Publications by authors named "Yanqin Yang"

91 Publications

Higher levels of allograft injury in black patients early after heart transplantation.

J Heart Lung Transplant 2021 Dec 23. Epub 2021 Dec 23.

Genomic Research Alliance for Transplantation (GRAfT), Bethesda, Maryland; Laborarory of Applied Precision Omics (APO), Division of Intramural Research, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland; Department of Medicine, Stanford University School of Medicine, Palo Alto, California. Electronic address:

Black patients suffer higher rates of antibody-mediated rejection and have worse long-term graft survival after heart transplantation. Donor-derived cell free DNA (ddcfDNA) is released into the blood following allograft injury. This study analyzed %ddcfDNA in 63 heart transplant recipients categorized by Black and non-Black race, during the first 200 days after transplant. Immediately after transplant, %ddcfDNA was higher for Black patients (mean [SE]: 8.3% [1.3%] vs 3.2% [1.2%], p = 0.001). In the first week post-transplant, the rate of decay in %ddcfDNA was similar (0.7% [0.68] vs 0.7% [0.11], p = 0.78), and values declined in both groups to a comparable plateau at 7 days post-transplant (0.46% [0.03] vs 0.45% [0.04], p = 0.78). The proportion of Black patients experiencing AMR was higher than non-Black patients (21% vs 9% [hazard ratio of 2.61 [95% confidence interval: 0.651-10.43], p = 0.18). Black patients were more likely to receive a race mismatched organ than non-Black patients (69% vs 35%, p = 0.01), which may explain the higher levels of early allograft injury.
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http://dx.doi.org/10.1016/j.healun.2021.12.006DOI Listing
December 2021

Artificial Intelligence of Things (AIoT) Enabled Floor Monitoring System for Smart Home Applications.

ACS Nano 2021 Nov 1. Epub 2021 Nov 1.

Department of Electrical and Computer Engineering, National University of Singapore, Singapore 117583, Singapore.

To enable smart homes and relative applications, the floor monitoring system with embedded triboelectric sensors has been proven as an effective paradigm to capture the ample sensory information from our daily activities, without the camera-associated privacy concerns. Yet the inherent limitations of triboelectric sensors such as high susceptibility to humidity and long-term stability remain a great challenge to develop a reliable floor monitoring system. Here we develop a robust and smart floor monitoring system through the synergistic integration of highly reliable triboelectric coding mats and deep-learning-assisted data analytics. Two quaternary coding electrodes are configured, and their outputs are normalized with respect to a reference electrode, leading to highly stable detection that is not affected by the ambient parameters and operation manners. Besides, due to the universal electrode pattern design, all the floor mats can be screen-printed with only one mask, rendering higher facileness and cost-effectiveness. Then a distinctive coding can be implemented to each floor mat through external wiring, which permits the parallel-array connection to minimize the output terminals and system complexity. Further integrating with deep-learning-assisted data analytics, a smart floor monitoring system is realized for various smart home monitoring and interactions, including position/trajectory tracking, identity recognition, and automatic controls. Hence, the developed low-cost, large-area, reliable, and smart floor monitoring system shows a promising advancement of floor sensing technology in smart home applications.
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http://dx.doi.org/10.1021/acsnano.1c07579DOI Listing
November 2021

A Novel Diagnostic Predictive Model for Idiopathic Short Stature in Children.

Front Endocrinol (Lausanne) 2021 17;12:721812. Epub 2021 Sep 17.

Department of Orthopaedics, The Second Affiliated Hospital of Nanchang University, Nanchang, China.

Objective: Idiopathic short stature (ISS), an endocrine-related disease, is difficult to diagnose. Previous studies have shown that many children with some inflammation-related diseases often have short stature, but whether inflammation is the underlying mechanism of ISS has not been studied. Here, we attempt to explore the role of inflammation in the occurrence and development of ISS and to demonstrate an available clinical diagnostic model of ISS.

Methods: Frozen serum samples were collected from ISS patients (n = 4) and control individuals (n = 4). Isobaric tags for relative and absolute quantitation (iTRAQ) combined with LC-MS/MS analysis were applied to quantitative proteomics analysis. To assess clusters of potentially interacting proteins, functional enrichment (GO and KEGG) and protein-protein interaction network analyses were performed, and the crucial proteins were detected by Molecular Complex Detection (MCODE). Furthermore, serum levels of two selected proteins were measured by ELISA between ISS patients (n = 80) and controls (n = 80). In addition, experiments were used to further explore the effects of crucial proteins on endochondral ossification.

Results: A total of 437 proteins were quantified, and 84 DEPs (60 upregulated and 24 downregulated) were identified between patients with ISS and controls. Functional enrichment analysis showed that the DEPs were primarily enriched in blood microparticle, acute inflammatory response, protein activation cascade, collagen-containing extracellular matrix, platelet degranulation, etc. According to the results of top 10 fold change DEPs and MCODE analysis, C1QA and C1QB were selected to further experiment. The expression levels of C1QA and C1QB were validated in serum samples. Based on the logistic regression analysis and ROC curve analysis, we constructed a novel diagnostic model by serum levels of C1QA and C1QB with a specificity of 91.2% and a sensitivity of 75% (AUC = 0.900, p <0.001). Finally, the western blotting analysis confirmed the expression levels of OCN, OPN, RUNX2, and Collagen X were downregulated in chondrocytes, and the outcome of Collagen II was upregulated.

Conclusion: Our study is the first to demonstrate the significant role of inflammation in the development of ISS. In addition, we identify C1QA and C1QB as novel serum biomarkers for the diagnosis of ISS.
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http://dx.doi.org/10.3389/fendo.2021.721812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8485046PMC
September 2021

Response by Shah et al to Letter Regarding Article, "Cell-Free DNA to Detect Heart Allograft Acute Rejection".

Circulation 2021 09 7;144(10):e198-e199. Epub 2021 Sep 7.

Genomic Research Alliance for Transplantation (GRAfT), Bethesda, MD (P.S., S.A-E., I.T., S.H., E.F., K.S., M.E.R., S.S.N., H.K., U.F., A.B., A.M., K.B., Y.Y., M.K.J., C.Marboe, G.J.B., H.A.V.).

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http://dx.doi.org/10.1161/CIRCULATIONAHA.121.055697DOI Listing
September 2021

Rapid characterization of the volatile profiles in Pu-erh tea by gas phase electronic nose and microchamber/thermal extractor combined with TD-GC-MS.

