Publications by authors named "Hui Qian"

286 Publications

Sesquiterpene-Loaded Co-Polymer Hybrid Nanoparticle Effects on Human Mast Cell Surface Receptor Expression, Granule Contents, and Degranulation.

Nanomaterials (Basel) 2021 Apr 8;11(4). Epub 2021 Apr 8.

Nanotechnology Research Centre, National Research Council Canada, Edmonton, AB TG6 2M9, Canada.

Biodegradable polymeric nanoparticles (NPs) such as poly(lactic-co-glycolic acid) (PLGA) and polyvinyl alcohol (PVA) have been used as drug delivery systems for natural and synthetic compounds and are designed to control the loading and release of biodegradable materials to target cells, tissues, and organs. Eremophilane-type sesquiterpenes have anti-inflammatory properties but are lipophilic, cytotoxic, and not biocompatible with many cells. To determine whether biodegradable PLGA/PVA could improve the biocompatibility of sesquiterpenes, sesquiterpene-loaded NPs were synthesized and their effects on human mast cells (LAD2), the major effector cells of allergic inflammation, were determined. NPs composed of PLGA/PVA and two types of sesquiterpenes (fukinone, PLGA/PVA-21 and 10βH-8α,12-epidioxyeremophil-7(11)-en-8β-ol, PLGA/PVA-22) were produced using a microfluidic synthesis method. The NPs' size distribution and morphology were evaluated by dynamic light scattering and cryogenic transmission electron microscopy (TEM). PLGA/PVA-21 and PLGA/PVA-22 were 60 to 70 nm and were readily internalized by LAD2 as shown by flow cytometry, fluorescence microscopy, and TEM. While unencapsulated sesquiterpenes decreased LAD2 cell viability by 20%, PLGA/PVA-21 and PLGA/PVA-22 did not alter LAD2 viability, showing that encapsulation improved the biocompatibility of the sesquiterpenes. PLGA/PVA-21 and PLGA/PVA-22 decreased the expression of genes encoding the subunits of the high affinity immunoglobulin E receptor (, , ) and the stem cell factor receptor (), suggesting that hybrid NPs could alter mast cell responses to antigens and shift their maturation. Similarly, PLGA/PVA-21 and PLGA/PVA-22 inhibited tryptase expression but had no effect on chymase expression, thereby promoting a shift to the tryptase-positive phenotype (MC). Lastly, PLGA/PVA-21 and PLGA/PVA-22 inhibited mast cell degranulation when the LAD2 cells were activated by IgE crosslinking and FcεRI. Overall, our results suggest that PLGA/PVA-21 and PLGA/PVA-22 alter human mast cell phenotype and activation without modifying viability, making them a more biocompatible approach than treating cells with sesquiterpenes alone.
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http://dx.doi.org/10.3390/nano11040953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068390PMC
April 2021

HucMSC exosome-delivered 14-3-3ζ alleviates ultraviolet radiation-induced photodamage via SIRT1 pathway modulation.

Aging (Albany NY) 2021 Apr 21;13(8):11542-11563. Epub 2021 Apr 21.

Key Laboratory of Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang 212013, Jiangsu, People's Republic of China.

Exosomes derived from human umbilical cord mesenchymal stem cells (hucMSC-ex) are nano-sized membrane-bound vesicles that have been reported to facilitate skin regeneration and repair. However, the roles played by hucMSC-ex in ultraviolet (UV) radiation-induced skin photodamage and the underlying mechanisms remain unknown. To investigate the functions of hucMSC-ex in a rat model of acute skin photodamage, immunofluorescence and immunohistochemical staining, quantitative real-time-polymerase chain reaction (qRT-PCR), western blot, and gene silencing assays were performed. We found that the subcutaneous injection of hucMSC-ex elicited antioxidant and anti-inflammatory effects against UV radiation-induced DNA damage and apoptosis. Further studies showed that the sirtuin 1 (SIRT1) expression level in skin keratinocytes (HaCaT) decreased in a time- and dose-dependent manner under UV radiation induced-oxidative stress conditions, which could be reversed by treatment with hucMSC-ex. The activation of SIRT1 significantly attenuated UV- and HO-induced cytotoxic damage by inhibiting oxidative stress and promoting the activation of autophagy. Our study found that 14-3-3ζ protein, which was delivered by hucMSC-ex, exerted a cytoprotective function via the modulation of a SIRT1-dependent antioxidant pathway. Collectively, our findings indicated that hucMSC-ex might represent a new potential agent for preventing or treating UV radiation-induced skin photodamage and aging.
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http://dx.doi.org/10.18632/aging.202851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8109102PMC
April 2021

3,3'-Diindolylmethane Promotes Gastric Cancer Progression β-TrCP-Mediated NF-κB Activation in Gastric Cancer-Derived MSCs.

Front Oncol 2021 24;11:603533. Epub 2021 Mar 24.

Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, Institute of Stem Cell, School of Medicine, Jiangsu University, Zhenjiang, China.

Gastric cancer is a malignant tumor characterized by high morbidity and invasion. Surgery combined with chemo-radiotherapy is the most common treatment for gastric cancer, while multiple drug resistance always results in treatment failure. Once the anti-tumor drugs enter the tumor foci, tumor cells as well as those found in the microenvironment are affected. However, the effects of drugs on tumor microenvironment (TME) are easily overlooked. In this study, we investigated the effects of the anti-cancer drug 3,3'-diindolylmethane (DIM) on gastric cancer-derived mesenchymal stem cells (GC-MSCs) and their subsequent impact on cancer progression. Surprisingly, we found that the therapeutic concentration of DIM upregulated the expression level of tumor-related factors such as CCL-2, IL-6, and IL-8 in GC-MSCs. The conditioned medium of DIM-treated GC-MSCs promoted the proliferation, invasion, and migration of gastric cancer cells and tumor growth . Mechanistically, DIM enhanced the expression of β-TrCP, an E3 ubiquitin ligase leading to IκBα degradation and NF-κB activation in GC-MSCs. The β-TrCP knockdown partially eliminated positive results caused by DIM. Our results showed that the therapeutic dosage of DIM induced cell death in cancer cells, while enhancing MSC paracrine functions in the stroma to offset the original DIM effect on cancer cells. These findings provide a new mechanism of anti-cancer drug resistance and remind us to adjust the chemotherapeutic scheme by combining the anti-cancer drug with an appropriate signaling pathway inhibitor to block the side effects of drug on targeted TME cells.
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http://dx.doi.org/10.3389/fonc.2021.603533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024625PMC
March 2021

Platelet-rich plasma promotes MSCs exosomes paracrine to repair acute kidney injury via AKT/Rab27 pathway.

