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Abstract Background Accumulating evidence indicates that circular RNAs (circRNAs) act as microRNA (miRNA) sponges to directly inhibit specific miRNAs and alter their ability to regulate gene expression at the post-transcriptional level; this mechanism is believed to occur in various cancers. However, the expression level, precise function and mechanism of circ_001680 in colorectal carcinoma (CRC) are largely unknown. Methods qRT-PCR was used to detect the expression of circ_001680 and miR-340 in human CRC tissues and their matched normal tissues. Bioinformatics analyses and dual-fluorescence reporter assays were used to evaluate whether circ_001680 could bind to miR-340. Circ_001680 overexpression and knockdown cell lines were constructed to investigate the proliferation and migration abilities in vivo and in vitro through function-based experiments, including CCK8, plate clone formation, transwell, and wounding healing assays. The relationships among circ_001680, miR-340 and BMI1 were investigated by bioinformatics analyses, dual-fluorescence reporter system, FISH, RIP and RNA pull down assays. Sphere forming assays and flow cytometry analyses were used to assess the effect of circ_001680 on the stemness characteristics of CRC cells. Results Circ_001680 was more highly expressed in of CRC tissue than in matched adjacent normal tissues from the same patients. Circ_001680 was observed to enhance the proliferation and migration capacity of CRC cells. Furthermore, dual-fluorescence reporter assays confirmed that circ_001680 affects the expression of BMI1 by targeting miR-340. More importantly, we also found that circ_001680 could promote the cancer stem cell (CSC) population in CRC and induce irinotecan therapeutic resistance by regulating the miR-340 target gene BMI1. Conclusions Our results demonstrated that circ_001680 is a part of a novel strategy to induce chemotherapy resistance in CRC through BMI1 upregulation. Moreover, circ_001680 may be a promising diagnostic and prognostic marker to determine the success of irinotecan-based chemotherapy.

Abstract Background Aberrant activation of Wnt/β-catenin signaling pathway is considered to be an important issue in progression and metastasis of various human cancers, especially in colorectal cancer (CRC). MiR-452 could activate of Wnt/β-catenin signaling. But the mechanism remains unclear. Methods The expression of miR-452 in CRC and normal tissues was detected by real-time quantitative PCR. The effect of miR-452 on CRC growth and invasion was conducted by functional experiments in vitro and in vivo. Bioinformatics and cell luciferase function studies verified the direct regulation of miR-452 on the 3’-UTR of the GSK3β, which leads to the activation of Wnt/β-catenin signaling. Results MiR-452 was upregulated in CRC compared with normal tissues and was correlated with clinical significance. The luciferase reporter system studies affirmed the direct regulation of miR-452 on the 3’-UTR of the GSK3β, which activate the Wnt/β-catenin signaling. The ectopic upregulation of miR-452 significantly inhibited the expression of GSK3β and enhanced CRC proliferation and invasion in vitro and in vivo. Meanwhile, knockdown of miR-452 significantly recovered the expression of GSK3β and attenuated Wnt/β-catenin-mediated cell metastasis and proliferation. More important, T-cell factor/lymphoid enhancer factor (TCF/LEF) family of transcription factors, which are crucial downstream molecules of the Wnt/β-catenin signaling pathway was verified as a valid transcription factor of miR-452’s promoter. Conclusions Our findings first demonstrate that miR-452-GSK3β-LEF1/TCF4 positive feedback loop induce CRC proliferation and migration.

Abstract Arising from the extreme/saddle point in electronic bands, Van Hove singularity (VHS) manifests divergent density of states (DOS) and induces various new states of matter such as unconventional superconductivity. VHS is believed to exist in one and two dimensions, but rarely found in three dimension (3D). Here, we report the discovery of 3D VHS in a topological magnet EuCd2As2 by magneto-infrared spectroscopy. External magnetic fields effectively control the exchange interaction in EuCd2As2, and shift 3D Weyl bands continuously, leading to the modification of Fermi velocity and energy dispersion. Above the critical field, the 3D VHS forms and is evidenced by the abrupt emergence of inter-band transitions, which can be quantitatively described by the minimal model of Weyl semimetals. Three additional optical transitions are further predicted theoretically and verified in magneto-near-infrared spectra. Our results pave the way to exploring VHS in 3D systems and uncovering the coordination between electronic correlation and the topological phase.

