Publications by authors named "Hongxia Yan"

56 Publications

Termination effects of single-atom decorated v-MoCT MXene for the electrochemical nitrogen reduction reaction.

J Colloid Interface Sci 2021 Jul 21;605:897-905. Epub 2021 Jul 21.

Key Laboratory of Ecophysics and Department of Physics, College of Science, Shihezi University, Shihezi 832003, PR China. Electronic address:

The lack of the green, economical and high-efficient catalysts restrict the development of electrochemical nitrogen reduction reaction (NRR). By means of density functional theory (DFT) calculations, we have systematically investigated the NRR catalytic performance of single atoms decorated v-MoCT (T = O, F, OH, Cl, and Li) MXene ([email protected]). Our calculation results reveal the introduction of single atom can significantly improve the NRR activity and selectivity on v-MoCO, and [email protected] system possesses the lowest limiting potential of only -0.33 V among all studied systems. The termination effects of [email protected] are further discussed and a descriptor of the adsorption energy of *NNH species (ΔE(*NNH)) is proposed to establish the relationship with NRR limiting potential (U(NRR)), in which a moderate (ΔE(*NNH)) is required for high NRR activity. Moreover, a good linear relationship between the ΔE(*NNH) and the excess electrons on Ir atom shows that different ΔE(*NNH) originates from the difference of valence state of Ir atom, which is due to the change of coordination environment. Importantly, the synergistic effects of Ir atom and the surface O-terminations during the first hydrogenation step lead to a promoted NRR performance. Our study might provide new possibilities for rational design of cost-effective MXene-based NRR electrocatalysts.
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http://dx.doi.org/10.1016/j.jcis.2021.07.083DOI Listing
July 2021

Regulation of RNA Polymerase II Activity is Essential for Terminal Erythroid Maturation.

Blood 2021 Jun 1. Epub 2021 Jun 1.

University of Rochester, Rochester, New York, United States.

The terminal maturation of human erythroblasts requires significant changes in gene expression in the context of dramatic nuclear condensation. Defects in this process are associated with inherited anemias and myelodysplastic syndromes. The progressively dense appearance of the condensing nucleus in maturing erythroblasts led to the assumption that heterochromatin accumulation underlies this process, but despite extensive study, the precise mechanisms underlying this essential biologic process remain elusive. To delineate the epigenetic changes associated with the terminal maturation of human erythroblasts, we performed mass spectrometry of histone post-translational modifications combined with ChIP-seq, ATAC-seq, and RNA-seq. Our studies revealed that the terminal maturation of human erythroblasts is associated with a dramatic decline in histone marks associated with active transcription elongation, without accumulation of heterochromatin. Chromatin structure and gene expression were instead correlated with dynamic changes in occupancy of elongation competent RNA polymerase II, suggesting that terminal erythroid maturation is controlled largely at the level of transcription. We further demonstrate that RNA Polymerase II "pausing" is highly correlated with transcriptional repression, with elongation competent RNA polymerase II becoming a scare resource in late stage erythroblasts, allocated to erythroid-specific genes. Functional studies confirmed an essential role for maturation stage-specific regulation of RNA polymerase II activity during erythroid maturation, and demonstrate a critical role for HEXIM1 in the regulation of gene expression and RNA polymerase II activity in maturing erythroblasts. Taken together, our findings reveal important insights into the mechanisms that regulate terminal erythroid maturation, and provide a novel paradigm for understanding normal and perturbed erythropoiesis.
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http://dx.doi.org/10.1182/blood.2020009903DOI Listing
June 2021

Comprehensive phenotyping of erythropoiesis in human bone marrow: Evaluation of normal and ineffective erythropoiesis.

Am J Hematol 2021 09 3;96(9):1064-1076. Epub 2021 Jun 3.

New York Blood Center, New York, New York, USA.

Identification of stage-specific erythroid cells is critical for studies of normal and disordered human erythropoiesis. While immunophenotypic strategies have previously been developed to identify cells at each stage of terminal erythroid differentiation, erythroid progenitors are currently defined very broadly. Refined strategies to identify and characterize BFU-E and CFU-E subsets are critically needed. To address this unmet need, a flow cytometry-based technique was developed that combines the established surface markers CD34 and CD36 with CD117, CD71, and CD105. This combination allowed for the separation of erythroid progenitor cells into four discrete populations along a continuum of progressive maturation, with increasing cell size and decreasing nuclear/cytoplasmic ratio, proliferative capacity and stem cell factor responsiveness. This strategy was validated in uncultured, primary erythroid cells isolated from bone marrow of healthy individuals. Functional colony assays of these progenitor populations revealed enrichment of BFU-E only in the earliest population, transitioning to cells yielding BFU-E and CFU-E, then CFU-E only. Utilizing CD34/CD105 and GPA/CD105 profiles, all four progenitor stages and all five stages of terminal erythroid differentiation could be identified. Applying this immunophenotyping strategy to primary bone marrow cells from patients with myelodysplastic syndrome, identified defects in erythroid progenitors and in terminal erythroid differentiation. This novel immunophenotyping technique will be a valuable tool for studies of normal and perturbed human erythropoiesis. It will allow for the discovery of stage-specific molecular and functional insights into normal erythropoiesis as well as for identification and characterization of stage-specific defects in inherited and acquired disorders of erythropoiesis.
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http://dx.doi.org/10.1002/ajh.26247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8355124PMC
September 2021

Application of a crisis management nursing system in the novel coronavirus pneumonia epidemic.

Am J Transl Res 2021 15;13(4):3689-3695. Epub 2021 Apr 15.

Director of The Hospital, The Third Affiliated Hospital of Qiqihar Medical University Qiqihar, Heilongjiang Province, China.

Objective: To explore the application of a nursing crisis management system in the novel coronavirus pneumonia epidemic.