J Food Sci 2021 Jun 30;86(6):2358-2373. Epub 2021 Apr 30.

Key Laboratory of Tea Biology and Resources Utilization, Ministry of Agriculture, Tea Research Institute, Chinese Academy of Agricultural Sciences, Hangzhou, China.

Aroma plays an important role in the quality of Pu-erh tea. However, the quality evaluation of Pu-erh tea aroma is heavily relied on the experience of sensory evaluation, and the theoretical research is relatively scarce. In the present work, the volatile compounds in Pu-erh tea were characterized by using gas phase electronic nose (e-nose) and microchamber/thermal extractor (µ-CTE) combined with thermal desorption coupled to gas chromatography-mass spectrometry (TD-GC-MS). A satisfactory discrimination model (R Y = 0.95, Q  = 0.807) was obtained by using orthogonal partial least squares discriminant analysis (OPLS-DA) based on the odor fingerprint of different brands of Pu-erh tea. In addition, based on the double criterion of multivariate analysis with VIP >1.0 and univariate analysis with p ≤ 0.001, 39 volatile components were identified to contribute greatly to the discrimination of five brands of Pu-erh tea. The results suggested that gas phase e-nose and µ-CTE combined with TD-GC/MS were simple, rapid techniques to characterize the volatile compounds in Pu-erh tea and were allowed to effectively distinguish different brands of Pu-erh tea, which would provide an important reference on the quality assessment of Pu-erh tea. PRACTICAL APPLICATION: This work demonstrates that the volatile compounds in Pu-erh tea are simply and rapidly characterized by using µ-CTE/TD-GC/MS and gas phase e-nose, allowing to effectively distinguish different brands of Pu-erh tea, which can provide an important reference for the quality assessment and authentication of Pu-erh tea.
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http://dx.doi.org/10.1111/1750-3841.15723DOI Listing
June 2021

Applications of genetic-epigenetic tissue mapping for plasma DNA in prenatal testing, transplantation and oncology.

Elife 2021 03 23;10. Epub 2021 Mar 23.

Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China.

We developed genetic-epigenetic tissue mapping (GETMap) to determine the tissue composition of plasma DNA carrying genetic variants not present in the constitutional genome through comparing their methylation profiles with relevant tissues. We validated this approach by showing that, in pregnant women, circulating DNA carrying fetal-specific alleles was entirely placenta-derived. In lung transplant recipients, we showed that, at 72 hr after transplantation, the lung contributed only a median of 17% to the plasma DNA carrying donor-specific alleles, and hematopoietic cells contributed a median of 78%. In hepatocellular cancer patients, the liver was identified as the predominant source of plasma DNA carrying tumor-specific mutations. In a pregnant woman with lymphoma, plasma DNA molecules carrying cancer mutations and fetal-specific alleles were accurately shown to be derived from the lymphocytes and placenta, respectively. Analysis of tissue origin for plasma DNA carrying genetic variants is potentially useful for noninvasive prenatal testing, transplantation monitoring, and cancer screening.
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http://dx.doi.org/10.7554/eLife.64356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997656PMC
March 2021

Genome-wide transcriptome study using deep RNA sequencing for myocardial infarction and coronary artery calcification.

BMC Med Genomics 2021 02 10;14(1):45. Epub 2021 Feb 10.

Division of Intramural Research, National Heart, Lung and Blood Institute, Bethesda, MD, USA.

Background: Coronary artery calcification (CAC) is a noninvasive measure of coronary atherosclerosis, the proximal pathophysiology underlying most cases of myocardial infarction (MI). We sought to identify expression signatures of early MI and subclinical atherosclerosis in the Framingham Heart Study (FHS). In this study, we conducted paired-end RNA sequencing on whole blood collected from 198 FHS participants (55 with a history of early MI, 72 with high CAC without prior MI, and 71 controls free of elevated CAC levels or history of MI). We applied DESeq2 to identify coding-genes and long intergenic noncoding RNAs (lincRNAs) differentially expressed in MI and high CAC, respectively, compared with the control.

Results: On average, 150 million paired-end reads were obtained for each sample. At the false discovery rate (FDR) < 0.1, we found 68 coding genes and 2 lincRNAs that were differentially expressed in early MI versus controls. Among them, 60 coding genes were detectable and thus tested in an independent RNA-Seq data of 807 individuals from the Rotterdam Study, and 8 genes were supported by p value and direction of the effect. Immune response, lipid metabolic process, and interferon regulatory factor were enriched in these 68 genes. By contrast, only 3 coding genes and 1 lincRNA were differentially expressed in high CAC versus controls. APOD, encoding a component of high-density lipoprotein, was significantly downregulated in both early MI (FDR = 0.007) and high CAC (FDR = 0.01) compared with controls.

Conclusions: We identified transcriptomic signatures of early MI that include differentially expressed protein-coding genes and lincRNAs, suggesting important roles for protein-coding genes and lincRNAs in the pathogenesis of MI.
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http://dx.doi.org/10.1186/s12920-020-00838-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874462PMC
February 2021

Oncogenic HPV promotes the expression of the long noncoding RNA lnc-FANCI-2 through E7 and YY1.

Proc Natl Acad Sci U S A 2021 01;118(3)

Tumor Virus RNA Biology Section, HIV Dynamics and Replication Program, National Cancer Institute, National Institutes of Health, Frederick, MD 21702;

Long noncoding RNAs (lncRNAs) play diverse roles in biological processes, but their expression profiles and functions in cervical carcinogenesis remain unknown. By RNA-sequencing (RNA-seq) analyses of 18 clinical specimens and selective validation by RT-qPCR analyses of 72 clinical samples, we provide evidence that, relative to normal cervical tissues, 194 lncRNAs are differentially regulated in high-risk (HR)-HPV infection along with cervical lesion progression. One such lncRNA, , is extensively characterized because it is expressed from a genomic locus adjacent to the gene encoding an important DNA repair factor. Both genes are up-regulated in HPV lesions and in in vitro model systems of HR-HPV18 infection. We observe a moderate reciprocal regulation of and in cervical cancer CaSki cells. In these cells, is transcribed from two alternative promoters, alternatively spliced, and polyadenylated at one of two alternative poly(A) sites. About 10 copies of per cell are detected preferentially in the cytoplasm. Mechanistically, HR-HPVs, but not low-risk (LR)-HPV oncogenes induce in primary and immortalized human keratinocytes. The induction is mediated primarily by E7, and to a lesser extent by E6, mostly independent of p53/E6AP and pRb/E2F. We show that YY1 interacts with an E7 CR3 core motif and transactivates the promoter of by binding to two critical YY1-binding motifs. Moreover, HPV18 increases YY1 expression by reducing miR-29a, which targets the 3' untranslated region of YY1 mRNA. These data have provided insights into the mechanisms of how HR-HPV infections contribute to cervical carcinogenesis.
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http://dx.doi.org/10.1073/pnas.2014195118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826414PMC
January 2021

Cell-Free DNA to Detect Heart Allograft Acute Rejection.

