Publications by authors named "Xiaoli Ma"

291 Publications

Monoclinic EuSn_{2}As_{2}: A Novel High-Pressure Network Structure.

Phys Rev Lett 2021 Apr;126(15):155701

Beijing National Laboratory for Condensed Matter Physics and Institute of Physics, Chinese Academy of Sciences, Beijing 100190, China.

The layered crystal of EuSn_{2}As_{2} has a Bi_{2}Te_{3}-type structure in rhombohedral (R3[over ¯]m) symmetry and has been confirmed to be an intrinsic magnetic topological insulator at ambient conditions. Combining ab initio calculations and in situ x-ray diffraction measurements, we identify a new monoclinic EuSn_{2}As_{2} structure in C2/m symmetry above ∼14  GPa. It has a three-dimensional network made up of honeycomblike Sn sheets and zigzag As chains, transformed from the layered EuSn_{2}As_{2} via a two-stage reconstruction mechanism with the connecting of Sn-Sn and As-As atoms successively between the buckled SnAs layers. Its dynamic structural stability has been verified by phonon mode analysis. Electrical resistance measurements reveal an insulator-metal-superconductor transition at low temperature around 5 and 15 GPa, respectively, according to the structural conversion, and the superconductivity with a T_{C} value of ∼4  K is observed up to 30.8 GPa. These results establish a high-pressure EuSn_{2}As_{2} phase with intriguing structural and electronic properties and expand our understandings about the layered magnetic topological insulators.
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http://dx.doi.org/10.1103/PhysRevLett.126.155701DOI Listing
April 2021

Genome-wide analysis of plant miRNA action clarifies levels of regulatory dynamics across developmental contexts.

Genome Res 2021 May 16;31(5):811-822. Epub 2021 Apr 16.

Center for Plant Molecular Biology, University of Tübingen, 72076 Tübingen, Germany.

Development of complex organisms requires the delicate and dynamic spatiotemporal regulation of gene expression. Central to this are microRNAs (miRNAs). These mobile small RNAs offer specificity in conveying positional information and versatility in patterning the outcomes of gene expression. However, the parameters that shape miRNA output during development are still to be clarified. Here, we address this question on a genome-wide scale, using the maize shoot apex as a model. We show that patterns and levels of miRNA accumulation are largely determined at the transcriptional level, but are finessed post-transcriptionally in a tissue-dependent manner. The stem cell environments of the shoot apical meristem and vasculature appear particularly liable to this. Tissue-specific effects are also apparent at the level of target repression, with target cleavage products in the vasculature exceeding those of other tissues. Our results argue against a clearance mode of regulation purely at the level of transcript cleavage, leading us to propose that transcript cleavage provides a baseline level of target repression, onto which miRNA-driven translational repression can act to toggle the mode of target regulation between clearance and rheostat. Our data show how the inherent complexities of miRNA pathways allow the accumulation and activity of these small RNAs to be tailored in space and time to bring about the gene expression versatility needed during development.
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http://dx.doi.org/10.1101/gr.270918.120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092011PMC
May 2021

[Identification of TCF3-ZNF384 fusion by transcriptome sequencing in B cell acute lymphoblastic leukemia and its laboratory and clinical characteristics].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2021 Apr;38(4):351-354

Department of Pathology and Laboratory Medicine, Beijing Ludaopei Hospital, Beijing 100176, China.

Objective: To detect fusion gene with pathological significance in a patient with refractory and relapsed acute B cell lymphoblastic leukemia (B-ALL) and to explore its laboratory and clinical characteristics.

Methods: Transcriptome sequencing was used to detect potential fusion transcripts. Other laboratory results and clinical data of the patient were also analyzed.

Results: The patient was found to harbor TCF3 exon 17-ZNF384 exon 7 in-frame fusion transcript. The minimal residual disease (MRD) has remained positive after multiple chemotherapy protocols including CD19-, CD22- targeted chimeric antigen receptor T cells immunotherapy. The patient eventually achieved complete remission and sustained MRD negativity after allogeneic hemopoietic stem cell transplantation (allo-HSCT).

Conclusion: Transcriptome sequencing can effectively detect potential fusion genes with clinical significance in leukemia. TCF3-ZNF384 positive B-ALL has unique laboratory and clinical characteristics, may not well respond to chemotherapy and immunotherapy, and is more likely to relapse. Timely allo-HSCT treatment may help such patients to achieve long-term disease-free survival. TCF3-ZNF384 positive B-ALL is not uncommon in pediatric patients but has not been effectively identified.
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http://dx.doi.org/10.3760/cma.j.cn511374-20200416-00273DOI Listing
April 2021

Direct and pleiotropic effects of the Masou Salmon Delta-5 Desaturase transgene in F1 channel catfish (Ictalurus punctatus).

Transgenic Res 2021 Apr 1;30(2):185-200. Epub 2021 Apr 1.

School of Fisheries, Aquaculture and Aquatic Sciences, Auburn University, 203 Swingle Hall, Auburn, AL, 36849, USA.

Channel catfish (Ictalurus punctatus) is the primary culture species in the US along with its hybrid made with male blue catfish, I. furcatus. In an effort to improve the nutritional value of channel catfish, the masou salmon Δ5-desaturase like gene (D5D) driven by the common carp beta-actin promoter (βactin) was inserted into channel catfish. The objectives of this study were to determine the effectiveness of βactin-D5D for improving n-3 fatty acid production in F1 transgenic channel catfish, as well as examine pleiotropic effects on growth, proximate analysis, disease resistance, and other performance traits. Transgenic F1 channel catfish showed a 33% increase in the relative proportion of n-3 fatty acids coupled with a 15% decrease in n-6 fatty acids and a 17% decrease in n-9 fatty acids when compared to non-transgenic full-siblings (P < 0.01, P < 0.01, P < 0.01). However, while the relative proportion of n-3 fatty acids was achieved, the total amount of fatty acids in the transgenic fish decreased resulting in a reduction of all fatty acids. Insertion of the βactin-D5D transgene into channel catfish also had large effects on the body composition, and growth of channel catfish. Transgenic channel catfish grew faster, were more disease resistant, had higher protein and moisture percentage, but lower fat percentage than full-sib controls. There were sex effects as performance changes were more dramatic and significant in males. The βactin-D5D transgenic channel catfish were also more uniform in their fatty acid composition, growth and other traits.
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http://dx.doi.org/10.1007/s11248-021-00242-1DOI Listing
April 2021

YAF2 exerts anti-apoptotic effect in human tumor cells in a FANK1- and phosphorylation-dependent manner.