Am J Transl Res 2021 15;13(3):1445-1457. Epub 2021 Mar 15.

Zhenjiang Key Laboratory of High Technology Research on Exosomes Foundation and Transformation Application, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University Zhenjiang 212013, Jiangsu, China.

Acute kidney injury (AKI) is defined by rapid deterioration of renal function, and is a common complication in hospitalized patients. Among the recent therapeutic options, mesenchymal stem cells (MSCs) are considered a promising therapeutic strategy for damaged tissue repair. Platelet rich plasma (PRP) regulates mesenchymal cells to repair tissue damage through the release of growth factors. In this study, we proposed a possible therapeutic use of MSCs stimulated by platelet-rich plasma (PRP-MSCs) in a glycerin-induced AKI murine model. and studies, showed that PRP-MSCs could significantly attenuate serum blood urea nitrogen and creatinine levels, and reverse the histopathological kidney damage. PRP-MSCs treatment reduced renal tubular cell apoptosis stimulated by glycerin. We confirmed that PRP promoted the proliferation and reinforced the stemness of MSCs by inducing YAP nucleus expression, and that PRP promoted MSCs exosomes in a paracrine manner to repair AKI through an activated AKT/Rab27 pathway. Our results revealed that the PRP stimulated MSCs paracrine pathway could effectively alleviate glycerin-induced AKI. Therefore, PRP pretreatment may be a new method to improve the therapeutic effect of MSCs.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014389PMC
March 2021

New glance at the role of TM6SF2 in lipid metabolism and liver cancer.

Hepatology 2021 Apr 7. Epub 2021 Apr 7.

Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas, Medical Center, Kansas City, KS, United States.

Non-alcoholic fatty liver disease (NAFLD) is rapidly becoming the most common cause of chronic liver diseases. NAFLD can progress to more severe conditions, such as non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma (HCC), which confer increased morbidity and mortality. However, many individuals with NAFLD do not progress to these more severe conditions. Such variations in the susceptibility of NAFLD progression suggest that it is likely affected by multiple factors, in particular, genetic factors.
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http://dx.doi.org/10.1002/hep.31851DOI Listing
April 2021

Insight into the evolution of microbial community and antibiotic resistance genes in anammox process induced by copper after recovery from oxytetracycline stress.

Bioresour Technol 2021 Jun 10;330:124945. Epub 2021 Mar 10.

School of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou 311121, China. Electronic address:

The influence of copper ion (Cu) on anaerobic ammonium oxidation (anammox) performance and microbial community structures after oxytetracycline (OTC) stress recovery were assessed. Experimental results demonstrated that anammox performance were stressed by 1.0 mg L Cu and inhibitions were reversible with total nitrogen removal rate higher than 3.08 ± 0.2 kg N m d. The residual OTC in the anammox sludge could combine with Cu introduced and thereby retarded inhibition on performance in the presence of 2.0 mg L Cu. Moreover, the positive relation of dominant bacterium Ca. Anammoxoglobus with the abundance of functional genes and parts of antibiotic resistance genes were observed, suggesting that regain of performance was the results of the gradual domestication of latent resistant species after inhibition. This investigation reveals new insights into resistance of anammox performance for Cu and OTC.
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http://dx.doi.org/10.1016/j.biortech.2021.124945DOI Listing
June 2021

Exosomes derived from autologous dermal fibroblasts promote diabetic cutaneous wound healing through the Akt/β-catenin pathway.

Cell Cycle 2021 Mar-Mar;20(5-6):616-629. Epub 2021 Mar 8.

Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, Institute of Stem Cell, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China.

Diabetic cutaneous wounds are one of the complications of diabetes mellitus (DM) and are difficult to cure at present. Autologous dermal fibroblasts (DFs) have shown great promise in skin regeneration and repair. However, whether exosomes derived from autologous dermal fibroblasts (DF-Ex) can be used to accelerate diabetic cutaneous wound healing is unclear. In this study, human umbilical vein endothelial cells (HUVECs) were treated with high glucose. We found that DF-Ex could reverse the damage produced by high glucose in HUVECs in vitro. A high-fat diet and streptozotocin were used to establish a rat model of type 2 diabetes mellitus (T2DM), and a diabetic cutaneous wound model was established in the T2DM rats. We discovered that subcutaneous injections of DF-Ex could significantly promote re-epithelialization, collagen deposition, skin cell proliferation, angiogenesis and inhibit inflammation to accelerate diabetic cutaneous wound healing. We further explored the underlying mechanism and found that DF-Ex exerted positive effects by activating the Akt/β-catenin pathway. This research revealed that DF-Ex may provide a new treatment strategy for diabetic cutaneous wound healing.
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http://dx.doi.org/10.1080/15384101.2021.1894813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018430PMC
March 2021

TET1 promotes RXRα expression and adipogenesis through DNA demethylation.

Biochim Biophys Acta Mol Cell Biol Lipids 2021 Jun 6;1866(6):158919. Epub 2021 Mar 6.

