KLRB1 expression is associated with lung adenocarcinoma prognosis and immune infiltration and regulates lung adenocarcinoma cell proliferation and metastasis through the MAPK/ERK pathway.

Background: Lung cancer is the most common primary malignant tumor of the lung, and as one of the malignant tumors that pose the greatest threat to the health of the population, the incidence rate has remained high in recent years. Previous studies have shown that KLRB1 is transcriptionally repressed in lung adenocarcinoma and correlates with lung adenocarcinoma prognosis. The objective of this study is to investigate the intrinsic mechanisms by which KLRB1 affects the malignant phenotypes of lung adenocarcinoma such as immune infiltration, proliferation, growth and metastasis. Methods: We assessed the expression levels of KLRB1 in publicly available databases and investigated its associations with clinical and pathological variables. Enrichment analysis was subsequently conducted to investigate possible signaling pathways and their associated biological functions. Statistical analysis, including Spearman correlation and the application of multigene prediction models, was utilized to assess the relationship between the expression of KLRB1 and the infiltration of immune cells. The diagnostic and prognostic value of KLRB1 was evaluated using Kaplan-Meier survival curves, diagnostic receptor operating characteristic (ROC) curves, histogram models, and Cox regression analysis. Specimens from lung adenocarcinoma (LUAD) patients were collected, the expression level of KLRB1 was detected by protein blotting analysis, and the expression level of KLRB1 was detected at the mRNA level by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR). Small interfering RNA (siRNA) was used to silence gene expression, and Transwell, Cell Counting Kit-8 (CCK-8) and colony formation assays were subsequently performed to analyze the effects of KLRB1 on LUAD cell migration, invasion and proliferation. Results: KLRB1 expression was lower in lung cancer tissue than in surrounding healthy tissue. Genes differentially expressed in the low and high KLRB1 expression groups were found to be significantly enriched in pathways related to immunity. KLRB1 exerted an impact on the MAPK/ERK signaling pathway, thereby modulating the growth and proliferation of LUAD cells. KLRB1 expression is linked to prognosis, immune infiltration, and cell migration and proliferation in LUAD. Conclusions: The evidence revealed a correlation between KLRB1 and both prognosis and immune infiltration in LUAD patients.

Single-cell landscape of undifferentiated pleomorphic sarcoma.

Undifferentiated pleomorphic sarcoma (UPS) is a highly aggressive malignant soft tissue tumor with a poor prognosis; however, the identity and heterogeneity of tumor populations remain elusive. Here, eight major cell clusters were identified through the RNA sequencing of 79,569 individual cells of UPS. UPS originates from mesenchymal stem cells (MSCs) and features undifferentiated subclusters. UPS subclusters were predicted to exist in two bulk RNA datasets, and had a prognostic value in The Cancer Genome Atlas (TCGA) dataset. The functional heterogeneity of malignant UPS cells and the immune microenvironment were characterized. Additionally, the fused cells were innovatively detected by expressing both monocyte/macrophage markers and other subcluster-associated genes. Based on the ligand-receptor interaction analysis, cellular interactions with epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) were abundant. Furthermore, 73% of patients with UPS (48/66) showed positive EGFR expression, which was associated with a poor prognosis. EGFR blockade with cetuximab inhibited tumor growth in a patient-derived xenograft model. Our transcriptomic studies delineate the landscape of UPS intratumor heterogeneity and serve as a foundational resource for further discovery and therapeutic exploration.

CDK12 loss inhibits cell proliferation by regulating TBK1 in non-small cell lung cancer cells.

