LncRNA DGUOK-AS1 Promotes Cell Progression in Lung Squamous Cell Carcinoma by Regulation of miR-653-5p/SLC6A15 Axis.

Long noncoding RNA (lncRNA) plays a key role in regulating cancer development. LncRNA deoxyguanosine kinase antisense RNA 1 (DGUOK-AS1) has been reported as a promoter in tumor. The work was designed to further investigate the mechanism of action of DGUOK-AS1 in lung squamous cell carcinoma (LUSC). DGUOK-AS1 level in LUSC cells was measured using RT-qPCR. Counting Kit-8 assays and colony forming assays were performed to evaluate LUSC cell viability and proliferation. Transwell assays were performed to detect cell migration and invasion. Luciferase reporter and RNA pulldown assays were used to verify the binding capacity of DGUOK-AS1 and miR-653-5p. RNA immunoprecipitation assays were performed to verify the relationship of DGUOK-AS1, miR-653-5p, and SLC6A15. DGUOK-AS1 was highly expressed in LUSC cells. DGUOK-AS1 knockdown suppressed LUSC cell proliferation, migration, and invasion. SLC6A15 was demonstrated to be targeted by miR-653-5p, and DGUOK-AS1 interacted with miR-653-5p to modulate SLC6A15 level in LUSC cells. Overexpression of SLC6A15 reversed the suppressive effects of DGUOK-AS1 knockdown on LUSC cell processes. In conclusion, DGUOK-AS1 promotes malignant behaviors of LUSC cells by upregulating SLC6A15 level through interaction with miR-653-5p.

GRELinker: A Graph-Based Generative Model for Molecular Linker Design with Reinforcement and Curriculum Learning.

Fragment-based drug discovery (FBDD) is widely used in drug design. One useful strategy in FBDD is designing linkers for linking fragments to optimize their molecular properties. In the current study, we present a novel generative fragment linking model, GRELinker, which utilizes a gated-graph neural network combined with reinforcement and curriculum learning to generate molecules with desirable attributes. The model has been shown to be efficient in multiple tasks, including controlling log P, optimizing synthesizability or predicted bioactivity of compounds, and generating molecules with high 3D similarity but low 2D similarity to the lead compound. Specifically, our model outperforms the previously reported reinforcement learning (RL) built-in method DRlinker on these benchmark tasks. Moreover, GRELinker has been successfully used in an actual FBDD case to generate optimized molecules with enhanced affinities by employing the docking score as the scoring function in RL. Besides, the implementation of curriculum learning in our framework enables the generation of structurally complex linkers more efficiently. These results demonstrate the benefits and feasibility of GRELinker in linker design for molecular optimization and drug discovery.

Comparison between thoracic low-dose computed tomography and conventional-dose computed tomography in evaluating anemia: A preliminary study in a Chinese screening cohort.

Purpose: To investigate and evaluate the value of thoracic low dose computed tomography (LDCT) scan in the diagnosis of anemia. Materials and methods: 661 patients who received thoracic computed tomography (CT) examination and underwent a peripheral blood examination were retrospectively included. 341 patients underwent conventional dose CT (CDCT), and 320 patients underwent LDCT. Regions of interest (ROI) were placed on the left ventricular cavity (LV), descending aorta (DAo), and interventricular septum (IVS). The corresponding CT attenuation was measured, and the CT attenuation difference between LV and IVS (IVS-LV) and between DAo and IVS (IVS-DAo) was calculated, respectively. One-way analysis of variance (ANOVA) and linear regression were performed to analyze the relationship between these indicators and Hb levels. The receiver operating characteristic (ROC) curve was used to evaluate prediction performance. Results: Both attenuation on LDCT and CDCT showed significant differences between the healthy group and the anemic group (P < 0.05). In the LDCT group, the LV and DAo were more relevant with the hemoglobin (Hb) level (correlation coefficient 0.618 and 0.602) than other indicators, with AUCs of 0.815 (95% CI: 0.763-0.868) and 0.803 (95% CI: 0.747-0.859), respectively. The linear regression formulas for Hb level with the LV and DAo were 19.14 + 0.15 × HU [95% CI: (16.52, 21.75) + (0.12, 0.17) × HU] and 19.46 + 0.16 × HU [95% CI: (16.55, 22.36) + (0.13, 0.18) × HU], respectively. Youden's index indicated that 37.5 HU and 38.5 HU were the best thresholds to diagnose anemia for LV and DAo, respectively. In the CDCT group, the LV and IVS-LV got obviously higher correlation coefficients (0.813 and 0.812), with AUCs of 0.831 (95% CI: 0.786-0.877) and 0.851 (95% CI: 0.808-0.894), respectively. The optimal thresholds for LV and IVS-LV were 40.5 HU and 9.5 HU, respectively. Conclusion: In LDCT examinations, an approximation of Hb level and detecting of anemia can be conducted based on simple attenuation measurements.

