Publications by authors named "Minglu Liu"

14 Publications

  • Page 1 of 1

Yohimbine Directly Induces Cardiotoxicity on Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

Cardiovasc Toxicol 2021 Nov 24. Epub 2021 Nov 24.

Department of Cardiothoracic Surgery, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, 1678 Dong Fang Road, Shanghai, 200127, China.

Yohimbine is a highly selective and potent α-adrenoceptor antagonist, which is usually treated as an adjunction for impotence, as well for weight loss and natural bodybuilding aids. However, it was recently reported that Yohimbine causes myocardial injury and controversial results were reported in the setting of cardiac diseases. Here, we used human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) as a model system to explore electrophysiologic characterization after exposure to Yohimbine. HiPSC-CMs were differentiated by employment of inhibitory Wnt compounds. For analysis of electrophysiological properties, conventional whole-cell patch-clamp recording was used. Specifically, spontaneous action potentials, pacemaker currents (I), sodium (Na) channel (I), and calcium (Ca) channel currents (I) were assessed in hiPSC-CMs after exposure to Yohimbine. HiPSC-CMs expressed sarcomeric-α-actinin and MLC2V proteins, as well as exhibited ventricular-like spontaneous action potential waveform. Yohimbine inhibited frequency of hiPSC-CMs spontaneous action potentials and significantly prolonged action potential duration in a dose-dependent manner. In addition, rest potential, threshold potential, amplitude, and maximal diastolic potential were decreased, whereas APD/APD was prolonged. Yohimbine inhibited the amplitude of I in low doses (IC = 14.2 μM, n = 5) and inhibited I in high doses (IC = 139.7 μM, n = 5). Whereas Yohimbine did not affect the activation curves, treatment resulted in left shifts in inactivation curves of both Na and Ca channels. Here, we show that Yohimbine induces direct cardiotoxic effects on spontaneous action potentials of I and I in hiPSC-CMs. Importantly, these effects were not mediated by α-adrenoceptor signaling. Our results strongly suggest that Yohimbine directly and negatively affects electrophysiological properties of human cardiomyocytes. These findings are highly relevant for potential application of Yohimbine in patients with atrioventricular conduction disorder.
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http://dx.doi.org/10.1007/s12012-021-09709-3DOI Listing
November 2021

Understanding the Role of Vib1 in Gene Expression during Cellulose Degradation.

J Fungi (Basel) 2021 Jul 29;7(8). Epub 2021 Jul 29.

State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.

Vib1, a member of the Ndt80/PhoG-like transcription factor family, has been shown to be essential for cellulase production of . Here, we combined transcriptomic and genetic analyses to gain mechanistic insights into the roles of Vib1 during cellulose degradation. Our transcriptome analysis showed that the deletion caused 586 genes with decreased expression and 431 genes with increased expression on cellulose. The downregulated genes were enriched for Gene Ontology terms associated with carbohydrate metabolism, transmembrane transport, oxidoreductase activity, and transcription factor activity. Of the 258 genes induced by cellulose, 229 showed no or decreased expression in Δ on cellulose, including almost all (hemi)cellulase genes, crucial sugar transporter genes (IDs:69957, 3405), and the genes encoding main transcriptional activators Xyr1 and Ace3. Additionally, Vib1 also regulated the expression of genes involved in secondary metabolism. Further comparison of the transcriptomes of Δ and Δ in cellulose revealed that the genes regulated by Vib1 had much overlap with Xyr1 targets especially for the gene set induced by cellulose, presumably whose expression requires the cooperativity between Vib1 and Xyr1. Genetic evidence indicated that Vib1 regulates cellulase gene expression partially via Xyr1. Our results will provide new clues for strain improvement.
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http://dx.doi.org/10.3390/jof7080613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8397228PMC
July 2021

Predictive Biomarkers of Dicycloplatin Resistance or Susceptibility in Prostate Cancer.

Front Genet 2021 27;12:669605. Epub 2021 Jul 27.