Biochem Biophys Res Commun 2021 May 27;554:99-106. Epub 2021 Mar 27.

Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, 100005, China. Electronic address:

YY1-associated factor 2 (YAF2) was frequently reported to modulate target gene transcription through both epigenetic and non-epigenetic means. However, other mechanisms were also utilized by YAF2 to carry out its biological functions. Here, we demonstrated that YAF2 from human tumor and non-tumor cells were mainly expressed as Serine 167 phosphorylated form. Further studies showed that the phosphorylated YAF2 up-regulated while its knockdown by specific siRNAs reduced fibronectin type III and ankyrin repeat domains 1 (FANK1) protein level. Mechanistic exploration disclosed that phosphorylated YAF2 inhibit proteasomal degradation of polyubiquitinated FANK1, leading to its increased stability. We then validated their interaction, and displayed that the FN3 domain of FANK1 binds to amino-terminal of YAF2. Functional studies showed that phosphorylated YAF2 inhibits tumor cell apoptosis in a FANK1-dependent manner. Taken together, our current findings demonstrated that phosphorylated YAF2 exhibits anti-apoptotic activity through targeting FANK1 expression in human tumor cells.
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http://dx.doi.org/10.1016/j.bbrc.2021.03.105DOI Listing
May 2021

HS Persulfidated and Increased Kinase Activity of MPK4 to Response Cold Stress in Arabidopsis.

Front Mol Biosci 2021 11;8:635470. Epub 2021 Mar 11.

School of Life Science, Shanxi University, Taiyuan, China.

Hydrogen sulfide (HS) is a gasotransmitter along with nitric oxide and carbon oxide, which is involved in plant growth and development as well as biotic and abiotic stress resistance. In a previous study, we reported that mitogen-activated protein kinases, especially MPK4, are important downstream components of HS involved in alleviating cold stress; however the underlying mechanism is unclear. In this study, we determined that the ability of HS to alleviate cold stress is impaired in mutants, but not in the upstream and mutants. MPK4 was basically persulfidated, and NaHS (HS donor) further increased the persulfidation level of MPK4. MEK2 was not persulfidated by HS. NaHS treatments increased the MPK4 activity level nearly tenfold. The persulfidation signal of MPK4 did not disappear after eight cystein residues in MPK4 were site-mutated, respectively. Above all, our results suggested that HS alleviates cold stress directly by persulfidating MPK4 and increasing the MPK4 kinase activity.
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http://dx.doi.org/10.3389/fmolb.2021.635470DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7991836PMC
March 2021

Identification of a novel AVEN-NUTM1 fusion gene in acute myeloid leukemia.

Int J Lab Hematol 2021 Mar 23. Epub 2021 Mar 23.

Division of Pathology & Laboratory Medicine, Hebei Yanda Lu Daopei Hospital, Langfang, China.

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http://dx.doi.org/10.1111/ijlh.13519DOI Listing
March 2021

Reciprocal Expression of Differentiated Embryonic Chondrocyte Expressed Genes Result in Functional Antagonism in Gastric Cancer.

Dig Dis Sci 2021 Mar 11. Epub 2021 Mar 11.

Research Center of Basic Medicine, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250013, People's Republic of China.

Background: Differentiated embryonic chondrocyte expressed genes (DECs) are critical regulators of cellular proliferation and differentiation. However, DEC1 and DEC2 as family member have opposite or identical roles in tumor, acting as an "accelerator" or a "brake" in progression.

Aims: The possible crosstalk between DEC1 and DEC2 in the gastric cancer (GC).

Methods: The association of DEC1 and DEC2 expression with prognosis was investigated by immunohistochemistry. The expression pattern of DECs in GC cells was examined using the CCLE database. DECs knockdown or overexpression was conducted via lentiviral transfection. The proliferation of GC cells was evaluated by CCK8, EdU, and Colony forming. ChIP and luciferase reporter assays were used to verify interaction between DEC1 and the DEC2 promoter. The combination downstream with DEC1 and DEC2 was predicted by bioinformation, with Western blot providing further verification.

Results: We found that reciprocal expression of DEC1 and DEC2 works together to sustain the progression of GC by promoting cell growth. We confirmed this observation in vivo, showing that inhibition DEC1expression could increase DEC2 expression. DEC1 suppresses DEC2 expression by directly binding to the E-box of the DEC2 promoter in GC cells. Furthermore, this regulation of DEC1 on DEC2 enables the further indirect or cooperative activation of additional downstream target genes, MAPK, and STAT3.

Conclusion: Our data demonstrate that DEC1 and DEC2 interact physically and functionally and identify a novel mode of cross-regulatory interaction between DECs that abrogates their functional activity.
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http://dx.doi.org/10.1007/s10620-021-06921-7DOI Listing
March 2021

Biological features and clinical outcome in infant neuroblastoma: a multicenter experience in Beijing.

Eur J Pediatr 2021 Feb 13. Epub 2021 Feb 13.

Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics, Ministry of Education, Key Laboratory of Major Diseases in Children, Hematology Oncology Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China.

