Publications by authors named "Yang Zeng"

179 Publications

Identification of Novel Mutations in : Expanding the Mutational Spectrum for Female Infertility.

Front Cell Dev Biol 2021 9;9:647130. Epub 2021 Apr 9.

Institute of Pediatrics, Children's Hospital of Fudan University and Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, China.

Oocyte maturation and fertilization are fundamental processes for successful human reproduction, and abnormalities in these processes will cause infertility. Recently, we identified biallelic mutations in that are responsible for human oocyte maturation arrest, fertilization failure, and early embryonic development arrest. In this study, we screened for further mutations in a new cohort of patients with abnormalities in oocyte maturation, fertilization, and early embryonic development. Through whole-exome sequencing, we identified the four novel mutations c.887G > A (p. Arg296Gln), c.964C > T (p.Arg322), c.1155G > C (p.Trp385Cys), and c.330 + 1G > A (p. Glu111Ilefs36) and one previously reported mutation c.965G > A (p.Arg322Gln) in in four infertile individuals from three independent families. The patients had different phenotypes of oocyte maturation arrest and fertilization failure resulting from the different mutations. This study confirms our previous research and expands the spectrum of known mutations in , providing new evidence supporting the function of in the genetic etiology of female infertility characterized by oocyte maturation arrest and fertilization failure.
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http://dx.doi.org/10.3389/fcell.2021.647130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063106PMC
April 2021

Genome-Wide Identification and Analysis of Chitinase-Like Gene Family in (Hemiptera: Aleyrodidae).

Insects 2021 Mar 17;12(3). Epub 2021 Mar 17.

Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Beijing 100081, China.

Chitinases are of great importance in chitin degradation and remodeling in insects. However, the genome-wide distribution of chitinase-like gene family in , a destructive pest worldwide, is still elusive. With the help of bioinformatics, we annotated 14 genes that encode putative chitinase-like proteins, including ten chitinases (Cht), three imaginal disk growth factors (), and one endo-β-N-acetylglucosaminidase () in the genome of the whitefly, . These genes were phylogenetically grouped into eight clades, among which 13 genes were classified in the glycoside hydrolase family 18 groups and one in the group. Afterwards, developmental expression analysis suggested that , and were highly expressed in nymphal stages and exhibit similar expression patterns, implying their underlying role in nymph ecdysis. Notably, nymphs exhibited a lower rate of survival when challenged by dsRNA targeting these three genes via a nanomaterial-promoted RNAi method. In addition, silencing of significantly resulted in a longer duration of development compared to control nymphs. These results indicate a key role of , and in nymph molting. Our research depicts the differences of chitinase-like family genes in structure and function and identified potential targets for RNAi-based whitefly management.
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http://dx.doi.org/10.3390/insects12030254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002649PMC
March 2021

Naringenin promotes SDF-1/CXCR4 signaling pathway in BMSCs osteogenic differentiation.

Folia Histochem Cytobiol 2021 11;59(1):66-73. Epub 2021 Mar 11.

Department of Oral Diagnostic and Surgical Sciences, Faculty of Dentistry, University of Otago, Dunedin, New Zealand, Dunedin, New Zealand.

Introduction: Naringenin, a dihydro-flavonoid compound that shows chemotactic activity, may have a good application prospect in repairing bone tissue, but its specific mechanism in bone regeneration, especially the osteogenic differentiation of stem cells, needs for a further study. The aim of this study was to investigate the effect of naringenin on the osteogenic differentiation and its roles in the C-X-C chemokine receptor type 4/stromal cell-derived factor 1 (SDF-1/CXCR4) signal pathway of bone marrow-derived mesenchymal stem cells (BMSCs).

Material And Methods: BMSCs were harvested from the femurs and tibias of 4-to-6-week-old male Sprague-Dawley rats. Cell Counting kit-8 assay was used to determine cytotoxicity of naringenin. Alkaline phosphatase (ALP) activity was measured in cell's precipitates and alizarin-red staining was performed to determine the osteogenic differentiation capacity of the BMSCs. Real-time polymerase chain reaction, enzyme-linked immunosorbent assay and western blotting were adopted to determine the expression of genes and proteins.

Results: The cellular morphology was spindle-shaped, and arranged in radial and whorled patterns. The flow cytometric analysis have confirmed the presence of characteristic surface proteins in the harvested BMSCs. Different concentrations (0-200 μg/ml) of naringenin have no influence on the viability and proliferation rate of the BMSCs. The highest ALP activity was found at culture day 7 and 9 when the concentration of naringenin was 75 and 100 μg/ml. Positive red or dark red stained cells with mineralized nodules can be observed on day 14. The expression of ALP, Runt-related transcription factor 2, CXCR4 and SDF-1a at the gene and protein levels in naringenin-treated cells were significantly higher than those in the control cells. Moreover, AMD3100, an inhibitor of CXCR4, suppressed the expression of the studied genes and proteins.

Conclusions: Naringenin does not show toxic effect on BMSCs. Naringenin promotes the expression of the SDF-1a gene and protein via the SDF-1/CXCR4 signaling pathway. A better understanding of the mechanisms of naringenin action would be helpful for developing specific therapeutic strategies to improve bone regeneration after injuries.
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http://dx.doi.org/10.5603/FHC.a2021.0008DOI Listing
March 2021

The complete chloroplast genome of a medical herb, Fisch. (Rosaceae), from Qinghai-Tibet Plateau in China.

Mitochondrial DNA B Resour 2021 Feb 8;6(2):349-350. Epub 2021 Feb 8.

The College of Biological Science, Qinghai Normal University, Xining, China.

