Publications by authors named "Chun Su"

46 Publications

Constrained chromatin accessibility in PU.1-mutated agammaglobulinemia patients.

J Exp Med 2021 Jul 5;218(7). Epub 2021 May 5.

Department of Genetics, University of Alabama at Birmingham, Birmingham, AL.

The pioneer transcription factor (TF) PU.1 controls hematopoietic cell fate by decompacting stem cell heterochromatin and allowing nonpioneer TFs to enter otherwise inaccessible genomic sites. PU.1 deficiency fatally arrests lymphopoiesis and myelopoiesis in mice, but human congenital PU.1 disorders have not previously been described. We studied six unrelated agammaglobulinemic patients, each harboring a heterozygous mutation (four de novo, two unphased) of SPI1, the gene encoding PU.1. Affected patients lacked circulating B cells and possessed few conventional dendritic cells. Introducing disease-similar SPI1 mutations into human hematopoietic stem and progenitor cells impaired early in vitro B cell and myeloid cell differentiation. Patient SPI1 mutations encoded destabilized PU.1 proteins unable to nuclear localize or bind target DNA. In PU.1-haploinsufficient pro-B cell lines, euchromatin was less accessible to nonpioneer TFs critical for B cell development, and gene expression patterns associated with the pro- to pre-B cell transition were undermined. Our findings molecularly describe a novel form of agammaglobulinemia and underscore PU.1's critical, dose-dependent role as a hematopoietic euchromatin gatekeeper.
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http://dx.doi.org/10.1084/jem.20201750DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105723PMC
July 2021

The complete chloroplast genome of Chinese medicinal herb (L.) Redouté (Iridaceae).

Mitochondrial DNA B Resour 2021 Feb 8;6(2):331-332. Epub 2021 Feb 8.

College of Agronomy, Henan Agricultural University, Zhengzhou, Henan, China.

The species of (L.) Redouté. is one of the Chinese traditional medicinal herb. In this study, we first report the complete chloroplast (cp) genome of . The chloroplast (cp) genome was determined to be 153,735 bp and the GC contents was 37.9%. The sequence includes a large single-copy (LSC) region of 83, 199 bp, a small single-copy (SSC) region of 18,168 bp, and two separated inverted regions of 26,184 bp each. It contains 132 genes, including 86 protein-coding genes, 38 tRNA genes, and 8 rRNA genes. Based on 10 chloroplast genomes data, the maximum likelihood phylogenetic analysis revealed that was sister to (Bootstrap = 100%) within Iridaceae. This result will be helpful for the conservation and breeding programs of the
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http://dx.doi.org/10.1080/23802359.2020.1866455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889214PMC
February 2021

3D promoter architecture re-organization during iPSC-derived neuronal cell differentiation implicates target genes for neurodevelopmental disorders.

Prog Neurobiol 2021 Jun 2;201:102000. Epub 2021 Feb 2.

Division of Human Genetics, The Children's Hospital of Philadelphia, 3615 Civic Center Boulevard, Philadelphia, PA, United States; Division of Diabetes and Endocrinology, The Children's Hospital of Philadelphia, 3615 Civic Center Boulevard, Philadelphia, PA, United States; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, 3615 Civic Center Boulevard, Philadelphia, PA, United States; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, 3615 Civic Center Boulevard, Philadelphia, PA, United States. Electronic address:

Neurodevelopmental disorders are thought to arise from interrupted development of the brain at an early age. Genome-wide association studies (GWAS) have identified hundreds of loci associated with susceptibility to neurodevelopmental disorders; however, which noncoding variants regulate which genes at these loci is often unclear. To implicate neuronal GWAS effector genes, we performed an integrated analysis of transcriptomics, epigenomics and chromatin conformation changes during the development from Induced pluripotent stem cell-derived neuronal progenitor cells (NPCs) into neurons using a combination of high-resolution promoter-focused Capture-C, ATAC-seq and RNA-seq. We observed that gene expression changes during the NPC-to-neuron transition were highly dependent on both promoter accessibility changes and long-range interactions which connect distal cis-regulatory elements (enhancer or silencers) to developmental-stage-specific genes. These genome-scale promoter-cis-regulatory-element atlases implicated 454 neurodevelopmental disorder-associated, putative causal variants mapping to 600 distal targets. These putative effector genes were significantly enriched for pathways involved in the regulation of neuronal development and chromatin organization, with 27 % expressed in a stage-specific manner. The intersection of open chromatin and chromatin conformation revealed development-stage-specific gene regulatory architectures during neuronal differentiation, providing a rich resource to aid characterization of the genetic and developmental basis of neurodevelopmental disorders.
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http://dx.doi.org/10.1016/j.pneurobio.2021.102000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096691PMC
June 2021

Lack of racial and ethnic-based differences in acute care delivery in intracerebral hemorrhage.

Int J Emerg Med 2021 Jan 19;14(1). Epub 2021 Jan 19.

Department of Emergency Medicine, Massachusetts General Hospital, Zero Emerson Place, Suite 3B, Boston, MA, 02114, USA.

Background And Aim: Early diagnosis and treatment of intracerebral hemorrhage (ICH) is thought to be critical for improving outcomes. We examined whether racial or ethnic disparities exist in acute care processes in the first hours after ICH.

Methods: We performed a retrospective review of a prospectively collected cohort of consecutive patients with spontaneous primary ICH presenting to a single urban tertiary care center. Acute care processes studied included time to computerized tomography (CT) scan, time from CT to inpatient bed request, and time from bed request to hospital admission. Clinical outcomes included mortality, Glasgow Outcome Scale, and modified Rankin Scale.

