Publications by authors named "Xiangyu Zhao"

74 Publications

Progressive Cellular Architecture in Microscale Gas Chromatography for Broad Chemical Analyses.

Sensors (Basel) 2021 Apr 29;21(9). Epub 2021 Apr 29.

Center for Wireless Integrated MicroSensing and Systems (WIMS2), University of Michigan, Ann Arbor, MI 48109, USA.

Gas chromatography is widely used to identify and quantify volatile organic compounds for applications ranging from environmental monitoring to homeland security. We investigate a new architecture for microfabricated gas chromatography systems that can significantly improve the range, speed, and efficiency of such systems. By using a cellular approach, it performs a partial separation of analytes even as the sampling is being performed. The subsequent separation step is then rapidly performed within each cell. The cells, each of which contains a preconcentrator and separation column, are arranged in progression of retentiveness. While accommodating a wide range of analytes, this progressive cellular architecture (PCA) also provides a pathway to improving energy efficiency and lifetime by reducing the need for heating the separation columns. As a proof of concept, a three-cell subsystem (PCA3mv) has been built; it incorporates a number of microfabricated components, including preconcentrators, separation columns, valves, connectors, and a carrier gas filter. The preconcentrator and separation column of each cell are monolithically implemented as a single chip that has a footprint of 1.8 × 5.2 cm. This subsystem also incorporates two manifold arrays of microfabricated valves, each of which has a footprint of 1.3 × 1.4 cm. Operated together with a commercial flame ionization detector, the subsystem has been tested against polar and nonpolar analytes (including alkanes, alcohols, aromatics, and phosphonate esters) over a molecular weight range of 32-212 g/mol and a vapor pressure range of 0.005-231 mmHg. The separations require an average column temperature of 63-68 °C within a duration of 12 min, and provide separation resolutions >2 for any two homologues that differ by one methyl group.
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http://dx.doi.org/10.3390/s21093089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8124901PMC
April 2021

Copy number signature analysis tool and its application in prostate cancer reveals distinct mutational processes and clinical outcomes.

PLoS Genet 2021 May 4;17(5):e1009557. Epub 2021 May 4.

School of Life Science and Technology, ShanghaiTech University, Shanghai, China.

Genome alteration signatures reflect recurring patterns caused by distinct endogenous or exogenous mutational events during the evolution of cancer. Signatures of single base substitution (SBS) have been extensively studied in different types of cancer. Copy number alterations are important drivers for the progression of multiple cancer. However, practical tools for studying the signatures of copy number alterations are still lacking. Here, a user-friendly open source bioinformatics tool "sigminer" has been constructed for copy number signature extraction, analysis and visualization. This tool has been applied in prostate cancer (PC), which is particularly driven by complex genome alterations. Five copy number signatures are identified from human PC genome with this tool. The underlying mutational processes for each copy number signature have been illustrated. Sample clustering based on copy number signature exposure reveals considerable heterogeneity of PC, and copy number signatures show improved PC clinical outcome association when compared with SBS signatures. This copy number signature analysis in PC provides distinct insight into the etiology of PC, and potential biomarkers for PC stratification and prognosis.
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http://dx.doi.org/10.1371/journal.pgen.1009557DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121287PMC
May 2021

Clinical exome sequencing identifies novel compound heterozygous mutations of the gene in primary infertile women with fertilization failure.

Gynecol Endocrinol 2021 Apr 27:1-6. Epub 2021 Apr 27.

Department of Medical Genetics, Linyi People's Hospital, Linyi, PR China.

Objective: The genetic basis of fertilization failure after intracytoplasmic sperm injection (ICSI) is largely unknown and the aim of this study is to investigate the genetic causes of fertilization failure in primary infertile women.

Methods: Six affected women diagnosed with infertility and fertilization failure were recruited. The genetically pathogenic factor of their fertilization failures were investigated by clinical exome sequencing. One hundred healthy controls were verified by Sanger sequencing.

Results: Novel compound heterozygous mutations c.625G > T and c.759-2A > G of in one affected individual were revealed by clinical exome sequencing. Trios analysis of the mutations represented an autosomal recessive pattern. The nonsense mutation c.625G > T (p.Glu209*) indicated the truncation of the WEE2 protein and c.759-2A > G was predicted to affect the splicing.

Conclusions: The novel variants extend the spectrum of mutations, which promotes the prognostic value of testing for mutations in infertile women with fertilization failure.
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http://dx.doi.org/10.1080/09513590.2021.1916458DOI Listing
April 2021

Natural killer cells play an important role in virus infection control: Antiviral mechanism, subset expansion and clinical application.

Clin Immunol 2021 06 20;227:108727. Epub 2021 Apr 20.

Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China. Electronic address:

With the global spread of coronavirus disease 2019 (COVID-19), the important role of natural killer (NK) cells in the control of various viral infections attracted more interest, via non-specific activation, such as antibody-dependent cell-mediated cytotoxicity (ADCC) and activating receptors, as well as specific activation, such as memory-like NK generation. In response to different viral infections, NK cells fight viruses in different ways, and different NK subsets proliferate. For instance, cytomegalovirus (CMV) induces NKG2C + CD57 + KIR+ NK cells to expand 3-6 months after hematopoietic stem cell transplantation (HSCT), but human immunodeficiency virus (HIV) induces KIR3DS1+/KIR3DL1 NK cells to expand in the acute phase of infection. However, the similarities and differences among these processes and their molecular mechanisms have not been fully discussed. In this article, we provide a summary and comparison of antiviral mechanisms, unique subset expansion and time periods in peripheral blood and tissues under different conditions of CMV, HIV, Epstein-Barr virus (EBV), COVID-19 and hepatitis B virus (HBV) infections. Accordingly, we also discuss current clinical NK-associated antiviral applications, including cell therapy and NK-related biological agents, and we state the progress and future prospects of NK cell antiviral treatment.
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http://dx.doi.org/10.1016/j.clim.2021.108727DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055501PMC
June 2021

Pan-cancer noncoding genomic analysis identifies functional promoter mutation hotspots.

iScience 2021 Apr 9;24(4):102285. Epub 2021 Mar 9.