School of Life Science and Technology, ShanghaiTech University, 393 Middle Huaxia Road, Shanghai 201210, China. Electronic address:

Adipose tissue is important for systemic metabolic homeostasis in response to environmental changes, and adipogenesis involves dynamic transcriptional regulation. Ten-eleven translocation (TET) enzymes (TET1, 2 and 3) oxidize the 5-methylcytosine (5mC) in DNA to 5-hydroxylmethylcytosine (5hmC), which associates with transcriptional activation. Step by step, 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) are further generated by TETs and the cytosine can be restored through base-excision repair. It is still unclear how DNA demethylation is involved in adipogenesis. Through a phenotypic screen, we found TET inhibition decreased adipocyte differentiation from mesenchymal stem cells (MSCs). Comparing with the undifferentiated MSCs, the differentiated adipocytes exhibited much higher levels of 5hmC and slightly increased 5fC and 5caC. Higher 5hmC was associated with better differentiation at single-cell level by image analysis. TET1 is upregulated in differentiation and depletion of it significantly impaired the gain of 5hmC. Furthermore, Tet1 depletion significantly hampered the adipocyte differentiation. Using RNA-seq, 5mC and 5hmC-DNA immunoprecipitation, we found that Tet1 knockout led to lower expression of genes associated with lipid metabolism and fat cell differentiation. Genes with loss of 5mC or gain of 5hmC in adipocytes include Lipe, Bmp4 and Rxra, etc. RXRα agonist partially rescued the inhibitory effect of Tet1 knockout for adipogenesis. So, Rxra is one of the critical TET1 modulated genes. Together, TET1-mediated active DNA demethylation plays an important role in adipogenesis.
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http://dx.doi.org/10.1016/j.bbalip.2021.158919DOI Listing
June 2021

Extracellular Vesicles: Novel Roles in Neurological Disorders.

Stem Cells Int 2021 17;2021:6640836. Epub 2021 Feb 17.

Key Laboratory of Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, 212013 Zhenjiang, Jiangsu, China.

Exosomes are small extracellular vesicles (EVs) secreted by almost all cells, which have been recognized as a novel platform for intercellular communication in the central nervous system (CNS). Exosomes are capable of transferring proteins, nucleic acids, lipids, and metabolites between neurons and glial cells, contributing to CNS development and maintenance of homeostasis. Evidence shows that exosomes originating from CNS cells act as suppressors or promoters in the initiation and progression of neurological disorders. Moreover, these exosomes have been shown to transfer molecules associated with diseases through the blood-brain barrier (BBB) and thus can be detected in blood. This unique feature enables exosomes to act as potential diagnostic biomarkers for neurological disorders. In addition, a substantial number of researches have indicated that exosomes derived from mesenchymal stem cells (MSCs) have repair effects on neurological disorders. Herein, we briefly introduce the roles of exosomes under physiological and pathological conditions. In particular, novel roles of exosomes as potential diagnostic biomarkers and therapeutic tools for neurological disorders are highlighted.
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http://dx.doi.org/10.1155/2021/6640836DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904361PMC
February 2021

Engineered Extracellular Vesicles for Cancer Therapy.

Adv Mater 2021 Apr 28;33(14):e2005709. Epub 2021 Feb 28.

Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki, FI-00014, Finland.

Extracellular vesicles (EVs) have emerged as a novel cell-free strategy for the treatment of many diseases including cancer. As a result of their natural properties to mediate cell-to-cell communication and their high physiochemical stability and biocompatibility, EVs are considered as excellent delivery vehicles for a variety of therapeutic agents such as nucleic acids and proteins, drugs, and nanomaterials. Increasing studies have shown that EVs can be modified, engineered, or designed to improve their efficiency, specificity, and safety for cancer therapy. Herein, a comprehensive overview of the recent advances in the strategies and methodologies of engineering EVs for scalable production and improved cargo-loading and tumor-targeting is provided. Additionally, the potential applications of engineered EVs in cancer therapy are discussed by presenting prominent examples, and the opportunities and challenges for translating engineered EVs into clinical practice are evaluated.
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http://dx.doi.org/10.1002/adma.202005709DOI Listing
April 2021

Evaluation of groundwater quality using an integrated approach of set pair analysis and variable fuzzy improved model with binary semantic analysis: A case study in Jiaokou Irrigation District, east of Guanzhong Basin, China.

Sci Total Environ 2021 May 20;767:145247. Epub 2021 Jan 20.

Northwest Engineering Corporation Limited, Xi'an 710054, Shaanxi, China.

The study proposes a new set pair analysis - variable fuzzy improved model (SPA-VFIM) by integrating the set pair analysis (SPA), variable fuzzy sets (VFS) theory, and binary semantic (BS). The SPA-VFIM method gets over the shortcomings of the existing SPA and VFS methods. The use of BS solves the problem of the weighted average principle (WAP) not being conducive to the timeliness of assessment. The existing and newly proposed methods were used to evaluate the groundwater quality in the Jiaokou Irrigation District, China, to show the advantages of the SPA-VFIM method. The results of SPA-VFIM method show that more than 80% of the groundwater, mainly distributed in the central and western parts of the study region, is assessed as level IV and level V, according to the Chinese Groundwater Quality Standards (GB/T 14848-2017). The assessment results are consistent with ground-based measurements of water quality, and NO, Na, SO, Total Hardness (TH), and Cl are the main pollutants. The SPA-VFIM and existing methods were compared. The results indicate that 57.69% and 76.92% of the assessment results by the SPA-VFIM method agree well with that of the SPA and VFS methods, respectively, indicating that the new SPA-VFIM method is reasonable and effective in groundwater quality. The results of groundwater quality assessment show that local authorities should pay more attention to areas with poor and very poor groundwater quality. These findings are beneficial to the future groundwater management plans dealing with drinking and irrigation and the sustainable development of water resources in this irrigation district.
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http://dx.doi.org/10.1016/j.scitotenv.2021.145247DOI Listing
May 2021

Assessing groundwater pollution and potential remediation processes in a multi-layer aquifer system.

