Shear stiffening gel-enabled twisted string for bio-inspired robot actuators.

A rotary motor combined with fibrous string demonstrates excellent performance because it is powerful, lightweight, and prone to large strokes; however, the stiffness range and force-generating capability of twisted string transmission systems are limited. Here, we present a variable stiffness artificial muscle generated by impregnating shear stiffening gels (STGs) into a twisted string actuator (TSA). A high twisting speed produces a large impact force and causes shear stiffening of the STG, thereby improving the elasticity, stiffness, force capacity, and response time of the TSA. We show that at a twisting speed of 4186 rpm, the elasticity of an STG-TSA reached 30.92 N/mm, whereas at a low twisting speed of 200 rpm, it was only 10.51 N/mm. In addition, the STG-TSA exhibited a more prominent shear stiffening effect under a high stiffness load. Our work provides a promising approach for artificial muscles to coactivate with human muscles to effectively compensate for motion.

Study on the Size Dependence of the Shell-Breaking Response of Micro/Nano Al Particles at High Temperature.

The reactivity of Al nanoparticles is significantly higher than that of micron Al particles, and the thermal reaction properties exhibit notable distinctions. Following the previous studies on micron Al particles, the shell-breaking response of Al nanoparticles under vacuum conditions was analyzed using COMSOL simulation. Relationships between thermal stabilization time, shell-breaking cause, shell-breaking response time, and particle size were obtained, and a systematic analysis of the differences between micrometer and nanometer-sized particles was conducted. The results indicate that the thermal stabilization time of both micrometer and nanometer particles increases with the enlargement of particle size. The stress generated by heating Al nanoparticles with sizes ranging from 25-100 nm is insufficient to rupture the outer shell. For particles within the size range of 200 nm to 70 µm, the primary cause of shell-breaking is compressive stress overload, while particles in the range of 80-100 µm experience shell rupture primarily due to tensile stress overload. These results provide an important basis for understanding the shell-breaking mechanism of microns and nanoparticles of Al and studying the oxidation mechanism.

FTO-Nrf2 axis regulates bisphenol F-induced leydig cell toxicity in an m6A-YTHDF2-dependent manner.

Studies have shown that Bisphenol F (BPF) as an emerging bisphenol pollutant also has caused many hazards to the reproductive systems of humans and animals. However, its specific mechanism is still unclear. The mouse TM3 Leydig cell was used to explore the mechanism of BPF-induced reproductive toxicity in this study. The results showed BPF (0, 20, 40 and 80 µM) exposure for 72 h significantly increased cell apoptosis and decreased cell viability. Correspondingly, BPF increased the expression of P53 and BAX, and decreased the expression of BCL2. Moreover, BPF significantly increased the intracellular ROS level in TM3 cells, and significantly decreased oxidative stress-related molecule Nrf2. BPF decreased the expression of FTO and YTHDF2, and increased the total cellular m6A level. ChIP results showed that AhR transcriptionally regulated FTO. Differential expression of FTO revealed that FTO reduced the apoptosis rate of BPF-exposed TM3 cells and increased the expression of Nrf2, MeRIP confirmed that overexpression of FTO reduced the m6A of Nrf2 mRNA. After differential expression of YTHDF2, it was found that YTHDF2 enhanced the stability of Nrf2, and RIP assay showed that YTHDF2 was bound to Nrf2 mRNA. Nrf2 agonist enhanced the protective effect of FTO on TM3 cells exposure to BPF. Our study is the first to demonstrate that AhR transcriptionally regulated FTO, and then FTO regulated Nrf2 in a m6A-modified manner through YTHDF2, thereby affecting apoptosis in BPF-exposed TM3 cells to induce reproductive damage. It provides new insights into the importance of FTO-YTHDF2-Nrf2 signaling axis in BPF-induced reproductive toxicity and provided a new idea for the prevention of male reproductive injury.

RNA binding protein YTHDF1 mediates bisphenol S-induced Leydig cell damage by regulating the mitochondrial pathway of BCL2 and the expression of CDK2-CyclinE1.