Results: Four hundred fifty-nine patients presented with ICH between 2006 and 2018 and met inclusion criteria (55% male; 75% non-Hispanic White [NHW]; mean age of 73). In minutes, median time to CT was 43 (interquartile range [IQR] 28, 83), time to bed request was 62 (IQR 33, 114), and time to admission was 142 (IQR 95, 232). In a multivariable analysis controlling for demographic factors, clinical factors, and disease severity, race/ethnicity had no effect on acute care processes. English language, however, was independently associated with slower times to CT (β = 30.7 min, 95% CI 9.9 to 51.4, p = 0.004) and to bed request (β = 32.8 min, 95% CI 5.5 to 60.0, p = 0.02). Race/ethnicity and English language were not independently associated with worse outcome.

Conclusions: We found no evidence of racial/ethnic disparities in acute care processes or outcomes in ICH. English as first language, however, was associated with slower care processes.
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http://dx.doi.org/10.1186/s12245-021-00329-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814635PMC
January 2021

Biological constraints on GWAS SNPs at suggestive significance thresholds reveal additional BMI loci.

Elife 2021 Jan 18;10. Epub 2021 Jan 18.

Center for Spatial and Functional Genomics, Children's Hospital of Philadelphia, Philadelphia, United States.

To uncover novel significant association signals (p<5×10), genome-wide association studies (GWAS) requires increasingly larger sample sizes to overcome statistical correction for multiple testing. As an alternative, we aimed to identify associations among suggestive signals (5 × 10≤p<5×10) in increasingly powered GWAS efforts using chromatin accessibility and direct contact with gene promoters as biological constraints. We conducted retrospective analyses of three GIANT BMI GWAS efforts using ATAC-seq and promoter-focused Capture C data from human adipocytes and embryonic stem cell (ESC)-derived hypothalamic-like neurons. This approach, with its extremely low false-positive rate, identified 15 loci at p<5×10 in the 2010 GWAS, of which 13 achieved genome-wide significance by 2018, including at , , and . Eighty percent of constrained 2015 loci achieved genome-wide significance in 2018. We observed similar results in waist-to-hip ratio analyses. In conclusion, biological constraints on sub-significant GWAS signals can reveal potentially true-positive loci for further investigation in existing data sets without increasing sample size.
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http://dx.doi.org/10.7554/eLife.62206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815306PMC
January 2021

Chloroplast phylogenomics and character evolution of eastern Asian Astragalus (Leguminosae): Tackling the phylogenetic structure of the largest genus of flowering plants in Asia.

Mol Phylogenet Evol 2021 03 30;156:107025. Epub 2020 Nov 30.

Department of Botany, National Museum of Natural History, Smithsonian Institution, Washington D.C., USA. Electronic address:

Astragalus, as the largest genus of the flowering plants, is well-known for its high species richness and morphological diversity. Previous studies suggested that many of the subgenera of Astragalus are not monophyletic and the phylogenetic relationships within the genus are still poorly known. In this study, we sampled 117 accessions of Astragalus and its close relatives, covering 55 sections of the genus plus 30 outgroup taxa to recover the main clades of eastern Asian Astragalus based on sequences of the whole chloroplast genome and 65 chloroplast CDSs. Astragalus is supported to be monophyletic and it is sister to the Oxytropis + Coluteoid clade. Within Astragalus, we recovered ten clades, and the ten clades differ substantially from Bunge's subgenera. The former segregate genus Astracantha is also monophyletic, but embedded within Astragalus s. str., supporting the merge of the spiny former genus Astracantha with Astragalus. We detected the atpF intron losses in the chloroplast genome of the Oxytropis + Coluteoid clade, i.e., the sister clade to Astragalus. Furthermore, we estimated the ancestral states of the trichome morphology and habit via the Bayesian Binary Method. The medifixed hair type is inferred to have developed at least five times and the annual habit originated at least six times. In addition, Astragalus is estimated to have originated in the mid Miocene (stem age, 16.09 Ma, 95% HPD: 12.46-20.50 Ma). The divergence times of the medifixed hair groups ranged from 4.03 to 0.87 Ma, mostly 2-1 Ma, which are correlated with the estimated phased uplifts of the Qinghai-Tibetan Plateau (QTP). We hypothesize that the uplifts of the QTP, which contributed to aridification in eastern Asia and the adjacent regions, may have accelerated the rapid speciation of Astragalus, especially the xerophilous groups (i.e. the medifixed hair groups).
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http://dx.doi.org/10.1016/j.ympev.2020.107025DOI Listing
March 2021

Variant-to-Gene-Mapping Analyses Reveal a Role for the Hypothalamus in Genetic Susceptibility to Inflammatory Bowel Disease.

Cell Mol Gastroenterol Hepatol 2021 16;11(3):667-682. Epub 2020 Oct 16.

Center for Spatial and Functional Genomics, Philadelphia, Pennsylvania; Division of Human Genetics, Philadelphia, Pennsylvania; Division of Diabetes and Endocrinology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address:

Background & Aims: Inflammatory bowel disease (IBD) is a polygenic disorder characterized principally by dysregulated inflammation impacting the gastrointestinal tract. However, there also is increasing evidence for a clinical association with stress and depression. Given the role of the hypothalamus in stress responses and in the pathogenesis of depression, useful insights could be gleaned from understanding its genetic role in IBD.

Methods: We conducted genetic correlation analyses on publicly available genome-wide association study summary statistics for depression and IBD traits to identify genetic commonalities. We used partitioned linkage disequilibrium score regression, leveraging our ATAC sequencing and promoter-focused Capture C data, to measure enrichment of IBD single-nucleotide polymorphisms within promoter-interacting open chromatin regions of human embryonic stem cell-derived hypothalamic-like neurons (HNs). Using the same data sets, we performed variant-to-gene mapping to implicate putative IBD effector genes in HNs. To contrast these results, we similarly analyzed 3-dimensional genomic data generated in epithelium-derived colonoids from rectal biopsy specimens from donors without pathologic disease noted at the time of colonoscopy. Finally, we conducted enrichment pathway analyses on the implicated genes to identify putative IBD dysfunctional pathways.