Fisch. (Rosaceae) is one of the genuine medicinal materials in Qinghai-Tibet Plateau, China. Here we report the first chloroplast (cp) genome of using Illumina NovaSeq 6000 platform. The length of its complete cp genome is 152,898 bp, containing four sub-regions; a large single copy region (LSC) of 84,160 bp and a small single copy region (SSC) of 18,128 bp are separated by a pair of inverted repeat regions (IRs) of 25,305bp. The complete cp genome of contains 130 genes, including 85 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. The overall GC content of the cp genome is 37.2%. The phylogenetic analysis, based on 17 cp genomes, suggested that is closely related to L. and species.
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http://dx.doi.org/10.1080/23802359.2020.1866447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872539PMC
February 2021

A novel homozygous variant in ZP2 causes abnormal zona pellucida formation and female infertility.

J Assist Reprod Genet 2021 Feb 18. Epub 2021 Feb 18.

Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200011, China.

Purpose: We aimed to identify pathogenic variants in two infertile sisters in a family with a thin zona pellucida (ZP) phenotype.

Methods: Whole-exome sequencing was performed in the two affected sisters, and Sanger sequencing was used to confirm the identified variants. The effects of the identified variant were further investigated in mouse oocytes and Chinese hamster ovary (CHO) cells.

Results: We identified a novel homozygous frameshift variant in ZP2 (c.1235_1236del, p.Q412Rfs*17) in the two affected individuals. Immunoblotting demonstrated that the variant produced a truncated ZP2 protein that was expressed at low levels in CHO cells. Immunofluorescence in mouse oocytes confirmed the decreased protein level of mutant ZP2, although the subcellular localization was not affected. In addition, immunoprecipitation showed that the pathogenic variant reduced the interaction between ZP2 and ZP3.

Conclusion: This study identified a novel pathogenic variant in ZP2 that produces a truncated ZP2 protein. The variant might disrupt the assembly of ZP2-ZP3 dimers, thus resulting in a thin ZP and female infertility.
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http://dx.doi.org/10.1007/s10815-021-02107-2DOI Listing
February 2021

Enhanced removal of As(III) and As(V) from water by a novel zirconium-chitosan modified spherical sodium alginate composite.

Int J Biol Macromol 2021 Apr 12;176:304-314. Epub 2021 Feb 12.

School of Chemistry and Molecular Engineering, East China University of Science and Technology, Shanghai 200237, PR China; Research Center of Analysis and Test, East China University of Science and Technology, Shanghai 200237, PR China. Electronic address:

Most nano-scaled adsorbents have trouble in separating from aqueous solution, thus, a need for new materials of facile separation and predominant adsorption performance has arisen. This present study focused on a novel segregative zirconium-chitosan modified sodium alginate (Zr-CTS/SA) composite preparation and its performance for As(III/V) removal from aqueous solution. The obtained composite presented a spherical structure with a diameter of 2.0-3.0 mm and favorable thermal stability. Experimental data showed that Zr-CTS/SA had considerable adsorbability for As(III) and As(V), the adsorption capacities were enhanced about at least 20 and 6 times separately compared with pristine SA beads. The adsorption processes of As(III) and As(V) could both be described with Langmuir isotherm model and the maximum adsorption capacities reached 43.19 and 76.78 mg g, respectively. The kinetic data of As(III) followed the intra-particle diffusion model while As(V) fitted the pseudo-first-order model. Moreover, the adsorption mechanisms of As(III/V) involved ligand exchange with Cl on the surface of Zr-CTS/SA, another reaction pathway for As(V) was the electrostatic attraction with protonated -OH and -NH groups. Note that the employment of Zr-CTS/SA in low-concentration arsenic solution exhibited a residue concentration as low as the 10 μg L WHO guideline for drinking water.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.02.077DOI Listing
April 2021

Homozygous variants in PANX1 cause human oocyte death and female infertility.

Eur J Hum Genet 2021 Jan 25. Epub 2021 Jan 25.

Institute of Pediatrics, Children's Hospital of Fudan University and the Shanghai Key Laboratory of Medical Epigenetics, the International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology and Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering, Fudan University, 200032, Shanghai, China.

PANX1, one of the members of the pannexin family, is a highly glycosylated channel-forming protein. Recently, we identified heterozygous variants in PANX1 that follow an autosomal dominant inheritance pattern and cause female infertility characterized by oocyte death. In this study, we screened for novel PANX1 variants in patients with the phenotype of oocyte death and discovered a new type of inheritance pattern accompanying PANX1 variants. We identified two novel homozygous missense variants in PANX1 [NM_015368.4 c.712T>C (p.(Ser238Pro) and c.899G>A (p.(Arg300Gln))] associated with the oocyte death phenotype in two families. Both of the homozygous variants altered the PANX1 glycosylation pattern in cultured cells, led to aberrant PANX1 channel activation, and resulted in mouse oocyte death after fertilization in vitro. It is worth noting that the destructive effect of the two homozygous variants on PANX1 function was weaker than that caused by the recently reported heterozygous variants. Our findings enrich the variational spectrum of PANX1 and expand the inheritance pattern of PANX1 variants to an autosomal recessive mode. This highlights the critical role of PANX1 in human oocyte development and helps us to better understand the genetic basis of female infertility due to oocyte death.
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http://dx.doi.org/10.1038/s41431-020-00807-4DOI Listing
January 2021

Dissecting human embryonic skeletal stem cell ontogeny by single-cell transcriptomic and functional analyses.

Cell Res 2021 Jan 20. Epub 2021 Jan 20.

Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China.