Bisphenol S (BPS) causes reproductive adverse effects on humans and animals. However, the detailed mechanism is still unclear. This research aimed to clarify the role of RNA binding protein YTHDF1 in Leydig cell damage induced by BPS. The mouse TM3 Leydig cells were exposed to BPS of 0, 20, 40, and 80 µmol/L for 72 h. Results showed that TM3 Leydig cells apoptosis rate markedly increased in BPS exposure group. Meanwhile, the apoptosis-related molecule BCL2 protein level decreased significantly, and Caspase9, Caspase3, and BAX increased significantly. Moreover, the cell cycle was blocked in the G1/S phase, CDK2 and CyclinE1 were considerably down-regulated in BPS exposure groups, and the protein level of RNA binding protein YTHDF1 decreased sharply. Furthermore, after overexpression of YTHDF1, the cell viability significantly increased, and the apoptosis rate significantly decreased in TM3 Leydig cells. In the meantime, BCL2, CDK2, and CyclinE1 were significantly up-regulated, and BAX, Caspase9, and Caspase3 were significantly down-regulated. Conversely, interference with YTHDF1 decreased cell proliferation and promoted apoptosis. Importantly, overexpression of YTHDF1 alleviated the cell viability decrease induced by BPS, and interference with YTHDF1 exacerbated the situation. RIP assays showed that the binding of YTHDF1 to CDK2, CyclinE1, and BCL2 significantly increased after overexpressing YTHDF1. Collectively, our study suggested that YTHDF1 plays an essential role in BPS-induced TM3 Leydig cell damage by regulating CDK2-CyclinE1 and BCL2 mitochondrial pathway at the translational level.

Microdroplet-Facilitated Assembly of Thermally Activated Delayed Fluorescence-Encoded Microparticles with Non-interfering Color Signals.

Encoded microparticles (EMPs) have shown demonstrative value for multiplexed high-throughput bioassays such as drug discovery and diagnostics. Herein, we propose for the first time the incorporation of thermally activated delayed fluorescence (TADF) dyes with low-cost, heavy metal-free, and long-lived luminescence properties into polymer matrices via a microfluidic droplet-facilitated assembly technique. Benefiting from the uniform droplet template sizes and polymer-encapsulated structures, the resulting composite EMPs are highly monodispersed, efficiently shield TADF dyes from singlet oxygen, well preserve TADF emission, and greatly increase the delayed fluorescence lifetime. Furthermore, by combining with phase separation of polymer blends in the drying droplets, TADF dyes with distinct luminescent colors can be spatially separated within each EMP. It eliminates optical signal interference and generates multiple fluorescence colors in a compact system. Additionally, in vitro studies reveal that the resulting EMPs show good biocompatibility and allow cells to adhere and grow on the surface, thereby making them promising optically EMPs for biolabeling.

TET1 involved in bisphenol A induced TM3 Leydig cell toxicity by regulating Cav3.3 hydroxymethylation.

Bisphenol A (BPA), an important environmental pollutant, is known to damage reproductive development. However, the underlying epigenetic mechanism in Leydig cells during BPA exposure has not been explored in detail. In this study, TM3 Leydig cells were treated with BPA (0, 20, 40 and 80 µM) for 72 h. The differentially expressed TET1 cell model was constructed to explore the mechanism of BPA-induced cytotoxicity. Results showed that BPA exposure significantly inhibited cell viability and increased apoptosis of TM3 Leydig cells. Meanwhile, the mRNA of TET1, Cav3.2 and Cav3.3 decreased significantly with the increase of BPA exposure. Importantly, TET1 significantly promoted proliferation of TM3 Leydig cells and inhibited apoptosis. Differentially expressed TET1 significantly affected BPA-induced toxicity in TM3 Leydig cells. Notably, TET1 elevated the mRNA levels of Cav3.2 and Cav3.3. MeDIP and hMeDIP confirmed that TET1 regulated the expression of Cav3.3 through DNA hydroxymethylation. Our study firstly presented that TET1 participated in BPA-induced toxicity in TM3 Leydig cells through regulating Cav3.3 hydroxymethylation modification. These findings suggest that TET1 acts as a potential epigenetic marker for reproductive toxicity induced by BPA exposure and may provide a new direction for the research on male reproductive damage.

ZIF-8 base-aptamer "gate-lock" probes enable the visualization of a cascade response between deoxynivalenol and cytochrome c inside living cells.