Environ Pollut 2020 Aug 24;263(Pt A):114669. Epub 2020 Apr 24.

Department of Physical and Environmental Sciences, University of Toronto, Scarborough, Toronto, Canada.

Pumping-induced leakage across aquitards may induce a deterioration of water quality in multi-layer aquifer systems. It is critical to understand long-term trends of water quality parameters when assessing the sustainability of groundwater abstraction. Daily drinking water needs of 2.2 million people in Yinchuan region of northwest China are solely met by groundwater resources, but long-term groundwater withdrawal has created an extensive cone of depression (294 km in area) in confined aquifer causing increased vertical recharge. In this study, a model was established and calibrated with head data, then was incorporated with field tracer tests to provide key information on the hydro-dispersive characteristics of the contaminant for assessing both the current and future state of the aquifer system. The results confirmed a close association between water quality deterioration and high downward fluxes of high chloride groundwater, most notably near the center of the cone of depression. On a temporal scale, water quality degradation remains slow, largely due to the high, pre-existing storage of good quality water. Modeling suggests that the water quality in the upper confined aquifer will lose its potability over a 25 km and 50 km area within 200 years under the current and intensified pumping conditions, respectively. Elevated chloride values were also detected toward the east of the cone, highlighting the impact of hydrological settings on the vertical groundwater flow. Modeling of potential aquifer remediation shows an even slower response with a further 250 years or more required for potability to be restored in affected areas. The findings can provide valuable guidance to for decision makers and support the sustainable management of aquifer exploitation.
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http://dx.doi.org/10.1016/j.envpol.2020.114669DOI Listing
August 2020

Groundwater quality assessment using a new integrated-weight water quality index (IWQI) and driver analysis in the Jiaokou Irrigation District, China.

Ecotoxicol Environ Saf 2021 Apr 30;212:111992. Epub 2021 Jan 30.

School of Water and Environment, Chang'an University, Xi'an 710054, Shaanxi, China; Key Laboratory of Subsurface Hydrology and Ecological Effects in Arid Region of the Ministry of Education, Chang'an University, Xi'an 710054, Shaanxi, China.

Groundwater is an important water resource in arid and semi-arid regions. The impact of human activities on groundwater is increasing. After 60 years running, the groundwater quality and its formation mechanism are imperative questions needed to be answered in Jiaokou Irrigation District, Guanzhong Basin, China. In this study, the quality of groundwater in Jiaokou Irrigation District was assessed by a new integrated-weight water quality index (IWQI), and the groundwater chemistry is studied through integrated statistical, geostatistical and hydrogeochemical approaches. The patterns for the average anion and cation concentrations were HCO > SO > Cl > NO > CO > NO, and Na > Mg Ca > K > NH, respectively. Statistics showed that the major water chemistry types were HCONa, SO·Cl-Na, and Cl·SO-Na. A new integrated-weight water quality index (IWQI) was proposed based on the entropy-weighted method and CRITIC method and showed excellent performance for explaining and evaluating the groundwater quality. The IWQI results show 65.33% of groundwater, mainly distributed in the central and western parts of this study area, was unsuitable for drinking. Furthermore, SO, HCO, Cl, NO, and Na had more important effects on groundwater quality. The weathering process affecting groundwater quality in the study area is carbonate dissolution, followed by silicate weathering and evaporite dissolution, whereas the major geochemical processes include the dissolution and precipitation of calcite, as well as the dissolution of dolomite and gypsum (anhydrite). Cation exchange also plays an important role in the hydrogeochemical evolution of groundwater with a long residence time. Anthropogenic activities affecting groundwater quality included long-term irrigation infiltration and excessive use of fertilizers. The findings and the results of the study can improve understanding of the processes driving groundwater chemistry in Jiaokou Irrigation District, and can be used for reference to other similar regions in the world.
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http://dx.doi.org/10.1016/j.ecoenv.2021.111992DOI Listing
April 2021

Circular RNA ITCH suppresses metastasis of gastric cancer via regulating miR-199a-5p/Klotho axis.

Cell Cycle 2021 Mar-Mar;20(5-6):522-536. Epub 2021 Jan 27.

Aoyang Institute of Cancer, Jiangsu University, Suzhou, China.

Circular RNAs (circRNAs) are considered as a new regulatory factor in growth, metastasis and therapeutic resistance of human cancers. But the clinical significance and underlying mechanism of circular RNA ITCH (circ-ITCH) in gastric cancer (GC) remain unknown. In the present study, we found that circ-ITCH was down-regulated in GC cell lines, GC tissues and their serum-derived exosomes. The level of circ-ITCH was related to invasion depth. Functional assays showed that circ-ITCH overexpression inhibited the proliferation, migration, invasion and epithelial mesenchymal transition (EMT) of GC cells, whereas circ-ITCH knockdown appeared an opposite effect. Bioinformatic analysis and luciferase reporter assay confirmed that circ-ITCH acted as miR-199a-5p sponge and increased the level of Klotho. The expression level of miR-199-5p was up-regulated in GC tissues and negatively correlated with that of circ-ITCH. MiR-199a-5p mimics reversed the effects on inhibiting metastasis induced by circ-ITCH overexpression and decreased the level of Klotho in GC cells. Our findings indicate that circ-ITCH suppresses metastasis of GC by acting as the sponge of miR-199a-5p and increasing Klotho expression, which serves as a potential biomarker and targets for the diagnosis and therapy of GC. CircRNAs: circular RNAs; GC: gastric cancer; circ-ITCH: circular RNA Itchy E3 ubiquitin protein ligase; ceRNA: competitive endogenous RNA; EMT: Epithelial-mesenchymal transition; siRNA: Small interfering RNA; TEM: transmission electron microscope; NTA: nanoparticle tracking analysis.
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http://dx.doi.org/10.1080/15384101.2021.1878327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018440PMC
January 2021

CircRNAs: Emerging Bladder Cancer Biomarkers and Targets.