Neuroblastoma (NB) is the most common extracranial solid tumor in childhood, with 37% of patients diagnosed during infancy. This study is aimed at evaluating the survival outcome in infants diagnosed with neuroblastoma. This was a retrospective cohort study including patients under the age of 12 months with neuroblastoma from four tertiary referral centers in Beijing, China (Beijing Children's Hospital, Beijing Tongren Hospital, Peking University First Hospital, and Capital Institute of Pediatrics). Two hundred and forty-seven infants with neuroblastoma were included (male = 132 and female = 115). 91.1% (n = 225) patients were classified as having low-risk or intermediate-risk disease and 8.9% (n = 22) as having high-risk disease. The most common metastatic site is distant lymph node (n=89, 36.0%), followed by liver (n=57, 23.1%), bone (n=42, 17.0%), bone marrow (n=37, 15.0%), soft tissue (n=25, 10%), and central nervous system (n=4, 1.6%). MYCN amplification was present in 9.9% of tumor samples, chromosome 1p or 11q aberration in 14%. Treatment involved surgery alone in 9.7% of patients (n=24, all with low-risk disease), surgery followed by adjuvant chemotherapy in 50.2% (n=124), neoadjuvant chemotherapy followed by surgery in 40.1% (n=97), and chemotherapy alone in 0.8% (n=2). 4.9% (n=12) patients died, and the major cause of death is disease progression. Three-year event-free and overall survival were 91.6%±2.1% and 97.4%±1.1%, respectively, in patients with low- or intermediate-risk disease, and 58.7%±11.5% and 63.6%±11.2%, respectively, in those with high-risk disease.Conclusions: Infants with neuroblastoma achieve a reasonable clinical outcome when treated with surgery with or without chemotherapy using a risk-stratified approach in China. Such information will facilitate counseling, therapeutic decision-making, and development of adapted standard-of-care guidelines for future patients in the country. What is Known: • NB is a disease of infancy; 37% of patients are diagnosed as infants. • Most children younger than 12 months of age have a good prognosis even in the presence of metastatic disease. What is New: • Infants with neuroblastoma achieve reasonable clinical outcome when treated with surgery with or without chemotherapy using a risk-stratified approach in China. • CNS metastasis in infants with neuroblastoma is very rare at diagnosis and had a worse prognosis than those without metastasis.
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http://dx.doi.org/10.1007/s00431-021-03989-1DOI Listing
February 2021

Comparative Transcriptome Analysis During the Seven Developmental Stages of Channel Catfish () and Tra Catfish () Provides Novel Insights for Terrestrial Adaptation.

Front Genet 2020 21;11:608325. Epub 2021 Jan 21.

School of Fisheries, Aquaculture and Aquatic Sciences, Auburn University, Auburn, AL, United States.

Tra catfish (), also known as striped catfish, is a facultative air-breather that uses its swim bladder as an air-breathing organ (ABO). A related species in the same order (Siluriformes), channel catfish (), does not possess an ABO and thus cannot breathe in the air. Tra and channel catfish serve as great comparative models for investigating possible genetic underpinnings of aquatic to land transitions, as well as for understanding genes that are crucial for the development of the swim bladder and the function of air-breathing in tra catfish. In this study, hypoxia challenge and microtomy experiments collectively revealed critical time points for the development of the air-breathing function and swim bladder in tra catfish. Seven developmental stages in tra catfish were selected for RNA-seq analysis based on their transition to a stage that could live at 0 ppm oxygen. More than 587 million sequencing clean reads were generated, and a total of 21,448 unique genes were detected. A comparative genomic analysis between channel catfish and tra catfish revealed 76 genes that were present in tra catfish, but absent from channel catfish. In order to further narrow down the list of these candidate genes, gene expression analysis was performed for these tra catfish-specific genes. Fourteen genes were inferred to be important for air-breathing. Of these, , , and were identified to be the most likely genes related to air-breathing ability in tra catfish. This study provides a foundational data resource for functional genomic studies in air-breathing function in tra catfish and sheds light on the adaptation of aquatic organisms to the terrestrial environment.
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http://dx.doi.org/10.3389/fgene.2020.608325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859520PMC
January 2021

Hydrogen sulfide promotes flowering in heading Chinese cabbage by S-sulfhydration of BraFLCs.

Hortic Res 2021 Feb 1;8(1):19. Epub 2021 Feb 1.

School of Life Science and Shanxi Key Laboratory for Research and Development of Regional Plants, Shanxi University, Taiyuan, Shanxi Province, 030006, China.

Heading Chinese cabbage (Brassica rapa L. syn. B. campestris L. ssp. chinensis Makino var. pekinensis (Rupr.) J. Cao et Sh. Cao) is a cruciferous Brassica vegetable that has a triplicate genome, owing to an ancient genome duplication event. It is unclear whether the duplicated homologs have conserved or diversified functions. Hydrogen sulfide (HS) is a plant gasotransmitter that plays important physiological roles in growth, development, and responses to environmental stresses. The modification of cysteines through S-sulfhydration is an important mechanism of HS, which regulates protein functions. HS promotes flowering in Arabidopsis and heading Chinese cabbage. Here we investigated the molecular mechanisms of HS used to promote flowering in the latter. Four, five, and four BraFLC, BraSOC I, and BraFT homologs were identified in heading Chinese cabbage. Different BraFLC proteins were bound to different CArG boxes in the promoter regions of the BraSOC I and BraFT homologs, producing different binding patterns. Thus, there may be functionally diverse BraFLC homologs in heading Chinese cabbage. Exogenous HS at 100 μmol L significantly promoted flowering by compensating for insufficient vernalization. BraFLC 1 and BraFLC 3 underwent S-sulfhydration by HS, after which their abilities to bind most BraSOC I or BraFT promoter probes weakened or even disappeared. These changes in binding ability were consistent with the expression pattern of the BraFT and BraSOC I homologs in seedlings treated with HS. These results indicated that HS signaling regulates flowering time. In summary, HS signaling promoted plant flowering by weakening or eliminating the binding abilities of BraFLCs to downstream promoters through S-sulfhydration.
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http://dx.doi.org/10.1038/s41438-020-00453-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848000PMC
February 2021

Infectious lung masses misdiagnosed as metastatic rhabdomyosarcoma: Two case reports.