Methods: A retrospective nursing method was implemented. A total of 280 cases of patients were diagnosed with coronavirus pneumonia in the isolation ward of our hospital. The 280 cases of newly diagnosed pneumonia were divided into two groups: the nursing crisis management system group (n=150, the nursing crisis management was given) and the non-nursing crisis management system (n=130, routine nursing management was given). The psychological status (profile of mood states (POMS) score) of nursing staff before and after the implementation of the nursing crisis management, the psychological status of patients after the implementation of nursing crisis management (POMS score), emotion, cognition, behavior severity, patients' satisfaction with nursing, treatment compliance (Morisky Medication Compliance Scale (MMAS) score) of patients, the rate of cure of patients and the infection rate of nursing staff were compared.

Results: Compared with the non-nursing crisis management system group, the POMS scores of patients and nurses in the nursing crisis management system group decreased (all P<0.05). Compared with the non-nursing crisis management system group, the emotional, cognitive and behavioral scores of patients in the nursing crisis management system group were lower, while the MMAS score, satisfaction with nursing and cure rate were significantly increased (all P<0.05). The 142 nursing staff did not catch coronavirus.

Conclusion: During the novel coronavirus pneumonia outbreak and the current normal epidemic prevention and control periods, our crisis management mode was introduced into nursing work. The construction of the nursing crisis management mode under the epidemic situation can improve the psychological state and improve the management efficiency of the patients and nurses. The patients' satisfaction is high and the treatment compliance is good.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129237PMC
April 2021

Skin effect of facial cleansing: Should not be overemphasized compared with the long-term potential risk.

J Cosmet Dermatol 2021 Apr 30. Epub 2021 Apr 30.

Department of Dermatology, International Mongolian Hospital of Inner Mongolia, Hohhot, China.

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http://dx.doi.org/10.1111/jocd.14190DOI Listing
April 2021

Disulfide-Containing Polysiloxane with Multicolor Fluorescence and Visible-Light Excitation: Design, Synthesis, and Mechanism Exploration.

J Phys Chem B 2021 05 23;125(17):4321-4329. Epub 2021 Apr 23.

Key Laboratory of Polymer Science and Technology of Shaanxi Province, School of Chemistry and Chemical Engineering, Northwestern Polytechnical University, Xi'an 710129, China.

Aggregation-induced emission (AIE) polysiloxane has attracted growing attention in recent years due to its outstanding biocompatibility. However, polysiloxane usually requires high-energy UV light for excitation and exhibits monochromatic blue emission. Moreover, the experimental selection process of polysiloxane with designed features is time-consuming and laborious. So, in this paper, we developed a new molecular structure selection strategy using theoretical calculations instead of experiments, and a linear disulfide-containing polysiloxane (L1) is selected and synthesized. To our surprise, L1 can be excited by low-energy visible light (Ex = 508 nm and Em = 588 nm) and emit multicolor fluorescence under different excitation wavelengths. A further study of the luminescence mechanism was carried out through calculations about the quantum states of L1. Moreover, L1 shows multiple stimuli-responsiveness, such as redox, pH, metal ions, and solvent. This work provides an integrated route for the molecular design of macromolecular AIE luminogens with attractive fluorescence properties.
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http://dx.doi.org/10.1021/acs.jpcb.1c00191DOI Listing
May 2021

Pan-coronavirus fusion inhibitors possess potent inhibitory activity against HIV-1, HIV-2, and simian immunodeficiency virus.

Emerg Microbes Infect 2021 Dec;10(1):810-821

NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology and Center for AIDS Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.

EK1 peptide is a membrane fusion inhibitor with broad-spectrum activity against human coronaviruses (CoVs). In the outbreak of COVID-19, we generated a lipopeptide EK1V1 by modifying EK1 with cholesterol, which exhibited significantly improved antiviral activity. In this study, we surprisingly found that EK1V1 also displayed potent cross-inhibitory activities against divergent HIV-1, HIV-2, and simian immunodeficiency virus (SIV) isolates. Consistently, the recently reported EK1 derivative EK1C4 and SARS-CoV-2 derived fusion inhibitor lipopeptides (IPB02 ∼ IPB09) also inhibited HIV-1 Env-mediated cell-cell fusion and infection efficiently. In the inhibition of a panel of HIV-1 mutants resistant to HIV-1 fusion inhibitors, EK1V1 and IPB02-based inhibitors exhibited significantly decreased or increased activities, suggesting the heptad repeat-1 region (HR1) of HIV-1 gp41 being their target. Furthermore, the sequence alignment and molecular docking analyses verified the target site and revealed the mechanism underlying the resistance. Combined, we conclude that this serendipitous discovery provides a proof-of-concept for a common mechanism of viral fusion and critical information for the development of broad-spectrum antivirals.
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http://dx.doi.org/10.1080/22221751.2021.1917309DOI Listing
December 2021

A Direct and Sensitive Method for Determination of 5-Fluorouracil in Colorectal Cancer Cells: Evaluating the Effect of Stromal Cell on Drug Resistance of Cancer Cells.

J Anal Methods Chem 2021 25;2021:6689488. Epub 2021 Feb 25.

Department of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.

Fibroblasts in the stroma play a critical role in tumor evolution. In this study, we assessed the influence of colonic fibroblasts on colon cancer cells treated with 5-fluorouracil (5-FU), and mouse colon cancer cell lines MC38 and colonic fibroblasts NIH3T3 were used in this study. A sensitive and rapid UHPLC-MS/MS method for the quantitation of 5-FU from the cell and their medium has been successfully developed and validated. The cells were lysed with methanol, and the mixture was evaporated and then redissolved to extract intracellular 5-FU. The analysis was performed on UHPLC-MS/MS using an Atlantis T3-C18 column (3 m, 2. 1 ∗ 100 mm) and gradient elution with acetonitrile and 0.1% formic acid in water. Method validation included the following parameters: the matrix effect range 88.82%-93.64% and the recovery range 93.52%-94.56%. The intraday and interday precision and accuracy were <11% and within ±6%, and the stability, specificity, carry-over, dilution effect, and linearity all conformed to the criteria. The method was applied to detect the concentration of 5-FU inside cells and cell culture medium. The preliminary results present that NIH3T3 could enhance the drug resistance of MC38 to 5-FU with a decreased intracellular concentration of 5-FU in MC38, which showed a positive relationship with NIH3T3 number.
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http://dx.doi.org/10.1155/2021/6689488DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7932793PMC
February 2021

An IDH1-vitamin C crosstalk drives human erythroid development by inhibiting pro-oxidant mitochondrial metabolism.