Front Oncol 2020 8;10:606485. Epub 2021 Jan 8.

Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China.

Circular RNAs (circRNAs) are newly discovered intriguing RNAs due to the covalently closed loop structure, high stability, tissue specificity, and functional diversity. In recent years, a large number of circRNAs have been identified through high-throughput sequencing technology and bioinformatics methods, the abnormal expression of circRNAs are closely related to many diseases including bladder cancer (BC). CircRNAs have been proven to have several functions, such as acting as a regulator of parental gene transcription, miRNA sponge and interacting with proteins to regulate its expression. In addition, some circRNAs have been identified to encode proteins. CircRNAs have the characteristics of high abundance, high stability, wide distribution in body fluids, tissue specificity, and developmental stage specificity, which determine that circRNAs has great potential to be utilized as biomarkers for BC. Herein, we briefly summarize the biogenesis, functions and roles, and the current research progress of circRNAs in BC with a focus on the potential application for BC diagnosis, treatment, and prognosis.
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http://dx.doi.org/10.3389/fonc.2020.606485DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821354PMC
January 2021

Spermatorrhea in a Chinese patient with temporal lobe epilepsy: a case report.

J Int Med Res 2021 Jan;49(1):300060520982814

Department of Neurology and Research Center of Neurology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Epilepsy is a chronic neurological disorder that is characterized by episodes of seizure. Sexual dysfunction has been reported in patients with seizure, which mostly manifests as erectile dysfunction and premature ejaculation in men. In this study, we report the case of a 65-year-old Chinese man with frequent spermatorrhea. Electroencephalography suggested local epilepsy in the left temporal lobe. After treatment with anti-epilepsy drugs, the symptoms disappeared and did not recur. To the best of our knowledge, this is the first reported case of epilepsy-induced spermatorrhea. The symptoms of spermatorrhea are probably a rare manifestation of seizure. When repetitive stereotyped symptoms occur, seizure should be considered, and tentative anti-epileptic treatment may be a good option.
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http://dx.doi.org/10.1177/0300060520982814DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812405PMC
January 2021

The clinical efficacy of acupoint sticking combined with massage to treatment functional dyspepsia: A protocol of systematic review and meta-analysis.

Medicine (Baltimore) 2020 Dec;99(51):e23869

GuangHua Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai, China.

Background: The objective of this meta-analysis was to summarize and identify the available evidence from studies to estimate the clinical value of acupoint sticking combined with massage (ASM) in the treatment of functional dyspepsia (FD), and provide clinicians with evidence on which to base their clinical decision making.

Methods: This review will include all studies comparing clinical efficacy of ASM in the treatment of FD. The search strategy will be performed in 10 databases. We will not establish any limitations to language and publication status, published from inception to the August 2020. Two reviewers will screen, select studies, extract data, and assess quality independently. Outcome is alleviation of global dyspeptic symptoms, alleviation of individual dyspeptic symptoms, quality-of-life improvement, and safety. The methodological quality including the risk of bias of the included studies will be evaluated. We will carry out statistical analysis using RevMan 5.3 software.

Results: This study will summarize current evidence to assess the efficacy and safety of ASM in the treatment of FD.

Conclusion: The findings of this study will provide helpful evidence for the clinician, and will promote further studies, as well as studying the value of ASM.

Registration Number: INPLASY2020110072 (DOI number: 10.37766/inplasy2020.11.0072).
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http://dx.doi.org/10.1097/MD.0000000000023869DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7748355PMC
December 2020

Hidden Intermediate State and Second Pathway Determining Folding and Unfolding Dynamics of GB1 Protein at Low Forces.

Phys Rev Lett 2020 Nov;125(19):198101

Research Institute for Biomimetics and Soft Matter, Fujian Provincial Key Lab for Soft Functional Materials Research, Department of Physics, Xiamen University, Xiamen 361005, China.

Atomic force microscopy experiments found that GB1, a typical two-state model protein used for study of folding and unfolding dynamics, can sustain forces of more than 100 pN, but its response to low forces still remains unclear. Using ultrastable magnetic tweezers, we discovered that GB1 has an unexpected nonmonotonic force-dependent unfolding rate at 5-160 pN, from which a free energy landscape with two main barriers and a hidden intermediate state was constructed. A model combining two separate models by Dudko et al. with two pathways between the native state and this intermediate state is proposed to rebuild the unfolding dynamics over the full experimental force range. One candidate of this transient intermediate state is the theoretically proposed molten globule state with a loosely collapsed conformation, which might exist universally in the folding and unfolding processes of two-state proteins.
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http://dx.doi.org/10.1103/PhysRevLett.125.198101DOI Listing
November 2020

Extracellular vesicles: A bright star of nanomedicine.

Biomaterials 2021 Feb 6;269:120467. Epub 2020 Nov 6.