J Med Imaging Radiat Oncol 2021 Jan 24. Epub 2021 Jan 24.

Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics, Ministry of Education, Key Laboratory of Major Diseases in Children, Hematology Oncology Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.

Rhabdomyosarcoma (RMS) with regional lymph node involvement has a high rate of distant metastases. Lung is the most common site, accounting for 70% of all metastases. The differential diagnosis of lung lesions due to an infectious aetiology versus metastases is usually evaluated by computed tomography (CT) or magnetic resonance imaging. However, it is rare for patients of RMS to present with infectious nodules or masses in the lung during follow-up. More importantly, infections can mimic the imaging characteristics of metastatic RMS in CT. We report two such cases where children diagnosed with head and neck embryonal RMS with lymph node metastasis, presented with pulmonary masses 0.5 and 4 years after end of treatment, without the typical signs and symptoms suggestive of an infection. Chest CT suggested a provisional diagnosis of metastases and biopsies confirmed infectious aetiology (Mycobacterium tuberculosis, Cryptococcus).
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http://dx.doi.org/10.1111/1754-9485.13138DOI Listing
January 2021

Retracted: Pleuromutilin Inhibits Proliferation and Migration of A2780 and Caov-3 Ovarian Carcinoma Cells and Growth of Mouse A2780 Tumor Xenografts by Down-Regulation of pFAK2.

Med Sci Monit 2021 Jan 21;27:e930778. Epub 2021 Jan 21.

Department of Minimally Invasive Gynecological Centre, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China (mainland).

Some cells or groups of cells in figures appear to be visible multiple times. Because the manuscript contains non-credible results this journal is retracting the above publication. Reference: Bo Zhang, Xiaoli Ma, Yuan Li, Sijing Li, Jiumei Cheng: Pleuromutilin Inhibits Proliferation and Migration of A2780 and Caov-3 Ovarian Carcinoma Cells and Growth of Mouse A2780 Tumor Xenografts by Down-Regulation of pFAK2. Med Sci Monit, 2020; 26: e920407. DOI: 10.12659/MSM.920704.
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http://dx.doi.org/10.12659/MSM.930778DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837332PMC
January 2021

Dynamic evolution of ponatinib-resistant mutations in BCR-ABL1-positive leukaemias revealed by next-generation sequencing.

Br J Haematol 2020 12 10;191(5):e113-e116. Epub 2020 Sep 10.

Division of Pathology & Laboratory Medicine, Hebei Yanda Lu Daopei Hospital, Langfang, China.

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http://dx.doi.org/10.1111/bjh.17068DOI Listing
December 2020

The development and initial evaluation of referral flowchart for suspected neuroblastoma for pediatricians in nononcology clinics in China.

Pediatr Blood Cancer 2021 May 31;68(5):e28869. Epub 2020 Dec 31.

Center for Clinical Epidemiology & Evidence-based Medicine, Beijing Children's Hospital, National Center for Children's Health, Key Laboratory of Major Diseases in Children, Ministry of Education, Capital Medical University, Beijing, China.

Background: The delayed diagnosis of neuroblastoma (NB) is common in China, which results in the prognosis of NB in China lagging behind that in developed countries.

Methods: A referral flowchart for suspected NB was implemented in nononcology clinics at Beijing Children's Hospital (BCH). Patients with symptoms of suspected NB were referred from nononcology clinics in BCH to oncology clinics and confirmed NB cases were regarded as referral group. The control group comprised patients initially diagnosed with NB who came directly to oncology clinics in BCH from other regions nationwide. The age at NB diagnosis was compared as primary outcome, and the 5-year overall survival (OS) and event-free survival (EFS) were compared via the Kaplan-Meier method and log-rank tests.

Results: In total, 3337 children with suspected NB were screened consecutively from 687 070 pediatric patients. Through examination of urine vanillylmandelic acid and homovanillic acid, or B-ultrasound, 102 of 3337 patients were referred to oncologists for comprehensive evaluations. Eventually, 29 referred patients were diagnosed as NB and the hospital-based diagnosis rate of NB was 4.2 per 100 000 visits. The median age at diagnosis in the referral group was 21.0 months, which was 9 months earlier than that of the control group (30.0 months, P = .026). The 5-year OS rate was 72.4% in the referral group, which was higher than that of the control group (66.7%) but without statistical significance (P = .664).

Conclusion: Delayed NB detection could be avoided by training pediatricians in nononcology clinics to detect suspected NB and refer these patients to oncologists.
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http://dx.doi.org/10.1002/pbc.28869DOI Listing
May 2021

CRISPR/Cas9-mediated knock-in of alligator cathelicidin gene in a non-coding region of channel catfish genome.

Sci Rep 2020 12 17;10(1):22271. Epub 2020 Dec 17.

School of Fisheries, Aquaculture and Aquatic Sciences, Auburn University, Auburn, AL, 36849, USA.

CRISPR/Cas9-based gene knockout in animal cells, particularly in teleosts, has proven to be very efficient with regards to mutation rates, but the precise insertion of exogenous DNA or gene knock-in via the homology-directed repair (HDR) pathway has seldom been achieved outside of the model organisms. Here, we succeeded in integrating with high efficiency an exogenous alligator cathelicidin gene into a targeted non-coding region of channel catfish (Ictalurus punctatus) chromosome 1 using two different donor templates (synthesized linear dsDNA and cloned plasmid DNA constructs). We also tested two different promoters for driving the gene, zebrafish ubiquitin promoter and common carp β-actin promoter, harboring a 250-bp homologous region flanking both sides of the genomic target locus. Integration rates were found higher in dead fry than in live fingerlings, indicating either off-target effects or pleiotropic effects. Furthermore, low levels of mosaicism were detected in the tissues of P individuals harboring the transgene, and high transgene expression was observed in the blood of some P fish. This can be an indication of the localization of cathelicidin in neutrophils and macrophage granules as also observed in most antimicrobial peptides. This study marks the first use of CRISPR/Cas9 HDR for gene integration in channel catfish and may contribute to the generation of a more efficient system for precise gene integration in catfish and other aquaculture species, and the development of gene-edited, disease-resistant fish.
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http://dx.doi.org/10.1038/s41598-020-79409-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746764PMC
December 2020

Versatile Types of Polysaccharide-Based Drug Delivery Systems: From Strategic Design to Cancer Therapy.