Lung cancer is one of the most common malignant tumors and has a poor prognosis and a low survival rate. Traditional treatments, such as radiotherapy and chemotherapy, still face some challenges because of high drug resistance and toxicity. Therefore, it is necessary to discover a new kind of targeted drug with low toxicity and high efficiency. CDK12 is a cell cycle-dependent kinase whose main function is to activate RNA polymerase II (RNAPII) and promote the transcriptional extension of RNA. However, the role and molecular mechanism of CDK12 in lung cancer are still unclear. In this study, the mutation and RNA-Seq data of CDK12 in lung adenocarcinoma and squamous cell carcinoma were downloaded from The Cancer Genome Atlas (TCGA) database and analyzed with the custom scripts. Cell proliferation was evaluated by Cell Counting Kit-8 (CCK-8) and cell colony formation assays. A subcutaneous tumor experiment in nude mice was used to examine the effects of CDK12 knockdown on the in vivo tumor growth of NSCLC cells. The cell cycle distribution and the apoptosis rate of lung cancer cells were assessed by flow cytometry. Regulation of TANK-binding kinase 1 (TBK1) by CDK12 was evaluated by quantitative PCR, immunoprecipitation and Western blot analysis. In this study we have analyzed the mutation and expression data of The Cancer Genome Atlas (TCGA) database and found that CDK12 is highly expressed in lung cancer tissues. Clinical correlation analysis showed that high expression of CDK12 in NSCLC reduces patient survival, but its high expression is only related to early tumor progression and has no significant correlation with late tumor progression and metastasis. Furthermore, we present evidence that CDK12 depletion in lung cancer cell lines not only leads to the inhibition of cell growth and induces apoptosis but also inhibits tumor growth of NSCLC cells in vivo. CDK12 positively regulates the expression of the oncogene TBK1 in lung cancer cells. These results revealed that CDK12 affects the progression of non-small cell lung cancer through positive regulation of TBK1 expression, suggesting that CDK12 might be a potential molecular target for the treatment of non-small cell lung cancer.

Mediation Effect of Obesity on the Association of Age at Menarche With Blood Pressure Among Women in Southwest China.

Background Previous studies have been inconsistent about the association between age at menarche and high blood pressure. Little is known about such association across a wide range of menarcheal ages in less developed ethnic minority regions in China. We aimed to explore the association between age at menarche and high blood pressure (BP; ≥140/90 mm Hg) and to examine the mediating effect of obesity and the moderating effect of menopausal status on this association. Methods and Results A total of 45 868 women from the baseline data of the CMEC (China Multi-Ethnic Cohort) were included in this study. Binary logistic regression was used to analyze the relationship between age at menarche and high BP, and the mediation model was used to evaluate the mediating effects of body mass index and waist circumference on the association of age at menarche with high BP. The mean age at enrollment and age at menarche of participants in our study were 49.3 (SD=10.7) and 14.7 (SD=2.1) years, respectively. Late menarche was associated with a lower risk of high BP (odds ratio, 0.831 [95% CI, 0.728-0.950]). The risk of high BP decreased by 3.1% with each year's delay in the onset of menarche (P for trend <0.001). Body mass index and waist circumference could partially mediate the association of age at menarche and high BP with the indirect effect of body mass index (odds ratio, 0.998 [95% CI, 0.997-0.998]) and waist circumference (odds ratio, 0.999 [95% CI, 0.998-0.999]). In addition, the mediation effects were modified by the status of menopause. Conclusions Women with late menarche have a lower risk of high BP, and obesity could be one of the important mediators. Obesity prevention is an efficient strategy to reduce the association between age at menarche and high BP, especially in premenopausal women.

Structural transformation and electrochemical properties of a nanosized flower-like R-MnO2 cathode in a sodium battery.

High-energy density and low-cost sodium-ion batteries are being sought to meet increasing energy demand. Here, R-MnO2 is chosen as a cathode material of sodium-ion batteries owing to its low cost and high energy density. The structural transformation from the tunnel R-MnO2 to the layered NaMnO2 and electrochemical properties during the charge/discharge are investigated at the atomic level by combining XRD and related electrochemical experiments. Na≤0.04MnO2 has a tunnel R-MnO2 phase structure, Na≥0.42MnO2 has a layered NaMnO2 phase structure, and Na0.04-0.42MnO2 is their mixed phase. Mn3+ 3d4[t2gß3dz2(1)3dx2-y2(0)] in NaMnO2 loses one 3dz2 electron and the redox couple Mn3+/Mn4+ delivers 206 mA h g-1 during the initial charge. The case that the Fermi energy level difference between R-MnO2 and NaMnO2 is lower than that between the layered Na(12-x)/12MnO2 and NaMnO2 makes the potential plateau of R-MnO2 turning into NaMnO2 lower than that of the layered Na(12-x)/12MnO2 to NaMnO2. This can be confirmed by our experiment from the 1st-2nd voltage capacity profile of R-MnO2 in EC/PC (ethylene carbonate/propylene carbonate) electrolyte. The study would give a new view of the production of sustainable sodium battery cathode materials.