Cell Rep 2021 02;34(5):108723

Institut de Génétique Moléculaire de Montpellier, Univ. Montpellier, CNRS, Montpellier, France; Laboratory of Excellence GR-Ex, Paris 75015, France. Electronic address:

The metabolic changes controlling the stepwise differentiation of hematopoietic stem and progenitor cells (HSPCs) to mature erythrocytes are poorly understood. Here, we show that HSPC development to an erythroid-committed proerythroblast results in augmented glutaminolysis, generating alpha-ketoglutarate (αKG) and driving mitochondrial oxidative phosphorylation (OXPHOS). However, sequential late-stage erythropoiesis is dependent on decreasing αKG-driven OXPHOS, and we find that isocitrate dehydrogenase 1 (IDH1) plays a central role in this process. IDH1 downregulation augments mitochondrial oxidation of αKG and inhibits reticulocyte generation. Furthermore, IDH1 knockdown results in the generation of multinucleated erythroblasts, a morphological abnormality characteristic of myelodysplastic syndrome and congenital dyserythropoietic anemia. We identify vitamin C homeostasis as a critical regulator of ineffective erythropoiesis; oxidized ascorbate increases mitochondrial superoxide and significantly exacerbates the abnormal erythroblast phenotype of IDH1-downregulated progenitors, whereas vitamin C, scavenging reactive oxygen species (ROS) and reprogramming mitochondrial metabolism, rescues erythropoiesis. Thus, an IDH1-vitamin C crosstalk controls terminal steps of human erythroid differentiation.
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http://dx.doi.org/10.1016/j.celrep.2021.108723DOI Listing
February 2021

Apatinib and fractionated stereotactic radiotherapy for the treatment of limited brain metastases from primary lung mucoepidermoid carcinoma: A case report.

Medicine (Baltimore) 2020 Oct;99(43):e22925

Department of Radiation Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.

Rationale: Apatinib is a novel anti-angiogenic agent that targets vascular endothelial growth factor receptor-2, thereby inhibiting tumor angiogenesis, and is effective in the treatment of brain metastases (BM) and peritumoral brain edema (PTBE). There are no previous reports of combination therapy with apatinib and fractionated stereotactic radiotherapy (FSRT) for BM from primary lung mucoepidermoid carcinoma (MEC).

Patient Concerns: A 63-year-old man underwent left lower lobectomy and mediastinal lymph node dissection in April 2018.

Diagnoses: Postoperative pathology demonstrated high-grade MEC. The patient developed 3 BM with PTBE 3 months after undergoing surgery.

Interventions: The patient received a combination of FSRT and apatinib (250-500 mg/d) as maintenance therapy.

Outcomes: The 3 BM showed nearly complete responses, and the PTBE areas shrank visibly. A new BM lesion occurred 7 months after the first FSRT and was treated with a second dose of FSRT. The patient developed extensive metastasis and atelectasis 9 months later. He died of pulmonary infection in December 2019. The overall survival time was 20 months.

Lessons: Limited BM from primary lung MEC may be treated effectively with combination therapy with apatinib and FSRT when chemotherapy alone is not effective or tolerated. Further studies are needed to investigate the clinical outcomes and toxicities associated with the treatment.
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http://dx.doi.org/10.1097/MD.0000000000022925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581043PMC
October 2020

Cross-reactive neutralization of SARS-CoV-2 by serum antibodies from recovered SARS patients and immunized animals.

Sci Adv 2020 11 6;6(45). Epub 2020 Nov 6.

NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

The current coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus genetically close to SARS-CoV. To investigate the effects of previous SARS-CoV infection on the ability to recognize and neutralize SARS-CoV-2, we analyzed 20 convalescent serum samples collected from individuals infected with SARS-CoV during the 2003 SARS outbreak. All patient sera reacted strongly with the S1 subunit and receptor binding domain (RBD) of SARS-CoV; cross-reacted with the S ectodomain, S1, RBD, and S2 proteins of SARS-CoV-2; and neutralized both SARS-CoV and SARS-CoV-2 S protein-driven infections. Analysis of antisera from mice and rabbits immunized with a full-length S and RBD immunogens of SARS-CoV verified cross-reactive neutralization against SARS-CoV-2. A SARS-CoV-derived RBD from palm civets elicited more potent cross-neutralizing responses in immunized animals than the RBD from a human SARS-CoV strain, informing strategies for development of universal vaccines against emerging coronaviruses.
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http://dx.doi.org/10.1126/sciadv.abc9999DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673700PMC
November 2020

Photodynamic therapy for nevus sebaceous of Jadassohn affecting esthetically areas: a potential therapeutic approach.

Dermatol Ther 2020 11 28;33(6):e14313. Epub 2020 Sep 28.

Department of Dermatology, International Mongolian Hospital of Inner Mongolia, Hohhot, Inner Mongolia, China.

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http://dx.doi.org/10.1111/dth.14313DOI Listing
November 2020

Combining competitive sequestration with nonlinear hybridization chain reaction amplification: an ultra-specific and highly sensitive sensing strategy for single-nucleotide variants.

Anal Chim Acta 2020 Sep 26;1130:107-116. Epub 2020 Jul 26.