Int J Mol Sci 2020 Dec 1;21(23). Epub 2020 Dec 1.

Institute of Biomedical Materials and Engineering, College of Materials Science and Engineering, Qingdao University, Qingdao 266071, China.

Chemotherapy is still the most direct and effective means of cancer therapy nowadays. The proposal of drug delivery systems (DDSs) has effectively improved many shortcomings of traditional chemotherapy drugs. The technical support of DDSs lies in their excellent material properties. Polysaccharides include a series of natural polymers, such as chitosan, hyaluronic acid, and alginic acid. These polysaccharides have good biocompatibility and degradability, and they are easily chemical modified. Therefore, polysaccharides are ideal candidate materials to construct DDSs, and their clinical application prospects have been favored by researchers. On the basis of versatile types of polysaccharides, this review elaborates their applications from strategic design to cancer therapy. The construction and modification methods of polysaccharide-based DDSs are specifically explained, and the latest research progress of polysaccharide-based DDSs in cancer therapy are also summarized. The purpose of this review is to provide a reference for the design and preparation of polysaccharide-based DDSs with excellent performance.
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http://dx.doi.org/10.3390/ijms21239159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7729619PMC
December 2020

Preparation, characterization, and evaluation of antioxidant activity and bioavailability of a self-nanoemulsifying drug delivery system (SNEDDS) for buckwheat flavonoids.

Acta Biochim Biophys Sin (Shanghai) 2020 Dec;52(11):1265-1274

Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Biotechnology, Shanxi University, Taiyuan 030006, China.

The self-nanoemulsifying drug delivery system has shown many advantages in drug delivery. In this study, a self-nanoemulsifying drug delivery system of buckwheat flavonoids was prepared for enhancing its antioxidant activity and oral bioavailability. A nanoemulsion of buckwheat flavonoids was developed and characterized, and its antioxidant, in vitro release, and in vivo bioavailability were determined. The nanoemulsion was optimized by the central composite design response surface experiment, and its particle size, polymer dispersity index (PDI), zeta potential, morphology, encapsulation efficiency, and stability were evaluated. The antioxidant activity was tested by measuring its 2,2-diphenyl-1-picrylhydrazyl scavenging activity, hydroxyl radical scavenging activity, and superoxide anion scavenging ability. In vitro release of buckwheat flavonoids nanoemulsion showed a higher cumulative release than the suspension, and the release fitting model followed the Ritger-Peppas and Weibull models. The effective concentration of the nanoemulsion was evaluated in vivo using a Wistar rat model, and the area under the plasma concentration-time curve of the buckwheat flavonoids nanoemulsion was 2.2-fold higher than that of the buckwheat flavonoid suspension. The Cmax of the nanoemulsion was 2.6-fold greater than that of the suspension. These results indicate that the nanoemulsion is a promising oral drug delivery system that can improve the oral bioavailability to satisfy the clinical requirements.
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http://dx.doi.org/10.1093/abbs/gmaa124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7731523PMC
December 2020

α5-nAChR and survivin: Two potential biological targets in lung adenocarcinoma.

J Cell Physiol 2021 Mar 28;236(3):1787-1797. Epub 2020 Jul 28.

Research Center of Basic Medicine, Central Hospital Affiliated to Shandong First Medical University, Jinan, China.

Recent studies have shown that the overexpression of α5 nicotinic acetylcholine receptor (α5-nAChR) is associated with nicotine-related lung carcinogenesis. Survivin is one of the biomarkers of a worse prognosis for smoking-related lung cancer. The aim of this study is to investigate the association of α5-nAChR, survivin, and clinical outcomes in lung adenocarcinoma (LUAD). We analyzed the expression level and correlation of CHRNA5 (encoding α5-nAChR) and BIRC5 (encoding survivin) in LUAD with The Cancer Genome Atlas data set. The relationship between overall survival (OS) and the expression of CHRNA5 or/and BIRC5 was evaluated by the Kaplan-Meier method and Cox proportional hazards model. Moreover, our results showed that the expression of α5-nAChR mediated survivin expression in lung cancer cells and in lung tumor xenografts. Relationships between the expression of α5-nAChR and/or survivin with clinical-pathological characteristics were analyzed using LUAD tissue samples. The results showed that expression of α5-nAChR was correlated with survivin expression in vitro and in vivo. The group coexpressing α5-nAChR and survivin had a worse prognosis than other subgroups in LUAD (p < .05). In conclusion, ascertaining the expression of both α5-nAChR and survivin provides a better measure of prognosis for LUAD patients. The combined inhibition of α5-nAChR and survivin may be a promising multitargeted gene therapeutic strategy in LUAD diagnosis.
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http://dx.doi.org/10.1002/jcp.29956DOI Listing
March 2021

Tumor necrosis factor receptor-associated factor 6 (TRAF6) inhibition modulates bone loss and matrix metalloproteinase expression levels in collagen-induced rheumatoid arthritis rat.

Ann Palliat Med 2020 Nov 10;9(6):4017-4028. Epub 2020 Nov 10.

Department of Rheumatology and Immunology, People's Hospital of Ningxia Hui Autonomous Region (the Affiliated People's Hospital of Ningxia Medical University and the First Affiliated Hospital of Northwest Minzu University), Ningxia, China.

