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Zhang, Yan

Publications and source records attributed to Zhang, Yan.

At least 91 records · Page 5

MiR-216a-5p/Hexokinase 2 axis regulates uveal melanoma growth through modulation of Warburg effect

Highlights: • microRNA-216a-5p (miR-216a-5p) inhibits HK2 expression by directly targeting its 3′-UTR in uveal melanoma cells. • miR-216a-5p dampens glycolysis in uveal melanoma cells via inhibition of HK2. • miR-216a-5p expression is negatively correlated with HK2 expression and predicts better outcome in uveal melanoma patients. Hexokinase-2 (HK2), the initial as well as the rate-limiting step in glycolysis, is overexpressed in many human cancers, and correlates with poor clinical outcomes. Aerobic glycolysis is a hallmark of cancer, and drugs targeting its enzymes, including HK2, are being developed. However, the mechanisms of HK2 inhibition and the physiological significance of the HK2 inhibitors in cancer cells are rarely reported. Here, we show that microRNA-216a-5p (miR-216a-5p) inhibits HK2 expression by directly targeting its 3′-UTR in uveal melanoma cells. Through inhibition of HK2, miR-216a-5p dampens glycolysis by reducing HK activity, glucose uptake, lactate production, ATP generation, extracellular acidification rate (ECAR), and increasing oxygen consumption rate (OCR) in uveal melanoma cells. Importantly, glycolysis regulated by miR-216a-5p is critical for its regulating uveal melanoma tumor growth both in vitro and in vivo. miR-216a-5p expression is negatively correlated with HK2 expression and predicts better outcome in uveal melanoma patients. Our findings provide clues regarding the role of miR-216a-5p as a tumor suppressor in uveal melanoma through the inhibition of HK2. Targeting HK2 through miR-216a-5p could be a promising therapeutic strategy in uveal melanoma.

60 APPLIED LIFE SCIENCES↗

Split‐dose 4‐L polyethylene glycol regimen for patients with previous colorectal surgery in bowel preparation before colonoscopy: A randomized, controlled, single‐blind study

OBJECTIVE We aimed to investigate the efficacy of a split‐dose 4‐L polyethylene glycol (PEG) regimen for the quality of bowel preparation in Asian patients with previous colorectal surgery for colorectal cancer (CRC). METHODS This was a prospective, single‐center, randomized controlled, endoscopist‐blinded study. Patients with previous colorectal surgery for CRC were randomly allocated to a routine, morning‐only 2‐L PEG (2‐MO) group or a split‐dose 4‐L PEG (4‐SD) group. The primary outcome was a successful bowel preparation rate. Secondary outcomes were polyp detection rate (PDR), adenoma detection rate (ADR), patient compliance, satisfaction, tolerance, willingness to repeat the preparation and difficulty of the bowel preparation process. RESULTS In total, 187 patients were included (93 in the 2‐MO group, 94 in the 4‐SD group) in this study. The rate of successful bowel preparation in the 4‐SD group was higher than in the 2‐MO group (89.4% vs 66.7%, P < 0.001) in an intention‐to‐treat analysis according to the Aronchick score. Patients’ satisfaction with the bowel preparation process in the 4‐SD group was superior to that in the 2‐MO group (93.4% vs 82.2%, P = 0.021). No significant differences were detected in PDR, ADR, patient compliance, tolerance, willingness to repeat the preparation or difficulty of the bowel preparation process. CONCLUSIONS The 4‐SD PEG regimen was superior to a routine, morning‐only 2‐L PEG preparation for bowel preparation in an Asian population with previous colorectal surgery.

Liu, Zhu↗

Series Solution for Magnetic Flux Density of Circular Current Loop and a Relevant Application

The series solution to the magnetic flux density of a circular current loop is presented in the paper. The convergences of these series are assessed. Comparing the result with elliptic integral method, the validity and feasibility of series solution were verified. A computer program has been developed by the method to calculate the magnetic flux density of a multi-coil magnet and its uniformity successfully.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

PAFAH1B2 is a HIF1a target gene and promotes metastasis in pancreatic cancer

Platelet-activating factor acetylhydrolase IB subunit beta (PAFAH1B2) plays important roles in inflammation and anaphylaxis. However, its primary function in pancreatic cancer remains unclear. In the current study, we report that PAFAH1B2 is overexpressed in pancreatic ductal adenocarcinoma (PDAC) and correlated inversely with patient survival. PAFAH1B2 overexpression induced epithelial–mesenchymal transition (EMT), migration and invasion in vitro and metastasis in vivo. Conversely, silencing PAFAH1B2 inhibited these aggressive phenotypes. Moreover, PAFAH1B2 overexpression in PDAC cells was directly mediated by HIF1a. PAFAH1B2 expression in PDAC clinical specimens correlated positively with HIF1a expression. Overall, our results defined PAFAH1B2 as a target gene of HIF1a and a critical driver of PDAC metastatic behaviors.