Abstract Blank holder force (BHF) is a crucial parameter in deep drawing, having close relation with the forming quality of sheet metal. However, there are different BHFs maintaining the best forming effect in different stages of deep drawing. The variable blank holder force (VBHF) varying with the drawing stage can overcome this problem at an extent. The optimization of VBHF is to determine the optimal BHF in every deep drawing stage. In this paper, a new heuristic optimization algorithm named Jaya is introduced to solve the optimization efficiently. An improved “Quasi-oppositional” strategy is added to Jaya algorithm for improving population diversity. Meanwhile, an innovated stop criterion is added for better convergence. Firstly, the quality evaluation criteria for wrinkling and tearing are built. Secondly, the Kriging models are developed to approximate and quantify the relation between VBHF and forming defects under random sampling. Finally, the optimization models are established and solved by the improved QO-Jaya algorithm. A VBHF optimization example of component with complicated shape and thin wall is studied to prove the effectiveness of the improved Jaya algorithm. The optimization results are compared with that obtained by other algorithms based on the TOPSIS method.

Abstract Background Fragile X syndrome (FXS) is a leading cause of autism spectrum disorder (ASD) and resulted from a loss of the FMR1-encoded fragile X messenger ribonucleoprotein 1 (FMRP) protein due to large CGG repeat expansions in the promoter region of the FMR1 gene. The microtubule-associated protein Tau is a promising target for Tauopathic diseases and our preliminary study found that Tau protein levels were increased in the brain of Fmr1 knockout (KO) mice, a model of FXS. However, whether Tau reduction can prevent autism-like features in Fmr1 KO mice and become a novel strategy for FXS treatment remain unknown. Methods Tau was genetically reduced in Fmr1 KO mice through crossing Fmr1 ± female mice with Mapt ± male mice. The male offspring with different genotypes were subjected to various autism-related behavioral tests, RNA sequencing, and biochemical analysis. Fmr1 KO male mice were treated with Tau-targeting antisense oligonucleotide (ASO) and then subjected to behavioral tests and biochemical analysis. Results Tau expression was increased in the cortex of Fmr1 KO mice. Genetically reducing Tau prevented social defects, stereotyped and repetitive behavior, and spine abnormality in Fmr1 KO mice. Tau reduction also reversed increased periodic activity and partially rescued Per1 expression reduction in Fmr1 KO mice. Moreover, Tau reduction reversed compromised P38/MAPK signaling in Fmr1 KO mice. Finally, Tau-targeting ASO also effectively alleviated autism-like phenotypes and promoted P38/MAPK signaling in Fmr1 KO mice. Limitations Our study is limited to male mice, in agreement with the higher incidence of FXS in males than females. Whether Tau reduction also exerts protection in females deserves further scrutiny. Moreover, although Tau reduction rescues impaired P38/MAPK signaling in Fmr1 KO mice, whether this is the responsible molecular mechanism requires further determination. Conclusion Our data indicate that Tau reduction prevents autism-like phenotypes in Fmr1 KO mice. Tau may become a new target for FXS treatment.

The topology optimization design of complex products can significantly improve material and power savings, and reduce inertial forces and mechanical vibrations effectively. In this study, a large-tonnage hydraulic press was chosen as a typically complex product to present the optimization method. We propose a new reliability topology optimization method based on the reliability-and-optimization decoupled model and teaching–learning-based optimization (TLBO) algorithm. The supports formed by the plate structure are considered as topology optimization objects, characterized by light weight and stability. The reliability optimization under certain uncertainties and structural topology optimization are processed collaboratively. First, the uncertain parameters in the optimization problem are modified into deterministic parameters using the finite difference method. Then, the complex nesting of the uncertainty reliability analysis and topology optimization are decoupled. Finally, the decoupled model is solved using the TLBO algorithm, which is characterized by few parameters and a fast solution. The TLBO algorithm is improved with an adaptive teaching factor for faster convergence rates in the initial stage and performing finer searches in the later stages. A numerical example of the hydraulic press base plate structure is presented to underline the effectiveness of the proposed method.