Zeolitic imidazolate framework (ZIF-8) base-aptamer "gate-lock" biomaterial probes have been synthesized for monitoring intracellular deoxynivalenol (DON) and cytochrome c (cyt c) levels. The aptamer and organic fluorescent dye were regarded as a recognition element and a sensing element, respectively. In the presence of DON, the aptamers of DON and cyt c were specifically bound with the DON and induced cyt c, leading to the dissociation of aptamers from the porous surface of the probes. The gate was subsequently opened to release methylene blue (MB) and Rhodamine 6G (Rh6G), and their fluorescence (emission of MB at 700 nm and Rh6G at 550 nm) significantly recovered within 6 h. Cell imaging successfully monitored the exposure of DON and the biological process of cyt c discharge triggered by the activation of the DON-induced apoptosis pathway. In addition, the response between DON and cyt c was observed during the apoptosis process, which is of high significance for the comprehensive and systematic development of mycotoxins cytotoxicity.

Polyphosphazene-Functionalized Microspheres as Efficient Catalysts for the Knoevenagel Reaction under Mild Conditions.

Inspired by the formation of microspheres by hexachlorocyclotriphosphazene and 4, 4'-sulfonyldiphenol, polyphosphazene-functionalized microspheres were developed. Benefits from the supported supper basic phosphazene, the yield exceeded 99 % at room temperature in the manner of second-order reaction kinetics toward Knoevenagel reaction and was still maintained at 99 % after 16 runs. In the experimental temperature from 0 °C to 90 °C, the yield increased from 92 % to 99 %, reflecting that the catalyst had strong applicability under mild conditions. This behavior was conducive to energy conservation. Meanwhile, simple separation and recovery further enhanced this advantage. In addition, the catalyst was also found to be insensitive to aqueous solution or organic solvents such as toluene, THF, EtOH and CH3 CN. This property gave the Knoevenagel reaction a vast choice. All these features exhibit that this novel catalyst is an attractive and applicable alternative in organic synthesis.

Synthesis of Half-Titanocene Complexes Containing π,π-Stacked Aryloxide Ligands, and Their Use as Catalysts for Ethylene (Co)polymerizations.

A family of half-titanocene complexes bearing π,π-stacked aryloxide ligands and their catalytic performances towards ethylene homo-/co- polymerizations were disclosed herein. All the complexes were well characterized, and the intermolecular π,π-stacking interactions could be clearly identified from single crystal X-ray analysis, in which a stronger interaction could be reflected for aryloxides bearing bigger π-systems, e.g., pyrenoxide. Due to the formation of such interactions, these complexes were able to highly catalyze the ethylene homopolymerizations and copolymerization with 1-hexene comonomer, even without any additiveson the aryloxide group, which showed striking contrast to other half-titanocene analogues, implying the positive influence of π,π-stacking interaction in enhancing the catalytic performances of the corresponding catalysts. Moreover, it was found that addition of external pyrene molecules was capable of boosting the catalytic efficiency significantly, due to the formation of a stronger π,π-stacking interaction between the complexes and pyrene molecules.

TET1 mediated male reproductive toxicity induced by Bisphenol A through Catsper-Ca2+ signaling pathway.

Bisphenol A (BPA) exposure has many adverse effects on the reproductive system in animals and humans. Ten-eleven translocation 1 (TET1) is closely related to a variety of biological processes through regulating the dynamic balance of DNA demethylation and methylation. However, the role and mechanism of TET1 during BPA induced reproductive toxicity are largely unknown. In this study, mouse spermatogonia cell line GC-2 was treated with BPA in the final concentration of 0, 20, 40 and 80 µM for 72 h. The cell model of differential TET1 gene expression was established to explore the role and mechanism. We found that the growth rate of GC-2 cells, and the intracellular calcium level decreased significantly with the increase of BPA dose, while TET1 and Catsper1-4 expression level decrease with a dose-dependent relationship. Furthermore, TET1 overexpression promoted the proliferation of GC-2 cell, the increase of calcium ion concentration, and the expression level of Catsper1-4, while knockdown of TET1 leads to the opposite results. Mechanistically, TET1 expression promoted the hydroxymethylation of Catsper1-4 and reduced their methylation level. In addition, the expression level of Catsper1-4 was positively correlated with TET1 gene expression level in semen samples of the population. Our study revealed for the first time that TET1 gene regulates the expression of related molecules in the Catsper calcium signal pathway through its hydroxymethylation modification to affect the calcium level, thereby participating in the process of BPA induced damage. These results indicated that TET1 gene may be a potential biomarker of BPA induced male reproductive toxicity.

A Novel Balance Control Strategy Based on Enhanced Stability Pyramid Index and Dynamic Movement Primitives for a Lower Limb Human-Exoskeleton System.