Results: We found significant genetic correlations (rg) of 0.122 with an adjusted P (P) = 1.4 × 10 for IBD: rg = 0.122; P = 2.5 × 10 for ulcerative colitis and genetic correlation (rg) = 0.094; P = 2.5 × 10 for Crohn's disease, and significant approximately 4-fold (P = .005) and approximately 7-fold (P = .03) enrichment of IBD single-nucleotide polymorphisms in HNs and colonoids, respectively. We implicated 25 associated genes in HNs, among which CREM, CNTF, and RHOA encode key regulators of stress. Seven genes also additionally were implicated in the colonoids. We observed an overall enrichment for immune and hormonal signaling pathways, and a colonoid-specific enrichment for microbiota-relevant terms.

Conclusions: Our results suggest that the hypothalamus warrants further study in the context of IBD pathogenesis.
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http://dx.doi.org/10.1016/j.jcmgh.2020.10.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7843407PMC
October 2020

Enhanced Production of Active Ecumicin Component with Higher Antituberculosis Activity by the Rare Actinomycete sp. MJM5123 Using a Novel Promoter-Engineering Strategy.

ACS Synth Biol 2020 11 25;9(11):3019-3029. Epub 2020 Sep 25.

Center for Nutraceutical and Pharmaceutical Materials, Myongji University, Yongin, Gyeonggi, 17058, Republic of Korea.

Ecumicins are potent antituberculosis natural compounds produced by the rare actinomycete sp. MJM5123. Here, we report an efficient genetic manipulation platform of this rare actinomycete. CRISPR/Cas9-based genome editing was achieved based on successful sporulation. Two genes in the ecumicin gene cluster were further investigated, and , which potentially encode a pretailoring cytochrome P450 hydroxylase and the core peptide synthase, respectively. Deletion of led to an enhanced ratio of the ecumicin compound EcuH16 relative to that of EcuH14, indicating that EcuN is indeed a P450 hydroxylase, and there is catalyzed hydroxylation at the C-3 position in unit phenylalanine to transform EcuH16 to the compound EcuH14. Furthermore, promoter engineering of by employing the strong promoter was performed and optimized. We found that integrating the endogenous ribosome-binding site (RBS) of together with the RBS from led to improved ecumicin production and resulted in a remarkably high EcuH16/EcuH14 ratio. Importantly, production of the more active component EcuH16 was considerably increased in the double RBSs engineered strain EPR1 compared to that in the wild-type strain, reaching 310 mg/L. At the same time, this production level was 2.3 times higher than that of the control strain EPA1 with only one RBS from . To the best of our knowledge, this is the first report of genome editing and promoter engineering on the rare actinomycete .
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http://dx.doi.org/10.1021/acssynbio.0c00248DOI Listing
November 2020

Effect of Fabrication Parameters on the Performance of 0.5 wt.% Graphene Nanoplates-Reinforced Aluminum Composites.

Materials (Basel) 2020 Aug 7;13(16). Epub 2020 Aug 7.

National Engineering Laboratory for Coalmine Backfilling Mining, Shandong University of Science and Technology, Tai'an 271019, China.

Aluminum composites reinforced by graphene nanoplates(GNP) with a mass fraction of 0.5% (0.5 wt.% GNP/Al) were fabricated using cold pressing and hot pressing. An orthogonal test was used to optimize the fabrication parameters. Ball milling time, ball milling speed, and ultrasonic time have the largest influence on the uniformity of the graphene in the composites. Afterwards, the microstructure, interfacial properties, and fracture morphology of the composites obtained with different parameters were further analyzed. The results show that ball milling time and ball milling speed have obvious influences on the mechanical properties of the composite. In this paper, when the ball milling speed is 300 r/min and the ball milling time is 6 h, the dispersion uniformity of graphene in the 0.5 wt.% GNP/Al composite is the best, the agglomeration is the lowest, and the mechanical properties of the composites are the best, among which the tensile strength is 156.8 MPa, 56.6% higher than that of pure aluminum fabricated by the same process (100.1 MPa), and the elongation is 19.9%, 39.8% lower than that of pure aluminum (33.1%).
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http://dx.doi.org/10.3390/ma13163483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7475921PMC
August 2020

Chloroplast Phylogenomics Reveals the Intercontinental Biogeographic History of the Liquorice Genus (Leguminosae: ).

Front Plant Sci 2020 17;11:793. Epub 2020 Jun 17.

Key Laboratory of Plant Resources Conservation and Sustainable Utilization, South China Botanical Garden, Chinese Academy of Sciences, Guangzhou, China.

The liquorice genus, L. (Leguminosae), is a medicinal herb with great economic importance and an intriguing intercontinental disjunct distribution in Eurasia, North Africa, the Americas, and Australia. , along with Boiss. and Fisch. & C.A.Mey., comprise s.l. Here we reconstructed the phylogenetic relationships and biogeographic history in s.l. using sequence data of whole chloroplast genomes. We found that s.l. is sister to the tribe Wisterieae and is divided into four main clades. Clade I, corresponds to and is sister to sensu Meng. is embedded within sensu Meng, and these two genera together form Clades II-IV. Based on biogeographic analyses and divergence time dating, s.l. originated during the late Eocene and its most recent common ancestor (MRCA) was distributed in the interior of Eurasia and the circum-Mediterranean region. A vicariance event, which was possibly a response to the uplifting of the Turkish-Iranian Plateau, may have driven the divergence between sensu Meng and in the Middle Miocene. The third and fourth main uplift events of the Qinghai-Tibetan Plateau may have led to rapid evolutionary diversification within sensu Meng. Subsequently, the MRCA of Clade II might have migrated to North America () via the Bering land bridge during the early Pliocene, and reached temperate South America () by long-distance dispersal (LDD). Within Clade III, the ancestor of arrived at southern Australia through LDD after the late Pliocene, whereas all other species (the SPEY clade) migrated to the interior of Eurasia and the Mediterranean region in the early Pleistocene. The MRCA of Clade IV was restricted in the interior of Eurasia, but its descendants have become widespread in temperate regions of the Old World Northern Hemisphere during the last million years.
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http://dx.doi.org/10.3389/fpls.2020.00793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7318913PMC
June 2020

Mapping effector genes at lupus GWAS loci using promoter Capture-C in follicular helper T cells.