Abstract Background Activated Cdc42-associated kinase 1 (ACK1) is a promising druggable target for cancer, but its inhibitors only showed moderate effects in clinical trials. The study aimed to investigate the underlying mechanisms and improve the antitumor efficacy of ACK1 inhibitors. Methods RNA-seq was performed to determine the downstream pathways of ACK. Using Lasso Cox regression analysis, we built a risk signature with ACK1-related autophagy genes in the lung adenocarcinoma (LUAD) patients from The Cancer Genome Atlas (TCGA) project. The performance of the signature in predicting the tumor immune environment and response to immunotherapy and chemotherapy were assessed in LUAD. CCK8, mRFP-GFP-LC3 assay, western blot, colony formation, wound healing, and transwell migration assays were conducted to evaluate the effects of the ACK1 inhibitor on lung cancer cells. A subcutaneous NSCLC xenograft model was used for in vivo study. Results RNA-seq revealed the regulatory role of ACK1 in autophagy. Furthermore, the risk signature separated LUAD patients into low- and high-risk groups with significantly different prognoses. The two groups displayed different tumor immune environments regarding 28 immune cell subsets. The low-risk groups showed high immune scores, high CTLA4 expression levels, high immunophenoscore, and low DNA mismatch repair capacity, suggesting a better response to immunotherapy. This signature also predicted sensitivity to commonly used chemotherapy and targeted drugs. In vitro, the ACK1 inhibitors (AIM-100 and Dasatinib) appeared to trigger adaptive autophagy-like response to protect lung cancer cells from apoptosis and activated the AMPK/mTOR signaling pathway, partially explaining its moderate antitumor efficacy. However, blocking lysosomal degradation with chloroquine/Bafilamycine A1 or inhibiting AMPK signaling with compound C/shPRKAA1 enhanced the ACK1 inhibitor’s cytotoxic effects on lung cancer cells. The efficacy of the combined therapy was also verified using a mouse xenograft model. Conclusions The resulting signature from ACK1-related autophagy genes robustly predicted survival and drug sensitivity in LUAD. The lysosomal degradation inhibition improved the therapeutic effects of the ACK1 inhibitor, suggesting a potential role for autophagy in therapy evasion.

Abstract Background Ubiquitin-conjugating enzyme E2 T (UBE2T) is a potential oncogene. However, Pan-cancer analyses of the functional, prognostic and predictive implications of this gene are lacking. Methods We first analyzed UBE2T across 33 tumor types in The Cancer Genome Atlas (TCGA) project. We investigated the expression level of UBE2T and its effect on prognosis using the TCGA database. The correlation between UBE2T and cell cycle in pan-cancer was investigated using the single-cell sequencing data in Cancer Single-cell State Atlas (CancerSEA) database. The Weighted Gene Co-expression Network analysis (WGCNA), Univariate Cox and Least absolute shrinkage and selection operator (LASSO) Cox regression models, and receiver operating characteristic (ROC) were applied to assess the prognostic impact of UBE2T-related cell cycle genes (UrCCGs). Furthermore, the consensus clustering (CC) method was adopted to divide TCGA-lung adenocarcinoma (LUAD) patients into subgroups based on UrCCGs. Prognosis, molecular characteristics, and the immune panorama of subgroups were analyzed using Single-sample Gene Set Enrichment Analysis (ssGSEA). Results derived from TCGA-LUAD patients were validated in International Cancer Genome Consortium (ICGC)-LUAD data. Results UBE2T is highly expressed and is a prognostic risk factor in most tumors. CancerSEA database analysis revealed that UBE2T was positively associated with the cell cycle in various cancers(r > 0.60, p