The lower limb exoskeleton is playing an increasing role in enabling individuals with spinal cord injury (SCI) to stand upright, walk, turn, and so on. Hence, it is essential to maintain the balance of the human-exoskeleton system during movements. However, the balance of the human-exoskeleton system is challenging to maintain. There are no effective balance control strategies because most of them can only be used in a specific movement like walking or standing. Hence, the primary aim of the current study is to propose a balance control strategy to improve the balance of the human-exoskeleton system in dynamic movements. This study proposes a new safety index named Enhanced Stability Pyramid Index (ESPI), and a new balance control strategy is based on the ESPI and the Dynamic Movement Primitives (DMPs). To incorporate dynamic information of the system, the ESPI employs eXtrapolated Center of Mass (XCoM) instead of the center of mass (CoM). Meanwhile, Time-to-Contact (TTC), the urgency of safety, is used as an automatic weight assignment factor of ESPI instead of the traditional manual one. Then, the balance control strategy utilizing DMPs to generate the gait trajectory according to the scalar and vector values of the ESPI is proposed. Finally, the walking simulation in Gazebo and the experiments of the human-exoskeleton system verify the effectiveness of the index and balance control strategy.

l-Cysteine-Modified Graphene Oxide-Based Membrane for Chiral Selective Separation.

A novel chiral separation membrane was fabricated by assembling l-cysteine (l-Cys)-modified graphene oxide sheets. l-Cys modification leads to an enantiomer separation membrane with an accessible interlayer spacing of 8 Å, which allows high solvent permeability. In the racemate separation experiments under isobaric conditions, the enantiomeric excess (ee) values of alanine (Ala), threonine (Thr), tyrosine (Tyr), and penicillamine (Pen) racemates in the permeation solution were 43.60, 44.11, 27.43, and 46.44%, respectively. In the racemate separation experiments under negative pressure, the separation performances of Ala, Thr, and Tyr were still maintained, and the enantiomeric excess (ee) values of the filtrate after separation were 56.80, 54.57, and 32.34%, respectively. These results indicate that the as-prepared GO-Cys membrane has a great practical value in the field of enantiomer separation.

MicroRNA-99a-3p/GRP94 axis affects metastatic progression of human papillary thyroid carcinoma by regulating ITGA2 expression and localization.

Papillary thyroid cancer (PTC) usually has favorable prognosis; however, distant metastasis is a leading cause of death associated with PTC. MicroRNA-99a-3p (miR-99a-3p) is a member of the miR-99 family that is shown to be a tumor suppressor in various human cancers including the anaplastic thyroid cancer, another type of thyroid cancer. The Cancer Genome Atlas database and our previous study reported that miR-99a-3p is downregulated in human PTC tissues as well as human papillary thyroid carcinoma B-CPAP and TPC-1 cell lines. However, its pathological role in PTC remains unclear, especially its impact on PTC metastasis. In the present study, the role of miR-99a-3p in PTC metastasis was molecularly evaluated in in vitro and in vivo models. Our functional study revealed that overexpressing miR-99a-3p significantly suppresses epithelial-mesenchymal transition (EMT) and anoikis resistance as well as migration and invasion of B-CPAP and TPC-1 cells. The mechanical study indicated that glucose-regulated protein 94 (GRP94) is the direct target of miR-99a-3p. Moreover, GRP94 overexpression reverses the inhibitory effect of miR-99a-3p on PTC metastasis. In addition, the miR-99a-3p/GRP94 axis exerts its effect via inhibiting the expression and cytoplasmic relocation of integrin 2α (ITGA2). Furthermore, in vivo experiments confirmed that miR-99a-3p significantly inhibits tumor growth and lung metastasis in PTC xenograft mice. Overall, our findings suggested that the miR-99a-3p/GRP94/ITGA2 axis may be a novel therapeutic target for the prevention of PTC metastasis.

Deoxynivalenol photocatalytic detoxification products alleviate intestinal barrier damage and gut flora disorder in BLAB/c mice.