Human skeletal stem cells (SSCs) have been discovered in fetal and adult long bones. However, the spatiotemporal ontogeny of human embryonic SSCs during early skeletogenesis remains elusive. Here we map the transcriptional landscape of human limb buds and embryonic long bones at single-cell resolution to address this fundamental question. We found remarkable heterogeneity within human limb bud mesenchyme and epithelium, and aligned them along the proximal-distal and anterior-posterior axes using known marker genes. Osteo-chondrogenic progenitors first appeared in the core limb bud mesenchyme, which give rise to multiple populations of stem/progenitor cells in embryonic long bones undergoing endochondral ossification. Importantly, a perichondrial embryonic skeletal stem/progenitor cell (eSSPC) subset was identified, which could self-renew and generate the osteochondral lineage cells, but not adipocytes or hematopoietic stroma. eSSPCs are marked by the adhesion molecule CADM1 and highly enriched with FOXP1/2 transcriptional network. Interestingly, neural crest-derived cells with similar phenotypic markers and transcriptional networks were also found in the sagittal suture of human embryonic calvaria. Taken together, this study revealed the cellular heterogeneity and lineage hierarchy during human embryonic skeletogenesis, and identified distinct skeletal stem/progenitor cells that orchestrate endochondral and intramembranous ossification.
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http://dx.doi.org/10.1038/s41422-021-00467-zDOI Listing
January 2021

Leaving no one behind: tracing every human thymocyte by single-cell RNA-sequencing.

Semin Immunopathol 2021 Feb 15;43(1):29-43. Epub 2021 Jan 15.

Department of Rheumatology and Immunology and State Key Laboratory of Biotherapy, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, China.

The thymus is the primary organ for T-cell development, providing an essential microenvironment consisting of the appropriate cytokine milieu and specialized stromal cells. Thymus-seeding progenitors from circulation immigrate into the thymus and undergo the stepwise T-cell specification, commitment, and selection processes. The transcriptional factors, epigenetic regulators, and signaling pathways involved in the T-cell development have been intensively studied using mouse models. Despite our growing knowledge of T-cell development, major questions remain unanswered regarding the ontogeny and early events of T-cell development at the fetal stage, especially in humans. The recently developed single-cell RNA-sequencing technique provides an ideal tool to investigate the heterogeneity of T-cell precursors and the molecular mechanisms underlying the divergent fates of certain T-cell precursors at the single-cell level. In this review, we aim to summarize the current progress of the study on human thymus organogenesis and thymocyte and thymic epithelial cell development, which is to shed new lights on developing novel strategies for in vitro T-cell regeneration and thymus rejuvenation.
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http://dx.doi.org/10.1007/s00281-020-00834-9DOI Listing
February 2021

Ilepcimide inhibited sodium channel activity in mouse hippocampal neurons.

Epilepsy Res 2021 Feb 15;170:106533. Epub 2020 Dec 15.

Institute of Neuroscience and Department of Neurology of the Second Affiliated Hospital of Guangzhou Medical University, China; Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou, China. Electronic address:

Ilepcimide (ICM), a clinically effective antiepileptic drug, has been used in China for decades; however, its antiepileptic mechanism remains unclear. ICM is structurally similar to antiepileptic drug lamotrigine (LTG). LTG exerts its anticonvulsant effect by inhibiting voltage-gated Na channel (Na) activity. Thus it is speculated that ICM also exert its antiepileptic activity by inhibiting sodium channel activity. We studied the inhibition of Na activity by ICM in acutely isolated mouse hippocampal pyramidal neurons. We evaluated ICM-mediated tonic, concentration-dependent, and voltage-dependent inhibition of Na, and the effects of ICM and LTG on Na biophysical properties. Na currents in hippocampal pyramidal neurons were tonically inhibited by ICM in a concentration- and voltage-dependent manner. The half-maximal inhibitory concentration (IC) of ICM at a holding potential (V) of -90 mV was higher than that at a V of -70 mV. Compared with the control groups, in the presence of 10 μM ICM, the current densities of Na channels were reduced, the half-maximal availability of the inactivation curve (V) was shifted to more negative potentials, and the recovery from inactivation was delayed. These data can contribute to further investigation of the inhibitory effect of ICM on the sodium channel, suggesting that the main reason for the anticonvulsant effect of ICM is the small influx of sodium ions. ICM can prevent abnormal discharge of neurons, which may prevent epilepsy.
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http://dx.doi.org/10.1016/j.eplepsyres.2020.106533DOI Listing
February 2021

Decoding Human Megakaryocyte Development.

Cell Stem Cell 2021 Mar 18;28(3):535-549.e8. Epub 2020 Dec 18.

State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China; CAMS Center for Stem Cell Medicine, PUMC Department of Stem Cell and Regenerative Medicine, Tianjin 300020, China. Electronic address:

Despite our growing understanding of embryonic immune development, rare early megakaryocytes (MKs) remain relatively understudied. Here we used single-cell RNA sequencing of human MKs from embryonic yolk sac (YS) and fetal liver (FL) to characterize the transcriptome, cellular heterogeneity, and developmental trajectories of early megakaryopoiesis. In the YS and FL, we found heterogeneous MK subpopulations with distinct developmental routes and patterns of gene expression that could reflect early functional specialization. Intriguingly, we identified a subpopulation of CD42bCD14 MKs in vivo that exhibit high expression of genes associated with immune responses and can also be derived from human embryonic stem cells (hESCs) in vitro. Furthermore, we identified THBS1 as an early marker for MK-biased embryonic endothelial cells. Overall, we provide important insights and invaluable resources for dissection of the molecular and cellular programs underlying early human megakaryopoiesis.
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http://dx.doi.org/10.1016/j.stem.2020.11.006DOI Listing
March 2021

The inactive Dnmt3b3 isoform preferentially enhances Dnmt3b-mediated DNA methylation.