School of Life Science and Technology, ShanghaiTech University, Shanghai 201203, China.

Noncoding DNA sequences occupy more than 98% of the human genome; however, few cancer noncoding drivers have been identified compared with cancer coding drivers, probably because cancer noncoding drivers have a distinct mutation pattern due to the distinct function of noncoding DNA. Here we performed pan-cancer whole genome mutation analysis to screen for functional noncoding mutations that influence protein factor binding. Recurrent mutations were identified in the promoter of gene. These promoter hotspot mutations disrupt the binding of ELK4 transcription repressor, lead to the up-regulation of transcription. Physiologically ELK4 binds to the unmutated hotspot sites and is involved in DNA damage-induced transcriptional repression. Overall, our study not only identifies a detailed mechanism for gene deregulation in human cancers but also finds functional noncoding genetic alterations, with implications for the further development of function-based noncoding driver discovery pipelines.
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http://dx.doi.org/10.1016/j.isci.2021.102285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024666PMC
April 2021

Natural Plant Extracts and Compounds for Rheumatoid Arthritis Therapy.

Medicina (Kaunas) 2021 Mar 15;57(3). Epub 2021 Mar 15.

Interdisciplinary Graduate Program in Advanced Convergence Technology and Science, Jeju National University, Jeju 63243, Korea.

Natural plant extracts and compounds (NPECs), which originate from herbs or plants, have been used in the clinical treatment of rheumatoid arthritis (RA) for many years. Over the years, many scientists have carried out a series of studies on the treatment of RA by NPEC. They found a high quantity of active NPECs with broad application prospects. In view of various complex functions of these NPECs, exploring their potential as medicines for RA treatment will be beneficial for RA patients. Thus, to help advance the development of high-quality NPECs for RA, we herein aimed to review the research progress of NPECs in the treatment of RA in recent years. Our findings showed that, from the pharmacological perspective, natural plant extracts or mixed herbal compounds effectively regulate the immune system to alleviate RA by inhibiting pro-inflammatory cytokines. Further, individualized medication can be applied according to each patient's physical condition. However, the pathogenesis of RA and its immune mechanism has not been fully understood and requires further studies.
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http://dx.doi.org/10.3390/medicina57030266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001474PMC
March 2021

Therapeutic Single Compounds for Osteoarthritis Treatment.

Pharmaceuticals (Basel) 2021 Feb 6;14(2). Epub 2021 Feb 6.

Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon 16499, Korea.

Osteoarthritis (OA) is an age-related degenerative disease for which an effective disease-modifying therapy is not available. Natural compounds derived from plants have been traditionally used in the clinic to treat OA. Over the years, many studies have explored the treatment of OA using natural extracts. Although various active natural extracts with broad application prospects have been discovered, single compounds are more important for clinical trials than total natural extracts. Moreover, although natural extracts exhibit minimal safety issues, the cytotoxicity and function of all single compounds in a total extract remain unclear. Therefore, understanding single compounds with the ability to inhibit catabolic factor expression is essential for developing therapeutic agents for OA. This review describes effective single compounds recently obtained from natural extracts and the possibility of developing therapeutic agents against OA using these compounds.
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http://dx.doi.org/10.3390/ph14020131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914480PMC
February 2021

Seedling-derived leaf and root tip as alternative explants for callus induction and plant regeneration in maize.

Physiol Plant 2021 Jan 27. Epub 2021 Jan 27.

State Key Laboratory of Crop Biology, Shandong Agricultural University, Taian, China.

While being one of the world's most important crops, maize (Zea mays L.) is still relatively difficult to regenerate in tissue culture, which severely limits its improvement by genetic engineering. Currently, immature zygotic embryos provide the predominant material for transformation and regeneration. However, the procedures involved are often laborious and season-dependent. Therefore, new explants to replace or complement immature embryos are desirable. Here, we exploited root tips and young leaves isolated from 3-day-old dark-grown seedlings as alternative explant sources for establishing plant regeneration. As novel explants, the root tips could generate embryogenic calli similar to that from the young leaves. The rate of primary callus induction from root tips reached 97.2% and almost as high as 98.8% from immature embryos. The difference in callus induction rates among these explants may be closely related to the differences in expression level of stem cell-related genes in callus tissue. Moreover, the alternative explants are easy to obtain in large quantities. These combined results indicate that explants from seedling-derived root tips and leaf tissue have the potential to replace immature embryos for plant regeneration and transformation.
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http://dx.doi.org/10.1111/ppl.13347DOI Listing
January 2021

Inhibition of ER stress-activated JNK pathway attenuates TNF-α-induced inflammatory response in bone marrow mesenchymal stem cells.

Biochem Biophys Res Commun 2021 Feb 15;541:8-14. Epub 2021 Jan 15.