Background: Rheumatoid arthritis (RA) is a main characterized by persistent synovitis, systemic inflammation, and autoantibodies. Tumor necrosis factor receptor-associated factor 6 (TRAF6) is an E3 ubiquitin ligase and is a crucial cytoplasm signal adaptor that can regulate critical biological processes. This research aims to explore the function of TRAF6 on bone loss and matrix metalloproteinase (MMP) expression in collagen-induced RA rats.

Methods: The RA model in rats (Sprague Dawley rat, 5-6 weeks old, weight 246.88±8.31 g) was set up via using collagen-induced RA. The shRNA-TRAF6 knockdown efficiency was tested using real-time reverse transcription-polymerase chain reaction (qRT-PCR) and western blot, respectively. The rats were divided into four groups: the control group, RA group, RA + shRNA-NC group, and RA + TRAF6-shRNA group. The tartrate-resistant acidic phosphatase (TRAP), hematoxylin and eosin (H&E), and Saffron O staining were employed to test the bone injury. The mRNA and protein expressive of Osteoclast-associated receptor (OSCAR), TRAP, Osterix (Osx), Collagen type I alpha 1 (COL1A1), Distal-less homeobox2 (Dlx2), tissue inhibitor of metalloproteinase (TIMP), matrix metalloproteinase-1(MMP-1), Cyclooxygenase 2 (COX2) and qRT-PCR performed MMP-13 and western blot, respectively.

Results: The mRNA and protein expression levels of TRAF6 were down-regulated in the RA + TRAF6- shRNA group. After the levels of TRAF6 were inhibited, the levels of bone volume/total volume (BV/TV), trabecular bone thickness (Tb.Th), and trabecular bone number (Tb.N) were increased, while the levels of trabecular bone space (Tb.Sp), Osteocalcin and ALP were deceased. The mRNA and protein expression levels of OSCAR, TRAP, MMP-1, COX2, and MMP-13 were reduced obviously in the RA + TRAF6- shRNA group compared with the RA + shRNA-NC group, while the levels of TIMP-1, OSX, CoL1A1, and DLx2 were enhanced obviously.

Conclusions: Inhibition of TRAF6 reduces bone loss and MMP expression levels in collagen-induced RA rat, and supplies an alternative treatment method in RA.
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http://dx.doi.org/10.21037/apm-20-1894DOI Listing
November 2020

Adsorption of ciprofloxacin to functionalized nano-sized polystyrene plastic: Kinetics, thermochemistry and toxicity.

Sci Total Environ 2021 Jan 16;750:142370. Epub 2020 Sep 16.

College of Chemistry and Chemical Engineering, Xinjiang Normal University, Urumqi 830054, China. Electronic address:

Plastic debris is ubiquitous in aquatic systems and has been proven vehicles for the transport of various pollutants including trace organic compounds. Nanoplastics have large specific surface area and hydrophobic characteristics and therefore are capable of adsorbing other organic or inorganic chemicals from the environment. Antibiotics, as another class of emerging contaminants, have raised significant research concern in recent years as they pose threats to the ecosytems and human health. Nevertheless, little information is available on the adsorption behaviors of antibiotics onto nano-sized plastics. The toxicity of combined nanoplastics and antibiotics is also largely unknown. In this study, the physicochemical and thermodynamic interactions between representative nanoplastics, which containing a carboxyl functional group of polystyrene nanoplastics (PS-COOH), and typical antibiotic, i.e., ciprofloxacin (CIP) were investigated in a batch adsorption experiment. The specific thermodynamic correlation function of PS-COOH combined with CIP was obtained through isothermal titration microcalorimetry (ITC) analysis. The adsorption kinetics and isotherm of CIP on PS-COOH closely fit the pseudo-second-order kinetic model (r = 0.99) and Freundlich isotherm (r = 0.99). The ITC results showed that the adsorption reaction of PS-COOH with CIP was a spontaneous exothermic reaction. The adsorption of antibiotics on nanoplastics may aggravate the negative impacts of these two pollutants on aqueous ecosystems, and we hypothesized that would be reflected in the survival rate of model organism of Caenorhabditis elegans when exposed to this combination. This work used a mechanistic approach to unravel the adsorption behavior of antibiotics on nanoplastics and shed light on their potential impact on aquatic ecosystems.
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http://dx.doi.org/10.1016/j.scitotenv.2020.142370DOI Listing
January 2021

Acute myeloid leukemia following a primary mediastinal germ cell tumor.

Pediatr Investig 2020 Sep 27;4(3):218-221. Epub 2020 Sep 27.

Beijing Key Laboratory of Pediatric Hematology Oncology; National Discipline of Pediatrics, Ministry of Education; MOE Key Laboratory of Major Diseases in Children; Hematology Oncology Center Beijing Children's Hospital Capital Medical University National Center for Children's Health Beijing China.

Introduction: There is a known association between primary mediastinal germ cell tumor (PMGCT) and hematologic malignancy that is not linked to treatment. They are exceptionally rare entities with a low morbidity and a poor prognosis.

Case Presentation: An 11-year-old boy presented with an anterior mediastinal mass diagnosed as a malignant germ cell tumor on the basis of an excisional biopsy. He was found to have acute myeloid leukemia (AML) two years after the chemotherapy for his germ cell tumor. The clinical course was very aggressive with a survival time of only 1 week after diagnosis of AML associated with PMGCT.

Conclusion: AML associated with PMGCT needs to be diagnosed correctly. Relevant examinations should be carried out in patients with PMGCTs during and after chemotherapy, and long-term follow-up is still necessary to reduce the risk of morbidity and mortality.
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http://dx.doi.org/10.1002/ped4.12217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520107PMC
September 2020

Challenges and opportunities for managing pediatric central nervous system tumors in China.

Pediatr Investig 2020 Sep 27;4(3):211-217. Epub 2020 Sep 27.

Department of Oncology St. Jude Children's Research Hospital Memphis TN USA.