The Indicative Value of Serum Tumor Markers for Metastasis and Stage of Non-Small Cell Lung Cancer.

Objective: This study aimed to explore the roles of serum tumor markers for metastasis and stage of non-small cell lung cancer (NSCLC). Methods: This study recruited 3272 NSCLC patients admitted to the Tianjin Union Medical Center and the Tianjin Medical University Cancer Institute and Hospital. The predictive abilities of some serum tumor markers (carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC-Ag), cytokeratin-19 fragment (CYFRA 21-1), neuron-specific enolase (NSE), pro-gastrin-releasing peptide (ProGRP), total prostate-specific antigen (TPSA) and carbohydrate antigen 199 (CA199)) for NSCLC metastasis (intrapulmonary, lymphatic and distant metastasis) and clinical stage were analyzed. Results: Tumor markers exhibited different numerical and proportional distributions in NSCLC patients. Elevated CEA, CYFRA 21-1 and CA199 levels were indicative of tumor metastasis and stage. Increased CEA and CA199 provided an accurate prediction of intrapulmonary and distant metastasis with the area under the receiver operator characteristic curve (AUC) of 0.69 both (p < 0.001); Increased CEA, CYFRA 21-1 and CA199 provided an accurate prediction of lymphatic metastasis with the AUC of 0.62 (p < 0.001). Conclusion: Combined detection of serum tumor markers can indicate tumor metastasis and stage in NSCLC patients.

The advent of membrane-less zinc-anode aqueous batteries with lithium battery-like voltage.

Zinc (Zn)-anode batteries, although safe and non-flammable, are precluded from promising applications because of their low voltage (<2 V) and poor rechargeability. Here, we report the fabrication of rechargeable membrane-less Zn-anode batteries with high voltage properties (2.5 to 3.4 V) achieved through coupling cathodes and Zn-anodes in gelled concentrated acid and alkaline solutions separated by a gelled buffer interlayer containing the working ions. The concentrated gelled buffer interlayers perform dual functions of regulating the pH of the system and acting as the source and sink of the working ions. With this strategy we show low-cost membrane-less 2.5 to 3.4 V Zn-manganese dioxide (MnO2) batteries capable of cycling 10-100% of 617 mA h g-1-MnO2 and 20-30% of 820 mA h g-1-Zn and demonstrate their application in electric vehicles. This strategy is then applied to other oxide-based cathode systems like Cu2O and V2O5, where voltages of 2 to 3 V are obtained in membrane-less batteries.

Hydroxyl Conducting Hydrogels Enable Low-Maintenance Commercially Sized Rechargeable Zn-MnO2 Batteries for Use in Solar Microgrids.

Zinc (Zn)-manganese dioxide (MnO2) rechargeable batteries have attracted research interest because of high specific theoretical capacity as well as being environmentally friendly, intrinsically safe and low-cost. Liquid electrolytes, such as potassium hydroxide, are historically used in these batteries; however, many failure mechanisms of the Zn-MnO2 battery chemistry result from the use of liquid electrolytes, including the formation of electrochemically inert phases such as hetaerolite (ZnMn2O4) and the promotion of shape change of the Zn electrode. This manuscript reports on the fundamental and commercial results of gel electrolytes for use in rechargeable Zn-MnO2 batteries as an alternative to liquid electrolytes. The manuscript also reports on novel properties of the gelled electrolyte such as limiting the overdischarge of Zn anodes, which is a problem in liquid electrolyte, and finally its use in solar microgrid applications, which is a first in academic literature. Potentiostatic and galvanostatic tests with the optimized gel electrolyte showed higher capacity retention compared to the tests with the liquid electrolyte, suggesting that gel electrolyte helps reduce Mn3+ dissolution and zincate ion migration from the Zn anode, improving reversibility. Cycling tests for commercially sized prismatic cells showed the gel electrolyte had exceptional cycle life, showing 100% capacity retention for >700 cycles at 9.5 Ah and for >300 cycles at 19 Ah, while the 19 Ah prismatic cell with a liquid electrolyte showed discharge capacity degradation at 100th cycle. We also performed overdischarge protection tests, in which a commercialized prismatic cell with the gel electrolyte was discharged to 0 V and achieved stable discharge capacities, while the liquid electrolyte cell showed discharge capacity fade in the first few cycles. Finally, the gel electrolyte batteries were tested under IEC solar off-grid protocol. It was noted that the gelled Zn-MnO2 batteries outperformed the Pb-acid batteries. Additionally, a designed system nameplated at 2 kWh with a 12 V system with 72 prismatic cells was tested with the same protocol, and it has entered its third year of cycling. This suggests that Zn-MnO2 rechargeable batteries with the gel electrolyte will be an ideal candidate for solar microgrid systems and grid storage in general.