Department of Oral and Maxillofacial Surgery, Shenyang Stomatological hospital, Shenyang, Liaoning, People's Republic of China. Electronic address:

Bone marrow mesenchymal stem cells (BMMSCs) are characterized by their pluripotent differentiation and self-renewal capability and have been widely applied in regenerative medicine, gene therapy, and tissue repair. However, inflammatory response after BMMSCs transplantation was found to impair the osteogenic differentiation of BMMSCs. Thus, understanding the mechanisms underlying inflammation response will benefit the clinical use of BMMSCs. In this study, using a cell model of TNF-α-induced inflammatory response, we found that TNF-α treatment greatly elevated intracellular oxidative stress and induced endoplasmic reticulum (ER) stress by elevating the expression levels of ER sensors, such as PERK, ATF6 and IRE1A. Oxidative stress and ER stress formed a feedback loop to mediate TNF-α-induced inflammation response in BMMSCs. Moreover, c-Jun N-terminal kinase (JNK) signal pathway that coupled to the ER stress was significantly activated by increasing its phosphorylation upon TNF-α treatment. Importantly, pharmacological inhibition of ER stress effectively eliminated the phosphorylation of JNK and attenuated the TNF-α-induced inflammation response. In conclusion, our results indicated that TNF-α induced oxidative and ER stress, thereby leading to JNK activation, and generating inflammation response in BMMSCs. This pathway underlying TNF-α-induced inflammation response may provide new strategies to improve BMMSCs osteogenesis and other inflammation-associated bone diseases.
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http://dx.doi.org/10.1016/j.bbrc.2020.12.101DOI Listing
February 2021

Activity pattern study of Asiatic black bear (Ursus thibetanus) in the Qinling Mountains, China, by using infrared camera traps.

Environ Sci Pollut Res Int 2021 May 15;28(20):25179-25186. Epub 2021 Jan 15.

Conservation Ecology Center, Smithsonian Conservation Biology Institute, Front Royal, VA, 22630, USA.

The study of activity patterns is important for understanding the capacity of animals for adapting their behavior based on their habitat conditions. Among bears, daily activity patterns are considered to be strongly influenced by regional climate conditions. We monitored the activity patterns (active vs. inactive) of the Asiatic black bear (Ursus thibetanus) using infrared camera traps (from May 2013 to November 2016) in the Qinling Mountains, China. We used 125 photos, with 19,132 camera days from 55 camera locations. Based on relative independent capture (RIC), bears were found to be intensively active during June (5.86 ± 1.05 SE), July (8.45 ± 2.74), September (14.83 ± 6.13), and October (8.70 ± 3.43), with activity levels gradually decreasing beyond October. After this decline, activities eventually come to a halt when the bears enter in hibernation. We found that their hibernation period was shorter in the Qinling bears, with only 3 months of denning from January to March. Based on their daily patterns, bears were predominantly active during the daytime both in spring (70.83 ± 35.41%) and summer (52.09 ± 28.89%), but more active at twilight during autumn (51.12 ± 42.88%). We assumed that food preferences and food availability (due to warmer regional climatic conditions) might be responsible for such deviations in daily and monthly activity patterns.
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http://dx.doi.org/10.1007/s11356-020-12325-3DOI Listing
May 2021

GSK5182, 4-Hydroxytamoxifen Analog, a New Potential Therapeutic Drug for Osteoarthritis.

Pharmaceuticals (Basel) 2020 Nov 27;13(12). Epub 2020 Nov 27.

Interdisciplinary Graduate Program in Advanced Convergence Technology and Science, Jeju National University, Jeju City 63243, Korea.

Estrogen-related receptors (ERRs) are the first identified orphan nuclear receptors. The ERR family consists of ERRα, ERRβ, and ERRγ, regulating diverse isoform-specific functions. We have reported the importance of ERRγ in osteoarthritis (OA) pathogenesis. However, therapeutic approaches with ERRγ against OA associated with inflammatory mechanisms remain limited. Herein, we examined the therapeutic potential of a small-molecule ERRγ inverse agonist, GSK5182 (4-hydroxytamoxifen analog), in OA, to assess the relationship between ERRγ expression and pro-inflammatory cytokines in mouse articular chondrocyte cultures. ERRγ expression increased following chondrocyte exposure to various pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α. Pro-inflammatory cytokines dose-dependently increased ERRγ protein levels. In mouse articular chondrocytes, adenovirus-mediated ERRγ overexpression upregulated matrix metalloproteinase (MMP)-3 and MMP-13, which participate in cartilage destruction during OA. Adenovirus-mediated ERRγ overexpression in mouse knee joints or ERRγ transgenic mice resulted in OA. In mouse joint tissues, genetic ablation of obscured experimental OA. These results indicate that ERRγ is involved in OA pathogenesis. In mouse articular chondrocytes, GSK5182 inhibited pro-inflammatory cytokine-induced catabolic factors. Consistent with the in vitro results, GSK5182 significantly reduced cartilage degeneration in ERRγ-overexpressing mice administered intra-articular Ad-. Overall, the ERRγ inverse agonist GSK5182 represents a promising therapeutic small molecule for OA.
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http://dx.doi.org/10.3390/ph13120429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761342PMC
November 2020

Production of lentiviral vectors in suspension cells using low proportion of supercoiled circular plasmid DNA.

Cytotechnology 2020 Oct 29. Epub 2020 Oct 29.

Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, No. 11 South Street of Xizhimen, Xicheng District, 100044, Beijing, China.

The supercoiled circular (SC) topology form of plasmid DNA has been regarded to be advantageous over open circular or linearized analogue in transfection and expression efficiency, and therefore are largely demanded in the biopharmaceutical manufacturing. However, production of high-purity SC plasmid DNA would result in high manufacturing cost. The effect of SC proportion in plasmid DNA on the quality of packaged lentiviral vectors has never been reported. In this study, we established an efficient system for production of high-titer lentiviral vectors using suspension HEK293SF cells in serum-free media, and the lentiviral titer was not associated with the proportion of SC plasmid DNA. Plasmids DNA with different proportion of SC, open-circular, and linearized forms were prepared using the thermal denaturation method, and were transfected to adherent HEK293T or suspension HEK293SF cells for packaging of lentiviral vectors. The titer of lentiviral vectors from HEK293T cells, but not from HEK293SF cells, was significantly impaired when the proportion of SC plasmid DNA decreased from 60-80% to 30-40%. Further decrease of SC plasmid proportion to 3% led to a dramatic reduction of lentiviral titer no matter the packaging cell line was. However, lentiviral vectors from HEK293SF cells still showed a high titer even when the proportion of SC plasmid DNA was 3%. This study demonstrated that extremely high proportion of SC plasmid DNA was not required for packaging of high-titer lentiviral vector in HEK293SF cells, at least under our manufacturing process.
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http://dx.doi.org/10.1007/s10616-020-00433-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695760PMC
October 2020

ZmSKS13, a cupredoxin domain-containing protein, is required for maize kernel development via modulation of redox homeostasis.