Abstract Assembling functional materials into one‐dimensional arrays is an efficient method for the integration of devices. However, the complicated assembly methods and poor stability of patterns still restrict their further applications. In this work, the well‐dispersible nanosheets are prepared by introducing a bionic adhesive strategy. The oriented arrays with uniform morphology and precise position are realized by the liquid‐film‐induced capillary bridge assembly method. Owing to the abundant interactions between catechol structure and targeted substrates, the micro‐wires present extraordinary stability in adhesion tests. Field‐effect transistors (FETs) based on these micro‐wires are also fabricated, and enhanced carrier mobility is achieved, exhibiting to be 41 times higher than pristine film‐structured FETs. Micro‐wires have a certain stability and improved electrical properties at the same time, which endows this strategy with practicality and application prospect.

BackgroundPatients with stage pN3 esophageal cancer (EC) have a large number of metastatic lymph nodes (mLNs) and have poor prognosis. This study was to elucidate whether subclassification of pN3 according to the number of mLNs could improve the discrimination ability of EC patients.MethodsThis study retrospectively analyzed patients with pN3 EC from the Surveillance, Epidemiology, and End Results (SEER) database as a training cohort and SEER validation cohort. Patients with pN3 esophageal cancer from the Affiliated Cancer Hospital of Harbin Medical University were used as the validation cohort. The optimal cutoff value of mLNs was identified using the X-tile software, and group pN3 into pN3-I and pN3-II based on mLNs. Kaplan-Meier method and log-rank test were used to analyze the disease-specific survival (DSS). The Cox proportional hazards regression analysis was used to identify the independent prognostic factors.ResultsFor the training cohort, patients with 7 to 9 mLNs were categorized as pN3-I, while those with more than 9 mLNs were categorized as pN3-II. There were 183 (53.8%) pN3-I and 157 (46.2%) pN3-II. The 5-year DSS rates of pN3-I and pN3-II in the training cohort were 11.7% and 5.2% (P=0.033), and the pN3 subclassification was an independent risk factor associated with patient prognosis. More RLNs may not improve patient prognosis, but the use of mLNs/RLNs is effective in predicting patient prognosis. Furthermore, the pN3 subclassification was well validated in the validation cohort.ConclusionSubclassification of pN3 can better distinguish survival differences in EC patients.

The morphology and porosity of zeolites have an important effect on adsorption and catalytic performance. In the work, simple inorganic salts, i.e., Na salts were used to synthesize MWW zeolite using the organic compound 1-Butyl-2,3-dimethyl-1H-imidazol-3-ium hydroxide as a structure-directing agent and the morphology was regulated by the alkali metals. The sample synthesized without Na salts shows a dense hexagon morphology, while different morphologies like ellipsoid, wool ball, and uniform hexagon appear when using NaOH, Na2CO3, and NaHCO3, respectively. Moreover, the impact of Na salts on the induction, nucleation, and the evolution of crystal growth was studied. Different kinds of Na salts have a different impact on the crystalline induction time in the order of NaHCO3 (36 h) < Na2CO3 (72 h) = NaOH (72 h). Meanwhile, the crystalline mechanism with the cooperation of inorganic salts and the organic SDAs is proposed. NaOH- and Na2CO3-MWW zeolite crystallized with a network of hydrogel via the nonclassical pathway in the system; however, the product is synthesized via a classical route in the NaHCO3 environment. This work provides information about MWW zeolite crystallization and modulating diverse morphologies by adjusting the process.