Department of Medical Oncology, Chinese PLA General Hospital, Beijing, China.

Background: Prostate cancer (PCa) is among the leading causes of cancer mortality. Dicycloplatin is a newer generation platinum-based drug that has less side effects than cisplatin and carboplatin. However, its effects in PCa is mixed due to lack of appropriate stratifying biomarkers. Aiming to search for such biomarkers, here, we analyze a group of PCa patients with different responses to dicycloplatin.

Methods: We carried out whole-exome sequencing on cell-free DNA (cfDNA) and matched leukocyte DNA from 16 PCa patients before treatment with dicycloplatin. We then compared the clinical characteristics, somatic mutations, copy number variants (CNVs), and mutational signatures between the dicycloplatin-sensitive (nine patients) and dicycloplatin-resistant (seven patients) groups and tested the identified mutations, CNV, and their combinations as marker of dicycloplatin response.

Results: The mutation frequency of seven genes (, , , , , , and ) and CNV rate of four genes (, , , and ) were higher in the resistant group than in the sensitive group, while the CNV rate in six genes (, , , , , and ) were lower in the resistant group than in the sensitive group. A combination of simultaneous mutation in two genes (/ or /) and deletion of together were found capable to predict dicycloplatin resistance with 100% sensitivity and 100% specificity.

Conclusion: We successfully used cfDNA to monitor mutational profiles of PCa and designed an effective composite marker to select patients for dicycloplatin treatment based on their mutational profile.
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http://dx.doi.org/10.3389/fgene.2021.669605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353331PMC
July 2021

Case Report: Pseudoprogression With Nivolumab and Bevacizumab Followed by Recurrent Immune-Related Pneumonitis in Urothelial Carcinoma With Lung Metastasis.

Front Oncol 2020 2;10:611810. Epub 2021 Feb 2.

Department of Oncology, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China.

Background: Combination therapy with immune checkpoint inhibitors (ICIs) and antiangiogenic agents is generally effective and well tolerated and might be effective for metastatic urothelial carcinoma (UC). However, ICI treatment is often associated with unique responses, such as pseudoprogression and ICI-related pneumonitis (CIP), which may influence clinical decision making and affect treatment. Although there have been many studies on the mechanism of pseudoprogression and CIP, the characteristics and relationship of these special events in a clinical setting remain rarely reported.

Case Presentation: Here, we present a patient with lung metastatic UC who underwent surgery and two lines of chemotherapy. The programmed cell death-1 (PD-1) inhibitor nivolumab and antiangiogenics agent bevacizumab were used as maintenance treatments. The patient experienced pseudoprogression after 2 PD-1 inhibitor cycles. The lesions in both lungs were enlarged on computed tomography (CT) imaging, and treatments were continued for another two cycles, after which the tumor size decreased to below baseline, followed by a durable response. However, after 4 months of pseudoprogression, the patient then developed CIP. The CIP was responsive to glucocorticoid therapy but recurred during ICI rechallenge, leading to the termination of immune therapy. Ultimately, the patient achieved durable, stable disease for over 18 months without further anticancer treatment.

Conclusions: Our case shows that pseudoprogression can occur in UC during immunotherapy even when combined with an effective antiangiogenic agent. In addition, pseudoprogression may be correlated with future adverse effects and a durable response. In the management of CIP, early rechallenge with ICIs may lead to CIP recurrence, which could be more severe and needs to be treated early and with appropriate drugs. Clinicians should be aware of atypical responses to ICIs and adjust the treatment plan accordingly.
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http://dx.doi.org/10.3389/fonc.2020.611810DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884808PMC
February 2021

Hyperprogression to camrelizumab in a patient with esophageal squamous cell carcinoma harboring EGFR kinase domain duplication.

J Immunother Cancer 2020 06 23;8(1). Epub 2020 Jun 23.