Circulation 2021 03 13;143(12):1184-1197. Epub 2021 Jan 13.

Genomic Research Alliance for Transplantation, Bethesda, MD (S.A.-E., P.S., I.T., S.H., E.F., K.S., M.E.R., S.S.N., H.K., U.F., A.B., A.M., K.B., Y.Y., M.K.J., C.M., G.J.B., H.A.V.).

Background: After heart transplantation, endomyocardial biopsy (EMBx) is used to monitor for acute rejection (AR). Unfortunately, EMBx is invasive, and its conventional histological interpretation has limitations. This is a validation study to assess the performance of a sensitive blood biomarker-percent donor-derived cell-free DNA (%ddcfDNA)-for detection of AR in cardiac transplant recipients.

Methods: This multicenter, prospective cohort study recruited heart transplant subjects and collected plasma samples contemporaneously with EMBx for %ddcfDNA measurement by shotgun sequencing. Histopathology data were collected to define AR, its 2 phenotypes (acute cellular rejection [ACR] and antibody-mediated rejection [AMR]), and controls without rejection. The primary analysis was to compare %ddcfDNA levels (median and interquartile range [IQR]) for AR, AMR, and ACR with controls and to determine %ddcfDNA test characteristics using receiver-operator characteristics analysis.

Results: The study included 171 subjects with median posttransplant follow-up of 17.7 months (IQR, 12.1-23.6), with 1392 EMBx, and 1834 %ddcfDNA measures available for analysis. Median %ddcfDNA levels decayed after surgery to 0.13% (IQR, 0.03%-0.21%) by 28 days. Also, %ddcfDNA increased again with AR compared with control values (0.38% [IQR, 0.31-0.83%], versus 0.03% [IQR, 0.01-0.14%]; <0.001). The rise was detected 0.5 and 3.2 months before histopathologic diagnosis of ACR and AMR. The area under the receiver operator characteristic curve for AR was 0.92. A 0.25%ddcfDNA threshold had a negative predictive value for AR of 99% and would have safely eliminated 81% of EMBx. In addition, %ddcfDNA showed distinctive characteristics comparing AMR with ACR, including 5-fold higher levels (AMR ≥2, 1.68% [IQR, 0.49-2.79%] versus ACR grade ≥2R, 0.34% [IQR, 0.28-0.72%]), higher area under the receiver operator characteristic curve (0.95 versus 0.85), higher guanosine-cytosine content, and higher percentage of short ddcfDNA fragments.

Conclusions: We found that %ddcfDNA detected AR with a high area under the receiver operator characteristic curve and negative predictive value. Monitoring with ddcfDNA demonstrated excellent performance characteristics for both ACR and AMR and led to earlier detection than the EMBx-based monitoring. This study supports the use of %ddcfDNA to monitor for AR in patients with heart transplant and paves the way for a clinical utility study. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02423070.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.049098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221834PMC
March 2021

Aroma dynamic characteristics during the process of variable-temperature final firing of Congou black tea by electronic nose and comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry.

Food Res Int 2020 11 2;137:109656. Epub 2020 Sep 2.

Key Laboratory of Tea Biology and Resources Utilization, Ministry of Agriculture, Tea Research Institute, Chinese Academy of Agricultural Sciences, Hangzhou 310008, China. Electronic address:

The drying technology is crucial to the quality of Congou black tea. In this study, the aroma dynamic characteristics during the variable-temperature final firing of Congou black tea was investigated by electronic nose (e-nose) and comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (GC × GC-TOFMS). Varying drying temperatures and time obtained distinctly different types of aroma characteristics such as faint scent, floral aroma, and sweet fragrance. GC × GC-TOFMS identified a total of 243 volatile compounds. Clear discrimination among different variable-temperature final firing samples was achieved by using partial least squares discriminant analysis (R2Y = 0.95, Q2 = 0.727). Based on a dual criterion of variable importance in the projection value (VIP > 1.0) and one-way ANOVA (p < 0.05), ninety-one specific volatile biomarkers were identified, including 2,6-dimethyl-2,6-octadiene and 2,5-diethylpyrazine with VIP > 1.5. In addition, for the overall odor perception, e-nose was able to distinguish the subtle difference during the variable-temperature final firing process.
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http://dx.doi.org/10.1016/j.foodres.2020.109656DOI Listing
November 2020

Investigation on green tea lipids and their metabolic variations during manufacturing by nontargeted lipidomics.

Food Chem 2021 Mar 17;339:128114. Epub 2020 Sep 17.

Key Laboratory of Tea Biology and Resources Utilization, Ministry of Agriculture, Tea Research Institute, Chinese Academy of Agricultural Sciences, Hangzhou 310008, China. Electronic address:

Lipids are hydrophobic metabolites implicated in tea flavor quality. Understanding their transformations during tea manufacture is of particular interest. To date, the detailed lipid composition and variations during green tea manufacture are largely unknown. Herein, we performed a comprehensive characterization of the dynamic changes of lipids during green tea manufacture, by applying nontargeted lipidomics using ultrahigh performance liquid chromatography-quadrupole-Orbitrap mass spectrometry (UHPLC-Q-Exactive/MS) combined with chemometric tools. Totally, 283 lipid species were detected, covering 20 subclasses. Significant lipidomic variations were observed during green tea manufacture, especially in the fixation stage, mainly associated with chlorophyll decomposition, phosphatidic acids (PAs) reduction and glycolipids degradation, which potentially contribute to tea color and aroma quality. Specifically, the most prominent decrease of PAs content during green tea manufacture was identified for the first time. This study provides insights into the lipid metabolic fates upon green tea manufacture, and their roles in green tea sensory quality.
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http://dx.doi.org/10.1016/j.foodchem.2020.128114DOI Listing
March 2021

Influence of fixation methods on the chestnut-like aroma of green tea and dynamics of key aroma substances.