DYNC1H1 regulates NSCLC cell growth and metastasis by IFN-γ-JAK-STAT signaling and is associated with an aberrant immune response.

It is urgent to identify new biomarkers and therapeutic targets to ameliorate the clinical prognosis of patients with lung cancer. The functional significance and molecular mechanism of dynein cytoplasmic 1 heavy chain 1 (DYNC1H1) in nonsmall cell lung cancer (NSCLC) progression is still elusive. In our current study, publicly available data and Western blotting experiments confirmed that DYNC1H1 expression was upregulated in lung cancer samples compared with noncancerous samples. Quantitative real-time PCR (qPCR) results indicated that high DYNC1H1 expression in lung cancer tissues was significantly associated with clinical tumor stage and distal metastasis; moreover, its high expression was negatively correlated with prognosis. Functional experiments demonstrated that DYNC1H1 loss of function caused a significant decrease in cell viability and cell proliferative ability, inhibition of the cell cycle, and promotion of both migration potential and invasion potential in vitro. Animal experiments by tail vein injection of lung cancer cells showed that DYNC1H1 knockdown significantly decreased lung cancer metastasis. Mechanistically, the results from a human protein array showed changes in the IFN-γ-JAK-STAT signaling pathway, and analysis of The Cancer Genome Atlas (TCGA) immune data demonstrated that disturbance of the immune microenvironment might be involved in the impaired growth and metastatic ability mediated by DYNC1H1 loss in NSCLC. DYNC1H1 might serve as a promising biological marker of prognosis and a potential clinical therapeutic target for patients with NSCLC.

Cr-Doped Fe1-xCrxF3·0.33H2O Nanomaterials as Cathode Materials for Sodium-Ion Batteries.

Due to the high theoretical specific capacity and low cost, FeF3·0.33H2O has become one of the potential choices of cathode materials for sodium-ion batteries. However, the poor intrinsic conductivity limits its practical applications. Herein, the atomic substitution is used to improve its intrinsic conductivity. The first-principles calculation results show that Cr3+ doping can reduce the band gap of FeF3·0.33H2O to improve its intrinsic conductivity. The discharge specific capacity of Fe0.95Cr0.05F3·0.33H2O with a narrowest band gap is 194.02 mA h/g at 0.1 C within the range of 1.4-4.0 V, which is higher than that of FeF3·0.33H2O (136.47 mA h/g). Using the electrochemical impedance spectroscopy and galvanostatic intermittent titration technique tests, it is found that Rct of Fe0.95Cr0.05F3·0.33H2O is reduced and DNa+ is almost unchanged, as compared to FeF3·0.33H2O.

Depression and Deliberate Self-Harm Among Rural Adolescents of Sichuan Province in Western China: A 2-Year Longitudinal Study.