Department of Oncology, North Ruijin Hospital, Shanghai Jiao Tong University, Shanghai, China

Background: Previous studies have reported that the amplification of some genes, such as and (), may be related to hyperprogressive disease (HPD). Exploring somatic gene alterations might be an effective method to predict HPD. Herein we characterize the somatic alterations in a patient with esophageal squamous cell carcinoma (ESCC) who developed HPD to investigate the potential origins of HPD.

Case Presentation: A man in his mid-40s was diagnosed with ESCC. After the failure of first-line treatment with cisplatin and docetaxel, the patient participated in a phase III randomized, open, multicenter clinical trial (CTR20170307) and subsequently received camrelizumab. After 4 weeks of immunotherapy, the tumor size increased by 79% compared with baseline imaging; the progressive pace was 2.5-fold higher than preimmunotherapy, and a new liver metastasis appeared. A rare EGFR exon 2-28 duplication was discovered in both preimmunotherapy and postimmunotherapy tumor tissues.

Conclusion: This is the first report on a patient with ESCC harboring rare kinase domain duplication in exons 2-28 and developing HPD in the process of camrelizumab treatment. This case suggested that kinase domain duplication might be associated with HPD. Administration of immune checkpoint inhibitor monotherapy in this subgroup of patients harboring kinase domain duplication should be performed with caution. These results need to be further confirmed in a larger cohort of patients.
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http://dx.doi.org/10.1136/jitc-2020-000793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312344PMC
June 2020

MRI-based radiomics nomogram to predict synchronous liver metastasis in primary rectal cancer patients.

Cancer Med 2020 07 31;9(14):5155-5163. Epub 2020 May 31.

Department of Radiology, Changhai Hospital, Shanghai, China.

At the time of diagnosis, approximately 15%-20% of patients with rectal cancer (RC) presented synchronous liver metastasis (SLM), which is the most common cause of death in patients with RC. Therefore, preoperative, noninvasive, and accurate prediction of SLM is crucial for personalized treatment strategies. Recently, radiomics has been considered as an advanced image analysis method to evaluate the neoplastic heterogeneity with respect to diagnosis of the tumor and prediction of prognosis. In this study, a total of 1409 radiomics features were extracted for each volume of interest (VOI) from high-resolution T2WI images of the primary RC. Subsequently, five optimal radiomics features were selected based on the training set using the least absolute shrinkage and selection operator (LASSO) method to construct the radiomics signature. In addition, radiomics signature combined with carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) was included in the multifactor logistic regression to construct the nomogram model. It showed an optimal predictive performance in the validation set as compared to that in the radiomics model. The favorable calibration of the radiomics nomogram showed a nonsignificant Hosmer-Lemeshow test statistic (P > .05). The decision curve analysis (DCA) showed that the radiomics nomogram is clinically superior to the radiomics model. Therefore, the nomogram amalgamating the radiomics signature and clinical risk factors serve as an effective quantitative approach to predict the SLM of primary RC.
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http://dx.doi.org/10.1002/cam4.3185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367643PMC
July 2020

Association of circulating miR-125b and survival in patients with osteosarcoma-A single center experience.

J Bone Oncol 2016 Nov 16;5(4):167-172. Epub 2016 Jun 16.

Department of Orthopedics, The Second Clinical Hospital of Lanzhou University, Lanzhou, China.

Background: It is known that miRNAs play various roles in malignant tumors. This study is designed to investigate whether miR-125b levels can be used to predict the clinical response of patients with osteosarcoma (OS) to cisplatin-based chemotherapy.

Methods: From January 2010 to July 2015, 82 patients with resectable OS and 56 patients with unresectable OS were enrolled. Blood samples were collected and quantitative real-time PCR was applied to determine miR-125b expression. Clinical data was collected through medical records, and patients were treated according to National Comprehensive Cancer Network guidelines on OS.

