Publications by authors named "Chunyan Zhao"

183 Publications

A general RNA force field: comprehensive analysis of energy minima of molecular fragments of RNA.

J Mol Model 2021 Apr 26;27(5):137. Epub 2021 Apr 26.

School of Information Science & Engineering, Lanzhou University, No. 222 South Tianshui Road, Lanzhou, 730000, China.

Force fields are actively used to study RNA. Development of accurate force fields relies on a knowledge of how the variation of properties of molecules depends on their structure. Detailed scrutiny of RNA's conformational preferences is needed to guide such development. Towards this end, minimum energy structures for each of a set of 16 small RNA-derived molecules were obtained by geometry optimization at the HF/6-31G(d,p), B3LYP/apc-1, and MP2/cc-pVDZ levels of theory. The number of minima computed for a given fragment was found to be related to both its size and flexibility. Atomic electrostatic multipole moments of atoms occurring in the [HO-P(O)-CH-] fragment of 30 sugar-phosphate-sugar geometries were calculated at the HF/6-31G(d,p) and B3LYP/apc-1 levels of theory, and the transferability of these properties between different conformations was investigated. The atomic multipole moments were found to be highly transferable between different conformations with small standard deviations. These results indicate necessary elements of the development of accurate RNA force fields.
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http://dx.doi.org/10.1007/s00894-021-04746-9DOI Listing
April 2021

Comparison of the caregivers' and community health professionals' views on home health care services for disabled older adults: a cross-sectional study in Beijing, China.

BMC Health Serv Res 2021 Apr 26;21(1):389. Epub 2021 Apr 26.

School of General Practice and Continuing Education, Capital Medical University, Beijing, 100069, China.

Background: In an era of an increasingly ageing society, part of healthcare for older adults can be provided in patients' homes, and the need for home health care services (HHCSs) is increasing. This study sought to determine whether a gap exists between the views of community health professionals and the caregivers of disabled older adults towards HHCSs in Beijing, China.

Methods: A cross-sectional study with two comparative questionnaire surveys was conducted in Beijing, China. One survey was administered to the caregivers of disabled older adults, and the other was administered to health professionals in community health service institutions (CHSIs). T-tests and Wilcoxon signed-rank tests were used to explore potential differences between the views of caregivers and community health professionals towards HHCSs.

Results: We received 370 valid questionnaires from caregivers and 224 questionnaires from health professionals. Of the 370 caregivers, 314 (84.9%) were willing to apply for HHCSs for the older adults, but only 20.5% (N = 76) received HHCSs. Over 80% of the caregivers accepted out-of-pocket costs less than 100 yuan per visit. Caregivers' demands on home nursing services were significantly higher than those of health guidance services (Z = - 7.725, P < 0.001). Most of the 224 health professionals chose "health professionals' personal safety cannot be guaranteed" as a problem limiting the provision of HHCSs (N = 151, 40.8%). The health professionals' attitudes towards home nursing services were significantly less positive than those towards health guidance services (Z = - 10.081, P < 0.001). For home nursing services, health professionals' attitude scores were lower than the caregivers' demand scores (Z = - 4.960, P < 0.001), while for health guidance services, health professionals' attitude scores were higher than the caregivers' demand scores (Z = - 8.373, P < 0.001).

Conclusions: Gaps exist between the views of caregivers and health professionals on HHCSs. Compared to health professionals with a higher willingness to provide health guidance services, caregivers need home nursing services. Feasible policies should be implemented to safeguard the rights and interests of health professionals, and qualified health professionals should be trained for HHCSs.
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http://dx.doi.org/10.1186/s12913-021-06400-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077684PMC
April 2021

CHOP Increases TRIB3-Dependent miR-208 Expression to Potentiate Vascular Smooth Muscle Cell Proliferation and Migration by Downregulating TIMP3 in Atherosclerosis.

Cardiovasc Drugs Ther 2021 Apr 15. Epub 2021 Apr 15.

Department of Physiology, College of Basic Medical Sciences, Jilin University, No. 126, Xinmin Street, Changchun, 130021, Jilin Province, People's Republic of China.

Background: C/EBP homologous protein (CHOP) has been identified as a suitable therapeutic target to combat atherosclerosis but the mechanism has not been fully studied. Here, we sought to define the role and underlying mechanism of CHOP in atherosclerosis.