Food Res Int 2020 10 25;136:109479. Epub 2020 Jun 25.

Tea Research Institute, Chinese Academy of Agricultural Sciences, 9 Meiling South Road, Hangzhou, Zhejiang 310008, PR China. Electronic address:

Fixation is the key process to ensure green tea quality; however, the effect of various fixation methods on the formation of green tea with a chestnut-like aroma and the evolution of key volatile compounds has not been assessed to date. In this study, we compared four types of fixation methods for green tea: roller-hot air-steam, roller-hot air, roller-steam, and single roller. Infrared-assisted headspace solid-phase microextraction and gas chromatography-tandem dual mass spectrometry technology were used to detect the volatile compounds of green tea samples during processing. Partial least-squares discriminant analysis (PLS-DA), multiple experiment viewer (MEV), odor activity value (OAV), and least-significant difference analyzes were then applied to clarify the best fixation method for forming a chestnut-like aroma and associated compounds, and to explore the change law of key volatile compounds using different green tea fixation processes. One hundred and eighty-four volatile compounds were detected in the processed samples, with roller-hot air fixation found as the optimal method for generating an intense and long-lasting chestnut-like aroma and floral taste, based on sensory evaluation. The PLS-DA model clearly distinguished the four kinds of fixation samples and obtained 32 differential volatile compounds. Combining OAVs with screening by MEV analysis, 2,6,10,10-tetramethyl-1-oxaspiro [4.5] dec-6-ene, linalool, cedrol, 3-methyl-butanal, trans-β-ionone, and τ-cadinol emerged as key differential volatile compounds between green teas with and without a chestnut-like aroma. The evolution of these six differential volatile compounds throughout the tea-making process confirmed that rolling-hot air coupling treatment is most conducive to produce a chestnut-like aroma, which is beneficial to form and transform 2,6,10,10-tetramethyl-1-oxaspiro[4.5] dec-6-ene, 3-methyl-butanal, and τ-cadinol with baking aromas and fruity substances. These results provide a theoretical basis and technical guidance for the precise and directional processing of high-quality green tea with a chestnut-like aroma.
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http://dx.doi.org/10.1016/j.foodres.2020.109479DOI Listing
October 2020

Research Progress and Existing Problems for Abscopal Effect.

Cancer Manag Res 2020 3;12:6695-6706. Epub 2020 Aug 3.

Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, People's Republic of China.

Radiation therapy plays a vital role in the treatment of tumours. In particular, the occurrence of the "abscopal effect" brings about a favourable turn for the treatment of patients with advanced metastatic malignant tumours. Because of the abscopal effect, non-irradiated areas are also treated. However, the abscopal effect occurs by chance, not through seeking. Although the abscopal effect has been studied enthusiastically, the desired result does not appear to be achieved. Moreover, its combination with immunotherapy appears to be overwhelming. There is an opinion that abscopal effect is difficult to achieve by irradiation of a single tumour, and irradiation of multiple or total lesions is advocated to increase the possibility of obtaining clinically meaningful outcomes. Obviously, there are still questions about the mechanism, condition and possibility underlying the occurrence of the abscopal effect. Can the abscopal effect truly change the future treatment strategy as the researchers expect? What are the current problems? This article reviewed the research in recent years to explore the progress and controversy surrounding the abscopal effect of radiation therapy.
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http://dx.doi.org/10.2147/CMAR.S245426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7413699PMC
August 2020

Inhibition of mitochondria NADH-Ubiquinone oxidoreductase (complex I) sensitizes the radioresistant glioma U87MG cells to radiation.

Biomed Pharmacother 2020 Sep 1;129:110460. Epub 2020 Jul 1.

College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China. Electronic address:

Radiation is a current standard treatment of glioma. The fractionated radiotherapy with low dose of radiation over weeks has been employed in glioma patients, while radiotherapy can only offer palliation due to the radioresistance. We cumulatively radiated a glioblastoma cell line, U87MG, and screened radioresistant glioma cells. A transcriptome sequencing was performed to analyze the transcription differences between the raidoresistant and control cells, which showed the mitochondria NADH-ubiquinone oxidoreductase (Complex I) subunits were up-regulated in the radioresistant cells. The copy numbers of mitochondria were increased in the radioresistant glioma cells. After using mitochondria Complex I inhibitors, rotenone and metformin, to treat glioma cells, we found the resistant glioma cells re-sensitized to radiation. These results demonstrate that Complex I is associated with the fractioned radiation-induced radioresistance of glioma and would be a potent target for clinical radiotherapy of glioma.
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http://dx.doi.org/10.1016/j.biopha.2020.110460DOI Listing
September 2020

Wearable Triboelectric-Human-Machine Interface (THMI) Using Robust Nanophotonic Readout.

ACS Nano 2020 07 2;14(7):8915-8930. Epub 2020 Jul 2.

Department of Electrical and Computer Engineering, National University of Singapore, 4 Engineering Drive 3, Singapore 117576, Singapore.

With the rapid advances in wearable electronics and photonics, self-sustainable wearable systems are desired to increase service life and reduce maintenance frequency. Triboelectric technology stands out as a promising versatile technology due to its flexibility, self-sustainability, broad material availability, low cost, and good scalability. Various triboelectric-human-machine interfaces (THMIs) have been developed including interactive gloves, eye blinking/body motion-triggered interfaces, voice/breath monitors, and self-induced wireless interfaces. Nonetheless, THMIs conventionally use electrical readout and produce pulse-like signals due to the transient charge flows, leading to unstable and lossy transfer of interaction information. To address this issue, we propose a strategy by equipping THMIs with robust nanophotonic aluminum nitride (AlN) modulators for readout. The electrically capacitive nature of AlN modulators enables THMIs to work in the open-circuit condition with negligible charge flows. Meanwhile, the interaction information is transduced from THMIs' voltage to AlN modulators' optical output the electro-optic Pockels effect. Thanks to the negligible charge flow and the high-speed optical information carrier, stable, information-lossless, and real-time THMIs are achieved. Leveraging the design flexibility of THMIs and nanophotonic readout circuits, various linear sensitivities independent of force speeds are achieved in different interaction force ranges. Toward practical applications, we develop a smart glove to realize continuous real-time robotics control and virtual/augmented reality interaction. Our work demonstrates a generic approach for developing self-sustainable HMIs with stable, information-lossless, and real-time features for wearable systems.
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http://dx.doi.org/10.1021/acsnano.0c03728DOI Listing
July 2020

Quantitation of pyrazines in roasted green tea by infrared-assisted extraction coupled to headspace solid-phase microextraction in combination with GC-QqQ-MS/MS.