MOE Key Laboratory of Material Physics and Chemistry Under Extraordinary Conditions, School of Science, Northwestern Polytechnical University, Xi'an, 710129, China. Electronic address:

Highly specific and sensitive detection of single-nucleotide variants (SNVs) is of central importance in disease diagnosis and pharmacogenomics. However, it remains a great challenge to successfully detect very low amounts of mutant SNV sequences in real samples in which a SNV sequence may be surrounded by high levels of closely related wild-type sequences. Herein, we propose an ultra-specific and highly sensitive SNV sensing strategy by combining the competitive sequestration with the nonlinear hybridization chain reaction (HCR) amplification. The rationally designed sequestration hairpin can effectively sequester the large amount of wild-type sequence and thus dramatically improve the hybridization specificity in recognizing SNVs. To improve the detection sensitivity, a new fluorescent signal probe is fabricated by intercalating SYBR Green I dye into the nonlinear HCR based DNA dendrimer to further bind with SNVs for signal amplification. The hyperbranched DNA dendrimer possesses large numbers of DNA duplexes for dye intercalation, thus the signal probe shows strong fluorescence intensity, leading to large fluorescence signal amplification. Taking advantage of the improved hybridization specificity of the competitive sequestration and the enhanced fluorescence response of the nonlinear HCR amplification, the developed sensing strategy enables ultra-specific and highly sensitive detection of SNVs. Taking human pancreatic cancers and colorectal carcinomas related KRAS gene mutations as models, the developed strategy shows remarkably high specificity against 17 SNVs (discrimination factors ranged from 126 to 1001 with a median of 310), and achieves high sensitivity for 6 KRAS mutations (the best resultant detection limit reached 15 pM for KRAS G13D (c.38G > A)). Notably, combined with PCR amplification, our SNV sensing strategy could detect KRAS G12D (c.35G > A) from extracted human genomic DNA samples at abundance as low as 0.05%. This work expands the rule set of designing specific and sensitive SNV sensing strategies and shows promising potential application in clinical diagnosis.
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http://dx.doi.org/10.1016/j.aca.2020.07.022DOI Listing
September 2020

Fetal hemoglobin rescues ineffective erythropoiesis in sickle cell disease.

Haematologica 2020 08 27. Epub 2020 Aug 27.

Inserm - INTS - University of Paris, Paris, France;

While ineffective erythropoiesis has long been recognized as a key contributor to anemia in thalassemia, its role in anemia of sickle cell disease (SCD) has not been critically explored. Using in vitro and in vivo derived human erythroblasts we assessed the extent of ineffective erythropoiesis in SCD. Modeling the bone marrow hypoxic environment, we found that hypoxia induces death of sickle erythroblasts starting at the polychromatic stage, positively selecting cells with high levels of fetal hemoglobin (HbF). Cell death was associated with cytoplasmic sequestration of heat shock protein 70 and was rescued by induction of HbF synthesis. Importantly, we document that in bone marrow of SCD patients similar cell loss occurs during the final stages of terminal differentiation. Our study provides evidence for ineffective erythropoiesis in SCD and highlights an anti-apoptotic role for HbF during the terminal stages of erythroid differentiation. These findings imply that the beneficial effect on anemia of increased HbF levels is not only due to the increased life span of red cells but also a consequence of decreased ineffective erythropoiesis.
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http://dx.doi.org/10.3324/haematol.2020.265462DOI Listing
August 2020

Fabrication and investigation on Ag nanowires/TiO nanosheets/graphene hybrid nanocomposite and its water treatment performance.

Adv Compos Hybrid Mater 2020 Jun 29:1-13. Epub 2020 Jun 29.

College of Bioresources Chemical and Materials Engineering, Shaanxi University of Science & Technology, Xi'an, 710021 China.

In this paper, a novel Ag nanowires/TiO nanosheets/graphene nanocomposite was fabricated via a facile method of hydrothermal and calcination, and then the water treatment performance of it was evaluated for methylene blue (MB) and removal. The as-prepared Ag nanowires/TiO nanosheets/graphene nanocomposite was characterized by Fourier-transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), field-emission scanning electron microscopy (FE-SEM), energy-dispersive X-ray spectroscopy (EDX), UV-visible diffuse reflection spectroscopy (DRS), molecular dynamics simulation, and gas chromatography-mass spectrometry (GC-MS). All data revealed that the Ag/TiO/graphene nanocomposite showed a rich cell structure. The photocatalytic activity of Ag/TiO/graphene nanocomposite is higher than those of pristine TiO nanosheets and TiO/graphene nanocomposite. Under optimized conditions, the degradation efficiency was 100% and 71% for MB (30 mg/L) and with 10 mg Ag/TiO/graphene nanocomposite under UV and visible light irradiation for 2 h, respectively. Ag/TiO/graphene also showed excellent bacteria-killing activity. Meanwhile, the Ag/TiO/graphene nanocomposite exhibited microstructure stability and cyclic stability. The water treatment performance was enhanced mainly attributed to the excellent adsorption performance of graphene and the high efficiency in separation of electron-hole pairs induced by the remarkable synergistic effects of TiO, Ag, and graphene. On the basis of the experimental results, the photocatalytic mechanism and MB degradation mechanism were proposed. It is hoped that our work could avert the misleading message to the readership, hence offering a valuable source of reference on fabricating composite photocatalyst with stable microstructure and excellent performance for their application in the environment clean-up. Graphical abstract.
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http://dx.doi.org/10.1007/s42114-020-00164-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7321717PMC
June 2020

Expression and diagnostic value of miR-34c and miR-141 in serum of patients with colon cancer.

Oncol Lett 2020 Oct 7;20(4):98. Epub 2020 Aug 7.

Department of Oncological Radiotherapy, Hubei Cancer Hospital, Wuhan, Hubei 430079, P.R. China.