60 APPLIED LIFE SCIENCES↗

Roseburia intestinalis-derived flagellin is a negative regulator of intestinal inflammation

Highlights: • Identifying differentially expressed lncRNAs in R. intestinalis flagellin-challenged mice. • R. intestinalis flagellin induces HIF1A-AS2 expression via Stat1 phosphorylation. • Knockdown of HIF1A-AS2 abolishes R. intestinalis flagellin protective role through activation of NF-κB/Jnk pathway. Our previous study showed that the Roseburia intestinalis (R. intestinalis), one of the dominant intestinal bacterial microbiota, was significantly decreased in Crohn's disease patients and protected colon epithelial cells from inflammatory damage. However, the roles of lncRNAs in R. intestinalis flagellin-mediated anti-inflammation remain unclear. In this study, we investigate global lncRNA expression profiles using microarray analysis of ulcerative colitis samples from DSS/Flagellin-challenged mice and identified a Flagellin-induced upregulated lncRNA (HIF1A-AS2). Flagellin induced HIF1A-AS2 expression in a dose- and time-dependent manner via p38-stat1 activation. Selective pharmacological inhibitors of Stat1 and p38, and genetic knockdown of these genes abolished Flagellin-induced HIF1A-AS2 expression. In addition, luciferase reporter assay showed that Flagellin activated HIF1A-AS2 promotor via increasing stat1 phosphorylation. Silencing of HIF1A-AS2 abolished Flagellin-mediated anti-inflammatory effects, evaluating by upregulation of cytokines expression, including TNF-α, IL-1β, IL-6 and IL-12, but not TNFβ. In addition, knockdown of HIF1A-AS2 significantly increased p65 and Jnk phosphorylation, and sufficiently abolished Flagellin-mediated anti-inflammatory affects in vivo. Our study provides new insights into the mechanisms that lncRNAs regulate flagellin-mediated alleviation of colonic inflammation. It is indicated that HIF1A-AS2 may be a modulator of intestinal inflammation and represent a novel target for future therapeutics.

60 APPLIED LIFE SCIENCES↗

Synergistically Enhancing the Therapeutic Effect of Radiation Therapy with Radiation Activatable and Reactive Oxygen Species-Releasing Nanostructures

Nanoparticle-based radio-sensitizers can amplify the effects of radiation therapy on tumor tissue even at relatively low concentrations while reducing the potential side effects to healthy surrounding tissues. In this study, we investigated a hybrid anisotropic nanostructure, composed of gold (Au) and titanium dioxide TiO 2 , as a radio-sensitizer for radiation therapy of triple negative breast cancer (TNBC). In contrast to other gold-based radio sensitizers, dumbbell-like Au-TiO 2 nanoparticles (DATs) show a synergistic therapeutic effect on radiation therapy, mainly because of strong asymmetric electric coupling between the high atomic number metals and dielectric oxides at their interfaces. The generation of secondary electrons and reactive oxygen species (ROS) from DATs triggered by X-ray irradiation can significantly enhance the radiation effect. After endocytosed by cancer cells, DATs can generate a large amount of ROS under X-ray irradiation, eventually inducing cancer cell apoptosis. Significant tumor growth suppression and overall improvement in survival rate in a TNBC tumor model have been successfully demonstrated under DATs uptake for a radio-sensitized radiation therapy.

59 BASIC BIOLOGICAL SCIENCES↗

Knockdown of long non-coding RNA MAP3K20 antisense RNA 1 inhibits gastric cancer growth through epigenetically regulating miR-375

Highlights: • lncRNA MLK7-AS1 is an independent prognostic factor for gastric cancer patients. • Knockdown of MLK7-AS1 inhibits gastric cancer cell growth. • MLK7-AS1 negatively and epigenetically controls miR-375 expression. Emerging evidence has demonstrated that long noncoding RNAs (lncRNAs) play a critical role in tumorigenesis of gastric cancer. LncRNA MAP3K20 antisense RNA 1 (MLK7-AS1) has been identified as one of gastric cancer-specific lncRNAs. However, its precise role in gastric cancer remains unknown. In this study, we found that lncRNA MLK7-AS1 was significantly increased in gastric cancer tissues compared with in adjacent tissues. Gastric cancer patients with high MLK7-AS1 expression had a shorter survival and poorer prognosis. By loss-function assay, we demonstrated that knockdown of MLK7-AS1 inhibited cell proliferation and induced apoptosis in HGC27and MKN-45 cells. Furthermore, we identified miR-375 as a target of MLK7-AS1. MLK7-AS1 interacted with Dnmt1 and recruited it to miR-375 promotor, hyper-methylating miR-375 promotor and repressing miR-375 expression. Taken together, our findings demonstrate that knockdown of MLK7-AS1 by siRNA inhibits gastric cancer growth by epigenetically regulating miR-375. Thus, MLK7-AS1 may be a useful prognostic marker and therapeutic target for gastric cancer patients.