Objective: To explore the change in the prevalence and association of depression and deliberate self-harm and their common and independent influencing factors among western Chinese rural adolescents. Methods: A total of 2,744 junior and senior high school students from two rural schools in Sichuan Province, China, participated in the baseline survey and were invited to participate in two follow-up surveys. The Center for Epidemiologic Studies-Depression Scale, a deliberate self-harm item, the Social Support Rating Scale, the Rosenberg Self-esteem Scale and the Connor-Davidson Resilience Scale were administered. A bivariate four-level logistic regression model was used for analysis. Results: The prevalence of depression and deliberate self-harm were 39.6 and 21.2%, respectively. Regular physical exercise, a good relationship with parents, high resilience, and high self-esteem were common protective factors for both depression and deliberate self-harm. Feeling disliked by teachers was a common risk factor for both. Being female, having a mother who emigrated as a migrant worker before the student was 3 years old, feeling disliked by classmates and having a poor family economic status were associated only with an increased risk of depression. Participants with medium social support were less likely to report deliberate self-harm than those with low or high support. Depression and deliberate self-harm were clustered at the class level. Conclusions: The comorbidity of depression and deliberate self-harm in rural adolescents should be given ample attention. Interventions should consider the class clustering of depression and deliberate self-harm and their common and unique influencing factors.

Application of the health action process approach model for reducing excessive internet use behaviors among rural adolescents in China: a school-based intervention pilot study.

OBJECTIVE: There are few studies regarding Internet use behaviors of Chinese rural adolescents based on behavioral theory. The aim of this study is to examine the applicability and effectiveness of the health action process approach model (HAPA) in the intervention of excessive Internet use behaviors among rural adolescents in China. METHODS: Three hundred twenty-seven participants who met the excessive Internet use criteria were involved in this study. Four interventions based on the HAPA model were conducted during 2015-2017. The structural equation model (SEM) was applied to fit the HAPA model. RESULTS: The rate of average daily time spent online on weekends more than 4 h dropped from 57.2 to 39.1% (P < 0.001). The rate of daily game time more than 2 h decreased from 51.1 to 35.2% (P < 0.001). The result of SEM showed that both the applicability and effectiveness of the HAPA model were well in the intervention of excessive Internet use behaviors with good fitted indicators (χ2/df = 2.066, GFI = 0.889, CFI = 0.938, TLI = 0.928, IFI = 0.938, RMSEA = 0.057). The direct and indirect effects of the main pathways in the HAPA model were statistically significant (P < 0.05). The comparison analysis of HAPA model variables identified that outcome expectancy, intention, maintenance self-efficacy had been improved significantly after interventions. CONCLUSION: The intervention measures based on the HAPA model can effectively reduce excessive Internet use behaviors of Chinese rural adolescents, mainly through strengthen outcome expectancy, intention, and maintenance self-efficacy.

Regulating the Solvation Structure of Nonflammable Electrolyte for Dendrite-Free Li-Metal Batteries.

High-energy-density Li-metal batteries are of great significance in the energy storage field. However, the safety hazards caused by Li dendrite growth and flammable organic electrolytes significantly hinder the widespread application of Li-metal batteries. In this work, we report a highly safe electrolyte composed of 4 M lithium bis(fluorosulfonyl)imide (LiFSI) dissolved in the single solvent trimethyl phosphate (TMP). By regulating the solvation structure of the electrolyte, a combination of nonflammability and Li dendrite growth suppression was successfully realized. Both Raman spectroscopy and molecular dynamics simulations revealed improved dendrite-free Li anode originating from the unique solvation structure of the electrolyte. Symmetric Li/Li cells fabricated using this nonflammable electrolyte had a long cycle life of up to 1000 h at a current density of 0.5 mA cm-2. Furthermore, the Li4Ti5O12/TMP-4/Li full cells also exhibited excellent cycling performance with a high initial discharge capacity of 170.5 mAh g-1 and a capacity retention of 92.7% after 200 cycles at 0.2 C. This work provides an effective approach for the design of safe electrolytes with favorable solvation structure toward the large-scale application of Li-metal batteries.