New Phytol 2021 02 3;229(4):2163-2178. Epub 2020 Nov 3.

The Key Laboratory of Plant Development and Environment Adaptation Biology, Ministry of Education, School of Life Science, Shandong University, Qingdao, 266237, China.

The SKU5 similar (SKS) genes encode a family of multi-copper-oxidase-like proteins with cupredoxin domains similar to those in laccase and ascorbate oxidase. Although SKS proteins are known to function in root growth and cotyledon vascular patterning in Arabidopsis, their role in plant reproductive processes is poorly understood. Here, we identified a seed mutant of maize (Zea mays), generated by ethyl methane sulfonate (EMS) mutagenesis, that we designated defective kernel-zk1 (dek-zk1). The mutant produced small, shriveled kernels with an aberrant basal endosperm transfer layer (BETL) and placento-chalazal (PC) layer and irregular starch granules. Map-based cloning revealed that Dek-zk1 encodes an SKU5 similar 13 (GenBank: ONM36900.1), so it was named ZmSKS13. ZmSKS13 comprises a paralogous pair with Zm00001d012524, but the transcript abundance of ZmSKS13 in developing kernels is 15 times higher than that of Zm00001d012524, resulting in dek-zk1 mutation conveying a distinct kernel phenotype. ZmSKS13 loss of function led to overaccumulation of reactive oxygen species (ROS) and severe DNA damage in the nucellus and BETL and PC layer cells, and exogenous antioxidants significantly alleviated the defects of the mutant kernels. Our results thus demonstrate that ZmSKS13 is a novel regulator that plays a crucial role in kernel development in maize through the modulation of ROS homeostasis.
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http://dx.doi.org/10.1111/nph.16988DOI Listing
February 2021

Unmanipulated haploidentical hematopoietic stem cell transplantation for children with myelodysplastic syndrome.

Pediatr Transplant 2020 11 28;24(7):e13864. Epub 2020 Sep 28.

Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Research Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China.

Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal disorders and is rare in children. Allogeneic hematopoietic stem cell transplantation (HSCT) is commonly used in children with MDS with excess blasts and in patients with refractory cytopenia of childhood (RCC) associated with monosomy 7, complex karyotype, severe neutropenia, or transfusion dependence. We recruited 27 children with MDS who received haploidentical hematopoietic stem cell transplantation (haplo-HSCT). At transplantation, 10 patients had RCC, 12 patients had advanced MDS (RAEB and RAEB-T), and 5 patients had myelodysplasia-related acute myeloid leukemia (MDR-AML). All patients received granulocyte colony-stimulating factor (G-CSF)-mobilized bone marrow cells and peripheral blood stem cells. At a median follow-up of 24.1 months (range: 2.0-74.5 months) after HSCT, the estimated probabilities of 3-year disease-free survival (DFS) and overall survival (OS) were both 81.9% (95% CI, 66.8-100.0%). The estimated 3-year incidences of relapse (CIR) and non-relapse mortality (NRM) were both 7.4% (95% CI, 1.2%-21.4%). The 100-day cumulative incidence of grade II-IV aGVHD was 52.6% (95% CI, 42.9-62.3%), while that of grade III-IV aGVHD was 11.1% (95% CI, 5.1-17.1%). The 3-year cumulative incidences of overall and extensive cGVHD were 42.3% (95% CI, 19.8%-57.5%) and 21.1% (95% CI, 2.5%-63.2%), respectively. Univariate analysis showed that chronic GVHD significantly affected OS and DFS. Haploidentical HSCT may be an effective treatment option with easier donor availability for pediatric patients with MDS.
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http://dx.doi.org/10.1111/petr.13864DOI Listing
November 2020

Gut microbiome alterations and its link to corticosteroid resistance in immune thrombocytopenia.

Sci China Life Sci 2021 May 25;64(5):766-783. Epub 2020 Aug 25.

Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, 100044, China.

Quantitative metagenomic studies have linked the gut microbiota to autoimmune disorders. Here, we performed deep shotgun metagenomic sequencing of fecal samples from 99 immune thrombocytopenia (ITP) patients and 52 healthy controls. Dysbiosis in the gut microbiome of ITP was detected phylogenetically and functionally, and classifier based on species markers distinguished individuals with ITP from healthy controls. In particular, the abundance of Ruminococcus gnavus, Bifidobacterium longum and Akkermansia muciniphila was markedly increased in treatment-naïve ITP patients, and the alterations of microbial species were correlated with clinical indices. Functionally, the secondary bile acid biosynthesis and flagellar assembly were depleted in the gut microbiota of ITP, which may contribute to the onset of ITP by affecting the immune system. Furthermore, we found that corticosteroid treatment affected the gut microbiome of ITP. Compared with corticosteroid-sensitive ITP patients, we identified that the corticosteroid-resistant ITP patients displayed a distinct gut microbiome, which was different from that of the treatment-naïve ITP patients. Together, we provided support for the critical role of gut microbiota in the development of ITP and established a foundation for further research characterizing gut microbiota in relation to corticosteroid resistance of ITP.
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http://dx.doi.org/10.1007/s11427-020-1788-2DOI Listing
May 2021

Pulmonary nodule detection on chest radiographs using balanced convolutional neural network and classic candidate detection.

Artif Intell Med 2020 07 22;107:101881. Epub 2020 May 22.

Shanghai University of Medicine and Health Sciences, Shanghai, China.