60 APPLIED LIFE SCIENCES↗

Long-distance propagation of short-wavelength spin waves

Recent years have witnessed a rapidly growing interest in exploring the use of spin waves for information transmission and computation toward establishing a spin-wave-based technology that is not only significantly more energy efficient than the CMOS technology, but may also cause a major departure from the von-Neumann architecture by enabling memory-in-logic and logic-in-memory architectures. A major bottleneck of advancing this technology is the excitation of spin waves with short wavelengths, which is a must because the wavelength dictates device scalability. Here, we report the discovery of an approach for the excitation of nm-wavelength spin waves. The demonstration uses ferromagnetic nanowires grown on a 20-nm-thick Y 3 Fe 5 O 12 film strip. The propagation of spin waves with a wavelength down to 50 nm over a distance of 60,000 nm is measured. The measurements yield a spin-wave group velocity as high as 2600 m s –1 , which is faster than both domain wall and skyrmion motions.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Surface transformation by a “cocktail” solvent enables stable cathode materials for sodium ion batteries

Coating the surfaces of active materials has become an effective and indispensable path towards the stable operation of practical rechargeable batteries. Improving the affordability of coating processes can bring enormous manufacturing advantages to battery applications. Here in this paper, we report a cheap, simple and efficient method to create conformal coating layers on the primary particles of sodium layered oxide materials for improving battery performance. Mimicking the cathode–electrolyte interfacial reaction in practical cells, we create conformal coating layers via the spontaneous reaction between the oxidative cathode surfaces and a cocktail of reductive organic solvents. The conformal coating layers consist of metal–organic compounds with reduced transition metal cations, i.e., artificial cathode–electrolyte interphases (CEIs). The cells containing these coated cathode materials deliver much improved cycle life while maintaining reasonably high reversible capacity and rate capability. Furthermore, the structural stability and water resistance are enhanced, which can practically help simplify the storage protocol of cathode powders prior to battery manufacturing. The surfaces of most oxide cathode materials (e.g., lithium cathodes and sodium cathodes) are highly oxidative, and thus we expect that the present method, with tailored experimental parameters, can be readily applied to most battery systems.

25 ENERGY STORAGE↗

Maternal trans-general analysis of the human mitochondrial DNA pattern

There is an intimate connection between mitochondrial DNA (mtDNA) methylation and some diseases, such as cancer. MtDNA is almost strictly maternally inherited. However, whether the aberrant mtDNA methylation involved in breast cancer progression and whether mtDNA methylation can be transmitted through maternal line are poorly understood. Here we applied bisulfite sequencing to global mitochondrial DNA and whole genomic DNA methylation array from fifteen members of five three-female-generation families with one breast cancer patient in each family. We found that mtDNA methylation was maternally inherited in D-loop region and eight aberrant mtDNA methylation sites were correlated with breast cancer. Furthermore, conjoint analysis showed that mtDNA methylation sites could be potential biomarkers combined with nuclear DNA methylation sites for breast cancer risk prediction. - Highlights: • MtDNA methylation was modestly maternally inherited, especially in D-loop region. • Eight aberrant mtDNA methylation sites were correlated with breast cancer. • Nine nDNA methylation sites were identified as potential breast cancer-related sites. • MtDNA-nDNA methylation sites could be potential biomarkers for breast cancer. • A hypothetical model of mtDNA methylation maternal inheritance was proposed.

60 APPLIED LIFE SCIENCES↗

Reduced electron exposure for energy-dispersive spectroscopy using dynamic sampling

Analytical electron microscopy and spectroscopy of biological specimens, polymers, and other beam sensitive materials has been a challenging area due to irradiation damage. There is a pressing need to develop novel imaging and spectroscopic imaging methods that will minimize such sample damage as well as reduce the data acquisition time. The latter is useful for high-throughput analysis of materials structure and chemistry. Here, in this work, we present a novel machine learning based method for dynamic sparse sampling of EDS data using a scanning electron microscope. Our method, based on the supervised learning approach for dynamic sampling algorithm and neural networks based classification of EDS data, allows a dramatic reduction in the total sampling of up to 90%, while maintaining the fidelity of the reconstructed elemental maps and spectroscopic data. In conclusion, we believe this approach will enable imaging and elemental mapping of materials that would otherwise be inaccessible to these analysis techniques.

36 MATERIALS SCIENCE↗