Deoxynivalenol (DON), a trichothecene mycotoxin, is one of the most globally prevalent mycotoxins mainly produced by Fusarium species. DON exposure can cause spectrum of symptoms such as nausea, vomiting, gastroenteritis, growth retardation, immunosuppression, and intestinal flora disorders in humans and animals. Therefore, the implication of DON degradation technology is of great significance for food safety. Recently, photocatalytic degradation technology has been applied for DON control. However, the toxicity of the intermediates identified in the degradation process was often ignored. In this work, based on previous successful degradation of DON and evaluation of the in vitro toxicity of DON photocatalytic detoxification products (DPDPs), we further studied the in vivo toxicity of DPDPs and mainly explored their effects on intestinal barrier function and intestinal flora in mice. The results demonstrated that the DPDPs treated with photocatalyst for 120 min effectively increased the expression of intestinal tight junction proteins and improved the disorder of gut flora. Meanwhile, compared with DON-exposed mice, the DPDPs reduced the level of inflammation and oxidative stress of intestinal tissue, and improved growth performance, enterohepatic circulation, energy metabolism, and autonomic activity. All the results indicated that the toxicity of the DPDPs irradiated for 120 min was much lower than that of DON or even nontoxic. Therefore, we hope that this photocatalytic degradation technology can be used as a promising tool for the detoxification of mycotoxins.

Cyclometalated Ir(III) complexes as potential electron acceptors for organic solar cells.

Cyclometalated iridium(iii) complexes have been investigated as promising electron donor (D) materials in organic solar cells (OSCs) due to their unique octahedral configuration for optimized morphology and their significantly long lifetimes potentially for enhanced exciton dissociation. However, the application as electron acceptor (A) materials has never been reported. In order to fill this blank, herein, two cyclometalated heteroleptic Ir complexes, TRIr and 2TRIr, based on electron donating-accepting type organic ligands with different π-conjugation lengths are reported as electron acceptor materials in comparison with their corresponding main organic ligands. The two Ir complexes exhibit suitable HOMO/LUMO energy levels of -5.55/-3.47 eV and -5.44/-3.48 eV, which are ∼0.1 eV higher in the HOMO and ∼0.15 eV deeper in the LUMO than the TR and 2TR ligands, respectively. 2TRIr with extended ligand π-conjugation displays a poor triplet feature, while TRIr demonstrates obvious metal-to-ligand charge transfer (MLCT) transition absorption, with a triplet component photoluminescence (PL) lifetime of 85 ns in neat films. When blended with PBDB-T in bulk heterojunction (BHJ) OSCs, the power conversion efficiencies (PCEs) are 2-3 times higher than their relevant ligands, with values of 1.20% and 1.62% for TRIr and 2TRIr, and 0.58% and 0.47% for the TR and 2TR ligand-based devices, respectively. TRIr and 2TRIr based active layer blends exhibit poorer hole and electron mobilities, whereas compared with their relatively linear planar ligands, both of the two octahedral Ir complexes exhibit an optimized surface morphology for less bimolecular recombination and more efficient exciton dissociation, thus contributing to improved photovoltaic performance.

The role of the HIF-1α/ALYREF/PKM2 axis in glycolysis and tumorigenesis of bladder cancer.

BACKGROUND: As a rate-limiting enzyme of glycolysis, pyruvate kinase muscle isozyme M2 (PKM2) participates in tumor metabolism and growth. The regulatory network of PKM2 in cancer is complex and has not been fully studied in bladder cancer. The 5-methylcytidine (m5C) modification in PKM2 mRNA might participate in the pathogenesis of bladder cancer and need to be further clarified. This study aimed to investigate the biological function and regulatory mechanism of PKM2 in bladder cancer. METHODS: The expression of PKM2 and Aly/REF export factor (ALYREF) was measured by Western blotting, qRT-PCR, and immunohistochemistry. The bioprocesses of bladder cancer cells were demonstrated by a series of experiments in vitro and in vivo. RNA immunoprecipitation, RNA-sequencing, and dual-luciferase reporter assays were conducted to explore the potential regulatory mechanisms of PKM2 in bladder cancer. RESULTS: In bladder cancer, we first demonstrated that ALYREF stabilized PKM2 mRNA and bound to its m5C sites in 3'-untranslated regions. Overexpression of ALYREF promoted bladder cancer cell proliferation by PKM2-mediated glycolysis. Furthermore, high expression of PKM2 and ALYREF predicted poor survival in bladder cancer patients. Finally, we found that hypoxia-inducible factor-1alpha (HIF-1α) indirectly up-regulated the expression of PKM2 by activating ALYREF in addition to activating its transcription directly. CONCLUSIONS: The m5C modification in PKM2 mRNA in the HIF-1α/ALYREF/PKM2 axis may promote the glucose metabolism of bladder cancer, providing a new promising therapeutic target for bladder cancer.