Food Res Int 2020 08 17;134:109167. Epub 2020 Mar 17.

Key Laboratory of Tea Biology and Resource Utilization, Ministry of Agriculture, Tea Research Institute, Chinese Academy of Agricultural Sciences, Hangzhou 310008, China. Electronic address:

Pyrazines play an important role in the characteristic flavor of roasted green tea due to powerful strong odours and low sensory thresholds. It is important to analyze these compounds reliably and rapidly in roasted green tea. In this study, infrared-assisted extraction coupled to headspace solid-phase microextraction (IRAE-HS-SPME) and gas chromatography-triple quadrupole-tandem mass spectrometry (GC-QqQ-MS/MS) were developed and validated to determine the pyrazines in roasted green tea. Good linear correlation coefficients (0.9955-0.9996) were obtained over the concentration ranges of 10-5000 ng/mL. The limits of detection (LODs) and limits of quantification (LOQs) for the pyrazines were in the range of 1.46-3.27 ng/mL and 4.89-10.90 ng/mL, respectively. The average recoveries varied from 84% to 119%. The method was used to analyze the pyrazines in roasted green tea manufactured by different final firing methods, the results revealed that microwave final firing method had maximum contents of pyrazines, and significantly improved the aroma quality. In addition, there were great disparities of pyrazines in flatten-shaped green tea and strip-shaped green tea according to the appearance. The result is expected to better understand the role of pyrazines related to aroma quality of roasted green tea and improve processing technology.
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http://dx.doi.org/10.1016/j.foodres.2020.109167DOI Listing
August 2020

Rapid Sensing of Key Quality Components in Black Tea Fermentation Using Electrical Characteristics Coupled to Variables Selection Algorithms.

Sci Rep 2020 01 31;10(1):1598. Epub 2020 Jan 31.

Tea Research Institute, The Chinese Academy of Agricultural Sciences, Hangzhou, 310008, China.

Based on the electrical characteristic detection technology, the quantitative prediction models of sensory score and physical and chemical quality Index (theaflavins, thearubigins, and theabrownins) were established by using the fermented products of Congou black tea as the research object. The variation law of electrical parameters during the process of fermentation and the effects of different standardized pretreatment methods and variable optimization methods on the models were discussed. The results showed that the electrical parameters vary regularly with the test frequency and fermentation time, and the substances that hinder the charge transfer increase gradually during the fermentation process. The Zero-mean normalization (Zscore) preprocessing method had the best noise reduction effect, and the prediction set correlation coefficient (Rp) value of the original data could be increased from 0.172 to 0.842. The mixed variable optimization method (MCUVE-CARS) of Monte Carlo uninformed variable elimination (MC UVE) and competitive adaptive reweighted sampling (CARS) was proved that the characteristic electrical parameters were the loss factor (D) and reactance (X) of the low range. Based on the characteristic variables screened by MCUVE-CARS, the quantitative prediction models for each fermentation quality indicator were established. The Rp values of the sensory score, theaflavin, thearubigin and theabrownins of the predicted models were 0.924, 0.811, 0.85 and 0.938 respectively. The relative percent deviation (RPD) values of the sensory score, theaflavins, thearubigins and theabrownins of the predicted models were 2.593, 1.517, 1,851 and 2.920 respectively, and it showed that these models have good performance and could realize quantitative characterization of key fermentation quality indexes.
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http://dx.doi.org/10.1038/s41598-020-58637-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6994467PMC
January 2020

Rutin, γ-Aminobutyric Acid, Gallic Acid, and Caffeine Negatively Affect the Sweet-Mellow Taste of Congou Black Tea Infusions.

Molecules 2019 Nov 20;24(23). Epub 2019 Nov 20.

Key Laboratory of Tea Biology and Resources Utilization, Ministry of Agriculture, Tea Research Institute, Chinese Academy of Agricultural Sciences, Hangzhou 310008, China.

The sweet-mellow taste sensation is a unique and typical feature of premium congou black tea infusions. To explore the key taste-active compounds that influence the sweet-mellow taste, a sensory and molecular characterization was performed on thirty-three congou black tea infusions presenting different taste qualities, including the sweet-mellow, mellow-pure, or less-mellow taste. An integrated application of quantitative analysis of 48 taste-active compounds, taste contribution analysis, and further validation by taste supplementation experiments, combined with human sensory evaluation revealed that caffeine, γ-aminobutyric acid, rutin, succinic acid, citric acid, and gallic acid negatively affect the sweet-mellow taste, whereas glucose, sucrose, and ornithine positively contribute to the sweet-mellow taste of congou black tea infusions. Particularly, rutin, γ-aminobutyric acid, gallic acid, and caffeine, which impart the major inhibitory effect to the manifestation of the sweet-mellow taste, were identified as the key influencing components through stepwise screening and validation experiments. A modest level of these compounds was found to be favorable for the development and manifestation of the sweet-mellow taste. These compounds might potentially serve as the regulatory targets for oriented-manufacturing of high-quality sweet-mellow congou black tea.
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http://dx.doi.org/10.3390/molecules24234221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6930661PMC
November 2019

Quality Evaluation of Green and Dark Tea Grade Using Electronic Nose and Multivariate Statistical Analysis.

J Food Sci 2019 Dec 21;84(12):3411-3417. Epub 2019 Nov 21.

Natl. "111" Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei Univ. of Technology, Wuhan, 430068, China.

Aroma assessment remains difficult and uncertain in the present sensory assessment system. It is highly desirable to develop a new assessment method to discriminate the quality of various teas in the tea market. In the present work, based on linear discriminant analysis and principal component analysis, the aroma of dry and wet samples of different Xi-hu Longjing and Pu-erh teas were tested and differentiated by electronic noses (e-nose). The results confirm that e-nose can discriminate different priced Xi-hu Longjing tea samples in the range of 80-800 RMB/500 g and varying storage years of Pu-erh tea samples. Furthermore, for the detection of both dry and wet samples of Longjing and Pu-erh teas, the results reveal that all samples have specific aroma characteristics that e-nose can recognize. More importantly, contribution analysis in sensors indicates that nitrogen oxides, methane and alcohols are the characteristic components that contribute to the fragrances of different priced Xi-hu Longjing teas, while nitrogen oxides, aromatic benzene and amines make the fragrances of Pu-erh teas with different storage years disparate. PRACTICAL APPLICATION: This work demonstrates that e-nose can rapidly distinguish tea products with different price levels and varying storage years. With the advantages of ease of use, high portability and flexibility, e-nose will be widely expanded and applied in refined processing and the development of flavored foods.
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http://dx.doi.org/10.1111/1750-3841.14917DOI Listing
December 2019

Long intergenic noncoding RNA profiles of pheochromocytoma and paraganglioma: A novel prognostic biomarker.