Computer-aided detection (CADe) systems play a crucial role in pulmonary nodule detection via chest radiographs (CXRs). A two-stage CADe scheme usually includes nodule candidate detection and false positive reduction. A pure deep learning model, such as faster region convolutional neural network (faster R-CNN), has been successfully applied for nodule candidate detection via computed tomography (CT). The model is yet to achieve a satisfactory performance in CXR, because the size of the CXR is relatively large and the nodule in CXR has been obscured by structures such as ribs. In contrast, the CNN has proved effective for false positive reduction compared to the shallow method. In this paper, we developed a CADe scheme using the balanced CNN with classic candidate detection. First, the scheme applied a multi-segment active shape model to accurately segment pulmonary parenchyma. The grayscale morphological enhancement technique was then used to improve the conspicuity of the nodule structure. Based on the nodule enhancement image, 200 nodule candidates were selected and a region of interest (ROI) was cropped for each. Nodules in CXR exhibit a large variation in density, and rib crossing and vessel tissue usually present similar features to the nodule. Compared to the original ROI image, the nodule enhancement ROI image has potential discriminative features from false positive reduction. In this study, the nodule enhancement ROI image, corresponding segmentation result, and original ROI image were encoded into a red-green-blue (RGB) color image instead of the duplicated original ROI image as input of the CNN (GoogLeNet) for false positive reduction. With the Japanese Society of Radiological Technology database, the CADe scheme achieved high performance of the published literatures (a sensitivity of 91.4 % and 97.1 %, with 2.0 false positives per image (FPs/image) and 5.0 FPs/image, respectively) for nodule cases.
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http://dx.doi.org/10.1016/j.artmed.2020.101881DOI Listing
July 2020

A High-Energy Aqueous Manganese-Metal Hydride Hybrid Battery.

Adv Mater 2020 Sep 16;32(38):e2001106. Epub 2020 Aug 16.

State Key Laboratory of Materials-Oriented Chemical Engineering Jiangsu Collaborative Innovation Center for Advanced Inorganic Functional Composites, College of Materials Science and Engineering, Nanjing Tech University, Nanjing, 211816, China.

Aqueous rechargeable batteries show great application prospects in large-scale energy storage because of their reliable safety and low cost. However, a key challenge in developing this battery system lies in its low energy density. Herein, a high-energy manganese-metal hydride (Mn-MH) hybrid battery is reported in which a Mn-based cathode operated by the Mn /MnO deposition-dissolution reactions, a hydrogen-storage alloy anode that absorbs and desorbs hydrogen in an alkaline solution, and a proton-exchange membrane separator are employed. Given the benefit derived from the high solubility and high specific capacity of the Lewis acidic MnCl in the cathode and the low electrode potential of the MH anode, this aqueous Mn-MH hybrid battery exhibits impressive electrochemical properties with admirable discharge voltage plateaus up to 2.2 V, a competitive energy density of about 240 Wh kg (based on the total mass of the 5.5 m MnCl solution and the hydrogen storage alloy electrode system), good cycling stability over 130 cycles, and a desirable rate capability. This work demonstrates a new strategy for achieving high-performance and low-cost aqueous rechargeable batteries.
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http://dx.doi.org/10.1002/adma.202001106DOI Listing
September 2020

Secreted Peptide PIP1 Induces Stomatal Closure by Activation of Guard Cell Anion Channels in .

Front Plant Sci 2020 8;11:1029. Epub 2020 Jul 8.

Key Laboratory of Plant Development and Environmental Adaption Biology, Ministry of Education, School of Life Science, Shandong University, Qingdao, China.

Plant stomata which consist of a pair of guard cells, are not only finely controlled to balance water loss as transpiration and CO absorption for photosynthesis, but also serve as the major sites to defend against pathogen attack, thus allowing plants to respond appropriately to abiotic and biotic stress conditions. The regulatory signaling network for stomatal movement is complex in nature, and plant peptides have been shown to be involved in signaling processes. Arabidopsis secreted peptide PIP1 was previously identified as an endogenous elicitor, which induced immune response through its receptor, RLK7. PIP1-RLK7 can activate stomatal immunity against the bacterial strain DC3118. However, the molecular mechanism of PIP1 in stomatal regulation is still unclear and additional new factors need to be discovered. In this study, we further clarified that PIP1 could function as an important regulator in the induction of stomatal closure. The results showed that PIP1 could promote stomata to close in a certain range of concentrations and response time. In addition, we uncovered that PIP1-RLK7 signaling regulated stomatal response by activating S-type anion channel SLAC1. PIP1-induced stomatal closure was impaired in , , and mutants, indicating that and were required for PIP1-regulated stomatal movement. Our research further deciphered that which acts as an essential ABA-signaling component, also played a role in PIP1-induced stomatal closure. In addition, ROS participated in PIP1-induced stomatal closure and PIP1 could activate Ca permeable channels. In conclusion, we reveal the role of peptide PIP1 in triggering stomatal closure and the possible mechanism of PIP1 in the regulation of stomatal apertures. Our findings improve the understanding of the role of PIP1 in stomatal regulation and immune response.
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http://dx.doi.org/10.3389/fpls.2020.01029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7360795PMC
July 2020

Efficacy and Safety of CD28- or 4-1BB-Based CD19 CAR-T Cells in B Cell Acute Lymphoblastic Leukemia.

Mol Ther Oncolytics 2020 Sep 24;18:272-281. Epub 2020 Jun 24.

Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, National Clinical Research Center for Hematologic Disease, No. 11 South Street of Xizhimen, Xicheng District, Beijing 100044, China.