Nat Commun 2020 07 3;11(1):3294. Epub 2020 Jul 3.

Department of Pathology, The Children's Hospital of Philadelphia, 3615 Civic Center Boulevard, Philadelphia, PA, USA.

Systemic lupus erythematosus (SLE) is mediated by autoreactive antibodies that damage multiple tissues. Genome-wide association studies (GWAS) link >60 loci with SLE risk, but the causal variants and effector genes are largely unknown. We generated high-resolution spatial maps of SLE variant accessibility and gene connectivity in human follicular helper T cells (TFH), a cell type required for anti-nuclear antibodies characteristic of SLE. Of the ~400 potential regulatory variants identified, 90% exhibit spatial proximity to genes distant in the 1D genome sequence, including variants that loop to regulate the canonical TFH genes BCL6 and CXCR5 as confirmed by genome editing. SLE 'variant-to-gene' maps also implicate genes with no known role in TFH/SLE disease biology, including the kinases HIPK1 and MINK1. Targeting these kinases in TFH inhibits production of IL-21, a cytokine crucial for class-switched B cell antibodies. These studies offer mechanistic insight into the SLE-associated regulatory architecture of the human genome.
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http://dx.doi.org/10.1038/s41467-020-17089-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335045PMC
July 2020

IL-1 Transcriptional Responses to Lipopolysaccharides Are Regulated by a Complex of RNA Binding Proteins.

J Immunol 2020 03 17;204(5):1334-1344. Epub 2020 Jan 17.

Division of Allergy Immunology, Children's Hospital of Philadelphia, Philadelphia, PA 19104;

The and genes lie in close proximity on chromosome 2 near the gene for their natural inhibitor, Despite diverse functions, they are all three inducible through TLR4 signaling but with distinct kinetics. This study analyzed transcriptional induction kinetics, chromosome looping, and enhancer RNA production to understand the distinct regulation of these three genes in human cells. , , and were rapidly induced after stimulation with LPS; however, mRNA production was less inhibitable by iBET151, suggesting it does not use pause-release regulation. Surprisingly, chromatin looping contacts between and were highly intermingled, although those of were distinct, and we focused on comparing and transcriptional pathways. Our studies demonstrated that enhancer RNAs were produced from a subset of the regulatory regions, that they were critical for production of the mRNAs, and that they bound a diverse array of RNA binding proteins, including p300 but not CBP. We, furthermore, demonstrated that recruitment of p300 was dependent on MAPKs. Integrator is another RNA binding protein recruited to the promoters and enhancers, and its recruitment was more dependent on NF-κB than MAPKs. We found that integrator and NELF, an RNA polymerase II pausing protein, were associated with RNA in a manner that facilitated interaction. We conclude that and share many regulatory contacts, signaling pathways, and interactions with enhancer RNAs. A complex of protein interactions with enhancer RNAs emphasize the role of enhancer RNAs and the overall structural aspects of transcriptional regulation.
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http://dx.doi.org/10.4049/jimmunol.1900650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7033021PMC
March 2020

Glycyrrhizic acid promotes neural repair by directly driving functional remyelination.

Food Funct 2020 Jan;11(1):992-1005

National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, The Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, The Ministry of Education, College of Life Sciences, Shaanxi Normal University, Xi'an, Shaanxi 710119, China.

Natural compounds are a rich source of effective candidate drugs for the treatment of neurological disorders. Glycyrrhizic acid (GA), the major water-soluble ingredient isolated from Glycyrrhiza glabra, is reported to show anti-inflammatory and immunomodulatory activities. However, its effect on CNS demyelinating disease is unclear. In this study, we showed that GA ameliorated the clinical disease severity of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), especially at the chronic stage of clinical EAE. Histological evaluation demonstrated that, in the prophylactic treatment regimen, GA significantly inhibited inflammatory demyelination in the CNS. During the chronic stage when myelin and axon damage has already occurred, GA induced oligodendrocyte progenitor cell (OPC) differentiation into mature oligodendrocytes, thus effectively accelerating remyelination. Evidence from the cuprizone-induced mouse model of de- and remyelination, ex vivo organotypic slice cultures, and in vitro OPC maturation experiments indicated that the observed efficacy of this compound resulted directly from enhanced remyelination rather than immune suppression. Furthermore, we found that GA promoted oligodendrocyte maturation through modulating GSK-3β signaling pathways. Our data led to the conclusion that GA could be used as a potential therapeutic candidate for the treatment of demyelinating diseases such as MS, which remains refractory to available treatments.
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http://dx.doi.org/10.1039/c9fo01459dDOI Listing
January 2020

SHR4z, a novel decoy effector from the haustorium of the parasitic weed Striga gesnerioides, suppresses host plant immunity.

New Phytol 2020 05 31;226(3):891-908. Epub 2019 Dec 31.

Department of Biology, University of Virginia, Charlottesville, VA, 22904, USA.

Cowpea (Vigna unguiculata) cultivar B301 is resistant to races SG4 and SG3 of the root parasitic weed Striga gesnerioides, developing a hypersensitive response (HR) at the site of parasite attachment. By contrast, race SG4z overcomes B301 resistance and successfully parasitises the plant. Comparative transcriptomics and in silico analysis identified a small secreted effector protein dubbed Suppressor of Host Resistance 4z (SHR4z) in the SG4z haustorium that upon transfer to the host roots causes a loss of host immunity (i.e. decreased HR and increased parasite growth). SHR4z has significant homology to the short leucine-rich repeat (LRR) domain of SOMATIC EMBRYOGENESIS RECEPTOR-LIKE KINASE (SERK) family proteins and functions by binding to VuPOB1, a host BTB-BACK domain-containing ubiquitin E3 ligase homologue, leading to its rapid turnover. VuPOB1 is shown to be a positive regulator of HR since silencing of VuPOB1 expression in transgenic B301 roots lowers the frequency of HR and increases the levels of successful SG4 parasitism and overexpression decreases parasitism by SG4z. These findings provide new insights into how parasitic weeds overcome host defences and could potentially contribute to the development of novel strategies for controlling Striga and other parasitic weeds thereby enhancing crop productivity and food security globally.
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http://dx.doi.org/10.1111/nph.16351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7187149PMC
May 2020

A fossil-calibrated phylogeny reveals the biogeographic history of the Cladrastis clade, an amphi-Pacific early-branching group in papilionoid legumes.