Central nervous system (CNS) tumors represent the most deadly cancer in pediatric age group. In China, thousands of children are diagnosed with CNS tumors every year. Despite the improving socioeconomic status and availability of medical expertise within the country, unique challenges remain for the delivery of pediatric neuro-oncology service. In this review, we discuss the existing hurdles for improving the outcome of children with CNS tumors in China. Need for precise disease burden estimation, lack of intra- and inter-hospital collaborative networks, high probability of treatment abandonment, along with financial toxicities from treatment represent the key challenges that Chinese healthcare providers encounter. The tremendous opportunities for advancing the status of pediatric neuro-oncology care in and beyond the country are explored.
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http://dx.doi.org/10.1002/ped4.12212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520110PMC
September 2020

Diagnosis and treatment of infantile malignant solid tumors in beijing, China: A multicenter 10-year retrospective study.

Pediatr Investig 2020 Sep 27;4(3):178-185. Epub 2020 Sep 27.

Beijing Children's Hospital Capital Medical University National Center for Children's Health Beijing China.

Importance: Cancer is the main cause of death by disease in children. Children experience the highest incidence of cancer in the first year of life. However, there is no comprehensive registration system for children with tumors in China.

Objective: To summarize the diagnosis and treatment of infant cancer and analyze the status of standardized diagnosis and management among several treatment centers in Beijing, China, thereby providing evidence to guide further clinical research.

Methods: From January 1, 2010 to December 31, 2019, patients with newly diagnosed infantile malignant solid tumors were admitted to six large tertiary pediatric solid tumor diagnosis and treatment centers in Beijing. The epidemiology, clinical features, and therapeutic effects of tumors in these patients were analyzed retrospectively. All patients were followed up until March 31, 2020.

Results: In total, 938 patients were enrolled in this study. There were 530 boys (56.5%) and 408 girls (43.5%); the median age was 6.0 months (range, 0-12.0 months). The three most common tumors were retinoblastoma in 366 patients (39.0%), neuroblastoma in 266 patients (28.4%), hepatoblastoma in 133 patients (14.2%), and central nervous system tumors in 52 patients (5.5%). The estimated 5-year overall survival rate was 81.3% ± 1.8%, and the 5-year event-free survival rate was 71.8% ± 2.9%. The 5-year overall survival rates of non-rhabdomyosarcoma soft tissue sarcoma, neuroblastoma, and retinoblastoma were 100%, 88% ± 2.2%, and 86.9% ±2.1%, respectively. The 5-year event-free survival rates were 81.1% ± 2.7% for neuroblastoma, 81.6% ± 9.8% for non-rhabdomyosarcoma soft tissue sarcoma, and 72.7% ± 14.1% for extracranial malignant germ cell tumors.

Interpretation: The three most common infantile malignant solid tumors were retinoblastoma, neuroblastoma, and hepatoblastoma. Multidisciplinary combined diagnosis and treatment is needed for infantile tumors.
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http://dx.doi.org/10.1002/ped4.12213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520105PMC
September 2020

Treatment and outcomes of 1041 pediatric patients with neuroblastoma who received multidisciplinary care in China.

Pediatr Investig 2020 Sep 27;4(3):157-167. Epub 2020 Sep 27.

Department of Otorhinolaryngology Head and Neck Surgery Beijing Children's Hospital Capital Medical University National Center for Children's Health Beijing China.

Importance: Neuroblastoma is the most common extracranial malignant solid tumor in children. Multidisciplinary care is critical to improving the survival of pediatric patients with neuroblastoma.

Objective: To systematically summarize the clinical characteristics of children with neuroblastoma and evaluate their prognosis with multidisciplinary care provided in a single center.

Methods: This retrospective study analyzed the clinical data of 1041 patients with neuroblastoma who were diagnosed, treated, and followed-up in the Hematology-Oncology Center of Beijing Children's Hospital from 2007 to 2019.

Results: The median age at diagnosis was 34 months; 80.8% of the patients were younger than 5 years of age. Notably, 243 patients (23.3%) were classified as low-risk, 249 patients (23.9%) were classified as intermediate-risk, and 549 (52.7%) were classified as high-risk. Furthermore, 956 patients underwent surgical resections; 986 (94.7%) patients received chemotherapy; and 176 patients with high-risk neuroblastoma received hematopoietic stem cell transplantation. The 5-year event-free survival (EFS) rate was 91.3% and 5-year overall survival (OS) rate was 97.5% in low-risk group; in the intermediate-risk group, these rates were 85.1% and 96.7%, respectively, while they were 37.7% and 48.9% in the high-risk group ( 0.001 for both). The 5-year EFS and OS rates were significantly higher in patients diagnosed between 2015 and 2019 than in patients diagnosed between 2007 and 2014 ( 0.001). In total, 278 patients (26.7%) exhibited tumor relapse or progression; the median interval until relapse or progression was 14 months. Of the 233 patients who died, 83% died of relapse or progression of neuroblastoma and 4.3% died of therapy-related complications.

Interpretation: The 5-year OS rate was low in high-risk patients, compared with low-and intermediate-risk patients. Multidisciplinary care is critical for improvement of survival in pediatric patients with neuroblastoma. Additional treatment strategies should be sought to improve the prognosis of patients with high-risk neuroblastoma.
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http://dx.doi.org/10.1002/ped4.12214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520112PMC
September 2020

Comparative Genomic and Transcriptomic Analyses Revealed Twenty-Six Candidate Genes Involved in the Air-Breathing Development and Function of the Bighead Catfish Clarias macrocephalus.

Mar Biotechnol (NY) 2021 Feb 28;23(1):90-105. Epub 2020 Oct 28.

School of Fisheries, Aquaculture and Aquatic Sciences, Auburn University, Auburn, AL, 36849, USA.