CD19-directed chimeric antigen receptor-T (CAR-T) cells with a 4-1BB or CD28 co-stimulatory domain have shown impressive antitumor activity against relapsed or refractory B cell acute lymphoblastic leukemia (r/r B-ALL). However, a parallel comparison of their performances in r/r B-ALL therapy has not been sufficiently reported. Here, we manufactured 4-1BB- and CD28-based CD19 CAR-T cells using the same process technology and evaluated their efficacy and safety in r/r B-ALL therapy based on pre-clinical and exploratory clinical investigations. In B-ALL-bearing mice, a similar antitumor effect and CAR-T kinetics in peripheral blood were observed at the CAR-T dose of 1 × 10/mouse. However, when the dose was decreased to 1 × 10/mouse, 4-1BB CAR-T cells were more potent in eradicating tumor cells and showed longer persistence than CD28 CAR-T cells. Retrospective analysis of an exploratory clinical study that used 4-1BB- or CD28-based CAR-T cells to treat r/r B-ALL was performed. Compared with CD28 CAR-T cells, 4-1BB CAR-T cells resulted in higher antitumor efficacy and less severe adverse events. This study demonstrated that the performance of 4-1BB CAR-T cells was superior to that of CD28 CAR-T cells in suppressing CD19 B-ALL, at least under our manufacturing process.
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http://dx.doi.org/10.1016/j.omto.2020.06.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7378699PMC
September 2020

Clinical Exome Sequencing Identifies a Novel Mutation of the Gene in a Chinese Family with Renal Agenesis.

Genet Test Mol Biomarkers 2020 Aug 25;24(8):520-526. Epub 2020 Jun 25.

Department of Clinical Laboratory, Linyi People's Hospital, Linyi, Shandong Province, P.R. China.

Renal agenesis (RA) is one of the most severe congenital anomalies of the kidney and urinary tract; it is known to be highly genetically heterogeneous. The purpose of this study was to explore the clinical significance of genetic diagnostics in a Chinese RA family. Five members of an RA family and 100 healthy people were recruited. Clinical exome sequencing was conducted to explore the underlying genetic cause in the affected family. Exome sequencing identified a novel missense mutation (c.2333T>A, p.Val778Asp) in the gene. This variant was not detected in controls and was predicted to be highly damaging to the physiological function of the GREB1L protein. We identified a novel c.2333T>A variant in the gene that extends the mutational spectrum associated with renal agenesis.
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http://dx.doi.org/10.1089/gtmb.2020.0036DOI Listing
August 2020

SH1-dependent maize seed development and starch synthesis via modulating carbohydrate flow and osmotic potential balance.

BMC Plant Biol 2020 Jun 8;20(1):264. Epub 2020 Jun 8.

The Key Laboratory of Plant Development and Environment Adaptation Biology, Ministry of Education, School of Life Science, Shandong University, Qingdao, 266237, China.

Background: As the main form of photoassimilates transported from vegetative tissues to the reproductive organs, sucrose and its degradation products are crucial for cell fate determination and development of maize kernels. Despite the relevance of sucrose synthase SH1 (shrunken 1)-mediated release of hexoses for kernel development, the underlying physiological and molecular mechanisms are not yet well understood in maize (Zea mays).

Results: Here, we identified a new allelic mutant of SH1 generated by EMS mutagenesis, designated as sh1*. The mutation of SH1 caused more than 90% loss of sucrose synthase activity in sh1* endosperm, which resulted in a significant reduction in starch contents while a dramatic increase in soluble sugars. As a result, an extremely high osmolality in endosperm cells of sh1* was generated, which caused kernel swelling and affected the seed development. Quantitative measurement of phosphorylated sugars showed that Glc-1-P in endosperm of sh1* (17 μg g FW) was only 5.2% of that of wild-type (326 μg g FW). As a direct source of starch synthesis, the decrease of Glc-1-P may cause a significant reduction in carbohydrates that flow to starch synthesis, ultimately contributing to the defects in starch granule development and reduction of starch content.

Conclusions: Our results demonstrated that SH1-mediated sucrose degradation is critical for maize kernel development and starch synthesis by regulating the flow of carbohydrates and maintaining the balance of osmotic potential.
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http://dx.doi.org/10.1186/s12870-020-02478-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7282075PMC
June 2020

Isolation and characterization of a 295-bp strong promoter of maize high-affinity phosphate transporter gene ZmPht1; 5 in transgenic Nicotiana benthamiana and Zea mays.

Planta 2020 May 18;251(6):106. Epub 2020 May 18.

The Key Laboratory of Plant Development and Environment Adaptation Biology, Ministry of Education, School of Life Science, Shandong University, Qingdao, 266237, China.

Main Conclusion: The small 295-bp ZmPht1; 5 promoter is sufficient to drive high-intensity expression of target genes, especially under phosphate deprivation conditions, and is therefore useful for crop improvement via transgenic techniques. Phosphate (Pi) deficiency has become a major challenge and limiting factor in world agricultural production. Manipulating the gene expression using appropriate promoters to improve the Pi absorption and utilization efficiency of crops could reduce the requirement for Pi fertilizers. In the study, a 295-bp strong promoter (M2P-7) of maize high-affinity phosphate transporter ZmPht1; 5 was isolated and functionally validated in transgenic Nicotiana benthamiana and maize by analyzing the ZmPht1; 5 promoter (M2P-1) and its 5' truncated variants (M2P-2 ~ M2P-8) in different sizes under normal and Pi-deprivation conditions. The M2P-7 displayed the highest promoter activities among 5' truncated fragments in all tested tissues of transgenic Nicotiana benthamiana at different development stages, which was 1.5 and 3 times higher than the well-used CaMV35S promoter under normal and Pi-deprivation conditions, respectively. In maize, the M2P-7 promoter activity was comparable to the maize ubiquitin1 promoter widely used in monocots under normal condition, which was about 1.3 times that of the ubiquitin1 promoter under Pi-deprivation environments. Moreover, the M2P-7 fragment is only 295 bp in length, thus reducing the construct size, and is therefore beneficial for genetic transformation. Thus, the small promoter M2P-7 of plant origin could be of great use for monocotyledonous and dicotyledonous crop improvement via transgenic techniques based on its promoter activities, expression patterns and small size.
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http://dx.doi.org/10.1007/s00425-020-03400-7DOI Listing
May 2020

Room-Temperature Stable Inorganic Halide Perovskite as Potential Solid Electrolyte for Chloride Ion Batteries.