Results: Our study found that patients with low miR-125b expression had shorter disease-free survival (<0.001) in the OS group, which was verified by Kaplan-Meier analysis and univariate and multivariate Cox analyses (<0.001). For patients with unresectable OS, low miR-125b expression was found to be associated with advanced tumor stages (=0.006). No complete remission was observed, and there were 13 patients with partial remission, 21 with stable disease, and 22 with disease progression. Negative correlation was found between miR-125b expression and response to chemotherapy (<0.001, =-0.606). Furthermore, ROC analysis indicated that miR-125b at the cut point of 0.61 yielded an area under the ROC curve of 0.793 (<0.001, 95% CI: 0.664-0.890) in distinguishing chemotherapy-resistant OS from chemotherapy-sensitive OS, with sensitivity and specificity at 76.9% and 79.1%, respectively. Kaplan-Meier analysis and univariate and multivariate Cox analyses showed that patients with low miR-125b expression suffered shorter overall survival (=0.014, =0.024, and =0.049, respectively).

Conclusion: Down-regulation of circulating miR-125b might have the potential to predict cisplatin-based chemotherapy resistance and poor prognosis in OS.
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http://dx.doi.org/10.1016/j.jbo.2016.06.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5154701PMC
November 2016

Discovery of the mineral brucite (magnesium hydroxide) in the tropical calcifying alga Polystrata dura (Peyssonneliales, Rhodophyta).

J Phycol 2015 Jun 18;51(3):403-7. Epub 2015 May 18.

Department of Geoscience and Materials Science Program, University of Wisconsin, Madison 1215 West Dayton Street, Madison, Wisconsin, 53706-1600, USA.

Red algae of the family Peyssonneliaceae typically form thin crusts impregnated with aragonite. Here, we report the first discovery of brucite in a thick red algal crust (~1 cm) formed by the peyssonnelioid species Polystrata dura from Papua New Guinea. Cells of P. dura were found to be infilled by the magnesium-rich mineral brucite [Mg(OH)2 ]; minor amounts of magnesite and calcite were also detected. We propose that cell infill may be associated with the development of thick (> ~5 mm) calcified red algal crusts, integral components of tropical biotic reefs. If brucite infill within the P. dura crust enhances resistance to dissolution similarly to crustose coralline algae that infill with dolomite, then these crusts would be more resilient to future ocean acidification than crusts without infill.
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http://dx.doi.org/10.1111/jpy.12299DOI Listing
June 2015

COMPUTED TOMOGRAPHY DOSE INDEX MEASUREMENT FOR Hi-ART MEGAVOLTAGE HELICAL CT.

Radiat Prot Dosimetry 2016 Nov 8;171(3):370-374. Epub 2015 Dec 8.

Department of Radiation Oncology, Sichuan Cancer Hospital, Chengdu 610041, China.

On-line megavoltage computed tomography (MVCT) images are used to verify patient daily set-up in Hi-ART helical TomoTherapy unit. To evaluate the patient dose from MVCT scanning in image guidance, weighted computed tomography (CT) dose index (CTDI) was measured with PTW TM30009 CT pencil chamber in head and body phantoms for slice thicknesses of 2, 4 and 6 mm with different scan lengths. Dose length products (DLPs) were subsequently calculated. The CTDI and DLP were compared with XVI kV CBCT and Brilliance simulator CT for routine clinical protocols. It was shown that CTDI and DLP had close relationship with the slice thickness and the scan length. The dose distribution in the transversal plane was very inhomogeneous due to the attenuation of the couch. Patient dose from MVCT was lower than XVI CBCT for the head scan, while larger for body scan. CTDI, which is measured easily and reproducibly, can be used to assess the patient dose in MVCT. Regular measurement should be performed in QA & QC programmes. Appropriate slice thickness and scan range should be chosen to reduce the patient dose.
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http://dx.doi.org/10.1093/rpd/ncv393DOI Listing
November 2016

Size-Dependent Melting Behavior of Colloidal In, Sn, and Bi Nanocrystals.

Sci Rep 2015 Nov 17;5:16353. Epub 2015 Nov 17.