Zhenjiang Key Laboratory of High Technology Research on Exosomes Foundation and Transformation Application, 301 Xuefu Road, Zhenjiang, Jiangsu, PR China; Jiangsu University, 301 Xuefu Road, Zhenjiang, Jiangsu, PR China; Aoyang Institute of Cancer, Jiangsu University, 279 Jingang Road, Suzhou, 215600, Jiangsu, PR China. Electronic address:

Extracellular vesicles (EVs) have unique structural, compositional, and morphological characteristics as well as predominant physiochemical stability and biocompatibility properties. They play a crucial role in pathophysiological regulation, and also have broad prospects for clinical application in the diagnosis, prognosis, and therapy of disease, and tissue regeneration and repair. Herein, the biosynthesis and physiological functions and current methods for separation and identification of EVs are summarized. Specifically, engineered EVs may be used to enhance targeted therapy in cancer and repair damaged tissues, and they may be developed as an individualized imaging diagnostic reagent, among other potential applications. We will focus on reviewing recent studies on engineered EVs in which alterations enhanced their therapeutic capability or diagnostic imaging potential via physical, chemical, and biological modification approaches. This review will clarify the superior biological functions and powerful therapeutic potential of EVs, particularly with regard to new designs based on EVs and their utilization in a new generation of nanomedicine diagnosis and treatment platforms.
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http://dx.doi.org/10.1016/j.biomaterials.2020.120467DOI Listing
February 2021

The deubiquitinating enzyme USP1 modulates ERα and modulates breast cancer progression.

J Cancer 2020 12;11(23):6992-7000. Epub 2020 Oct 12.

Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, 212000, China.

Breast cancer is one of the most common malignancies worldwide, while the luminal types (ERα positive) accounts for two third of all breast cancer cases. Although ERα positive breast cancer could be effective controlled by endocrine therapy, most of the patients will develop endocrine resistance, which becomes a headache clinical issue for breast cancer field. Endocrine resistance could be caused by multiple pathway disorders, the dys-regulation of ERα signaling might be a critical factor, which makes it urgent and important to reveal the potential molecular mechanism of ERα signaling. In our current study, we identified a new deubiquitination enzyme USP1 through screening the whole DUB (Deubiquitinases) siRNA library. The expression of USP1 is elevated in human breast cancer compared with normal mammary tissues. Importantly, USP1 expression levels are specially correlated with poor survival in ERα positive patients. USP1 depletion inhibited breast cancer cell progression and ERα signaling activity. Immuno-precipitation assays indicate that USP1 associates with ERα and promotes its stability possibly via inhibiting ERα K48-linked poly-ubiquitination. In conclusion, our data implicate a non-genomic mechanism by USP1 via stabilizing ERα protein controls ERα target gene expression linked to breast cancer progression.
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http://dx.doi.org/10.7150/jca.50477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591989PMC
October 2020

Autophagy and liver cancer.

Clin Mol Hepatol 2020 10 1;26(4):606-617. Epub 2020 Oct 1.

Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS, USA.

Autophagy is a highly conserved catabolic process that degrades cytosolic proteins and organelles via formation of autophagosomes that fuse with lysosomes to form autolysosomes, whereby autophagic cargos are degraded. Numerous studies have demonstrated that autophagy plays a critical role in the regulation of liver physiology and homeostasis, and impaired autophagy leads to the pathogenesis of various liver diseases such as viral hepatitis, alcohol associated liver diseases (AALD), non-alcoholic fatty liver diseases (NAFLD), and liver cancer. Recent evidence indicates that autophagy may play a dual role in liver cancer: inhibiting early tumor initiation while promoting progression and malignancy of already formed liver tumors. In this review, we summarized the progress of current understanding of how hepatic viral infection, alcohol consumption and diet-induced fatty liver diseases impair hepatic autophagy. We also discussed how impaired autophagy promotes liver tumorigenesis, and paradoxically how autophagy is required to promote the malignancy and progression of liver cancer. Understanding the molecular mechanisms underlying how autophagy differentially affects liver cancer development and progression may help to design better therapeutic strategies for prevention and treatment of liver cancer.
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http://dx.doi.org/10.3350/cmh.2020.0169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641568PMC
October 2020

Geospatial Distribution and Potential Noncarcinogenic Health Risk Assessment of Nitrate Contaminated Groundwater in Southern India: A Case Study.

Arch Environ Contam Toxicol 2021 Jan 3;80(1):107-119. Epub 2020 Oct 3.

School of Water and Environment, Chang'an University, No. 126 Yanta Road, Xi'an, 710054, Shaanxi, China.

Groundwater nitrate pollution is a serious threat to human health in many regions of the world. The present study was performed to assess the nitrate contamination in groundwater in the region of Nirmal province, South India, where people purely depend on groundwater for drinking purposes. The associated human health risks for different age groups (male, female, and children) also were evaluated based on the United States Environmental Protection Agency model. Results indicate that nitrate concentration in groundwater is in the range of 0.8-130 mg/L with a mean of 36.51 mg/L. Furthermore, 26.47% of groundwater samples exceeded the WHO drinking water guidelines for NO in the study region. The contribution of oral ingestion is very higher than the dermal contact in the total hazard quotient or noncarcinogenic health risk. The total hazard quotient values ranged from 0.02 to 3.13 for adult males, 0.02 to 3.70 for adult females, and 0.03 to 4.32 for children. The health risk assessment highlights that children are more exposed to the noncarcinogenic health risks of nitrate than adult females and males in the study region. Therefore, specific groundwater quality measures should be formulated to address the health risk problems for children in the study region.
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http://dx.doi.org/10.1007/s00244-020-00762-7DOI Listing
January 2021

Preparation of PP-g-(AA-MAH) Fibers Using Suspension Grafting and Melt-Blown Spinning and its Adsorption for Aniline.

Polymers (Basel) 2020 Sep 22;12(9). Epub 2020 Sep 22.

School of Environmental Science and Engineering, Nanjing Tech University, Nanjing 211816, China.