Int J Cancer 2020 04 11;146(8):2326-2335. Epub 2019 Oct 11.

Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD.

Many long intergenic noncoding RNAs (lincRNAs) serve as cancer biomarkers for diagnosis or prognostication. To understand the role of lincRNAs in the rare neuroendocrine tumors pheochromocytoma and paraganglioma (PCPG), we performed first time in-depth characterization of lincRNA expression profiles and correlated findings to clinical outcomes of the disease. RNA-Seq data from patients with PCPGs and 17 other tumor types from The Cancer Genome Atlas and other published sources were obtained. Differential expression analysis and a machine-learning model were used to identify transcripts specific to PCPGs, as well as established PCPG molecular subtypes. Similarly, lincRNAs specific to aggressive PCPGs were identified, and univariate and multivariate analysis was performed for metastasis-free survival. The results were validated in independent samples using RT-PCR. From a pan-cancer context, PCPGs had a specific and unique lincRNA profile. Among PCPGs, five different molecular subtypes were identified corresponding to the established molecular classification. Upregulation of 13 lincRNAs was found to be associated with aggressive/metastatic PCPGs. RT-PCR validation confirmed the overexpression of four lincRNAs in metastatic compared to non-metastatic PCPGs. Kaplan-Meier analysis identified five lincRNAs as prognostic markers for metastasis-free survival of patients in three subtypes of PCPGs. Stratification of PCPG patients with a risk-score formulated using multivariate analysis of lincRNA expression profiles, presence of key driver mutations, tumor location, and hormone secretion profiles showed significant differences in metastasis-free survival. PCPGs thus exhibit a specific lincRNA expression profile that also corresponds to the established molecular subgroups and can be potential marker for the aggressive/metastatic PCPGs.
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http://dx.doi.org/10.1002/ijc.32654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454041PMC
April 2020

De novo mutations in mitochondrial DNA of iPSCs produce immunogenic neoepitopes in mice and humans.

Nat Biotechnol 2019 10 19;37(10):1137-1144. Epub 2019 Aug 19.

Department of Surgery, Division of Cardiothoracic Surgery, Transplant and Stem Cell Immunobiology Lab, University of California, San Francisco, San Francisco, CA, USA.

The utility of autologous induced pluripotent stem cell (iPSC) therapies for tissue regeneration depends on reliable production of immunologically silent functional iPSC derivatives. However, rejection of autologous iPSC-derived cells has been reported, although the mechanism underlying rejection is largely unknown. We hypothesized that de novo mutations in mitochondrial DNA (mtDNA), which has far less reliable repair mechanisms than chromosomal DNA, might produce neoantigens capable of eliciting immune recognition and rejection. Here we present evidence in mice and humans that nonsynonymous mtDNA mutations can arise and become enriched during reprogramming to the iPSC stage, long-term culture and differentiation into target cells. These mtDNA mutations encode neoantigens that provoke an immune response that is highly specific and dependent on the host major histocompatibility complex genotype. Our results reveal that autologous iPSCs and their derivatives are not inherently immunologically inert for autologous transplantation and suggest that iPSC-derived products should be screened for mtDNA mutations.
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http://dx.doi.org/10.1038/s41587-019-0227-7DOI Listing
October 2019

Rapid progression to AML in a patient with germline mutation and acquired Q61K mutation.

Leuk Res Rep 2019 10;12:100176. Epub 2019 Jun 10.

Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, United States.

GATA2 deficiency syndrome is caused by autosomal dominant, heterozygous germline mutations with widespread effects on immune, pulmonary and vascular systems. Patients commonly develop hematological abnormalities including bone marrow failure, myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). We present a patient with mutation and MDS who progressed to AML over four months. Whole exome and targeted deep sequencing identified a new p.Q61K mutation in the bone marrow at the time of AML development. Rapid development of AML is possible in the setting of germline mutation despite stable MDS, supporting close monitoring and consideration of early allogeneic transplantation.
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http://dx.doi.org/10.1016/j.lrr.2019.100176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6582196PMC
June 2019

Glial cell line-derived neurotrophic factor (GDNF) mediates hepatic stellate cell activation via ALK5/Smad signalling.

Gut 2019 12 6;68(12):2214-2227. Epub 2019 Jun 6.

Central Laboratory, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Objective: Although glial cell line-derived neurotrophic factor (GDNF) is a member of the transforming growth factor-β superfamily, its function in liver fibrosis has rarely been studied. Here, we investigated the role of GDNF in hepatic stellate cell (HSC) activation and liver fibrosis in humans and mice.

Design: GDNF expression was examined in liver biopsies and sera from patients with liver fibrosis. The functional role of GDNF in liver fibrosis was examined in mice with adenoviral delivery of the GDNF gene, GDNF sgRNA CRISPR/Cas9 and the administration of GDNF-blocking antibodies. GDNF was examined on HSC activation using human and mouse primary HSCs. The binding of activin receptor-like kinase 5 (ALK5) to GDNF was determined using surface plasmon resonance (SPR), molecular docking, mutagenesis and co-immunoprecipitation.

Results: GDNF mRNA and protein levels are significantly upregulated in patients with stage F4 fibrosis. Serum GDNF content correlates positively with α-smooth muscle actin (α-SMA) and Col1A1 mRNA in human fibrotic livers. Mice with overexpressed GDNF display aggravated liver fibrosis, while mice with silenced GDNF expression or signalling inhibition by GDNF-blocking antibodies have reduced fibrosis and HSC activation. GDNF is confined mainly to HSCs and contributes to HSC activation through ALK5 at His and Asp and through downstream signalling via Smad2/3, but not through GDNF family receptor alpha-1 (GFRα1). GDNF, ALK5 and α-SMA colocalise in human and mouse HSCs, as demonstrated by confocal microscopy.