Mechanical Engineering, Arizona State University, Tempe, Arizona 85287.

Colloidal nanocrystals are a technologically important class of nanostructures whose phase change properties have been largely unexplored. Here we report on the melting behavior of In, Sn, and Bi nanocrystals dispersed in a polymer matrix. This polymer matrix prevents the nanocrystals from coalescing with one another and enables previously unaccessed observations on the melting behavior of colloidal nanocrystals. We measure the melting temperature, melting enthalpy, and melting entropy of colloidal nanocrystals with diameters of approximately 10 to 20 nm. All of these properties decrease as nanocrystal size decreases, although the depression rate for melting temperature is comparatively slower than that of melting enthalpy and melting entropy. We also observe an elevated melting temperature during the initial melt-freeze cycle that we attribute to surface stabilization from the organic ligands on the nanocrystal surface. Broad endothermic melting valleys and very large supercoolings in our calorimetry data suggest that colloidal nanocrystals exhibit a significant amount of surface pre-melting and low heterogeneous nucleation probabilities during freezing.
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http://dx.doi.org/10.1038/srep16353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4648084PMC
November 2015

Modifying Thermal Transport in Colloidal Nanocrystal Solids with Surface Chemistry.

ACS Nano 2015 Dec 13;9(12):12079-87. Epub 2015 Nov 13.

School for Engineering of Matter, Transport & Energy, Arizona State University , Tempe, Arizona 85287, United States.

We present a systematic study on the effect of surface chemistry on thermal transport in colloidal nanocrystal (NC) solids. Using PbS NCs as a model system, we vary ligand binding group (thiol, amine, and atomic halides), ligand length (ethanedithiol, butanedithiol, hexanedithiol, and octanedithiol), and NC diameter (3.3-8.2 nm). Our experiments reveal several findings: (i) The ligand choice can vary the NC solid thermal conductivity by up to a factor of 2.5. (ii) The ligand binding strength to the NC core does not significantly impact thermal conductivity. (iii) Reducing the ligand length can decrease the interparticle distance, which increases thermal conductivity. (iv) Increasing the NC diameter increases thermal conductivity. (v) The effect of surface chemistry can exceed the effect of NC diameter and becomes more pronounced as NC diameter decreases. By combining these trends, we demonstrate that the thermal conductivity of NC solids can be varied by an overall factor of 4, from ∼0.1-0.4 W/m-K. We complement these findings with effective medium approximation modeling and identify thermal transport in the ligand matrix as the rate-limiter for thermal transport. By combining these modeling results with our experimental observations, we conclude that future efforts to increase thermal conductivity in NC solids should focus on the ligand-ligand interface between neighboring NCs.
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http://dx.doi.org/10.1021/acsnano.5b05085DOI Listing
December 2015

Icariin recovers the osteogenic differentiation and bone formation of bone marrow stromal cells from a rat model of estrogen deficiency-induced osteoporosis.

Mol Med Rep 2015 Jul 17;12(1):382-8. Epub 2015 Feb 17.

School of Physical Education, Tianshui Normal University, Tianshui, Gansu 741000, P.R. China.