Mol Phylogenet Evol 2020 02 7;143:106673. Epub 2019 Nov 7.

Key Laboratory of Plant Resources Conservation and Sustainable Utilization, South China Botanical Garden, Chinese Academy of Sciences, Guangzhou 510650, China. Electronic address:

The early-branching Cladrastis clade of papilionoid legumes (Leguminosae, Papilionoideae) has an intriguing amphi-Pacific disjunct distribution in eastern Asia and temperate-tropical Americas. Here we used nuclear and three plastid regions to reconstruct the phylogenetic relationships and divergence times in the Cladrastis clade, as well as the evolution of morphological characters that might have been key in its biogeographic history. The ancestral character state estimation revealed that the most recent common ancestor of the Cladrastis clade was deciduous trees possessing compressed, winged fruits. The Cladrastis clade was inferred to have originated in the mid-latitude thermophilic forests of North America in the early Eocene, followed by the split between ancestors of wing-fruited Platyosprion and the non-wing-fruited group, and later the divergence of Cladrastis s.s. from the non-wing-fruited group in middle Eocene. Platyosprion and Cladrastis s.s. display an "out-of-North-America" biogeographic pattern and might have migrated to Asia via the Bering land bridge (BLB) or the North Atlantic land bridges (NALB) during middle to late Eocene. Our results, coupled with the relatively well documented fossil record for the clade, suggest that Platyosprion experienced an extinction event in North America caused by climatic cooling around the Eocene-Oligocene transition, which drove a major vegetation shift in western North America, in turn serving as a barrier for the vicariance of Pickeringia and Styphnolobium. The evolution of shrubby habit and sclerophyllous leaves in the former might be adaption to the chaparral vegetation in southwestern North America; the latter gained the trait of moniliform, succulent fruit. Styphnolobium further dispersed southward to tropical North America in the Oligocene, and eastward to Asia through BLB during middle Miocene. Subsequent sundering of BLB facilitated the vicariance of St. affine and St. japonicum.
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http://dx.doi.org/10.1016/j.ympev.2019.106673DOI Listing
February 2020

The complete chloroplast genome sequence of Bunge (Fabaceae).

Mitochondrial DNA B Resour 2019 Oct 24;4(2):3762-3763. Epub 2019 Oct 24.

Department of Botany, National Museum of Natural History, Smithsonian Institution, Washington, DC, USA.

The first complete chloroplast genome of Bunge is reported and characterized in this study. The whole chloroplast genome was 122,461 base pairs in length with 110 genes, including 76 protein-coding genes, 30 tRNAs, and 4 rRNAs. In addition, the intron was absent. Maximum-likelihood (ML) phylogenetic analysis indicated that and species of were closely related, which is congruent with previous studies.
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http://dx.doi.org/10.1080/23802359.2019.1682479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7707422PMC
October 2019

Genome-scale Capture C promoter interactions implicate effector genes at GWAS loci for bone mineral density.

Nat Commun 2019 03 19;10(1):1260. Epub 2019 Mar 19.

Center for Spatial and Functional Genomics, Children's Hospital of Philadelphia, Philadelphia, 19104, PA, USA.

Osteoporosis is a devastating disease with an essential genetic component. GWAS have discovered genetic signals robustly associated with bone mineral density (BMD), but not the precise localization of effector genes. Here, we carry out physical and direct variant to gene mapping in human mesenchymal progenitor cell-derived osteoblasts employing a massively parallel, high resolution Capture C based method in order to simultaneously characterize the genome-wide interactions of all human promoters. By intersecting our Capture C and ATAC-seq data, we observe consistent contacts between candidate causal variants and putative target gene promoters in open chromatin for ~ 17% of the 273 BMD loci investigated. Knockdown of two novel implicated genes, ING3 at 'CPED1-WNT16' and EPDR1 at 'STARD3NL', inhibits osteoblastogenesis, while promoting adipogenesis. This approach therefore aids target discovery in osteoporosis, here on the example of two relevant genes involved in the fate determination of mesenchymal progenitors, and can be applied to other common genetic diseases.
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http://dx.doi.org/10.1038/s41467-019-09302-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6425012PMC
March 2019

Analysis of the complete genome sequence of a marine-derived strain sp. S063 CGMCC 14582 reveals its biosynthetic potential to produce novel anti-complement agents and peptides.

PeerJ 2019 3;7:e6122. Epub 2019 Jan 3.

State Key Laboratory of Microbial Metabolism and School of Life Science and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.