Methods: Mouse models of atherosclerosis in ApoE mice were established by high-fat feeding, where miR-208 expression was determined. Then atherosclerotic plaque tissues were isolated from the model mice. Loss- and gain-function assays were performed on trypsinized vascular smooth muscle cells (VSMCs) to test the in vitro effect of CHOP in controlling the tribbles homologue 3 (TRIB3)/microRNA-208 (miR-208)/tissue inhibitor of metalloproteinases-3 (TIMP3) axis in atherosclerosis by determining cell proliferation and migration as well as blood lipid levels. Moreover, expression of α-smooth muscle actin (α-SMA) and type I collagen expression was determined using immunofluorescence staining to assess plaque stability in mice.

Results: miR-208 expression was elevated in atherosclerosis samples and miR-208 overexpression promoted proliferation and migration of VSMCs but diminished plaque stability in mice. TIMP3 was targeted by miR-208, which could be abrogated by upregulation of TIMP3. In addition, CHOP increased TRIB3 expression to upregulate miR-208 and to downregulate TIMP3, which potentiated VSMC proliferation and migration in vitro and in vivo.

Conclusion: Taken together, inhibition of CHOP may inhibit the proliferation and migration of VSMCs as well as reduce the levels of TC, TG, and LDL-C but increase the level of HDL-C through the TRIB3/miR-208/TIMP3 axis, thereby inhibiting the progression of atherosclerosis.
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http://dx.doi.org/10.1007/s10557-021-07154-6DOI Listing
April 2021

24 h urinary creatinine excretion during pregnancy and its application in appropriate estimation of 24 h urinary iodine excretion.

J Trace Elem Med Biol 2021 Jul 26;66:126751. Epub 2021 Mar 26.

Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, National Health and Family Planning Commission & Education Bureau of Heilongjiang Province, Key Laboratory of Etiology and Epidemiology (23618504), Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Harbin, 150086 Heilongjiang, China. Electronic address:

Background: Urinary creatinine can be used to adjust urinary iodine to evaluate iodine nutritional status during pregnancy. However, the reference intervals and impact factors of urinary creatinine are unknown.

Methods: 24 h urine creatinine concentration (24 hUCr) and spot UCr at four different time periods of the day of pregnant women from Part 1 (n = 743) were measured. Linear regression analysis was performed to identify the impact factors of 24 h urinary creatinine excretion (24 hUCrE) and obtain the estimated 24 h urinary creatinine excretion (24 hUCrE). Then measured urinary iodine concentration (UIC) of 24 h and at fasting of pregnant women from Part 2 (n = 325), used spot urinary iodine to creatinine concentration ratio (UIC/UCr) and 24 hUCrE to calculate the estimated 24 h urinary iodine excretion (24 hUIE), finally checked the consistency and correlation of 24 hUIE and 24 h urinary iodine excretion (24 hUIE).

Results: In Part 1, the median 24 hUCrE was 1.24(IQR0.98-1.76)g, and the reference interval was 0.61-2.93 g. The median 24 hUCr was 0.76 (IQR0.57-1.01)g/L, and the reference interval was 0.36-1.88 g/L. Multiple linear regression results showed that pregnancy weight was an influencing factor to 24 hUCrE after adjusting by gestational weeks, age, pre-pregnancy BMI, and percentage of body fat (F = 45.029, p<0.001). In Part 2, there was no statistically significant difference between 24 hUIE and 24 hUIE (Z =-0.767, p = 0.443). Using 24hUIE as the gold standard, the relative average difference in 24hUIE was 4.2 %, the relative average differences for UIC and UIC/UCr were 32.4 % and 37.2 %. The reference interval of 24 hUIE and 24 hUIE were 88.43-585.90 μg and 50.97-700.39 μg, respectively.

Conclusions: The reference intervals of 24 hUCrE, spot UCr, 24 hUIE, and 24 hUIE during pregnancy were established. 24 hUCrE has important application value in iodine nutrition evaluation to gain more lead time for pregnant women with iodine nutrition-related diseases.
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http://dx.doi.org/10.1016/j.jtemb.2021.126751DOI Listing
July 2021

Genome-wide estrogen receptor β chromatin binding in human colon cancer cells reveals its tumor suppressor activity.

Int J Cancer 2021 Mar 22. Epub 2021 Mar 22.