Genes Dev 2020 Nov 1;34(21-22):1546-1558. Epub 2020 Oct 1.

Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.

The de novo DNA methyltransferases Dnmt3a and Dnmt3b play crucial roles in developmental and cellular processes. Their enzymatic activities are stimulated by a regulatory protein Dnmt3L (Dnmt3-like) in vitro. However, genetic evidence indicates that Dnmt3L functions predominantly as a regulator of Dnmt3a in germ cells. How Dnmt3a and Dnmt3b activities are regulated during embryonic development and in somatic cells remains largely unknown. Here we show that Dnmt3b3, a catalytically inactive Dnmt3b isoform expressed in differentiated cells, positively regulates de novo methylation by Dnmt3a and Dnmt3b with a preference for Dnmt3b. Dnmt3b3 is equally potent as Dnmt3L in stimulating the activities of Dnmt3a2 and Dnmt3b2 in vitro. Like Dnmt3L, Dnmt3b3 forms a complex with Dnmt3a2 with a stoichiometry of 2:2. However, rescue experiments in triple-knockout (TKO) mouse embryonic stem cells (mESCs) reveal that Dnmt3b3 prefers Dnmt3b2 over Dnmt3a2 in remethylating genomic sequences. Dnmt3a2, an active isoform that lacks the N-terminal uncharacterized region of Dnmt3a1 including a nuclear localization signal, has very low activity in TKO mESCs, indicating that an accessory protein is absolutely required for its function. Our results suggest that Dnmt3b3 and perhaps similar Dnmt3b isoforms facilitate de novo DNA methylation during embryonic development and in somatic cells.
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http://dx.doi.org/10.1101/gad.341925.120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7608744PMC
November 2020

The combined therapy of a traditional Chinese medicine formula and Western medicine for a critically ill case infected with COVID-19.

Complement Ther Med 2020 Aug 9;52:102473. Epub 2020 Jun 9.

Department of Nephrology, Institute of Nephritic and Urinary Disease, Guizhou Provincial People's Hospital, Guiyang, Guizhou, China. Electronic address:

Objective: Presentation of a case illustrating the benefits of traditional Chinese medicine (TCM) for treatment of Coronavirus disease 2019 (COVID-19) in critically ill patients.

Clinical Features And Outcome: A 58-year-old woman presented with cough, fever, dizziness, chest tightness, polypnea and poor appetite. She was admitted to Guizhou Provincial People's hospital, and diagnosed with critically ill type of COVID-19 in February 2020. According to the patient's symptoms and signs, the TCM syndrome differentiation was qi deficiency, dampness-stasis and toxin accumulation. Then she received the combined therapy of a modified Chinese herbal formula and Western medicine. During a twelve-day period of treatment, her respiratory distress and appetite quickly improved. Abnormal laboratory indicators were resumed in time and lung lesions in CT scan largely absorbed. No side effects associated with this Chinese herbal formula were found. Before discharge, two consecutive nasopharyngeal swabs were shown to be negative for severe acute respiratory coronavirus 2 (SARS-CoV-2).

Conclusions: Our case report suggests that collaborative treatments with traditional Chinese medicine prove beneficial in the management of COVID-19 in critically ill patients. In order to give optimal care for this COVID-19 crisis for the whole world, Chinese medicine practitioners and Western medical doctors should work together in frontline.
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http://dx.doi.org/10.1016/j.ctim.2020.102473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7282787PMC
August 2020

Novel mutations in LHCGR (luteinizing hormone/choriogonadotropin receptor): expanding the spectrum of mutations responsible for human empty follicle syndrome.

J Assist Reprod Genet 2020 Nov 28;37(11):2861-2868. Epub 2020 Aug 28.

Institute of Pediatrics, Children's Hospital of Fudan University and the Shanghai Key Laboratory of Medical Epigenetics, the International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology and Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, 200032, China.

Purpose: To screen novel mutations in LHCGR responsible for empty follicle syndrome and explore the pathological mechanism of mutations.

Methods: Four affected individuals diagnosed with infertility-associated anovulation or oligo-ovulation from three independent families were recruited. Sanger sequencing was used to identify the LHCGR mutations in affected individuals. Western blot was performed to evaluate the effects of mutations on LHCGR protein levels. Immunofluorescence was done to explore the effects of mutations on LHCGR subcellular localization. The ATP levels were measured to infer the functional effects of the mutations on LHCGR.

Results: In the present study, three novel biallelic mutations in LHCGR were identified in four affected individuals from three independent families with empty follicle syndrome or oligo-ovulation. All biallelic mutations were inherited from the proband of their parents. The western blot showed that the identified mutations decreased LHCGR protein level and altered the glycosylation pattern. The immunofluorescence showed an ectopic subcellular localization of LHCGR in cultured HeLa cells. Besides, the mutations in LHCGR also reduced the cellular ATP consumption.

Conclusion: These findings confirm previous studies and expand the mutational spectrum of LHCGR, which will provide genetic diagnostic marker for patients with empty follicle syndrome.
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http://dx.doi.org/10.1007/s10815-020-01931-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642116PMC
November 2020

LncRNA H19 Overexpression Activates Wnt Signaling to Maintain the Hair Follicle Regeneration Potential of Dermal Papilla Cells.

Front Genet 2020 4;11:694. Epub 2020 Aug 4.

Department of Histology and Embryology, Shantou University Medical College, Shantou, China.

