockdown. As a results, downregulation of USP13 dramatically inhibited A549 and H226 cell proliferation by AKT/MAPK signaling and suppressed tumor growth in nude mice. Collectively, we identified USP13 as a tumor promoter in NSCLC and provide a promising target in cancer therapy.

Cholesterol content in cell membrane maintains surface levels of ErbB2 and confers a therapeutic vulnerability in ErbB2-positive breast cancer.

BACKGROUND: ErbB2 overexpression identifies a subset of breast cancer as ErbB2-positive and is frequently associated with poor clinical outcomes. As a membrane-embedded receptor tyrosine kinase, cell surface levels of ErbB2 are regulated dynamically by membrane physical properties. The present study aims to investigate the influence of membrane cholesterol contents on ErbB2 status and cellular responses to its tyrosine kinase inhibitors. METHODS: The cholesterol abundance was examined in ErbB2-positive breast cancer cells using filipin staining. Cellular ErbB2 localizations were investigated by immunofluorescence with altered membrane cholesterol contents. The inhibitory effects of the cholesterol-lowering drug lovastatin were assessed using cell proliferation, apoptosis, immunoblotting and immunofluorescence assays. The synergistic effects of lovastatin with the ErbB2 inhibitor lapatinib were evaluated using an ErbB2-positive breast cancer xenograft mouse model. RESULTS: Membrane cholesterol contents positively correlated with cell surface distribution of ErbB2 through increasing the rigidity and decreasing the fluidity of cell membranes. Reduction in cholesterol abundance assisted the internalization and degradation of ErbB2. The cholesterol-lowering drug lovastatin significantly potentiated the inhibitory effects of ErbB2 kinase inhibitors, accompanied with enhanced ErbB2 endocytosis. Lovastatin also synergized with lapatinib to strongly suppress the in vivo growth of ErbB2-positive breast cancer xenografts. CONCLUSION: The cell surface distribution of ErbB2 was closely regulated by membrane physical properties governed by cholesterol contents. The cholesterol-lowering medications can hence be exploited for potential combinatorial therapies with ErbB2 kinase inhibitors in the clinical treatment of ErbB2-positive breast cancer.