Zincate-Blocking-Functionalized Polysulfone Separators for Secondary Zn-MnO2 Batteries.

Alkaline zinc-manganese dioxide (Zn-MnO2) batteries are well suited for grid storage applications because of their inherently safe, aqueous electrolyte and established materials supply chain, resulting in low production costs. With recent advances in the development of Cu/Bi-stabilized birnessite cathodes capable of the full 2-electron capacity equivalent of MnO2 (617 mA h/g), there is a need for selective separators that prevent zincate (Zn(OH)4)2- transport from the anode to the cathode during cycling, as this electrode system fails in the presence of dissolved zinc. Herein, we present the synthesis of N-butylimidazolium-functionalized polysulfone (NBI-PSU)-based separators and evaluate their ability to selectively transport hydroxide over zincate. We then examine their impact on the cycling of high depth of discharge Zn/(Cu/Bi-MnO2) batteries when inserted in between the cathode and anode. Initially, we establish our membranes' selectivity by performing zincate and hydroxide diffusion tests, showing a marked improvement in zincate-blocking (DZn (cm2/min): 0.17 ± 0.04 × 10-6 for 50-PSU, our most selective separator vs 2.0 ± 0.8 × 10-6 for Cellophane 350P00 and 5.7 ± 0.8 × 10-6 for Celgard 3501), while maintaining similar crossover rates for hydroxide (DOH (cm2/min): 9.4 ± 0.1 × 10-6 for 50-PSU vs 17 ± 0.5 × 10-6 for Cellophane 350P00 and 6.7 ± 0.6 × 10-6 for Celgard 3501). We then implement our membranes into cells and observe an improvement in cycle life over control cells containing only the commercial separators (cell lifetime extended from 21 to 79 cycles).

CD4/CD8 + T cells, DC subsets, Foxp3, and IDO expression are predictive indictors of gastric cancer prognosis.

BACKGROUND: The tumor microenvironment represents an abnormal niche containing numerous factors, such as T cells, dendritic cells (DCs), regulatory T cells (Tregs), and indoleamine 2,3-dioxygenase (IDO), involved in maintaining immune homeostasis and tolerance. All these factors may influence the choice of therapy and the clinical outcomes. METHODS: Flow cytometry was performed to identify CD4+/CD8 + T cells and DCs, and immunohistochemistry was used to evaluate IDO and Forkhead Box P3 (Foxp3) expression; these experiments were performed in order to explore the clinical and prognostic significance of CD4/CD8 + T cells, DCs, Tregs, and IDO expression in gastric carcinoma. RESULTS: Smaller tumor size was correlated with higher expression levels of peripheral CD4 + T cells (P = .003) and CD8 + T cells (P = .002), and lower IDO expression (P = .044) in tumors. Well-differentiated gastric carcinomas displayed higher peripheral (P = .029) and tumor-infiltrating CD4 + T cell (P = .009) populations and a higher tumor-infiltrating DC1/DC2 ratio (P = .048). Gastric cancer in the early T stages exhibited higher populations of peripheral DC2s (P = .044) and a higher tumor-infiltrating DC1/DC2 ratio (P = .012). Gastric cancer at the N0 stage had lower tumor-infiltrating DC2s (P = .032) and a higher DC1/DC2 ratio (P = .037). IDO expression was positively correlated with tumor-infiltrating Foxp3 + Tregs (P < .001) as well as DC2s (P < .001), whereas it was negatively correlated with the tumor-infiltrating CD4/CD8 + T cell ratio (P = .023). Tumor-infiltrating Foxp3 + Treg was positively correlated with tumor-infiltrating DC2s (r2  = 0.772; P < .001). At T, N, and TNM stages, the expression levels of peripheral DC2s, tumor-infiltrating DC1/DC2 ratios, Foxp3 + Tregs, and IDO were significantly correlated with prognosis (P < .05). The T stage and peripheral DC2s were significant risk factors for overall survival. CONCLUSION: Immunocompetent cells and humoral immune factors, including DC2s, CD4+/CD8 + T cells, Foxp3 + Tregs, and IDO, interact with each other to compose a complex community of tumor immune microenvironment, ultimately affecting tumor progression and survival of gastric cancer.

Multivariate analysis of clinicopathological and prognostic significance of miRNA 106b~25 cluster in gastric cancer.