Expression of miR-34c and miR-141 in serum of colon cancer patients and their association with clinicopathological features and diagnostic value for colon cancer were investigated. A total of 64 patients with colon cancer admitted to Hubei Cancer Hospital from January 2016 to March 2018 were included in the experimental group, and 64 healthy subjects undergoing physical examination during the same period were the control group. The expression of miR-34c and miR-141 in serum of patients in the two groups were detected by RT-qPCR, and the association of miR-34c and miR-141 with the clinicopathological characteristics of colon cancer patients was analyzed. The receiver operating characteristic (ROC) curve was used to assess the diagnostic efficiency of miR-34c and miR-141 in colon cancer. The expression of miR-141 in serum of patients in the experimental group was significantly higher than that in the control group (P<0.05). Expression of miR-34c in serum of patients in the experimental group was significantly lower than that in the control group (P<0.05) and the expression of miR-34c and miR-141 in serum of the experimental group were associated with tumor diameter, clinical stage, degree of differentiation and lymph node metastasis (P<0.05). AUC of serum miR-34c in the diagnosis of colon cancer was 0.857 (95% CI: 0.795-0.919), with the cut-off value of 0.800, the diagnostic sensitivity of 84.38%, and the specificity of 68.75% and AUC of serum miR-141 in the diagnosis of colon cancer was 0.876 (95% CI: 0.810-0.941), with the cut-off value of 0.282, the diagnostic sensitivity of 70.31%, and the specificity of 96.88%. The ROC curve for the diagnosis of colon cancer was further plotted in combination with serum miR-34c and miR-141. AUC of the two combined for the diagnosis of colon cancer was 0.929 (95% CI: 0.884-0.974), with the cut-off value of 0.566, the diagnostic sensitivity of 84.38%, and the specificity of 93.75%. In conclusion, miR-34c and miR-141 might be involved in the occurrence and progression of colon cancer and could be used as biological indicators for early diagnosis of colon cancer.
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http://dx.doi.org/10.3892/ol.2020.11959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7439149PMC
October 2020

Sleep of preschoolers during the coronavirus disease 2019 (COVID-19) outbreak.

J Sleep Res 2021 02 27;30(1):e13142. Epub 2020 Jul 27.

Department of Neurology, Center for Pediatric Sleep Disorders, Boston Children's Hospital, Waltham, MA, USA.

Coronavirus disease 2019 (COVID-19) has resulted in a significantly large number of psychological consequences, including sleep health. The present study evaluated sleep patterns, sleep disturbances, and associated factors in Chinese preschoolers confined at home during the COVID-19 outbreak. Caregivers of 1619 preschoolers (aged 4-6 years) recruited from 11 preschools in Zunyi, Guizhou province completed the Children's Sleep Habit Questionnaire (CSHQ) between 17th and 19th February 2020. Data were compared to a sociodemographically similar sample of preschoolers (included in the 11 preschools) in 2018. Compared to the 2018 sample, the confined preschoolers demonstrated changes in sleep patterns characterized by later bedtimes and wake times, longer nocturnal and shorter nap sleep durations, comparable 24-hr sleep duration, and fewer caregiver-reported sleep disturbances. Moreover, behavioural practices (sleeping arrangement, reduced electronic device use, regular diet) and parenting practices (harmonious family atmosphere and increased parent-child communication) were associated with less sleep disturbances in the confined sample. The present study provides the first description of the impact of prolonged home confinement during the COVID-19 outbreak on sleep patterns and sleep disturbances in preschoolers, as well as highlighting the importance of the link between sleep health and family factors. Given that disrupted and insufficient sleep has been linked to immune system dysfunction, our findings also have potential implications for resilience to infection in young children during the COVID-19 pandemic. Future studies should further explore deficient sleep as a risk factor for coronavirus infection.
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http://dx.doi.org/10.1111/jsr.13142DOI Listing
February 2021

Energy-Transfer-Induced Multiexcitation and Enhanced Emission of Hyperbranched Polysiloxane.

Biomacromolecules 2020 09 4;21(9):3724-3735. Epub 2020 Aug 4.

Queen Mary University of London Engineering School, Northwestern Polytechnical University, Xi'an, Shaanxi Province 710072, China.

Fluorescent hyperbranched polysiloxane (HBPSi) has attracted increasing attention due to its good biocompatibility. However, its emission mechanism remains an open question. Unfortunately, the excitation spectra of HBPSi are rarely systematically investigated and show a narrow excitation band, which hinders the emission mechanism study. Herein, we synthesized a series of novel HBPSi containing l-glutamic acid (HBPSi-GA). Surprisingly, these polymers have four excitation peaks and two emission peaks, which are caused by the energy transfer from free functional groups to heterogeneous electron delocalizations in different clusters. Meanwhile, the fluorescence and biocompatibility of HBPSi-GA are significantly improved with increasing l-glutamic acid. Furthermore, HBPSi-GA exhibits dual stimuli-responsive fluorescence to temperature and Fe as well as potential application in cell imaging. This research possesses important guidance to develop multiexcitation unconventional fluorescent polymers.
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http://dx.doi.org/10.1021/acs.biomac.0c00823DOI Listing
September 2020

Putative regulators for the continuum of erythroid differentiation revealed by single-cell transcriptome of human BM and UCB cells.

Proc Natl Acad Sci U S A 2020 06 26;117(23):12868-12876. Epub 2020 May 26.

Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, 510515 Guangzhou, China;

Fine-resolution differentiation trajectories of adult human hematopoietic stem cells (HSCs) involved in the generation of red cells is critical for understanding dynamic developmental changes that accompany human erythropoiesis. Using single-cell RNA sequencing (scRNA-seq) of primary human terminal erythroid cells (CD34CD235a) isolated directly from adult bone marrow (BM) and umbilical cord blood (UCB), we documented the transcriptome of terminally differentiated human erythroblasts at unprecedented resolution. The insights enabled us to distinguish polychromatic erythroblasts (PolyEs) at the early and late stages of development as well as the different development stages of orthochromatic erythroblasts (OrthoEs). We further identified a set of putative regulators of terminal erythroid differentiation and functionally validated three of the identified genes, , , and , by monitoring cell differentiation and apoptosis. We documented that knockdown of suppressed the commitment of HSCs to erythroid lineage and cell proliferation and delayed differentiation of colony-forming unit-erythroid (CFU-E) to the proerythroblast stage (ProE). In contrast, the knockdown of and delayed differentiation of PolyE to OrthoE stage. Taken together, the convergence and divergence of the transcriptional continuums at single-cell resolution underscore the transcriptional regulatory networks that underlie human fetal and adult terminal erythroid differentiation.
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http://dx.doi.org/10.1073/pnas.1915085117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293633PMC
June 2020

Design of Potent Membrane Fusion Inhibitors against SARS-CoV-2, an Emerging Coronavirus with High Fusogenic Activity.

J Virol 2020 07 1;94(14). Epub 2020 Jul 1.

NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

The 2019 coronavirus disease (COVID-19), caused by the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has posed serious threats to global public health and economic and social stabilities, calling for the prompt development of therapeutics and prophylactics. In this study, we first verified that SARS-CoV-2 uses human angiotensin-converting enzyme 2 (ACE2) as a cell receptor and that its spike (S) protein mediates high membrane fusion activity. The heptad repeat 1 (HR1) sequence in the S2 fusion protein of SARS-CoV-2 possesses markedly increased α-helicity and thermostability, as well as a higher binding affinity with its corresponding heptad repeat 2 (HR2) site, than the HR1 sequence in S2 of severe acute respiratory syndrome coronavirus (SARS-CoV). Then, we designed an HR2 sequence-based lipopeptide fusion inhibitor, termed IPB02, which showed highly potent activities in inhibiting SARS-CoV-2 S protein-mediated cell-cell fusion and pseudovirus transduction. IPB02 also inhibited the SARS-CoV pseudovirus efficiently. Moreover, the structure-activity relationship (SAR) of IPB02 was characterized with a panel of truncated lipopeptides, revealing the amino acid motifs critical for its binding and antiviral capacities. Therefore, the results presented here provide important information for understanding the entry pathway of SARS-CoV-2 and the design of antivirals that target the membrane fusion step. The COVID-19 pandemic, caused by SARS-CoV-2, presents a serious global public health emergency in urgent need of prophylactic and therapeutic interventions. The S protein of coronaviruses mediates viral receptor binding and membrane fusion, thus being considered a critical target for antivirals. Herein, we report that the SARS-CoV-2 S protein has evolved a high level of activity to mediate cell-cell fusion, significantly differing from the S protein of SARS-CoV that emerged previously. The HR1 sequence in the fusion protein of SARS-CoV-2 adopts a much higher helical stability than the HR1 sequence in the fusion protein of SARS-CoV and can interact with the HR2 site to form a six-helical bundle structure more efficiently, underlying the mechanism of the enhanced fusion capacity. Also, importantly, the design of membrane fusion inhibitors with high potencies against both SARS-CoV-2 and SARS-CoV has provided potential arsenals to combat the pandemic and tools to exploit the fusion mechanism.
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http://dx.doi.org/10.1128/JVI.00635-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343218PMC
July 2020

A DFT screening of single transition atoms supported on MoS as highly efficient electrocatalysts for the nitrogen reduction reaction.

Nanoscale 2020 May;12(18):10035-10043

Key Laboratory for Green Processing of Chemical Engineering of Xinjiang Bingtuan, School of Chemistry and Chemical Engineering, Shihezi University, Shihezi, 832003, PR China.

The development of low-cost and highly efficient materials for the electrocatalytic nitrogen reduction reaction (NRR) under ambient conditions is an attractive and challenging topic in chemistry. In this study, the electrocatalytic performance of a series of transition metal (TM) atoms supported on MoS2 nanosheets ([email protected]) was systematically investigated using density functional theory (DFT) calculations. It was found that Re supported on MoS2 ([email protected]) has the best NRR catalytic activity with a limiting potential of -0.43 V, along with high selectivity over the competing hydrogen evolution reaction (HER). Moreover, the ab initio molecular dynamics (AIMD) simulations at 500 K and density of states (DOS) calculations indicated the high thermodynamic stability and excellent electrical conductivity of [email protected] A linear trend between several parameters of single atom catalysts (SACs) and the adsorption Gibbs free energy change of the NH species (ΔG*NH) was observed, indicating the later as a simple descriptor for the facilitated screening of novel SACs. These results pave the way for exploring novel, highly efficient electrocatalysts for the electrochemical NRR under ambient conditions.
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http://dx.doi.org/10.1039/d0nr00030bDOI Listing
May 2020

A molecular device providing a remarkable spin filtering effect due to the central molecular stretch caused by lateral zigzag graphene nanoribbon electrodes.

Phys Chem Chem Phys 2020 Mar;22(12):6755-6762

National Laboratory of Solid State Microstructures, Collaborative Innovation Center of Advanced Microstructures, and Department of Physics, Nanjing University, Nanjing 210093, P. R. China and Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing 210093, P. R. China.

Through the density functional theory, we studied molecular devices composed of single tetrathiafulvalene (TTF) molecules connected with zigzag graphene nanoribbon electrodes by four different junctions. Interestingly, some devices have exhibited half-metallic behavior and can bring out a perfect spin filtering effect and remarkable negative differential resistance behavior. The current-voltage characteristics show that these four devices possess different spin current values. We found that all the TTF molecules were stretched due to interactions with the electrodes in the four devices. This leads to the Fermi levels of the three devices being down-shifted to the valence band; therefore, these devices exhibit half-metallic properties. The underlying mechanisms of the different spin current values are attributed to the different electron transmission pathways (via chemical bonds or through hopping between atoms). These results suggest that the device properties and conductance are controlled by different junctions. Our work predicts an effective way for designing high-performance spin-injected molecular devices.
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http://dx.doi.org/10.1039/d0cp00238kDOI Listing
March 2020

Steroid resistance in Diamond Blackfan anemia associates with p57Kip2 dysregulation in erythroid progenitors.

J Clin Invest 2020 04;130(4):2097-2110

Department of Molecular Medicine and Pediatrics, Donald and Barbara Zucker School of Medicine, Hofstra/Northwell, Hempstead, New York, USA.