Androgenetic alopecia (AGA) is a common hair loss disorder resulting in seriously abnormal social interaction and psychological disorders. Transplantation with autologous dermal papilla cells represents a prospective therapy. However, the ability of dermal papilla cells to induce hair follicle development is lost upon cell culturing. Long non-coding RNAs (lncRNAs) are an important class of genes involved in various biological functions, are aberrantly expressed in disease and may play roles in the regulation of Wnt signaling, a critical pathway in maintaining the hair follicle-inducing capability of dermal papilla cells. Examination of dermal papilla cells by lncRNA microarray revealed that H19 was highly expressed in early passage dermal papilla cells compared with late-passage dermal papilla cells. In this study, we constructed H19-overexpressing dermal papilla cells to examine the role of H19 on hair follicle inductivity. Dermal papilla cells infected with lentivirus encoding H19 maintained their cell shape, and continued to display both multiple-layer aggregation and hair follicle-inducing ability upon prolonged culture. H19 exerted these effects through inducing miR-29a to activate Wnt signaling by directly downregulating the expression of Wnt suppressors, including DKK1, Kremen2, and sFRP2, thereby forming a novel regulatory feedback loop between H19 and miR-29a to maintain hair follicle- inducing potential. These results suggest that lncRNA H19 maintains the hair follicle-inducing ability of dermal papilla cells through activation of the Wnt pathway and could be a target for treatment of androgenetic alopecia.
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http://dx.doi.org/10.3389/fgene.2020.00694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7417632PMC
August 2020

Plasmonic silver/silver oxide nanoparticles anchored bismuth vanadate as a novel visible-light ternary photocatalyst for degrading pharmaceutical micropollutants.

J Environ Sci (China) 2020 Oct 30;96:21-32. Epub 2020 Apr 30.

State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012, China.

The degradation of pharmaceutical micropollutants is an intensifying environmental problem and synthesis of efficient photocatalysts for this purpose is one of the foremost challenges worldwide. Therefore, this study was conducted to develop novel plasmonic Ag/AgO/BiVO nanocomposite photocatalysts by simple precipitation and thermal decomposition methods, which could exhibit higher photocatalytic activity for mineralized pharmaceutical micropollutants. Among the different treatments, the best performance was observed for the Ag/AgO/BiVO nanocomposites (5 wt.%; 10 min's visible light irradiation) which exhibited 6.57 times higher photodegradation rate than the pure BiVO. Further, the effects of different influencing factors on the photodegradation system of tetracycline hydrochloride (TC-HCl) were investigated and the feasibility for its practical application was explored through the specific light sources, water source and cycle experiments. The mechanistic study demonstrated that the photogenerated holes (h), superoxide radicals (•O) and hydroxyl radicals (•OH) participated in TC-HCl removal process, which is different from the pure BiVO reaction system. Hence, the present work can provide a new approach for the formation of novel plasmonic photocatalysts with high photoactivity and can act as effective practical application for environmental remediation.
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http://dx.doi.org/10.1016/j.jes.2020.03.038DOI Listing
October 2020

Drug-Bearing Peptide-Based Nanospheres for the Inhibition of Metastasis and Growth of Cancer.

Mol Pharm 2020 09 20;17(9):3165-3176. Epub 2020 Aug 20.

The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha Hunan 410081, China.

Employing a peptide-based nanoscale drug delivery system is an effective strategy to overcome the poor therapeutic outcomes of chemotherapeutic drugs. Here, we developed a self-assembling peptide-drug delivery system comprising a self-assembling anticancer peptide (R-lycosin-I), as revealed in our previous study, and 10-hydroxycamptothecin (HCPT) for cancer therapy. The results showed that peptide-drug conjugates (R-L-HCPT) could assemble into nanospheres of 40-60 nm in water. Compared with free HCPT, R-L-HCPT nanospheres not only inhibited tumor growth but also suppressed pulmonary metastatic nodules on B16-F10 cells . In summary, these results indicated that the self-assembling R-lycosin-I could provide a promising nanoscale platform for delivering small-molecule drugs. Moreover, our study might provide new opportunities for the development of a new class of functional peptide-drug-conjugated systems based on nanomaterials, which could synergistically enhance anticancer outcomes.
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http://dx.doi.org/10.1021/acs.molpharmaceut.0c00118DOI Listing
September 2020

A Chemosensory Protein Mediates Reproduction in .

Front Physiol 2020 30;11:709. Epub 2020 Jun 30.

Department of Plant Protection, Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Beijing, China.

The olfactory system serves a vital role in the evolution and survival of insects, being involved in behaviors such as host seeking, foraging, mating, and oviposition. Odorant-binding proteins (OBPs) and chemosensory proteins (CSPs) are involved in the olfactory recognition process. In this study, , a gene from the whitefly , was cloned and characterized. The open reading frame of encodes 136 amino acids, with four highly conserved cysteine residues. The temporal and spatial expression profiles showed that was highly expressed in the abdomens of females. Dietary RNA interference (RNAi)-based functional analysis showed substantially reduced fecundity in parthenogenetically reproduced females, suggesting a potential role of in reproduction. These combined results expand the function of CSPs beyond chemosensation.
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http://dx.doi.org/10.3389/fphys.2020.00709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7338578PMC
June 2020

Segmental aneuploidies in fetuses with isolated echogenic intracardiac focus among women younger than 35 years.

Sci Rep 2020 06 26;10(1):10496. Epub 2020 Jun 26.

Department of Obstetrics and Gynecology, West China Second University Hospital of Sichuan University, Chengdu, 610041, China.