Conclusions: GDNF promotes HSC activation and liver fibrosis through ALK5/Smad signalling. Inhibition of GDNF could be a novel therapeutic strategy to combat liver fibrosis.
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http://dx.doi.org/10.1136/gutjnl-2018-317872DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6842044PMC
December 2019

The ribosomal prolyl-hydroxylase OGFOD1 decreases during cardiac differentiation and modulates translation and splicing.

JCI Insight 2019 05 21;5. Epub 2019 May 21.

Cardiovascular Branch.

The mechanisms regulating translation and splicing are not well understood. We provide insight into a new regulator of translation, OGFOD1 (2-oxoglutarate and iron dependent oxygenase domain-containing protein 1), which is a prolyl-hydroxylase that catalyzes the posttranslational hydroxylation of Pro-62 in the small ribosomal protein S23. We show that deletion of OGFOD1 in an in vitro model of human cardiomyocytes decreases translation of specific proteins (e.g., RNA-binding proteins) and alters splicing. RNA sequencing showed poor correlation between changes in mRNA and protein synthesis, suggesting that posttranscriptional regulation was the primary cause for the observed differences. We found that loss of OGFOD1 and the resultant alterations in protein translation modulates the cardiac proteome, shifting it towards higher protein amounts of sarcomeric proteins such as cardiac troponins, titin and cardiac myosin binding protein C. Furthermore, we found a decrease of OGFOD1 during cardiomyocyte differentiation. These results suggest that loss of OGFOD1 modulates protein translation and splicing, thereby leading to alterations in the cardiac proteome and highlight the role of altered translation and splicing in regulating the proteome..
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http://dx.doi.org/10.1172/jci.insight.128496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6629114PMC
May 2019

Spiral Steel Wire Based Fiber-Shaped Stretchable and Tailorable Triboelectric Nanogenerator for Wearable Power Source and Active Gesture Sensor.

Nanomicro Lett 2019 May 11;11(1):39. Epub 2019 May 11.

Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou, 215123, People's Republic of China.

Continuous deforming always leads to the performance degradation of a flexible triboelectric nanogenerator due to the Young's modulus mismatch of different functional layers. In this work, we fabricated a fiber-shaped stretchable and tailorable triboelectric nanogenerator (FST-TENG) based on the geometric construction of a steel wire as electrode and ingenious selection of silicone rubber as triboelectric layer. Owing to the great robustness and continuous conductivity, the FST-TENGs demonstrate high stability, stretchability, and even tailorability. For a single device with ~ 6 cm in length and ~ 3 mm in diameter, the open-circuit voltage of ~ 59.7 V, transferred charge of ~ 23.7 nC, short-circuit current of ~ 2.67 μA and average power of ~ 2.13 μW can be obtained at 2.5 Hz. By knitting several FST-TENGs to be a fabric or a bracelet, it enables to harvest human motion energy and then to drive a wearable electronic device. Finally, it can also be woven on dorsum of glove to monitor the movements of gesture, which can recognize every single finger, different bending angle, and numbers of bent finger by analyzing voltage signals.
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http://dx.doi.org/10.1007/s40820-019-0271-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770917PMC
May 2019

Genome-Wide Profiling of Cervical RNA-Binding Proteins Identifies Human Papillomavirus Regulation of RNASEH2A Expression by Viral E7 and E2F1.

mBio 2019 01 29;10(1). Epub 2019 Jan 29.

Tumor Virus RNA Biology Section, RNA Biology Laboratory, Center for Cancer Research, NCI/NIH, Frederick, Maryland, USA

RNA-binding proteins (RBPs) control mRNA processing, stability, transport, editing, and translation. We recently conducted transcriptome analyses comparing normal (i.e., healthy) cervical tissue samples with human papillomavirus (HPV)-positive cervical cancer tissue samples and identified 614 differentially expressed protein-coding transcripts which are enriched in cancer-related pathways and consist of 95 known RBPs. We verified the altered expression of 26 genes with a cohort of 72 cervical samples, including 24 normal cervical samples, 25 cervical intraepithelial neoplasia grade 2 (CIN2) and CIN3 samples, and 23 cervical cancer tissue samples. LY6K (lymphocyte antigen 6 complex locus K), FAM83A (family member with sequence similarity 83), CELSR3, ASF1B, IQGAP3, SEMA3F, CLDN10, MSX1, CXCL5, ASRGL1, ELAVL2, GRB7, KHSRP, NOVA1, PTBP1, and RNASEH2A were identified as novel candidate genes associated with cervical lesion progression and carcinogenesis. HPV16 or HPV18 infection was found to alter the expression of 8 RBP genes (CDKN2A, ELAVL2, GRB7, HSPB1, KHSRP, NOVA1, PTBP1, and RNASEH2A) in human vaginal and foreskin keratinocytes. Both viral E6 and E7 decreased NOVA1 expression, but only E7 increased the expression of RNASEH2A in an E2F1-dependent manner. Proliferating cell nuclear antigen (PCNA) directs RNASEH2 activity with respect to DNA replication by removing the RNA primers to promote Okazaki fragment maturation, and two factors are closely associated with neoplasia progression. Therefore, we predict that the induction of expression of RNASEH2A via viral E7 and E2F1 may promote DNA replication and cancer cell proliferation. High-risk HPV infections lead to development of cervical cancer. This study identified the differential expression of 16 novel genes (LY6K, FAM83A, CELSR3, ASF1B, IQGAP3, SEMA3F, CLDN10, MSX1, CXCL5, ASRGL1, ELAVL2, GRB7, KHSRP, NOVA1, PTBP1, and RNASEH2A) in HPV-infected cervical tissue samples and keratinocytes. Eight of these genes (CDKN2A, ELAVL2, GRB7, HSPB1, KHSRP, NOVA1, PTBP1, and RNASEH2A) encode RNA-binding proteins. Further studies indicated that both HPV16 and HPV18 infections lead to the aberrant expression of selected RBP-encoding genes. We found that viral E6 and E7 decrease NOVA1 expression but that E7 increases RNASEH2A expression via E2F1. The altered expression of these genes may be utilized as biomarkers for high-risk (HR)-HPV carcinogenesis and progression.
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http://dx.doi.org/10.1128/mBio.02687-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6355981PMC
January 2019

Donor-derived cell-free DNA predicts allograft failure and mortality after lung transplantation.

EBioMedicine 2019 Feb 26;40:541-553. Epub 2019 Jan 26.