Research in physical exercise among rural adolescents based on the theory of planned behavior in Sichuan Province / 中国学校卫生

Objective@#To verify the applicability of the theory of planned behavior(TPB) in the physical exercise behaviors of rural adolescents in Sichuan Province, and to explore the possible influencing factors of physical exercise behaviors, and to provide a theoretical basis for further effective intervention measures.@*Methods@#A total of 2 302 students were selected from grade seven and grade ten of two rural middle schools in Zizhong, Sichuan Province. The survey was conducted with a structured questionnaire. Using TPB as the research framework and basis, the structural equation model was constructed for analysis.@*Results@#Lack of physical exercise was 1 527(66.3%).Physical exercise behavior was statistically different among schools, grades(t=-7.40，-2.90，10.90,P<0.05)， and genders. Based on TPB, the structural equation model was established and corrected to obtain the revised model, and the fitting index GFI=0.93, CFI=0.94, NFI=0.94, TLI=0.93, IFI=0.94,RMSEA=0.07, indicating the model fitted good. Exercise intention directly affected exercise behaviors. The standardized effect was 0.45(95%CI=0.39-0.52). Subjective norms and perceived power were the main two mediators of the relationship between value evaluation and exercise intention. The standardized effect values were 0.66(95%CI=0.57-0.73), 0.23(95%CI=0.16-0.93)(P<0.01).@*Conclusion@#There is serious lack of physical exercise in rural adolescents in Sichuan Province. TPB has a good applicability for physical exercise in rural adolescents in Sichuan Province. Subjective norm is the most important factors to promote exercise intentions.

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.

Biodegradable Bacterial Cellulose-Supported Quasi-Solid Electrolyte for Lithium Batteries.

The stringent safety and sustainability requirements for electrolytes used in lithium batteries have led to significant research efforts into alternative materials. Here, a quasi-solid electrolyte based on biodegradable bacterial cellulose (BC) was successfully synthesized via a simple ball milling method. The BC provides plenty of sites for the attachment of ionic liquid electrolytes (ILEs) as well as ion transport channels. Moreover, the O-H groups contained in the BC molecular chains interact with anions in ILEs to form hydrogen bonds, which promotes the dissociation of the lithium salts. The prepared electrolytes (BC-ILEs) have good thermal stability with a decomposition temperature exceeding 300 °C and high ionic conductivities. The Li/BC-ILE/LiFePO4 battery exhibits remarkable electrochemical performance. More importantly, the results of the Fehling test verify that the electrolyte can be degraded by cellulase. The quasi-solid electrolyte broadens the range of electrolytes for lithium batteries and provides new avenues to explore safe and eco-friendly materials.

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.

LncRNA FENDRR-mediated tumor suppression and tumor-immune microenvironment changes in non-small cell lung cancer.

BACKGROUND: Long noncoding RNAs (lncRNAs) play a key role in the development and progression of many cancer types, including lung cancer. The objective of this study is to examine the function and molecular mechanism of lncRNAs involved in non-small cell lung cancer (NSCLC). METHODS: First, 7 lung cancer-related differentially expressed LncRNAs were screened from 2 genomic profiling datasets. Of these lncRNAs, FOXF1 adjacent noncoding developmental regulatory RNA (FENDRR) was found to be the only one that was both significantly down-regulated in the patients with advanced pathology and negatively correlated with prognosis. Thus, lncRNA FENDRR was further studied in this project. Clinical correlation analysis was further conducted in the GSE30219 dataset and 73 paired lung cancer and noncancerous tissues stored in our lab; Subsequently, we evaluated FENDRR coding potential with the Phylogenetic Codon Substitution Frequencies (PhyloCSF), Coding-Potential Assessment Tool (CPAT), and Coding Potential Calculator (CPC) online analytical tool. The cell growth ability was measured by CCK8 assay and clonogenicity assay, the metastatic capacities were evaluated using Transwell migration and invasion assays. Mechanistically, we analyzed the correlation of FENDRR function in NSCLC with immune response by utilizing The Cancer Genome Atlas (TCGA) data. RESULTS: Results indicated a negative clinical correlation of FENDRR. Coding potential analysis showed FENDRR as a noncoding RNA. Elevated expression of FENDRR led to cell growth arrest, inhibition of proliferative ability, declined migration and invasion potential of NSCLC cells in vitro. Mechanistically, we discovered that FENDRR expression might be involved in aberrant immune response regulation. CONCLUSIONS: Taken together, our results provide a greater understanding of lncRNA FENDRR as a tumor suppressor with respect to tumor-immune interactions in NSCLC.