Studies on the occurrence of segmental aneuploidoidy in fetuses with isolated echogenic intracardiac focus (EIF) are scarce. The aim of this study was to analyze whether there is an association between abnormal segmental aneuploidies and isolated EIF. This was a prospective case-control study. The study participants in the case group were fetuses that were diagnosed with isolated EIF. Samples without fetal ultrasound abnormalities but received prenatal diagnosis for other reasons (serological screening high-risk, voluntary request) were set as controls. All pregnant women were younger than 35 years old at the expected date of childbirth. Copy number variation sequencing (CNV-seq) was performed for all samples. The case group and control group successfully underwent CNV-seq analysis and exhibited 1,099 and 5,616 amniotic fluid samples, respectively. The detection rates of abnormal segmental aneuploidies in the case group and control group were 0.6% (7/1,099) and 1.1% (64/5,616), respectively; no statistically significant difference was found between the two groups (x = 2.220, P = 0.136). Isolated EIF did not increase the risk of fetal segmental aneuploidies.
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http://dx.doi.org/10.1038/s41598-020-67501-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7320167PMC
June 2020

Photoresponse-Bias Modulation of a High-Performance MoS Photodetector with a Unique Vertically Stacked 2H-MoS/1T@2H-MoS Structure.

ACS Appl Mater Interfaces 2020 Jul 8;12(29):33325-33335. Epub 2020 Jul 8.

School of Optical and Electronic Information, Huazhong University of Science & Technology, Wuhan 430074, People's Republic of China.

Monolayer 2H-phase MoS-based photodetectors exhibit high photon absorption but suffer from low photoresponse, which severely limits their applications in optoelectronic fields. The metallic 1T phase of MoS, while transporting carriers faster, shows negligible response to visible light, which limits its usage in photodetectors. Herein, we propose an ultrafast-response MoS-based photodetector having a channel that consists of a 2H-MoS sensitizing monolayer on top of 1T@2H-MoS. The 1T@2H-MoS layer has a thickness of several nanometers and is a mixture of metallic 1T-MoS and semiconducting 2H-MoS, imparting metal-like properties to the photodetector. Compared with the monolayer 2H-MoS photodetector, we observed a drastic increase in the photoresponse of the 2H-MoS/1T@2H-MoS vertically stacked photodetector to a value of 1917 A W. Owing to the presence of metallic 1T-MoS within the metal-like 1T@2H-MoS, the performance of the 2H-MoS/1T@2H-MoS vertically stacked photodetector is voltage bias-modulated with an external quantum efficiency (EQE) of up to 448,384% and a specific detectivity of up to ∼10 Jones. The higher carrier density and higher mobility of the 1T@2H-MoS layer explain the better bias-modulated performance. In addition, the interface between 2H-MoS and 1T@2H-MoS ensures fewer dangling bonds and reduced lattice mismatching. Thus, this study presents an exclusive vertically stacked MoS-based photodetector that lays the foundation for the development of photodetectors exhibiting higher photoresponse.
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http://dx.doi.org/10.1021/acsami.0c04048DOI Listing
July 2020

Deciphering human macrophage development at single-cell resolution.

Nature 2020 06 20;582(7813):571-576. Epub 2020 May 20.

Key Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan University, Guangzhou, China.

Macrophages are the first cells of the nascent immune system to emerge during embryonic development. In mice, embryonic macrophages infiltrate developing organs, where they differentiate symbiotically into tissue-resident macrophages (TRMs). However, our understanding of the origins and specialization of macrophages in human embryos is limited. Here we isolated CD45 haematopoietic cells from human embryos at Carnegie stages 11 to 23 and subjected them to transcriptomic profiling by single-cell RNA sequencing, followed by functional characterization of a population of CD45CD34CD44 yolk sac-derived myeloid-biased progenitors (YSMPs) by single-cell culture. We also mapped macrophage heterogeneity across multiple anatomical sites and identified diverse subsets, including various types of embryonic TRM (in the head, liver, lung and skin). We further traced the specification trajectories of TRMs from either yolk sac-derived primitive macrophages or YSMP-derived embryonic liver monocytes using both transcriptomic and developmental staging information, with a focus on microglia. Finally, we evaluated the molecular similarities between embryonic TRMs and their adult counterparts. Our data represent a comprehensive characterization of the spatiotemporal dynamics of early macrophage development during human embryogenesis, providing a reference for future studies of the development and function of human TRMs.
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http://dx.doi.org/10.1038/s41586-020-2316-7DOI Listing
June 2020

Influence of the detection of parent-of-origin on the pregnancy outcomes of fetuses with copy number variation of unknown significance.

Sci Rep 2020 06 1;10(1):8864. Epub 2020 Jun 1.

Department of Obstetrics and Gynecology, West China Second University Hospital of Sichuan University, Chengdu, 610041, China.