Genome sequences of marine streptomycetes are valuable for the discovery of useful enzymes and bioactive compounds by genome mining. However, publicly available complete genome sequences of marine streptomycetes are still limited. Here, we present the complete genome sequence of a marine streptomycete sp. S063 CGMCC 14582. Species delineation based on the pairwise digital DNA-DNA hybridization and genome comparison ANI (average nucleotide identity) value showed that sp. S063 CGMCC 14582 possesses a unique genome that is clearly different from all of the other available genomes. Bioactivity tests showed that sp. S063 CGMCC 14582 produces metabolites with anti-complement activities, which are useful for treatment of numerous diseases that arise from inappropriate activation of the human complement system. Analysis of the genome reveals no biosynthetic gene cluster (BGC) which shows even low similarity to that of the known anti-complement agents was detected in the genome, indicating that sp. S063 CGMCC 14582 may produce novel anti-complement agents of microbial origin. Four BGCs which are potentially involved in biosynthesis of non-ribosomal peptides were disrupted, but no decrease of anti-complement activities was observed, suggesting that these four BGCs are not involved in biosynthesis of the anti-complement agents. In addition, LC-MS/MS analysis and subsequent alignment through the Global Natural Products Social Molecular Networking (GNPS) platform led to the detection of novel peptides produced by the strain. sp. S063 CGMCC 14582 grows rapidly and is salt tolerant, which benefits efficient secondary metabolite production via seawater-based fermentation. Our results indicate that sp. S063 has great potential to produce novel bioactive compounds, and also is a good host for heterologous production of useful secondary metabolites for drug discovery.
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http://dx.doi.org/10.7717/peerj.6122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321760PMC
January 2019

Plasma homocysteine levels and intracranial plaque characteristics: association and clinical relevance in ischemic stroke.

BMC Neurol 2018 Dec 6;18(1):200. Epub 2018 Dec 6.

Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, No.300 Guangzhou Road, Gulou district, Nanjing, 210029, Jiangsu Province, China.

Background: Elevated plasma homocysteine (Hcy) is an independent risk factor for ischemic stroke. This study aimed to evaluate the association between Hcy levels and intracranial plaque characteristics and to investigate their clinical relevance in ischemic stroke.

Methods: Ninety-four patients with intracranial atherosclerosis (ICAS) were enrolled. Plasma Hcy levels were measured. Intracranial plaque characteristics including plaque enhancement, stenosis ratio, T2 and T1 hyperintense components were assessed on high-resolution magnetic resonance imaging. Logistic regression model was constructed to analyze the association between high Hcy levels and plaque characteristics, and their synergistic effects to predict the likelihood for ischemic stroke, while adjusting for demographics and traditional atherosclerotic risk factors.

Results: Elevated Hcy level was associated with strong plaque enhancement independently of age, sex, serum creatinine levels and other atherosclerotic risk factors ((P < 0.001, OR 6.00, 95% confidence interval [CI] 2.28-15.74). Both strong plaque enhancement (P = 0.026, OR 5.63, 95% CI 1.23-25.81) and high Hcy level (P = 0.018, OR 6.20, 95% CI 1.36-28.26) were correlated with acute ischemic stroke. The combination of them strengthened the ability to stratify the likelihood for ischemic stroke, with an improved area under the receiver operating characteristic curve (AUC) of 0.871, significantly higher than that of strong plaque enhancement (0.755) and high Hcy level (0.715) alone (P < 0.05 for both).

Conclusions: High Hcy level appears to have association with intracranial strong plaque enhancement. The combined assessment of plasma Hcy levels and plaque enhancement may improve ischemic stroke risk stratification.
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http://dx.doi.org/10.1186/s12883-018-1203-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6282283PMC
December 2018

Genome mining of Streptomyces xinghaiensis NRRL B-24674 for the discovery of the gene cluster involved in anticomplement activities and detection of novel xiamycin analogs.

Appl Microbiol Biotechnol 2018 Nov 19;102(22):9549-9562. Epub 2018 Sep 19.

State Key Laboratory of Microbial Metabolism, School of Life Science and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China.

Marine actinobacterium Streptomyces xinghaiensis NRRL B-24674 has been characterized as a novel species, but thus far, its biosynthetic potential remains unexplored. In this study, the high-quality genome sequence of S. xinghaiensis NRRL B-24674 was obtained, and the production of anticomplement agents, xiamycin analogs, and siderophores was investigated by genome mining. Anticomplement compounds are valuable for combating numerous diseases caused by the abnormal activation of the human complement system. The biosynthetic gene cluster (BGC) nrps1 resembles that of complestatins, which are potent microbial-derived anticomplement agents. The identification of the nrps1 BGC revealed a core peptide that differed from that in complestatin; thus, we studied the anticomplement activity of this strain. The culture broth of S. xinghaiensis NRRL B-24674 displayed good anticomplement activity. Subsequently, the disruption of the genes in the nrps1 BGC resulted in the loss of anticomplement activity, confirming the involvement of this BGC in the biosynthesis of anticomplement agents. In addition, the mining of the BGC tep5, which resembles that of the antiviral pentacyclic indolosesquiterpene xiamycin, resulted in the discovery of nine xiamycin analogs, including three novel compounds. In addition to the BGCs responsible for desferrioxamine B, neomycin, ectoine, and carotenoid, 18 BGCs present in the genome are predicted to be novel. The results of this study unveil the potential of S. xinghaiensis as a producer of novel anticomplement agents and provide a basis for further exploration of the biosynthetic potential of S. xinghaiensis NRRL B-24674 for the discovery of novel bioactive compounds by genome mining.
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http://dx.doi.org/10.1007/s00253-018-9337-2DOI Listing
November 2018

Isolation and characterization of microsatellite loci from (Fabaceae).

Appl Plant Sci 2018 Jun 11;6(7):e01168. Epub 2018 Jul 11.

College of Life Sciences Northwest A&F University Yangling 712100 Shaanxi People's Republic of China.

Premise Of The Study: Microsatellite primers were developed for a perennial legume from northern China, (Fabaceae), to investigate population genetic structure of this taxon, as well as potential hybridization events with closely related taxa in this genus.

Methods And Results: One hundred and five primer pairs were designed from Illumina sequence data and screened for suitability. Fifteen of these primer pairs were polymorphic, and these primers amplified tri-, tetra-, and pentanucleotide repeats with 10-56 alleles per locus. Cross-amplification tests in three other species from northern China (, , and ) revealed that all of these loci can be amplified successfully and show polymorphism.