This paper uses polypropylene (PP) as the matrix and acrylic acid (AA) and maleic anhydride (MAH) as functional monomers to prepare PP-g-(AA-MAH) fibers by suspension grafting and melt-blown spinning technology that are easy to industrially scale-up. The fibers can be used to adsorb aniline. Results showed that the grafting ratio reached the maximum of 12.47%. The corresponding optimal conditions were grafting time of 3 h, AA: MAH = 0.75, total monomer content of 55%, benzoyl peroxide 1.4%, xylene concentration of 6 mL/g PP, and deionized water content of 8 mL/g PP. Owing to its good fluidity and thermal stability, the product of suspension grafting can be used for melt-blown spinning. Infrared spectroscopic and nuclear magnetic resonance spectroscopic analyses indicated that AA and MAH were successfully grafted onto PP fibers. After grafting, the hydrophilicity of PP-g-(AA-MAH) fiber increased. Therefore, it had higher absorptivity for aniline and the adsorption capacity could reach 42.2 mg/g at 45 min and pH = 7. Moreover, the PP-g-(AA-MAH) fibers showed good regeneration performance.
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http://dx.doi.org/10.3390/polym12092157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7569868PMC
September 2020

Application of Cryogenic Transmission Electron Microscopy for Evaluation of Vaccine Delivery Carriers.

Methods Mol Biol 2021 ;2183:499-511

Human Health Therapeutics, National Research Council Canada, Ottawa, ON, Canada.

Cryogenic transmission electron microscopy (Cryo-TEM) enables visualizing the physicochemical structure of nanocarriers in solution. Here, we demonstrate the typical applications of Cryo-TEM in characterizing archaeosome-based vesicles as antigen carriers, including the morphology and size of vaccine carriers. Cryo-TEM tomography, incorporated with immunogold labeling for identifying and localizing the antigens, reveals the antigen distribution within archaeosomes in three dimensions (3D).
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http://dx.doi.org/10.1007/978-1-0716-0795-4_28DOI Listing
March 2021

Groundwater chemistry, distribution and potential health risk appraisal of nitrate enriched groundwater: A case study from the semi-urban region of South India.

Ecotoxicol Environ Saf 2021 Jan 15;207:111277. Epub 2020 Sep 15.

School of Water and Environment, Chang'an University, No. 126 Yanta Road, Xi'an, 710054, Shaanxi, China; Key Laboratory of Subsurface Hydrology and Ecological Effects in Arid Region of the Ministry of Education, Chang'an University, No. 126 Yanta Road, Xi'an, 710054, Shaanxi, China.

In recent years, an elevated concentration of nitrate in groundwater has been a growing problem on a global scale. It directly shows the adverse effects on human health via various intake pathways. Herein, the aim of the present study was to evaluate the nitrate concentration in groundwater and its associated human health risk in various age groups (females, males and children) in the investigated region. For this purposes, thirty groundwater samples were collected and analyzed physico-chemical parameters including nitrate concentration. The results showed that, the concentration of nitrate ranges from 14 to 82 mg/L and about 43.3% of these groundwater samples beyond the safe level of 45 mg/L according to Indian guidelines. The higher nitrate contamination is observed in the vicinity of Sarvepalli and Timmapur villages where groundwater chemistry is majorly influenced by anthropogenic sources. Health risks were assessed through oral/ingestion and dermal contact exposure routes for females, males and children population in the study region. Oral exposure was much higher than dermal contacts. For the non-carcinogenic risk, the HI values of groundwater in the investigated region varied from 0.313 to 1.976 (mean of 0.941) for males, 0.370 to 2.336 (mean of 1.112) for females and 0.443 to 2.694 (mean of 1.314) for children. The health risk assessment for nitrate divulged that 60%, 57% and 50% of groundwater samples pose a non-carcinogenic health risk for children, females and males, respectively.
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http://dx.doi.org/10.1016/j.ecoenv.2020.111277DOI Listing
January 2021

Tumor-Educated Neutrophils Activate Mesenchymal Stem Cells to Promote Gastric Cancer Growth and Metastasis.

Front Cell Dev Biol 2020 13;8:788. Epub 2020 Aug 13.

Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China.

In response to tumor signals, mesenchymal stem cells (MSCs) are recruited to tumor sites and activated to promote tumor progression. Emerging evidences suggest that in addition to tumor cells, non-tumor cells in tumor microenvironment could also interact with MSCs to regulate their phenotype and function. However, the mechanism for MSCs regulation in gastric cancer has not been fully understood. In this study, we reported that tumor-educated neutrophils (TENs) induced the transformation of MSCs into cancer-associated fibroblasts (CAFs) which in turn remarkably facilitated gastric cancer growth and metastasis. Mechanistic study showed that TENs exerted their effects by secreting inflammatory factors including IL-17, IL-23 and TNF-α, which triggered the activation of AKT and p38 pathways in MSCs. Pre-treatment with neutralizing antibodies to these inflammatory factors or pathway inhibitors reversed TENs-induced transformation of MSCs to CAFs. Taken together, these data suggest that TENs promote gastric cancer progression through the regulation of MSCs/CAFs transformation.
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http://dx.doi.org/10.3389/fcell.2020.00788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438587PMC
August 2020

Potentially toxic elements (PTEs) pollution in surface soils in a typical urban region of south India: An application of health risk assessment and distribution pattern.

Ecotoxicol Environ Saf 2020 Oct 25;203:111055. Epub 2020 Jul 25.

School of Computing Engineering and Physical Sciences, University of the West of Scotland, Paisley PA1 2BE, UK.

The pollution level of potentially toxic elements (PTEs) in surface soils is detrimental to the ecosystem and human health. In this research, various indices such as an index of geo-accumulation (I), contamination factor (CF), degree of contamination (DC), and principal component analysis (PCA) were implemented to identify and evaluate the soil PTEs pollution; and then human health risk assessment model used to establish the link between heavy metals pollution and human health in the urban region of south India. Results exhibited that the mean concentration of Cr, Cu, Ni and Zn were found to be 1.45-6.03 times greater than the geochemical background values. Cr and Cu were the most profuse PTEs measured in the soils. The pollution indices suggest that soil of the study region is mainly moderate to highly polluted. The non-carcinogenic health risk assessment proposed by the United States Environmental Protection Agency (USEPA) suggested the mean hazard indices (HIs) were below one which denotes no significant of non-carcinogenic risks to both children and adults. Furthermore, carcinogenic risk assessment results advised ~80% of cancer risk was caused by Cr contents, while other heavy metals indicate that neither children nor adults in the study region were of carcinogenic risks.
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http://dx.doi.org/10.1016/j.ecoenv.2020.111055DOI Listing
October 2020

Hydrogeochemistry and fluoride contamination in Jiaokou Irrigation District, Central China: Assessment based on multivariate statistical approach and human health risk.