The widespread application of high-resolution chromosome detection technology in clinical practice has identified many variants of unknown significance (VOUS) in prenatal diagnosis. The purpose of this study was to prospectively analyze the chromosomal results of parents and the follow-up information of pregnancy outcomes of prenatal samples with VOUS, so as to determine the influence of the detection of parent-of-origin on the pregnancy outcomes of fetuses with VOUS. The present study analyzed amniotic fluid samples obtained from women with different risk indications between February 2017 and December 2018. The samples were subjected to copy number variation sequencing, and detection of parent-of-origin was suggested in cases of samples with VOUS. The pregnancy outcome was followed up. In a total of 14073 amniotic fluid samples, 729 cases of VOUS were detected (5.2%, 729/14073) and 721 cases were followed up successfully. Among the 721 cases, 525 patients agreed to detect the parent-of-origin (72.8%, 525/721). It was revealed that the VOUS in 460 of the fetuses were hereditary (87.6%, 460/525). The percentages of abnormal pregnancy outcomes (included pregnancy loss, fetal pathological abnormality, preterm delivery, neonatal death, birth defects) in the inherited, de novo, and refusal to detect the parent-of-origin (i.e. unknown origin) groups were 4.3% (20/460), 6.2% (4/65), and 6.6% (13/196), respectively. There was no significant difference among the three groups (P > 0.05). The rate of voluntary termination of pregnancy (TOP) in the unknown origin group was significantly higher than that in the group that had determined the parent-of-origin (14.3% vs 7.4%, P = 0.005). There is currently no evidence that suggests that the proportion of abnormal pregnancy outcomes is higher in fetuses with VOUS than in other fetuses. However, the present study revealed that determining the parent-of-origin affects the decision to undergo voluntary TOP, as the rate of voluntary TOP in the group that refused detection was higher than that in the group that consented.
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http://dx.doi.org/10.1038/s41598-020-65904-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7264138PMC
June 2020

Effects of bioporous carriers on the performance and microbial community structure in side-stream anaerobic membrane bioreactors.

Can J Microbiol 2020 Aug 30;66(8):475-489. Epub 2020 Mar 30.

School of Civil Engineering, Sichuan University of Science & Engineering, Zigong 643000, P.R. China.

The aim of this study was to investigate the effects of a volcanic rock porous carrier (VRPC) on sludge reduction, pollutant removal, and microbial community structure in an anaerobic side-stream reactor (ASSR). Three lab-scale membrane bioreactors (MBRs), including an anoxic-oxic MBR, which served as the control (C-MBR), an ASSR-coupled MBR (A-MBR), and an A-MBR filled with VRPC (FA-MBR) were stably and simultaneously operated for 120 days. The effect of the three reactors on the removal of chemical oxygen demand (COD) was almost negligible (all greater than 95%), but the average removal efficiency of ammonium nitrogen, total nitrogen, and total phosphorus was significantly improved by the insertion of an ASSR, especially when the ASSR was filled with VRPC. Finally, A-MBR and FA-MBR achieved 16.2% and 26.4% sludge reduction rates, with observed sludge yields of 0.124 and 0.109 g mixed liquid suspended solids/g COD, respectively. Illumina MiSeq sequencing revealed that microbial diversity and richness were highest in the VRPC, indicating that a large number of microorganisms formed on the carrier surface in the form of a biofilm. Abundant denitrifying bacteria (, unclassified, and ) were immobilized on the carrier biofilm, which contributed to increased nitrogen removal. The addition of a VRPC to the ASSR successfully immobilized abundant hydrolytic, fermentative, and slow-growing microorganisms, which all contributed to reductions in sludge yield.
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http://dx.doi.org/10.1139/cjm-2019-0632DOI Listing
August 2020

Glutaraldehyde Cross-Linking of Oligolysines Coating DNA Origami Greatly Reduces Susceptibility to Nuclease Degradation.

J Am Chem Soc 2020 02 11;142(7):3311-3315. Epub 2020 Feb 11.

Department of Biological Chemistry and Molecular Pharmacology , Harvard Medical School , Boston , Massachusetts 02115 , United States.

DNA nanostructures (DNs) have garnered a large amount of interest as a potential therapeutic modality. However, DNs are prone to nuclease-mediated degradation and are unstable in low Mg conditions; this greatly limits their utility in physiological settings. Previously, PEGylated oligolysines were found to protect DNs against low-salt denaturation and to increase nuclease resistance by up to ∼400-fold. Here we demonstrate that glutaraldehyde cross-linking of PEGylated oligolysine-coated DNs extends survival by up to another ∼250-fold to >48 h during incubation with 2600 times the physiological concentration of DNase I. DNA origami with cross-linked oligolysine coats are non-toxic and are internalized into cells more readily than non-cross-linked origami. Our strategy provides an off-the-shelf and generalizable method for protecting DNs in vivo.
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http://dx.doi.org/10.1021/jacs.9b11698DOI Listing
February 2020

The ZBTB24-CDCA7 axis regulates HELLS enrichment at centromeric satellite repeats to facilitate DNA methylation.

Protein Cell 2020 03;11(3):214-218

Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, TX, 78957, USA.

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http://dx.doi.org/10.1007/s13238-019-00682-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7026229PMC
March 2020

Genome-wide identification and analysis of nuclear receptors genes for lethal screening against Bemisia tabaci Q.

Pest Manag Sci 2020 Jun 7;76(6):2040-2048. Epub 2020 Feb 7.

Department of Plant Protection, Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Beijing, P. R. China.

Background: Nuclear receptors (NRs) play an essential role in diverse biological processes, such as insect metamorphosis. Here, transcriptome analysis and functional studies were used to determine whether NRs are involved in metamorphosis of whitefly Bemisia tabaci Q, a serious pest to crops, and to find some potential insecticide targets.

Results: Twenty NRs were identified in the Bemisia tabaci Q genome and categorized into the NR0-NR6 subfamilies. The phylogenetic tree of NRs from Bemisia tabaci Q and other representative species was constructed, which provided evolutionary insight into their genetic distances. The results of spatiotemporal gene expression indicated that the majority of NR gene expression was higher in the head than the abdomen and higher in eggs than adults. Further functional analysis using RNA interference (RNAi) showed that NR genes play an important role in Bemisia tabaci Q pupation and eclosion. With respect to high mortality and effects on growth, this was reflected in the unable to become pupa when the third-stage nymph treated with double-stranded RNA (dsRNA) and the developmental time delay (4-7 days) when pupae were treated with dsRNA for the 12 NR genes during molting compared with the development time in the control.