Organic vapor sensors based on polymer owing to their tunable molecular structures and designable functions have attracted considerable research interest. However, detecting multiple organic vapors with high accuracy and a low detection limit is still challenging. Herein, inspired by the mammalian olfactory recognition system, organic vapor sensors based on one-dimensional microfilament array structures with a wide range of sensing gases are demonstrated. By introducing aggregation-induced emission (AIE) molecules, sensors possess dual-optical sensing mechanisms of variation in fluorescence intensity and wavelength. By virtue of the synergistic effects of dual signals, superb accuracy and incredibly low detection limit are achieved for identifying analytes. In particular, the polymer/AIE microfilament array can detect acetone vapor down to 0.03% of saturated vapor pressure. In the saturated vapor of acetone, the fluorescence intensity of the sensor arrays was reduced by 53.7%, while the fluorescence wavelength was red-shifted by 21 nm. Combined with the principal component analysis (PCA) algorithm, the polymer/AIE molecular sensor arrays accomplished the classification and identification of acetone, ethanol, methylene chloride, toluene, and benzene. This bioinspired approach with dual sensing signals may broaden practical applications to high-performance gas sensors for precise molecular detection.

Abstract Patterned conducting polymer films with unique structures have promising prospects for application in various fields, such as actuation, water purification, sensing, and bioelectronics. However, their practical application is hindered because of the limitations of existing construction methods. Herein, a strategy is proposed for the superhydrophobic‐substrate‐assisted construction of free‐standing 3D microcavity‐patterned conducting polymer films (McPCPFs) at micrometer resolution. Easy‐peeling and nondestructive transfer properties are achieved through electrochemical polymerization along the solid/liquid/gas triphase interface on micropillar‐structured substrates. The effects of the wettability and geometrical parameters of the substrates on the construction of McPCPFs are systematically investigated in addition to the evolution of the epitaxial growth along the triphase interface at different polymerization times. The McPCPFs can be easily peeled from superhydrophobic surfaces using ethanol because of weak adhesion and nondestructively transferred to various substrates taking advantage of the capillarity. Furthermore, sensitive light‐driven McPCPF locomotion on organic liquid surfaces is demonstrated. Ultimately, a facile strategy for the construction of free‐standing 3D microstructure‐patterned conducting polymer films is proposed, which can improve productivity and applicability of the films in different fields and expand the application scope of superwettable interfaces.

Fabrication of ultrathin organic semiconductor nanostructures with precise alignment, tuneable morphology and high crystallinity remains challenging. Here the authors use an assembly technique with dewetting process controllability for patterning organic single-crystal arrays in a sub-hundred nanometer space.

Traditional optical organic vapor sensors with solvatochromic shift mechanisms have lower sensitivity due to weak intermolecular interactions. Here, the authors report a general strategy to prepare a higher sensitivity optical organic vapor sensor through polymeric swelling-induced variation of fluorescent intensity.

Abstract Hybrid heterojunction solar cells (HHSCs) have gained extensive research and attention due to simple device structure and low-cost technological processes. Here, HHSCs are presented based on a highly transparent conductive polymer poly(3,4ethylenedioxythiophene):poly(styrenesulfonate)(PEDOT:PSS) directly spin-coated on an n-type crystalline silicon with microscale surface textures, which are prepared by traditional chemical etching. We have studied interface properties between PEDOT:PSS and textured n-Si by varying coating conditions. Final power conversion efficiency (PCE) could arrive at 8.54% by these simple solution-based fabrication processes. The high conversion efficiency is attributed to the fully conformal contact between PEDOT:PSS film and textured silicon. Furthermore, the reflectance of the PEDOT:PSS layer on textured surface is analyzed by changing film thickness. In order to improve the performance of the device, silver nanowires were employed as electrodes because of its better optical transmittance and electrical conductivity. The highest PCE of 11.07% was achieved which displayed a 29.6% enhancement compared with traditional silver electrodes. These findings imply that the combination of PEDOT:PSS film and silver nanowire transparent electrodes pave a promising way for realizing high-efficiency and low-cost solar cells.

Lattice QCD is a frontier scientific field for studying elementary particles by numerical simulation methods, which has become one of the major scientific research applications of supercomputers.With the rapid development of Chinese supercomputers, the LQCD softwares need to be refactored due to the limitation of its traditional programming model.The characteristics of scientific applications on super computers from the perspective of lattice QCD were reviewed.A novel programming model targeted to Chinese super computers was proposed to adapt large-scale scientific applications with big data processing, which is a promising development direction for the basic softwares of Chinese supercomputing ecosystem.