Despite the effective clinical use of steroids for the treatment of Diamond Blackfan anemia (DBA), the mechanisms through which glucocorticoids regulate human erythropoiesis remain poorly understood. We report that the sensitivity of erythroid differentiation to dexamethasone is dependent on the developmental origin of human CD34+ progenitor cells, specifically increasing the expansion of CD34+ progenitors from peripheral blood (PB) but not cord blood (CB). Dexamethasone treatment of erythroid-differentiated PB, but not CB, CD34+ progenitors resulted in the expansion of a newly defined CD34+CD36+CD71hiCD105med immature colony-forming unit-erythroid (CFU-E) population. Furthermore, proteomics analyses revealed the induction of distinct proteins in dexamethasone-treated PB and CB erythroid progenitors. Dexamethasone treatment of PB progenitors resulted in the specific upregulation of p57Kip2, a Cip/Kip cyclin-dependent kinase inhibitor, and we identified this induction as critical; shRNA-mediated downregulation of p57Kip2, but not the related p27Kip1, significantly attenuated the impact of dexamethasone on erythroid differentiation and inhibited the expansion of the immature CFU-E subset. Notably, in the context of DBA, we found that steroid resistance was associated with dysregulated p57Kip2 expression. Altogether, these data identify a unique glucocorticoid-responsive human erythroid progenitor and provide new insights into glucocorticoid-based therapeutic strategies for the treatment of patients with DBA.
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http://dx.doi.org/10.1172/JCI132284DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7108903PMC
April 2020

Surface Modification Design for Improving the Strength and Water Vapor Permeability of Waterborne Polymer/SiO Composites: Molecular Simulation and Experimental Analyses.

Polymers (Basel) 2020 Jan 9;12(1). Epub 2020 Jan 9.

Department of Applied Chemistry, School of Science, Northwestern Polytechnical University, Xi'an 710129, China.

Polymer-based nanocomposites properties are greatly affected by interfacial interaction. Polyacrylate nanocomposites have been widely studied, but few studies have been conducted on their interface mechanism. Therefore, there was an urgent demand for providing a thorough understanding of the polymethyl acrylate/SiO (PMA/SiO) nanocomposites to obtain the desired macro-performance. In this paper, a methodology, which combined molecular dynamics simulation with experimental researches, was established to expound the effect of the surface structure of SiO particles which were treated with KH550, KH560 or KH570 (KH550-SiO, KH560-SiO and KH570-SiO) on the mechanical characteristic and water vapor permeability of polymethyl acrylate/SiO nanocomposites. The polymethyl acrylate/SiO nanocomposites were analyzed in binding energy and mean square displacement. The results indicate that PMA/KH570-SiO had the highest tensile strength, while PMA/KH550-SiO had the highest elongation at break at the same filler content; KH550-SiO spheres can significantly improve water vapor permeability of polyacrylate film.
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http://dx.doi.org/10.3390/polym12010170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7023158PMC
January 2020

High Fluorescent Hyperbranched Polysiloxane Containing β-Cyclodextrin for Cell Imaging and Drug Delivery.

Biomacromolecules 2019 11 24;20(11):4230-4240. Epub 2019 Oct 24.

Key Laboratory for Space Biosciences & Biotechnology, Faculty of Life Science , Northwestern Polytechnical University , Xi'an 710072 , P. R. China.

Hyperbranched polysiloxane (HBPSi) is attracting increasing attention due to its intrinsic fluorescence and good biocompatibility. However, it is very challenging to explore its biological applications because of the low fluorescence intensity and quantum yield. Herein, we introduced rigid β-cyclodextrin to the end of flexible polysiloxane chain to synthesize a novel fluorescent polymer (HBPSi-CD) and explore its biological applications. Results showed that the fluorescence intensity and quantum yield of HBPSi-CD, compared with HBPSi, were significantly enhanced. Theoretical calculations and transmission electron microscopy demonstrated that the synergy effect of intra/intermolecular hydrogen bonds and hydrophobic effect promoted the formation of large supramolecular self-assemblies and space electron delocalization systems, leading to intense fluorescence. Notably, the biocompatible HBPSi-CD not only lighted up mouse fibroblast cells, but also possessed high ibuprofen loading capacity (160 mg g) and superior pH-responsive drug release performance. This work promoted the development of biological applications of HBPSi.
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http://dx.doi.org/10.1021/acs.biomac.9b01217DOI Listing
November 2019

A Unique Epigenomic Landscape Defines Human Erythropoiesis.

Cell Rep 2019 09;28(11):2996-3009.e7

Department of Pediatrics, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Pathology, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA. Electronic address:

Mammalian erythropoiesis yields a highly specialized cell type, the mature erythrocyte, evolved to meet the organismal needs of increased oxygen-carrying capacity. To better understand the regulation of erythropoiesis, we performed genome-wide studies of chromatin accessibility, DNA methylation, and transcriptomics using a recently developed strategy to obtain highly purified populations of primary human erythroid cells. The integration of gene expression, DNA methylation, and chromatin state dynamics reveals that stage-specific gene regulation during erythropoiesis is a stepwise and hierarchical process involving many cis-regulatory elements. Erythroid-specific, nonpromoter sites of chromatin accessibility are linked to erythroid cell phenotypic variation and inherited disease. Comparative analyses of stage-specific chromatin accessibility indicate that there is limited early chromatin priming of erythroid genes during hematopoiesis. The epigenome of terminally differentiating erythroid cells defines a distinct subset of highly specialized cells that are vastly dissimilar from other hematopoietic and nonhematopoietic cell types. These epigenomic and transcriptome data are powerful tools to study human erythropoiesis.
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http://dx.doi.org/10.1016/j.celrep.2019.08.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6863094PMC
September 2019

Amino Functionalization of Reduced Graphene Oxide/Tungsten Disulfide Hybrids and Their Bismaleimide Composites with Enhanced Mechanical Properties.

Polymers (Basel) 2018 Oct 27;10(11). Epub 2018 Oct 27.

Department of Applied Mathematics, School of Natural and Applied Sciences, Northwestern Polytechnical University, Xi'an 710129, China.