Conclusions: These primer pairs can be used to assess the genetic diversity and population structure in future studies of , as well as studies of potential hybridization events with closely related taxa in this genus.
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http://dx.doi.org/10.1002/aps3.1168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6055551PMC
June 2018

One-pot co-catalysis of corncob with dilute hydrochloric acid and tin-based solid acid for the enhancement of furfural production.

Bioresour Technol 2018 Nov 1;268:315-322. Epub 2018 Aug 1.

Advanced Catalysis and Green Manufacturing Collaborative Innovation Center, Jiangsu Key Laboratory of Advanced Catalytic Materials and Technology, Changzhou University, Changzhou, PR China; Hubei Collaborative Innovation Center for Green Transformation of Bio-resources, Hubei University, Wuhan, PR China. Electronic address:

A newly synthesized solid acid catalyst SO/SnO-diatomite was prepared for synthesizing furfural from corncob in the presence of homogeneous Brönsted acid. The relationship between pKa of Brönsted acid and turnover frequency (TOF) of co-catalysis with Brönsted acid plus SO/SnO-diatomite was explored on the conversion of corncob to furfural. HCl (pKa = -7.0) (0.5 wt%) plus SO/SnO-diatomite (3.6 wt%) gave the highest furfural yield (40.1%) with TOF value at 2.98 h in the aqueous media. In the γ-valerolactone-water (6:4, v:v) biphasic media containing 15 g/L ZnCl, one-pot conversion of corncob with co-catalysts gave a furfural yield of 68.9% at 170 °C for 30 min. Additionally, an efficient SO/SnO-diatomite recycling was achieved with a productivity of 15.6 g furfural/(g solid acid·day) after 5 cycles of repeated use. Clearly, this one-pot co-catalysis process has high potential application for furfural production in future.
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http://dx.doi.org/10.1016/j.biortech.2018.07.147DOI Listing
November 2018

Genome Mining of the Marine Actinomycete sp. DUT11 and Discovery of Tunicamycins as Anti-complement Agents.

Front Microbiol 2018 20;9:1318. Epub 2018 Jun 20.

State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.

Marine actinobacteria are potential producers of various secondary metabolites with diverse bioactivities. Among various bioactive compounds, anti-complement agents have received great interest for drug discovery to treat numerous diseases caused by inappropriate activation of the human complement system. However, marine streptomycetes producing anti-complement agents are still poorly explored. In this study, a marine-derived strain sp. DUT11 showing superior anti-complement activity was focused, and its genome sequence was analyzed. Gene clusters showing high similarities to that of tunicamycin and nonactin were identified, and their corresponding metabolites were also detected. Subsequently, tunicamycin I, V, and VII were isolated from sp. DUT11. Anti-complement assay showed that tunicamycin I, V, VII inhibited complement activation through the classic pathway, whereas no anti-complement activity of nonactin was detected. This is the first time that tunicamycins are reported to have such activity. In addition, genome analysis indicates that sp. DUT11 has the potential to produce novel lassopeptides and lantibiotics. These results suggest that marine are rich sources of anti-complement agents for drug discovery.
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http://dx.doi.org/10.3389/fmicb.2018.01318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6019454PMC
June 2018

Plaque Distribution and Characteristics in Low-Grade Middle Cerebral Artery Stenosis and Its Clinical Relevance: A 3-Dimensional High-Resolution Magnetic Resonance Imaging Study.

J Stroke Cerebrovasc Dis 2018 Aug 8;27(8):2243-2249. Epub 2018 May 8.

Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China. Electronic address:

Objectives: The significance of atherosclerotic plaques in the parental artery with low-grade stenosis remains undetermined. We used three-dimensional high-resolution magnetic resonance imaging (3D HR-MRI) to investigate plaque distribution and characteristics of low-grade middle cerebral artery (MCA) stenosis and its clinical relevance with stroke events.

Methods: We retrospectively studied 22 symptomatic patients and 24 asymptomatic patients with low-grade MCA stenosis (<50%). By 3D HR-MRI, each identified plaque was classified as either culprit (plaque on the ipsilateral side of a stroke) or nonculprit (plaques in asymptomatic patients or not within the vascular territory of a stroke). Plaque enhancement grades and distribution were assessed and compared between the groups. The association between plaque enhancement and distribution and ischemic stroke was evaluated.

Results: We identified 22 culprit plaques and 31 nonculprit plaques. More culprit plaques showed contrast enhancement compared to the nonculprit plaques (95.5% versus 29.0%, P <.001). Culprit plaques were more frequently superiorly distributed than the nonculprit plaques (46.9% versus 17.5%, P <.01). Contrast enhancement (odds ratio [OR] 17.0, 95% confidence interval [CI] 3.7-77.4) and superior distribution (OR 4.2, 95% CI 1.4-12.1) of a plaque were associated with a recent ischemic stroke, of which single subcortical infarctions accounted for the largest percentage (50%).

Conclusions: Contrast enhancement and superior distribution may serve as indicators of culprit plaques in low-grade MCA stenosis, and they were significantly related to a recent ischemic stroke.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2018.04.010DOI Listing
August 2018

Atovaquone enhances doxorubicin's efficacy via inhibiting mitochondrial respiration and STAT3 in aggressive thyroid cancer.

J Bioenerg Biomembr 2018 08 23;50(4):263-270. Epub 2018 Apr 23.

Department of Endocrinology, The Third People's Hospital of Guangxi Zhuang Autonomous Region, Riverside Hospital of Guangxi Zhuang Autonomous Region, Heti Road 85, Qingxiu District, Nanning, 530021, China.