A number of recent studies have suggested that icariin (ICA), a class of phytochemical with numerous biological activities, may exert protective effects against postmenopausal bone loss. However, it remains unclear whether ICA regulates or improves the osteoblastic function of bone marrow stromal cells (BMSCs) in the treatment and prevention of osteoporosis. In the present study, the osteogenic differentiation of BMSCs from ovariectomy (OVX) rats was found to be significantly decreased in vitro compared with that in rats that had undergone a sham operation. Treatment with ICA at a dose of 10-5 M was shown to restore the osteogenic differentiation of BMSCs in OVX rats. The results indicated that ICA restored the differentiation and mineralization capacity of OVX-BMSCs, which had been induced by estrogen deficiency. The effects of this compound on alkaline phosphatase (ALP) activity and calcium deposition were also measured at various time points. The number of colonies and areas that stained positive for ALP expression, and mineralized bone nodules were analyzed histochemically at 14 and 21 days after the osteogenic induction. The expression of the runt-related transcription factor 2 and osterix bone metabolism biomarker proteins and genes were detected by western blotting and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The expression of factors involved in the estrogen signaling pathway, estrogen receptor α (ERα), progesterone receptor (PR) and trefoil factor 1 (PS-2), was also detected by western blotting and RT-qPCR. ICA enhanced the expression of ERα, PR, PS-2 in OVX‑BMSCs, but this effect was abrogated when ICI 182780, an ER antagonist was added. Transplantation of BMSCs into nude mice demonstrated that ICA restored the osteogenic capability of OVX‑BMSCs in vivo. Therefore, it may be that ICA acts through the estrogen pathway in order to improve and restore the osteogenic differentiation and mineralization of OVX‑BMSCs, which are inhibited by estrogen deficiency and increasing age.
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http://dx.doi.org/10.3892/mmr.2015.3369DOI Listing
July 2015

Metal matrix-metal nanoparticle composites with tunable melting temperature and high thermal conductivity for phase-change thermal storage.

ACS Nano 2015 Feb 28;9(2):1341-51. Epub 2015 Jan 28.

Department of Mechanical Engineering and ‡Department of Material Science & Engineering, Arizona State University , Tempe, Arizona 85287, United States.

Phase-change materials (PCMs) are of broad interest for thermal storage and management applications. For energy-dense storage with fast thermal charging/discharging rates, a PCM should have a suitable melting temperature, large enthalpy of fusion, and high thermal conductivity. To simultaneously accomplish these traits, we custom design nanocomposites consisting of phase-change Bi nanoparticles embedded in an Ag matrix. We precisely control nanoparticle size, shape, and volume fraction in the composite by separating the nanoparticle synthesis and nanocomposite formation steps. We demonstrate a 50-100% thermal energy density improvement relative to common organic PCMs with equivalent volume fraction. We also tune the melting temperature from 236-252 °C by varying nanoparticle diameter from 8.1-14.9 nm. Importantly, the silver matrix successfully prevents nanoparticle coalescence, and no melting changes are observed during 100 melt-freeze cycles. The nanocomposite's Ag matrix also leads to very high thermal conductivities. For example, the thermal conductivity of a composite with a 10% volume fraction of 13 nm Bi nanoparticles is 128 ± 23 W/m-K, which is several orders of magnitude higher than typical thermal storage materials. We complement these measurements with calculations using a modified effective medium approximation for nanoscale thermal transport. These calculations predict that the thermal conductivity of composites with 13 nm Bi nanoparticles varies from 142 to 47 W/m-K as the nanoparticle volume fraction changes from 10 to 35%. Larger nanoparticle diameters and/or smaller nanoparticle volume fractions lead to larger thermal conductivities.
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http://dx.doi.org/10.1021/nn505328jDOI Listing
February 2015

Phase change nanocomposites with tunable melting temperature and thermal energy storage density.

Nanoscale 2013 Aug 8;5(16):7234-7. Epub 2013 Jul 8.

Mechanical Engineering, Arizona State University, Tempe, USA.

Size-dependent melting decouples melting temperature from chemical composition and provides a new design variable for phase change material applications. To demonstrate this potential, we create nanocomposites that exhibit stable and tunable melting temperatures through numerous melt-freeze cycles. These composites consist of a monodisperse ensemble of Bi nanoparticles (NPs) embedded in a polyimide (PI) resin matrix. The Bi NPs operate as the phase change component whereas the PI resin matrix prevents nanoparticle coalescence during melt-freeze cycles. We tune melting temperature and enthalpy of fusion in these composites by varying the NP diameter. Adjusting the NP volume fraction also controls the composite's thermal energy storage density. Hence it is possible to leverage size effects to tune phase change temperature and energy density in phase change materials.
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http://dx.doi.org/10.1039/c3nr02842aDOI Listing
August 2013
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