ACS Appl Mater Interfaces 2020 Apr 13;12(16):18634-18641. Epub 2020 Apr 13.

College of Materials Science and Engineering, Nanjing Tech University, Nanjing 211816, China.

Solid electrolytes have attracted considerable interest in rechargeable batteries because of their potential high safety, inhibition of electrode dissolution, and large electrochemical window. However, their development in some new battery concepts such as room-temperature halide ion batteries has been scarce. Herein, we develop the inorganic halide perovskite of CsSnCl prepared by mechanical milling and subsequent mild heat treatment as the potential solid electrolyte for chloride ion batteries (CIB). Benefiting from its high structural stability against a phase transformation to monoclinic structure at room temperature, the as-prepared cubic CsSnCl achieves an impressive electrochemical performance with the highest ionic conductivity of 3.6 × 10 S cm and a large electrochemical window of about 6.1 V at 298 K. These values are much higher than 1.2 × 10 S cm and 4.25 V of the previously reported solid polymer electrolyte for CIBs. Importantly, the chloride ion transfer of the as-prepared CsSnCl electrolyte is demonstrated by employing the electrode couples of SnCl/Sn and BiCl/Bi.
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http://dx.doi.org/10.1021/acsami.0c03982DOI Listing
April 2020

A novel missense mutation of causes congenital cataract in a Chinese family.

Eur J Ophthalmol 2020 Mar 30:1120672120914497. Epub 2020 Mar 30.

Department of Ophthalmology, Linyi People's Hospital, Linyi, China.

Objective Of The Study: To identify the pathogenic gene and mutation site of a Chinese family with congenital cataract.

Methods: Eight family members and 100 controls were employed, and targeted exome sequencing was used to identify the genetically pathogenic factor of the proband.

Results: Targeted next-generation sequencing identified a novel missense mutation c.209A>C (p.Q70P) of gene in the family. Sanger sequencing results showed that this heterozygous mutation was a causative mutation, which was not found in unaffected family members and healthy controls. Bioinformatics predicts that the effect of this mutation on protein function is probably harmful.

Conclusion: We demonstrate that c.209A>C of gene is a pathogenic mutation in the family of congenital nuclear cataract in this study. This is the first report that this mutation leads to congenital nuclear cataract, which broadens the mutation spectrum of gene in congenital nuclear cataract.
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http://dx.doi.org/10.1177/1120672120914497DOI Listing
March 2020

Quaternary ammonium salt ion pair reagent sensitizing for determination of fluorescence whitening agent 85 in paper food packaging.

Spectrochim Acta A Mol Biomol Spectrosc 2020 Apr 3;231:118125. Epub 2020 Feb 3.

State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi 214122, PR China. Electronic address:

Fluorescent whitening agents (FWAs) are added to food packaging during manufacture to improve the whiteness and brightness. It is of great significance to develop a fast and sensitive FWAs detection method because their potential hazards to human health. Herein, we found that the quaternary ammonium salt ion pair reagents could enhance the fluorescence of FWAs, and then developed a fluorescent determination method for FWA 85 in paper food packaging. Under the optimized conditions, the linear range for the determination of FWA 85 was 5-200 ng/mL (R = 0.9996). The limit of detection was 1.20 ng/mL (S/N = 3) and the limit of quantitation was 3.99 ng/mL. The analytical feasibility was investigated further via determination of FWA 85 in paper food packing, which shows the recoveries were varied from 83.84% to 115.29% with RSDs from 1.64% to 7.22%. The method provides a new quaternary ammonium salt ion pair reagent sensitization for the detection of FWAs in paper food packaging.
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http://dx.doi.org/10.1016/j.saa.2020.118125DOI Listing
April 2020

High-Energy Interlayer-Expanded Copper Sulfide Cathode Material in Non-Corrosive Electrolyte for Rechargeable Magnesium Batteries.

Adv Mater 2020 Jan 9;32(4):e1905524. Epub 2019 Dec 9.

State Key Laboratory of Materials-Oriented Chemical Engineering, Jiangsu Collaborative Innovation Center for Advanced Inorganic Functional Composites, College of Materials Science and Engineering, Nanjing Tech University, Nanjing, 211816, China.

Rechargeable magnesium batteries (RMB) have been regarded as an alternative to lithium-based batteries because of their abundant elemental resource, high theoretical volumetric capacity, and multi-electron redox reaction without the dendrite formation of magnesium metal anode. However, their development is impeded by their poor electrode/electrolyte compatibility and the strong Coulombic effect of the multivalent Mg ions in cathode materials. Herein, copper sulfide material is developed as a high-energy cathode for RMBs with a non-corrosive Mg-ion electrolyte. Given the benefit of its optimized interlayer structure, good compatibility with the electrolyte, and enhanced surface area, the as-prepared copper sulfide cathode exhibits unprecedented electrochemical Mg-ion storage properties, with the highest specific capacity of 477 mAh g and gravimetric energy density of 415 Wh kg at 50 mA g , among the reported cathode materials of metal oxides, metal chalcogenides, and polyanion-type compounds for RMBs. Notably, an impressive long-term cycling performance with a stable capacity of 111 mAh g at 1 C (560 mA g ) is achieved over 1000 cycles. The results of the present study offer an avenue for designing high-performance cathode materials for RMBs and other multivalent batteries.
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http://dx.doi.org/10.1002/adma.201905524DOI Listing
January 2020

The Effect of Nano-Particles and Water Glass on the Water Stability of Magnesium Phosphate Cement Based Mortar.