Comprehensive Analysis of Immune Implication and Prognostic Value of IFI44L in Non-Small Cell Lung Cancer.

Interferon-induced protein 44-like (IFI44L), a type I interferon-stimulated gene (ISG), has been reported to be involved in innate immune processes and to act as a tumor suppressor in several cancers. However, its immune implication on lung cancer remains unclear. Here, we systemically analyzed the immune association of IFI44L with multiple tumor-infiltrating immune cells (TIICs) and immunomodulators through bioinformatics methods in The Cancer Genome Atlas (TCGA) lung cancer cohorts. Then, the IFI44L-related immunomodulators were selected to construct the prognostic signatures in the lung adenocarcinoma (LUAD) cohort and the lung squamous cell carcinoma (LUSC) cohort, respectively. Concordance index and time-dependent receiver operating characteristics (ROC) curves were applied to evaluate the prognostic signatures. GSE72094 and GSE50081 were used to validate the TCGA-LUAD signature and TCGA-LUSC signature, respectively. A nomogram was established by risk score and clinical features in the LUAD cohort. Finally, the prognostic value and biological function of IFI44L were verified in a real-world cohort and in vitro experiments. The results indicated that IFI44L showed significant correlation with TIICs in LUAD and LUSC samples. Functional enrichment analysis showed that IFI44L may participate in various cancer/immune-related pathways, including JAK/STAT signaling pathway and NF-κB signaling pathway. A total of 44 immunomodulators presented obvious association with IFI44L in the TCGA-LUAD cohort and a robust 10-immunomodulator signature was constructed. Patients in the higher-risk group presented worse prognosis than those in the lower-risk group. Notably, the risk signature was successfully validated in GSE72094. Multivariate Cox regression suggested that the risk signature could act as independent prognostic factors in both TCGA-LUAD and GSE72094 cohorts. Besides, a 17-immunomodulator signature was established in the TCGA-LUSC cohort and similar results were presented through analysis. The nomogram exhibited good accuracy in predicting overall survival (OS) outcome among TCGA-LUAD patients than the risk signature and other clinical features, with the area under curve values being 0.782 at 1 year, 0.825 at 3 years, and 0.792 at 5 years. Finally, tissue microarray analysis indicated that higher expression of IFI44L presented opposite relationship with pathological stage (p = 0.016) and a better outcome among lung cancer patients (p = 0.024). Functional experiments found that IFI44L overexpression significantly inhibited the proliferation, migration, and invasion in LUAD and LUSC cells; RT-qPCR experiments verified the correlation between the expression level of IFI44L with multiple immunomodulators in SPC-A-1 and NCI-H520 cells. In conclusion, our research highlighted that IFI44L is associated with tumor immune infiltration and provided information on IFI44L's immune implication, which indicates that IFI44L has potential clinical immunotherapeutic value and the proposed nomogram is a promising biomarker for non-small cell lung cancer patients.

Bioinformatic analysis of the expression and prognosis of ZNF589 in human breast cancer.