Genomic Research Alliance for Transplantation (GRAfT), 10 Center Drive, 7S261, Bethesda, MD 20982, United States; Division of Intramural Research, National Heart, Lung and Blood Institute, 10 Center Drive, 7S261, Bethesda, MD 20982, United States. Electronic address:

Background: Allograft failure is common in lung-transplant recipients and leads to poor outcomes including early death. No reliable clinical tools exist to identify patients at high risk for allograft failure. This study tested the use of donor-derived cell-free DNA (%ddcfDNA) as a sensitive marker of early graft injury to predict impending allograft failure.

Methods: This multicenter, prospective cohort study enrolled 106 subjects who underwent lung transplantation and monitored them after transplantation for the development of allograft failure (defined as severe chronic lung allograft dysfunction [CLAD], retransplantation, and/or death from respiratory failure). Plasma samples were collected serially in the first three months following transplantation and assayed for %ddcfDNA by shotgun sequencing. We computed the average levels of ddcfDNA over three months for each patient (avddDNA) and determined its relationship to allograft failure using Cox-regression analysis.

Findings: avddDNA was highly variable among subjects: median values were 3·6%, 1·6% and 0·7% for the upper, middle, and low tertiles, respectively (range 0·1%-9·9%). Compared to subjects in the low and middle tertiles, those with avddDNA in the upper tertile had a 6·6-fold higher risk of developing allograft failure (95% confidence interval 1·6-19·9, p = 0·007), lower peak FEV1 values, and more frequent %ddcfDNA elevations that were not clinically detectable.

Interpretation: Lung transplant patients with early unresolving allograft injury measured via %ddcfDNA are at risk of subsequent allograft injury, which is often clinically silent, and progresses to allograft failure. FUND: National Institutes of Health.
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http://dx.doi.org/10.1016/j.ebiom.2018.12.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412014PMC
February 2019

MDS-associated mutations in germline GATA2 mutated patients with hematologic manifestations.

Leuk Res 2019 01 4;76:70-75. Epub 2018 Dec 4.

Laboratory of Myeloid Malignancies, Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.

Germline mutation in GATA2 can lead to GATA2 deficiency characterized by a complex multi-system disorder that can present with many manifestations including variable cytopenias, bone marrow failure, myelodysplastic syndrome/acute myeloid leukemia (MDS/AML), and severe immunodeficiency. Penetrance and expressivity within families is often variable. There is a spectrum of bone marrow disease in symptomatic cytopenic patients ranging from hypocellular marrows without overt dysplasia to those with definitive MDS, AML, or chronic myelomonocytic leukemia. Relatives of probands with the same mutations may demonstrate minimal disease manifestations and normal marrows. A comprehensive clinical, hematological and genetic assessment of 25 patients with germline GATA2 mutation was performed. MDS-associated mutations were identified in symptomatic GATA2 patients both with overt MDS and in those with hypocellular/aplastic bone marrows without definitive dysplasia. Healthy relatives of probands harboring the same germline GATA2 mutations had essentially normal marrows that were overall devoid of MDS-associated mutations. The findings suggest that abnormal clonal hematopoiesis is a common event in symptomatic germline mutated GATA2 patients with MDS and also in those with hypocellular marrows without overt morphologic evidence of dysplasia, possibly indicating a pre-MDS stage warranting close monitoring for disease progression.
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http://dx.doi.org/10.1016/j.leukres.2018.11.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6340496PMC
January 2019

Triptolide interferes with XRCC1/PARP1-mediated DNA repair and confers sensitization of triple-negative breast cancer cells to cisplatin.

Biomed Pharmacother 2019 Jan 14;109:1541-1546. Epub 2018 Nov 14.

Department of Biotechnology, College of Basic Medical Sciences, Dalian Medical University, Dalian, P.R.China, 116044. Electronic address:

Triptolide is a natural compound isolated from the Tripterygium wilfordii, which possesses anti-inflammatory and anti-tumor activities. Triptolide reportedly inhibits RNA polymerase II-mediated transcription and ATM activities to interfere with DNA repair. However, the roles of triptolide in DNA repair are still largely unknown. Triple negative breast cancer cells (TNBC) are insensitive to targeted anti-tumoral drugs, thus DNA damage chemotherapeutic drugs are the available treatments used in clinic, while the drug resistance of TNBC causes the challenge for successful cure. In this study, we investigated the efficiency of cisplatin in combination with triptolide in treatment of TNBC. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay shows triptolide suppresses the growth of two triple-negative breast cancer cells, BT549 and MDA-MB-231. Triptolide induces DNA breaks and arrests TNBC in the cell cycle S phase, and sensitizes TNBC to cisplatin. Western blot analysis shows triptolide down-regulated the levels of PARP1 and XRCC1, and slightly decreases the levels of RAD51. The results demonstrate triptolide interferes with single strand-break and base excision repair. The over-expressed PARP1/XRCC1 help the TNBC to resist triptolide. Based on these results, we conclude triptolide confers sensitization of TNBC to cisplatin via interference with XRCC1/PARP1-mediated base excision repair.
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http://dx.doi.org/10.1016/j.biopha.2018.11.008DOI Listing
January 2019

Coaxial Triboelectric Nanogenerator and Supercapacitor Fiber-Based Self-Charging Power Fabric.

ACS Appl Mater Interfaces 2018 Dec 3;10(49):42356-42362. Epub 2018 Dec 3.

Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices , Soochow University , Suzhou 215123 , China.

Although there has been rapid advancement in wearable electronics, challenges still remain in developing wearable and sustainable power sources with simple fabrication and low cost. In this work, we demonstrate a flexible coaxial fiber by fabricating a one-dimensional triboelectric nanogenerator (TENG) outside and a supercapacitor (SC) inside, which can not only harvest mechanical energy but also store energy in the all-in-one fiber. In such a coaxial fiber, carbon fiber bundles are utilized as the electrode material for the TENG as well as the active and electrode material for the SC. Meanwhile, silicone rubber serves as the separator between the SC and TENG, as the triboelectric material for the TENG, and as the encapsulation material for the whole fiber as well. Moreover, both SC and TENG exhibit good performance and stability, which ensures their long-term use in daily life. Because of the flexibility and durability of the carbon fiber and silicone rubber, the proposed coaxial fibers show great flexibility, which could be further knitted as cloth for sustainably powering wearable electronic devices. This work presents a promising platform for wearable electronics as well as smart textiles.
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http://dx.doi.org/10.1021/acsami.8b15104DOI Listing
December 2018
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