Materials (Basel) 2019 Nov 14;12(22). Epub 2019 Nov 14.

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

This paper experimentally presented the water stability of magnesium phosphate cement (MPC) modified by nano-AlO (NA), nano-FeO (NF) and water glass (WG). The optimal addition of 6% NA, 2% NF and 1% WG significantly improved the water stability of MPC mortar by 86%, 101% and 96% after 28 days of water immersion, respectively. X-Ray Diffraction (XRD) and Scanning Electron Microscope (SEM) were used to analyze the water stability of MPC modified by NA, NF and WG. The results of the micrograph and composition analysis revealed that the proper amount of NA, NF or WG could fill the micro pores and improve the hydration of interior structures of MPC mortar. Thus, the microstructural compactness was satisfied to keep a good water stability of MPC mortar.
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http://dx.doi.org/10.3390/ma12223755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6888506PMC
November 2019

Cation-Disordered Lithium-Excess Li-Fe-Ti Oxide Cathode Materials for Enhanced Li-Ion Storage.

ACS Appl Mater Interfaces 2019 Nov 13;11(47):44144-44152. Epub 2019 Nov 13.

Cation-disordered Li-excess lithium-transition metal (Li-TM) oxides designed based on the percolation theory are regarded as a promising new type of high-performance cathode material for Li-ion batteries. Herein, cation-disordered rocksalt-type Li-Fe-Ti oxides of LiFeTiO, LiFeTiO, and LiFeTiO with different Li-to-transition metal ratios (Li/TM = 1, 1.49, or 1.63) are investigated to understand the effect of a Li excess on the electrochemical Li-ion storage properties. The Li excess leads to local structural fluctuations of the as-prepared Li-Fe-Ti oxides, contributing to the formation of 0-TM diffusion channels for rapid Li-ion migration. The as-prepared Li-excess Li-Fe-Ti oxide cathodes (Li/TM = 1.49 and Li/TM = 1.63) deliver a higher reversible capacity of over 220 mAh g and a better rate capability compared to the Li/TM = 1 electrode, which possesses a maximum discharge capacity of only about 165 mAh g. The redox reactions of Fe/Fe and O/O achieve the main capacity of the Li-excess Li-Fe-Ti oxide cathodes during cycling, as supported by Fe Mössbauer spectroscopy, O 1s X-ray photoelectron spectroscopy, and O K-edge soft X-ray absorption spectroscopy.
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http://dx.doi.org/10.1021/acsami.9b14137DOI Listing
November 2019

MiR-128-3p mediates TNF-α-induced inflammatory responses by regulating Sirt1 expression in bone marrow mesenchymal stem cells.

Biochem Biophys Res Commun 2020 01 18;521(1):98-105. Epub 2019 Oct 18.

Department of Pediatric Intensive Care Unit, Shengjing Hospital of China Medical University, Shenyang, Liaoning, People's Republic of China. Electronic address:

Tumor Necrosis Factor α (TNF-α), a multifunctional pro-inflammatory cytokine, is produced by macrophages/monocytes during acute inflammation, and plays a critical role in orchestrating the cytokine cascade in various inflammatory diseases. Previous studies demonstrated that TNF-α induces inflammatory responses in bone marrow mesenchymal stem cells (BMSCs) transplantation, leading to unsatisfactory effects and limit the clinical use of BMSCs. MicroRNAs are reported to involve in inflammation by regulating the expression of their targets in inflammatory response pathway. However, whether microRNAs mediate TNF-α-induced inflammatory responses in BMSCs remains elusive. Here, we found that TNF-α treatment induced an inflammatory response by increasing the levels of key inflammatory mediators, including IL-6, IL-1β, matrix metalloproteinase 9 (MMP9) and monocyte chemotactic protein-1 (MCP-1) in BMSCs. Moreover, real-time PCR result showed dramatically up-regulation of miR-128-3p after exposure to TNF-α. Interestingly, miR-128-3p over-expression exacerbated the TNF-α-induced inflammatory response, while suppression of miR-128-3p effectively eliminated the inflammatory response in BMSCs. Bioinformatic analysis identified sirtuin 1 is a direct target of miR-128-3p. Up-regulation of sirtuin 1 induced by resveratrol also diminished the TNF-α-induced inflammatory response in BMSCs. Altogether, our results indicated that miR-128-3p targets sirtuin 1 to mediate the TNF-α-induced inflammatory response in BMSCs, which may provide new strategies to protect against inflammatory-dependent impairments in BMSCs.
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http://dx.doi.org/10.1016/j.bbrc.2019.10.083DOI Listing
January 2020

Developmental retardation due to paternal 5q/11q translocation in a Chinese infant: clinical, chromosomal and microarray characterization.

J Genet 2019 Sep;98

Department of Medical Genetics, Linyi People's Hospital, Linyi 276003, Shandong, People's Republic of China.

Although it is known that the parental carriers of chromosomal translocation are considered to be at high risk for spontaneous abortion and embryonic death, normal gestation and delivery remain possible. This study aims to investigate the genetic factors of a Chinese infant with multiple malformations and severe postnatal development retardation. In this study, the routine cytogenetic analysis, chromosomal microarray analysis (CMA) and fluorescence hybridization (FISH) analysis were performed. Conventional karyotype analyses revealed normal karyotypes of all family members. CMA of the DNA of the proband revealed a 8.3 Mb duplication of 5q35.1-qter and a 6.9 Mb deletion of 11q24.3-qter. FISH analyses verified a paternal tiny translocation between the long arm of chromosomes 5 and 11. Our investigation serves to provide important information on genetic counselling for the patient and future pregnancies in this family. Moreover, the combined use of CMA and FISH is effective for clarifying pathogenically submicroscopic copy number variants.
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September 2019