Sci Total Environ 2020 Nov 24;741:140460. Epub 2020 Jun 24.

School of Water and Environment, Chang'an University, Xi'an 710054, Shaanxi, China; Key Laboratory of Subsurface Hydrology and Ecological Effects in Arid Region of the Ministry of Education, Chang'an University, Xi'an 710054, Shaanxi, China.

Too little and too much fluorine are potentially hazardous for human health. In the Jiaokou Irrigation District, ionic concentrations, hydrogeochemistry, and fluoride contaminations were analyzed using correlation matrices, principal component analysis (PCA), and health risk assessment. The patterns for the average cation and anion concentrations were Na > Mg > Ca > K and SO > HCO > Cl > NO > CO. The fluoride concentrations ranged between 0.29 and 8.92 mg/L (mean = 2.4 mg/L). 5% of the samples displayed lower than the recommended limit of 0.5 mg/L fluoride content, while 69% exceeded the allowable limits of 1.5 mg/L for drinking. The low F content is distributed in a small part of the southeast, while elevated F mainly in the central area of the study region. The PCA results indicated three principal components (PC), PC1 having the greatest variance (45.83%) and affected by positive loadings of TDS, Cl, SO, Na, and Mg, PC2 accounting for 17.03% and dominated by Ca, pH, HCO, and K, and PC3 representing 12.17% and mainly comprising of CO. High fluoride groundwater is of the SO-Cl-Na type, followed by HCO-Na type. Evaporation and ion exchange play important roles in producing high fluoride groundwater. Furthermore, saturation index and anthropogenic activities also promote the high fluoride concentrations. The values of the total hazard quotient of 93% groundwater samples were greater than 1 for infants, followed by 85% for children, 68% for teenagers, and 57% for adults. Non-carcinogenic health risks to infants may occur over the entire study area, while for adults, health risks are mainly found in Weinan and Pucheng. High fluorine may have a potential negative influence on neurodevelopment, especially for infants and children. Adults in this region have serious dental fluorosis and skeletal fluorosis because of long-term drinking of high fluoride groundwater. Therefore, measures, including using organic fertilizers, strengthening defluoridation process, and optimizing water supply strategies, are necessary in this area.
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http://dx.doi.org/10.1016/j.scitotenv.2020.140460DOI Listing
November 2020

Groundwater chemistry integrating the pollution index of groundwater and evaluation of potential human health risk: A case study from hard rock terrain of south India.

Ecotoxicol Environ Saf 2020 Dec 1;206:111217. Epub 2020 Sep 1.

CSIR-National Geophysical Research Institute, Hyderabad, 500 007, Telangana, India.

Groundwater is an important resource for drinking and irrigation purposes and also the significant route of human exposure in most of the arid and semi-arid regions of the world. In view of this, 43 groundwater samples were collected and analyzed for various physico-chemical parameters. Particularly, this study integrates the groundwater contamination by comparing it to national guidelines and the impact of fluoride and nitrate on health risk were quantified through the model recommended by the United States Environmental Protection Agency (USEPA). The groundwater of the investigated region is slightly alkaline in nature with hydrochemical facies of groundwater is predominantly characterized by Ca-Mg-HCO and Ca-Mg-Cl water types. The results show that the concentrations of groundwater nitrate and fluoride range from 2.2 to 165 mg/L and 0.84 to 4.3 mg/L, and 55.81% and 65% of groundwater exceed the national guidelines for drinking purposes, respectively. The pollution index of the groundwater (PIG) method unveiled that low quality and moderate quality of water account for 40% and 4.65% of collected groundwater samples, respectively. The results of non-carcinogenic health risk ranged from 0.63 to 5.31 ± 2.59 for adults, 0.85 to 7.18 ± 3.50 for children and 0.98 to 8.29 ± 4.04 for infants, indicating health risk was higher in infants and children as compared to the adults in the study region.
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http://dx.doi.org/10.1016/j.ecoenv.2020.111217DOI Listing
December 2020

Investigation of Mechanical Properties of Large Shape Memory Alloy Bars under Different Heat Treatments.

Materials (Basel) 2020 Aug 24;13(17). Epub 2020 Aug 24.

School of Civil Engineering, Zhengzhou University, Zhengzhou 450001, China.

Shape memory alloys (SMAs) are a class of functional materials that possess unique thermomechanical properties, such as shape memory effect (SME), superelasticity (SE), damping, and good fatigue and corrosion resistance, which enable them to become ideal materials for applications in earthquake engineering. Numerous studies have shown that the mechanical properties of superelastic SMAs mainly depend on the wire form, or the relationship between the microstructure and thermally induced phase transitions. However, extremely few studies have elucidated the effects of the heat-treatment strategy, size effect of large diameters, and cyclic loading. Herein, the mechanical properties of SMA bars, such as residual strain, energy dissipation, and equivalent damping ratio, were studied with different heat-treatment strategies, cyclic loadings, and strain amplitudes; this was achieved by conducting cyclic tensile tests on SMA bars with four different diameters. The results indicate that the maximum phase transformation stress was obtained with a 14 mm SMA bar subjected to heat treatment at 400 ℃ for 15 min. The mechanical properties were relatively stable after five loading-unloading cycles, which should be considered in engineering applications. The test results provide a mechanical basis for using large SMA bars in self-centering structures in seismic regions.
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http://dx.doi.org/10.3390/ma13173729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7504284PMC
August 2020