The clinical management of anaplastic thyroid carcinoma and follicular thyroid carcinoma is challenging and requires an alternative therapeutic strategy. Although atovaquone is an FDA-approved anti-malarial drug, studies has recently demonstrated its anti-cancer activities. In line with these efforts, our study shows that atovaquone is an attractive candidate for thyroid cancer treatment. We show that atovaquone significantly inhibits growth, migration and survival in a concentration-dependent manner in 8505C and FTC113 cells. Mechanistically, atovaquone inhibits mitochondrial complex III activity, leading to mitochondrial respiration inhibition and reduction of ATP production in thyroid cancer cells. The inhibitory effects of atovaquone is reversed in mitochondrial respiration-deficient 8505C ρ0 cells, confirming mitochondrial respiration as the mechanism of atovaquone's action in thyroid cancer. In addition, atovaquone suppresses phosphorylation of STAT3 in thyroid cancer wildype but not ρ0 cells, demonstrating that STAT3 phosphorylation inhibition by atovaquone is a consequence of mitochondrial respiration inhibition. Notably, we further demonstrate that atovaquone significantly augments doxorubicin's inhibitory effects via suppressing mitochondrial respiration and STAT3. Our findings suggest that atovaquone can be repurposed for thyroid cancer treatment. Our work also highlights that targeting mitochondrial respiration may represent potential therapeutic strategy in thyroid cancer.
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http://dx.doi.org/10.1007/s10863-018-9755-yDOI Listing
August 2018

Ectopic meningioma in a patient with neurofibromatosis Type 2: a case report and review of the literature.

BJR Case Rep 2018 Mar 23;4(3):20180007. Epub 2018 Apr 23.

Department of Radiology,The First Affiliated Hospital of Nanjing Medical University,Nanjing,China.

Ectopic meningioma occurring in the region of parapharyngeal space is rare in clinical practice and brings great challenge in its diagnosis. This report details such a case in a 14-year-old girl with neurofibromatosis Type 2, which is a highly infrequent association. The clinical manifestations, imaging findings, and pathological manifestations are described, and the relevant literature is reviewed to highlight characteristic imaging findings of ectopic meningiomas.
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http://dx.doi.org/10.1259/bjrcr.20180007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6711269PMC
March 2018

Leaching of metals from end-of-life solar cells.

Environ Sci Pollut Res Int 2019 Oct 10;26(29):29524-29531. Epub 2018 Apr 10.

Department of Power Mechanical Engineering, National Tsing Hua University, No. 101, Sec. 2, Kuang Fu Rd., 30013, Hsinchu, Taiwan ROC.

The issue of recycling waste solar cells is critical with regard to the expanded use of these cells, which increases waste production. Technology establishment for this recycling process is essential with respect to the valuable and hazardous metals present therein. In the present study, the leaching potentials of Acidithiobacillus thiooxidans, Acidithiobacillus ferrooxidans, Penicillium chrysogenum, and Penicillium simplicissimum were assessed for the recovery of metals from spent solar cells, with a focus on retrieval of the valuable metal Te. Batch experiments were performed to explore and compare the metal removal efficiencies of the aforementioned microorganisms using spent media. P. chrysogenum spent medium was found to be most effective, recovering 100% of B, Mg, Si, V, Ni, Zn, and Sr along with 93% of Te at 30 °C, 150 rpm and 1% (w/v) pulp density. Further optimization of the process parameters increased the leaching efficiency, and 100% of Te was recovered at the optimum conditions of 20 °C, 200 rpm shaking speed and 1% (w/v) pulp density. In addition, the recovery of aluminum increased from 31 to 89% upon process optimization. Thus, the process has considerable potential for metal recovery and is environmentally beneficial.
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http://dx.doi.org/10.1007/s11356-018-1918-1DOI Listing
October 2019

Improvement in Fatigue Performance of Aluminium Alloy Welded Joints by Laser Shock Peening in a Dynamic Strain Aging Temperature Regime.

Materials (Basel) 2016 Sep 26;9(10). Epub 2016 Sep 26.

School of Mechnical Engineering, Jiangsu University, Zhenjiang 212013, China.

As a new treatment process after welding, the process parameters of laser shock peening (LSP) in dynamic strain aging (DSA) temperature regimes can be precisely controlled, and the process is a non-contact one. The effects of LSP at elevated temperatures on the distribution of the surface residual stress of AA6061-T6 welded joints were investigated by using X-ray diffraction technology with the sin² method and Abaqus software. The fatigue life of the welded joints was estimated by performing tensile fatigue tests. The microstructural evolution in surface and fatigue fractures of the welded joints was presented by means of surface integrity and fracture surface testing. In the DSA temperature regime of AA6061-T6 welded joints, the residual compressive stress was distributed more stably than that of LSP at room temperature. The thermal corrosion resistance and fatigue properties of the welded joints were also improved. The experimental results and numerical analysis were in mutual agreement.
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http://dx.doi.org/10.3390/ma9100799DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5456636PMC
September 2016

Properties of a Laser Shock Wave in Al-Cu Alloy under Elevated Temperatures: A Molecular Dynamics Simulation Study.

Materials (Basel) 2017 Jan 18;10(1). Epub 2017 Jan 18.

School of Mechanical Engineering, Jiangsu University, Zhenjiang 212013, China.

The laser shock wave (LSW) generated by the interaction between a laser and a material has been widely used in laser manufacturing, such as laser shock peening and laser shock forming. However, due to the high strain rate, the propagation of LSW in materials, especially LSW at elevated temperatures, is difficult to study through experimental methods. A molecular dynamics simulation was used in this study to investigate the propagation of LSW in an Al-Cu alloy. The Hugoniot relations of LSW were obtained at different temperatures and the effects of elevated temperatures on shock velocity and shock pressure were analyzed. Then the elastic and plastic wave of the LSW was researched. Finally, the evolution of dislocations induced by LSW and its mechanism under elevated temperatures was explored. The results indicate that the shock velocity and shock pressure induced by LSW both decrease with the increasing temperatures. Moreover, the velocity of elastic wave and plastic wave both decrease with the increasing treatment temperature, while their difference decreases as the temperature increases. Moreover, the dislocation atoms increases with the increasing temperatures before 2 ps, while it decreases with the increasing temperatures after 2 ps. The reason for the results is related to the formation and evolution of extended dislocations.
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http://dx.doi.org/10.3390/ma10010073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5344562PMC
January 2017