BACKGROUND: Zinc finger protein 589 (ZNF589) is a member of the zinc finger protein (ZNF) family and plays an important role in the differentiation of haemopoietic system stem cells. However, its effects on tumorigenesis and progression have not yet been reported. The purpose of this study was to explore the prognosis and underlying mechanism of ZNF589 in breast cancer (BRCA) through a bioinformatic analysis. METHODS: ZNF589 transcription levels in a TCGA BC cohort were analysed and then validated using Oncomine and UALCAN. The prognostic value of ZNF589 was determined based on the overall survival (OS) and relapse-free survival (RFS) based on The Cancer Genome Atlas (TCGA) cohort and Kaplan-Meier (K-M) database. LinkedOmics and STRING were carried out to explore the potential co-expressed genes and interactive proteins as well as corresponding enrichment analysis. A Gene Set Enrichment Analysis (GSEA) was performed between two gene matrices separated by the median cut-off value of ZNF589. The methylation levels of the ZNF589 promoter were analysed using UALCAN. RESULTS: ZNF589 was downregulated in breast tumours, and lower expression was associated with poor OS (P=0.047) and RFS (P=0.0043) according to TCGA. A subgroup analysis showed that the downregulation of ZNF589 was significantly associated with poor OS in stage 3-4 patients (P=0.0249) and progesterone receptor (PR)-negative patients (P=0.0002). Consistently, lower ZNF589 predicted poor RFS in stage 3-4 patients (P=0.0090), hormone receptor-negative patients [oestrogen receptor (ER)-, P=0.0129; PR-, P=0.0130; human epidermal growth factor receptor 2 (HER2)-, P<0.0001] and triple-negative BRCA patients (P=0.0052). Univariate and multivariate Cox regressions indicated that ZNF589 could act as an independent prognostic biomarker for OS based on age and TNM stage. Functional enrichment analysis of co-expressed genes and a protein-protein interaction (PPI) network both suggested that ZNF589 expression was negatively correlated with cell cycle progression at the transcriptional and protein-interactive levels. Finally, we found that the downregulation of ZNF589 correlated with promoter hypermethylation, and the corresponding subgroup analysis presented similar results. CONCLUSIONS: Our study highlighted that ZNF589 could act as a potential prognostic biomarker and a tumour suppressor in BRCA. A functional enrichment analysis suggested that ZNF589 may participate in multiple cancer-related pathways, including the cell cycle. Epigenetic factor promoter methylation could contribute to the downregulation of ZNF589 expression. However, deeper research about its function and underlying mechanism in cancer progression is required.

Effects of dust dispersibility on the suppressant enhanced explosion parameter (SEEP) in flame propagation of Al dust clouds.

This work presents an overview about the suppressant enhanced explosion parameter (SEEP) phenomenon in aluminum dust explosion moderation. The SEEP phenomenon can be attributed to either the flammable gas produced by decomposition of insufficient chemical suppressant so as to form an explosible hybrid mixture, or to the improvement in dust dispersibility caused by small amounts of thermal inhibitor so as to form better dispersed dust clouds. Aluminum (Al) and four particle sizes of alumina (Al2O3) were used to confirm a physically caused SEEP phenomenon by performing flame propagation experiments. Higher flame spread velocities (FSVs) in Al dust clouds were found in the presence of 5 or 10% <150 and <45-µm Al2O3 powder. Adding micro-sized Al2O3 disrupted inter-particle contact in combustible dusts, decreased inter-particle forces, and formed dust clouds with better dispersibility, thereby decreasing the effective particle size distribution (PSD) of Al dust. A strong thermal effect brought about by 2.5 µm Al2O3 overcame the negative effect of improved dispersion, preventing SEEP from occurring. The addition of 50 nm Al2O3 increased cohesion of powder mixtures, and decreased dust dispersibility. With benefits from both dispersion suppression and the thermal effect, Al flame propagation was well quenched.

Epigenetic silencing of TET1 mediated hydroxymethylation of base excision repair pathway during lung carcinogenesis.

The methylcytosine dioxygenase Ten-eleven translocation 1 (TET1) is an important regulator for the balance of DNA methylation and hydroxymethylation through various pathways. Increasing evidence has suggested that TET1 probably involved in DNA methylation and demethylation dysregulation during chemical carcinogenesis. However, the role and mechanism of TET1 during lung cancer remains unclear. In this study, we found that TET1 expression was significantly down-regulated and the methylation level was significantly up-regulated in 3-methylcholanthrene (3-MCA) induced cell malignant transformation model, rat chemical carcinogenesis model, and human lung cancer tissues. Demethylation experiment further confirmed that DNA methylation negatively regulated TET1 gene expression. TET1 overexpression inhibited cell proliferation, migration and invasion in vitro and in vivo, while knockdown of TET1 resulted in an opposite phenotype. DNA hydroxymethylation level in the promoter region of base excision repair (BER) pathway key genes XRCC1, OGG1, APEX1 significantly decreased and the degree of methylation gradually increased in malignant transformed cells. After differential expression of TET1, the level of hydroxymethylation, methylation and expression of these genes also changed significantly. Furthermore, TET1 binds to XRCC1, OGG1, and APEX1 to maintain them hydroxymethylated. Blockade of BER pathway key gene alone or in combination significantly diminished the effect of TET1. Our study demonstrated for the first time that TET1 expression is regulated by DNA methylation and TET1-mediated hydroxymethylation regulates BER pathway to inhibit the proliferation, migration and invasion during 3-MCA-induced lung carcinogenesis. These results suggested that TET1 gene can be a potential biomarker and therapy target for lung cancer.