BACKGROUND: miRNA 106b~25 cluster were demonstrated to be an oncogene. In previous study, we had analyzed the diagnostic significance of miRNA 106b~25 based on its carcinogenesis effect. The significance of miRNA 106b~25 for prognosis of gastric cancer were not researched. METHODS: We applied multivariate analysis of PCA, PLS-DA and Cox Regression for clinicopathological features and survival time to explore the significance of miRNA 106b~25 expression in plasma and cancer tissues for gastric cancer. RESULTS: The expression of miRNA 106b, miRNA 93 and miRNA 25 in plasma were positively correlated with their expression in tumor tissues. Via PCA analysis, it was found that miRNA 106b~25 expression in plasma and tumor, T, N and TNM stage were correlated with each other. Via PLS-DA analysis, we identified that T, N and TNM stage were important factors for miRNA 106b~25 expression both in plasma and tumor (all VIP value > 1.2). According to loading weights of variables for the first and second components, it was found that the importance of the miRNA 106b~25s expression carried with the progressed stage of gastric cancer. In the survival analysis, COX regression showed that T stage, plasma miRNA 106b and tumor miRNA 93 were significant risk factors for overall survival [HR: 0.400 (0.205-0.780); P = 0.007; HR: 0.371 (0.142-0.969), P = 0.043; 0.295 (0.134-0.650), P = 0.002]. CONCLUSION: Plasma and tumor miRNA 106b~25 expression correlated with T, N and TNM stage. Increased miRNA 106b~25 expression was important characters carried with gastric cancer progression. T stage, plasma miRNA106b and tumor miRNA 93 significant risk factors for overall survival.

Regenerable Cu-intercalated MnO2 layered cathode for highly cyclable energy dense batteries.

Manganese dioxide cathodes are inexpensive and have high theoretical capacity (based on two electrons) of 617 mAh g-1, making them attractive for low-cost, energy-dense batteries. They are used in non-rechargeable batteries with anodes like zinc. Only ∼10% of the theoretical capacity is currently accessible in rechargeable alkaline systems. Attempts to access the full capacity using additives have been unsuccessful. We report a class of Bi-birnessite (a layered manganese oxide polymorph mixed with bismuth oxide (Bi2O3)) cathodes intercalated with Cu2+ that deliver near-full two-electron capacity reversibly for >6,000 cycles. The key to rechargeability lies in exploiting the redox potentials of Cu to reversibly intercalate into the Bi-birnessite-layered structure during its dissolution and precipitation process for stabilizing and enhancing its charge transfer characteristics. This process holds promise for other applications like catalysis and intercalation of metal ions into layered structures. A large prismatic rechargeable Zn-birnessite cell delivering ∼140 Wh l-1 is shown.

The subsets of dendritic cells and memory T cells correspond to indoleamine 2,3-dioxygenase in stomach tumor microenvironment.

The abnormal distributions of memory T cells (Tm) and dendritic cells (DC) in stomach cancer are not well understood. Indoleamine 2,3-dioxygenase (IDO), produced by DC, may be an important enzyme affecting function and proliferation of Tm. In this study, IDO expression was examined by immunohistochemical staining. The subsets of Tm and DC were counted by flow cytometry. The percentages of CD4 + Tm and CD4 + central Tm (Tcm) were lower in tumor tissues than in normal tissues (P < 0.05), while the CD4 + effector Tm (Tem) and CD8 + Tem percentages were higher in tumor tissues (P < 0.05). The ratio of myeloid DC (DC1)/plasmacytoid DC (DC2) was significantly lower in tumor tissues (P = 0.009). The high expression of IDO was more frequently observed in tumor tissues (P = 0.001). The percentages of CD4 + Tm and CD8 + Tm were positively associated with DC1 percentage and ratio of DC1/DC2 (P < 0.05). The higher CD8 + Tcm percentage was associated with higher DC2 percentage (P = 0.025). The patients with high IDO expression had significantly lower CD4 + Tm (P = 0.012) and CD8 + Tm percentages (P = 0.033), but higher CD8 + Tem percentage (P < 0.01). Concerning on clinicopathologic features, the higher DC2 percentage was associated with larger tumor size (P = 0.019). The CD4 + Tm and CD8 + Tem percentages were significantly associated with clinical stage and lymph node metastasis; the high IDO expressions were significantly associated with deeper tumor invasion (P = 0.016) and lymph node metastasis (P = 0.038). Thus, DC subsets, Tm subsets, and IDO expression were correlated with each other. They were associated with the established clinicopathologic features, such as tumor size, depth of invasion, lymph node metastasis, and clinical stage.