Conclusion: This study provides insight into NR functions during the metamorphosis stages of Bemisia tabaci Q. Several candidate genes could be potential insecticide targets for whitefly pest control due to their important roles in insect development. © 2020 Society of Chemical Industry.
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http://dx.doi.org/10.1002/ps.5738DOI Listing
June 2020

Analysis of the antennal transcriptome and odorant-binding protein expression profiles of the parasitoid wasp Encarsia formosa.

Genomics 2020 05 30;112(3):2291-2301. Epub 2019 Dec 30.

Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, No. 12 Zhongguancun South Street, Haidian District, Beijing 100081, China. Electronic address:

The parasitoid of whiteflies Encarsia formosa has been widely applied to reduce whitefly-mediated damage on vegetables and ornamental plants grown in greenhouses. Although its chemosensory behavior has been described, the mechanism by which E. formosa recognizes chemical volatiles at the molecular level remains unknown. In this study, we obtained 66,632 unigenes from antennae transcriptomic architecture of E. formosa, of which 19,473 (29.2%) were functionally annotated. All that matters is that we manually identified 39 odorant-binding proteins (OBPs) from above dataset, and further investigated the tissue and stage-specific expression profiles of all identified OBP genes by real-time quantitative PCR. Among these OBP genes, 32 were enriched in antennae, and 2 in body. In addition, 4 OBPs were highly expressed in pupae, and 32 in 6-hour-age adults after eclosion. In addition to identifying OBP genes from E. formosa, this study provides a molecular basis for further functional studies of OBPs and the interactions of hosts and parasitic wasps.
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http://dx.doi.org/10.1016/j.ygeno.2019.12.025DOI Listing
May 2020

Molecular characterization of an NADPH cytochrome P450 reductase from Bemisia tabaci Q: Potential involvement in susceptibility to imidacloprid.

Pestic Biochem Physiol 2020 Jan 7;162:29-35. Epub 2019 Sep 7.

Department of Plant Protection, Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Beijing 100081, PR China. Electronic address:

NADPH cytochrome P450 reductase (CPR) is an integral component of cytochrome P450-mediated biological reactions, such as the metabolism of xenobiotics, including insecticides. CPR has been reported to be associated with insecticide tolerance in several insects. However, the biochemical characteristics and biological function of CPR in Bemisia tabaci Q (BtCPR) remain undefined. In this study, BtCPR was cloned, and bioinformatic analysis showed that BtCPR is a transmembrane protein with a molecular weight (MW) of 76.73 kDa and contains conserved binding domains (FMN, FAD, and NADPH). Tissue- and developmental stage-dependent expression indicated that the highest expression levels of BtCPR occurred in head tissue and in male adults. Transcripts of BtCPR in the field B. tabaci Q strain were 1.62-fold higher than those of the laboratory B. tabaci Q strain. In both field and laboratory adults, the susceptibility of BtCPR-knockdown B. tabaci Q to imidacloprid substantially increased compared to that of the B. tabaci Q control group. Furthermore, the heterologous expression of BtCPR in Sf9 cells exhibited catalytic activity for cytochrome c reduction, following Michaelis-Menten kinetics. Sf9 cells overexpressing BtCPR had greater viability than the control cells when treated with imidacloprid. The results suggest that BtCPR could affect the susceptibility of B. tabaci Q to imidacloprid and could also be considered a novel target for pest control.
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http://dx.doi.org/10.1016/j.pestbp.2019.07.018DOI Listing
January 2020

Guiding T lymphopoiesis from pluripotent stem cells by defined transcription factors.

Cell Res 2020 01 15;30(1):21-33. Epub 2019 Nov 15.

State Key Laboratory of Experimental Hematology, CAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.

Achievement of immunocompetent and therapeutic T lymphopoiesis from pluripotent stem cells (PSCs) is a central aim in T cell regenerative medicine. To date, preferentially reconstituting T lymphopoiesis in vivo from PSCs remains a practical challenge. Here we documented that synergistic and transient expression of Runx1 and Hoxa9 restricted in the time window of endothelial-to-hematopoietic transition and hematopoietic maturation stages in a PSC differentiation scheme (iR9-PSC) in vitro induced preferential generation of engraftable hematopoietic progenitors capable of homing to thymus and developing into mature T cells in primary and secondary immunodeficient recipients. Single-cell transcriptome and functional analyses illustrated the cellular trajectory of T lineage induction from PSCs, unveiling the T-lineage specification determined at as early as hemogenic endothelial cell stage and identifying the bona fide pre-thymic progenitors. The induced T cells distributed normally in central and peripheral lymphoid organs and exhibited abundant TCRαβ repertoire. The regenerative T lymphopoiesis restored immune surveillance in immunodeficient mice. Furthermore, gene-edited iR9-PSCs produced tumor-specific T cells in vivo that effectively eradicated tumor cells. This study provides insight into universal generation of functional and therapeutic T cells from the unlimited and editable PSC source.
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http://dx.doi.org/10.1038/s41422-019-0251-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6951346PMC
January 2020

Correction to: c-MYC overexpression induces choroid plexus papillomas through a T-cell mediated inflammatory mechanism.

Acta Neuropathol Commun 2019 Nov 14;7(1):179. Epub 2019 Nov 14.

Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark Street, London, E1 2AT, UK.

In the original version of this article [1], there was 1 error in the affiliation of the European Institute of Oncology (affiliation 3). In this correction article the updated affiliation is shown for clarification.
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http://dx.doi.org/10.1186/s40478-019-0835-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6854732PMC
November 2019