A novel graphene-based nanocomposite particles (NH₂-rGO/WS₂), composed of reduced graphene oxide (rGO) and tungsten disulfide (WS₂) grafted with active amino groups (NH₂-rGO/WS₂), was successfully synthesized by an effective and facile method. NH₂-rGO/WS₂ nanoparticles were then used to fabricate new bismaleimide (BMI) composites (NH₂-rGO/WS₂/BMI) via a casting method. The results demonstrated that a suitable amount of NH₂-rGO/WS₂ nanoparticles significantly improved the mechanical properties of the BMI resin. When the loading of NH₂-rGO/WS₂ was only 0.6 wt %, the impact and flexural strength of the composites increased by 91.3% and 62.6%, respectively, compared to the neat BMI resin. Rare studies have reported such tremendous enhancements on the mechanical properties of the BMI resin with trace amounts of fillers. This is attributable to the unique layered structure of NH₂-rGO/WS₂ nanoparticles, fine interfacial adhesion, and uniform dispersion of NH₂-rGO/WS₂ in the BMI resin. Besides, the thermal gravimetrical analysis (TGA) revealed that the addition of NH₂-rGO/WS₂ could also improve the stability of the composites.
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http://dx.doi.org/10.3390/polym10111199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6290598PMC
October 2018

Unprecedented Multicolor Photoluminescence from Hyperbranched Poly(amino ester)s.

Macromol Rapid Commun 2019 Sep 2;40(17):e1800658. Epub 2019 Jan 2.

MOE Key Laboratory of Space Applied Physics and Chemistry, Shaanxi Key Laboratory of Macromolecular Science and Technology, School of Science, Northwestern Polytechnical University, Xi'an, 710072, P. R. China.

A novel kind of water-soluble fluorescent hyperbranched poly(amino ester) (PAE) is prepared through a one-pot polycondensation reaction of citric acid (CA) and N-methyldiethanolamine (NMDEA). The PAE exhibits enhanced and red-shift fluorescence with increasing solution concentration, showing distinct aggregation-induced emission character. Interestingly, the resulting PAE exhibits tunable photoluminescence from blue, cyan, and green to red irradiated by altering the excitation wavelengths. Such unique emission of non-conjugated PAE is attributed to the clustering of ester and tertiary amine groups derived from PAE self-assembly aggregates. Moreover, the fluorescence of PAE is very sensitive to Fe ions. The facile preparation and unique optical features make PAE potentially useful in numerous applications such as multicolor cellular imaging, Fe ions probe, and light-emitting diodes.
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http://dx.doi.org/10.1002/marc.201800658DOI Listing
September 2019

Diallyl disulfide down-regulates calreticulin and promotes C/EBPα expression in differentiation of human leukaemia cells.

J Cell Mol Med 2019 01 5;23(1):194-204. Epub 2018 Nov 5.

Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, Hunan, China.

Diallyl disulfide (DADS), the main active component of the cancer fighting allyl sulfides found in garlic, has shown potential as a therapeutic agent in various cancers. Previous studies showed DADS induction of HL-60 cell differentiation involves down-regulation of calreticulin (CRT). Here, we investigated the mechanism of DADS-induced differentiation of human leukaemia cells and the potential involvement of CRT and CCAAT enhancer binding protein-α (C/EBPα). We explored the expression of CRT and C/EBPα in clinical samples (20 healthy people and 19 acute myeloid leukaemia patients) and found that CRT and C/EBPα expressions were inversely correlated. DADS induction of differentiation of HL-60 cells resulted in down-regulated CRT expression and elevated C/EBPα expression. In severe combined immunodeficiency mice injected with HL-60 cells, DADS inhibited the growth of tumour tissue and decreased CRT levels and increased C/EBPα in vivo. We also found that DADS-mediated down-regulation of CRT and up-regulation of C/EBPα involved enhancement of reactive oxidative species. RNA immunoprecipitation revealed that CRT bound C/EBPα mRNA, indicating its regulation of C/EBPα mRNA degradation by binding the UG-rich element in the 3' untranslated region of C/EBPα. In conclusion, the present study demonstrates the C/EBPα expression was correlated with CRT expression in vitro and in vivo and the molecular mechanism of DADS-induced leukaemic cell differentiation.
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http://dx.doi.org/10.1111/jcmm.13904DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6307788PMC
January 2019

The Molecular Mechanism of Alpha-Synuclein Dependent Regulation of Protein Phosphatase 2A Activity.

Cell Physiol Biochem 2018 11;47(6):2613-2625. Epub 2018 Jul 11.

Department of Neurobiology, Beijing Institute of Brain Disorders, Capital Medical University, Key Laboratory for Neurodegenerative Disease of the Ministry of Education, Beijing Key Laboratory of Neural Regeneration and Repairing, Beijing Key Laboratory of Brain Major Disorders-State Key Lab Incubation Base, Beijing Neuroscience Disciplines, Beijing, China.

Background/aims: Alpha-synuclein (α-Syn) is a neuronal protein that is highly implicated in Parkinson's disease (PD), and protein phosphatase 2A (PP2A) is an important serine/threonine phosphatase that is associated with neurodegenerative diseases, such as PD. α-Syn can directly upregulate PP2A activity, but the underling mechanism remains unclear. Therefore, we investigated the molecular mechanism of α-Syn regulating PP2A activity.

Methods: α-Syn and its truncations were expressed in E.coli, and purified by affinity chromatography. PP2A Cα and its mutants were expressed in recombinant baculovirus, and purified by affinity chromatography combined with gel filtration chromatography. The interaction between α-Syn and PP2A Cα was detected by GST pull-down assay. PP2A activity was investigated by the colorimetric assay.

Results: The hydrophobic non-amyloid component (NAC) domain of α-Syn interacted with PP2A Cα and upregulated its activity. α-Syn aggregates reduced its ability to upregulate PP2A activity, since the hydrophobic domain of α-Syn was blocked during aggregation. Furthermore, in the hydrophobic center of PP2A Cα, the residue of I123 was responsible for PP2A to interact with α-Syn, and its hydrophilic mutation blocked its interaction with α-Syn as well as its activity upregulation by α-Syn.

Conclusions: α-Syn bound to PP2A Cα by the hydrophobic interaction and upregulated its activity. Blocking the hydrophobic domain of α-Syn or hydrophilic mutation on the residue I123 in PP2A Cα all reduced PP2A activity upregulation by α-Syn. Overall, we explored the mechanism of α-Syn regulating PP2A activity, which might offer much insight into the basis underlying PD pathogenesis.
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http://dx.doi.org/10.1159/000491657DOI Listing
August 2018
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