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.

Flexible Hydrogel Electrolyte with Superior Mechanical Properties Based on Poly(vinyl alcohol) and Bacterial Cellulose for the Solid-State Zinc-Air Batteries.

Flexible solid-state zinc-air batteries are promising energy technologies with low cost, superior performance and safety. However, flexible electrolytes are severely limited by their poor mechanical properties. Here, we introduce flexible bacterial cellulose (BC)/poly(vinyl alcohol) (PVA) composite hydrogel electrolytes (BPCE) based on bacterial cellulose (BC) microfibers and poly(vinyl alcohol) (PVA) by an in situ synthesis. Originating from the hydrogen bonds among BC microfibers and PVA matrix, these composites form load-bearing percolating dual network and their mechanical strength is increased 9 times (from 0.102 MPa of pristine PVA to 0.951 MPa of 6-BPCE). 6-BPCE shows extremely high ionic conductivities (80.8 mS cm-1). In addition, the solid-state zinc-air batteries can stably cycle over 440 h without large discharge and charge polarizations equipped with zinc anode and Co3O4@Ni cathode. Moreover, flexible solid-state zinc-air batteries can cycle well at any bending angle. As flexible electrolytes, they open up a new opportunity for the development of superior-performance, flexible, rechargeable, zinc-air batteries.

OTUB2 stabilizes U2AF2 to promote the Warburg effect and tumorigenesis via the AKT/mTOR signaling pathway in non-small cell lung cancer.

Increasing evidence has confirmed that deubiquitinating enzymes play an important role in lung cancer progression. In the current study, we investigated the expression profile of deubiquitinating enzymes in non-small cell lung cancer (NSCLC) tissues and identified OTUB2 as an upregulated deubiquitinating enzyme. The role of OTUB2 in NSCLC is unknown. Methods: Quantitative, real-time PCR and Western blot were used to detect OTUB2 and U2AF2 expression in NSCLC tissues. The correlations between OTUB2 and U2AF2 expression and clinicopathologic features were then analyzed. We used In vitro Cell Counting Kit-8 (CCK-8) , colony formation , and trans-well invasion assays to investigate the function of OTUB2 and U2AF2 in tumorigenesis. The regulation of glycolysis by OTUB2 and U2AF2 was assessed by determining the extracellular acid ratio, glucose consumption, and lactate production. The mechanism of OTUB2 was explored through co-immunoprecipitation and mass spectrometry analyses. A xenograft model was also used to study the tumorigenesis role of OTUB2 In vivo. Results: OTUB2 expression was significantly upregulated in primary NSCLC tissues and greatly associated with metastasis, advanced tumor stages, poor survival, and recurrence. In NSCLC cell lines, OTUB2 promoted cell growth, colony formation, migration, and invasive activities. Mechanistic investigations showed that OTUB2 stimulated the Warburg effect and induced the activation of the serine/threonine kinase/mechanistic target of rapamycin kinase (AKT/mTOR) pathway in different NSCLC cells. More importantly, OTUB2 promoted NSCLC progression, which was largely dependent on the direct binding to and deubiquitination of U2AF2, at least in NSCLC cells. U2AF2 expression was also significantly upregulated in primary NSCLC tissues and dramatically associated with metastasis, advanced tumor stages, poor survival, and recurrence. Importantly, a positive correlation between the protein expression of OTUB2 and U2AF2 in NSCLC tissues was found. In vivo experiments indicated that OTUB2 promoted xenograft tumor growth of NSCLC cell. In addition, our results suggest that high expression of OTUB2, U2AF2 and PGK1 is significantly associated with worse prognosis in NSCLC patients. Conclusion: Taken together, the present study provides the first evidence that OTUB2 acts as a pivotal driver in NSCLC tumorigenesis by stabilizing U2AF2 and activating the AKT/mTOR pathway and the Warburg effect. It may serve as a new potential prognostic indicator and therapeutic target in NSCLC.

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.