The bighead catfish (Clarias macrocephalus) and channel catfish (Ictalurus punctatus) are freshwater species in the Siluriformes order. C. macrocephalus has both gills and modified gill structures serving as an air-breathing organ (ABO), while I. punctatus does not possess such an organ, and cannot breathe in air, providing an excellent model for studying the molecular basis of ABO development in teleost fish. To investigate the critical time window for the development of air-breathing function, seven development stages were selected based on hypoxia challenge results, and RNA-seq was performed upon C. macrocephalus to compare with the non-air-breathing I. punctatus. Five-hundred million reads were generated and 25,239 expressed genes were annotated in C. macrocephalus. Among those, 8675 genes were differentially expressed across developmental stages. Comparative genomic analysis identified 1458 C. macrocephalus specific genes, which were absent in I. punctatus. Gene network and protein-protein interaction analyses identified 26 key hub genes involved in the air-breathing function. Three top candidate genes, mb, ngb, hbae, are mainly associated with oxygen carrying, oxygen binding, and heme binding activities. Our study provides a rich data set for exploring the genomic basis of air-breathing function in C. macrocephalus and offers insights into the adaption to hypoxic environments.
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http://dx.doi.org/10.1007/s10126-020-10005-4DOI Listing
February 2021

Synthesis of Acryl Group-Modified Adsorption Resins and Their Adsorption Properties for Matrine and Oxymatrine in Aqueous Solutions.

ACS Omega 2020 Oct 28;5(39):25297-25305. Epub 2020 Sep 28.

School of Chemistry and Chemical Engineering, North Minzu University, Yinchuan 750021, China.

Three series of resins with different functional groups (PS-EA, PS-MP, and PS-BA) based on D101 copolymer were prepared the atom transfer radical polymerization method. The adsorption capacities of functionalized resins toward matrine (MT) and oxymatrine (OM) depended on the specific surface area, the surface chemistry, and the good polarity match between the target compound and porous material. It is noted that the accumulation of functional groups uploaded on the surface of resins increased the adsorption affinity difference between the MT-functionalized resin system and OM-modified copolymer system. The selectivity of modified resins to MT and OM would attribute to polarity matching. The results could provide a possible strategy for the design of efficient adsorbents applied for the isolation the bioactive compound from complex natural products.
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http://dx.doi.org/10.1021/acsomega.0c03559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7542831PMC
October 2020

The clinicopathological features and prognosis of serum AFP positive gastric cancer: a report of 16 cases.

Int J Clin Exp Pathol 2020 1;13(9):2439-2446. Epub 2020 Sep 1.

Department of Pathology, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University Jinan 250013, People's Republic of China.

Alpha-fetoprotein (AFP)-producing gastric cancer (AFPGC) is a relatively rare type of gastric cancer (GC). To improve the early diagnosis and treatment of AFPGC, we thoroughly investigated the clinicopathological features and prognosis of AFPGC. 139 GC patients who had received treatment from January 2013 to March 2016 in Jinan Central Hospital were included in this study. Blood samples for the pretreatment AFP examinations were collected. The relationship between the serum AFP and the clinicopathological features and prognosis were analyzed. Among the 139 GC cases, 16 cases (11.5%) were AFPGC patients. Compared with the AFP-negative (non-AFPGC) group, the AFPGC patients were prone to have distant metastasis (P=0.029), particularly in the liver, and the abdominal metastasis accounted for 79.4% (27/34). AFPGC patients' cancer is clearly prone to occur in the upper third of the stomach (P=0.008) and among younger (≤60 years old) patients (P=0.044). Furthermore, among the young and middle-aged (≤60 years old) patients, there were no significant differences in the serum carcinoembryonic antigen (CEA), the cancer antigen 19-9 (CA19-9), or the combined (CEA+CA19-9) positive rate between the AFPGC and the non-AFPGC patients. A Kaplan-Meier survival analysis showed that the median overall survival (mOS) of patients with AFPGC was significantly less than it was among the non-AFPGC patients (P=0.042). The serum AFP level (<100 ng/ml vs ≥100 ng/ml) is a prognostic factor for overall survival in AFPGC patients (P=0.041). In conclusion, the real-time examination of serum AFP has great diagnostic and prognostic value for managing AFPGC, especially for young and middle-aged patients.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539873PMC
September 2020

Outcome of two pairs of monozygotic twins with pleuropulmonary blastoma: case report.

Ital J Pediatr 2020 Oct 7;46(1):148. Epub 2020 Oct 7.

Beijing Key Laboratory of Pediatric Hematology Oncology, National Discipline of Pediatrics, Ministry of Education, MOE Key Laboratory of Major Diseases in Children, Hematology Oncology Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.

Background: Pleuropulmonary blastomas (PPB) are rare aggressive paediatric lung malignancies and are among the most common DICER1-related disorders: it is estimated that 75-80% of children with a PPB have the DICER1 mutation. DICER1 mutations are responsible for familial tumour susceptibility syndrome with an increased risk of tumours. In approximately 35% of families with children manifesting PPB, further malignancies may be observed. Symptoms of DICER1 syndrome may vary, even within monozygotic twins. Preventive screening of carriers with DICER1 mutations is important and follow-up is undertaken as recommended by the 2016 International PPB Register.

Case Presentation: We present two pairs of monozygotic twins. In one pair of 4-year, 2-month old girls, both with DICER1 mutation, one developed PPB(II) and her identical sibling had acute transient hepatitis. In the other pair of 19-month-old female babies, one had a history of bronchopulmonary hypoplasia and developed PPB(III) without DICER1 mutation, and her identical sibling had allergic asthma. Both patients with PPB were treated with R0 resection and received 12 cycles of postoperative chemotherapy. At the most recent review, the twins had been followed up for six and eight years, respectively, and they all remained healthy. However, the height and weight of the patients with PPB were lower than those of their respective identical sister.

Conclusions: PPB is rare, especially in monozygotic twins. We emphasise the importance of genetic testing and follow-up in monozygotic twins with PPB. During the follow-up, children surviving PPB should be monitored closely for growth and development disorders which caused by chemotherapy.
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http://dx.doi.org/10.1186/s13052-020-00912-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7542690PMC
October 2020