Department of Protein Science, Science for Life Laboratory, KTH Royal Institute of Technology, Solna, Sweden.

Colorectal cancer (CRC) is the third leading cause of cancer death in the western world. In women, menopausal hormone therapy has been shown to reduce CRC incidence by 20%. Studies demonstrate that estrogen activating estrogen receptor beta (ERβ) protects against CRC. ERβ is a nuclear receptor that regulates gene expression through interactions with the chromatin. This molecular mechanism is, however, not well characterized in colon. Here, we present for the first time, the cistrome of ERβ in different colon cancer cell lines. We use cell lines engineered to express ERβ, optimize and validate an ERβ antibody for chromatin-immunoprecipitation (ChIP), and perform ChIP-Seq. We identify key binding motifs, including ERE, AP-1, and TCF sites, and we determine enrichment of binding to cis-regulatory chromatin sites of genes involved in tumor development, cell migration, cell adhesion, apoptosis, and Wnt signaling pathways. We compare the corresponding cistromes of colon and breast cancer and find that they are conserved for about a third of genes, including GREB1, but that ERβ tethering to TCF and KLF family motifs is characteristic for colon. We exemplify upregulation of putative CRC tumor suppressor gene CST5 where ERβ in colon cells binds to cis-regulatory regions nearby (-351 bp) the transcriptional start site. Our work provides a foundation for understanding the mechanism of action of ERβ in CRC prevention.
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http://dx.doi.org/10.1002/ijc.33573DOI Listing
March 2021

Integrative analysis regarding the correlation between GAS2 family genes and human glioma prognosis.

Cancer Med 2021 04 12;10(8):2826-2839. Epub 2021 Mar 12.

Department of Biochemistry and Molecular Biology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.

Background: Emerging oncogenes were reportedly linked to the complicated subtypes and pathogenesis of clinical gliomas. Herein, we first comprehensively explored the potential correlation between growth-arrest-specific two family genes (GAS2, GAS2L1, GAS2L2, GAS2L3) and gliomas by bioinformatics analysis and cellular experiments.

Methods: Based on the available datasets of TCGA (The Cancer Genome Atlas), CGGA (Chinese Glioma Genome Atlas), and Oncomine databases, we performed a series of analyses, such as gene expression, survival prognosis, DNA methylation, immune infiltration, and partner enrichment. We also utilized two glioma cell lines to conduct the colony formation and wound-healing assay.

Results: GAS2L3 gene was highly expressed in glioma tissues compared to normal brain tissues (p < 0.05). We further observed the relationship between the high expressed GAS2L3 and poor clinical prognosis of brain low-grade glioma (LGG) cases in our Cox proportional hazard model (hazard ratio [HR] = 0.1715, p < 0.001). Moreover, DNA hypomethylation status of GAS2L3 was correlated with the high expression of GAS2L3 in LGG tissues and the poor clinical prognosis of primary glioma cases (p < 0.05). We also found that the high expression of GAS2L3 was associated with the infiltration level of immune cells, especially the T cells (p < 0.0001). Functional enrichment analysis of GAS2L3-correlated genes and interaction partners further indicated that GAS2L3 might take part in the occurrence of glioma by influencing a series of biological behaviors, such as cell division, cytoskeleton binding, and cell adhesion. Additionally, our cellular experiment data suggested that a highly expressed GAS2L3 gene contributes to the enhanced proliferation and migration of glioma cells.

Conclusion: This study first analyzed the potential role of GAS2 family genes, especially GAS2L3, in the clinical prognosis and possible functional mechanisms of glioma, which gives a novel insight into the relationship between GAS2L3 and LGG.
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http://dx.doi.org/10.1002/cam4.3829DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026934PMC
April 2021

Blocking Fra-1 sensitizes triple-negative breast cancer to PARP inhibitor.

Cancer Lett 2021 May 27;506:23-34. Epub 2021 Feb 27.

Department of Biosciences and Nutrition, Karolinska Institutet, S-141 83 Huddinge, Sweden; Science for Life Laboratory, Department of Protein Science, CBH, KTH Royal Institute of Technology, Solna, Sweden. Electronic address:

The AP-1 member Fra-1 is overexpressed in TNBC and plays crucial roles in tumor progression and treatment resistance. In a previous large-scale screen, we identified PARP1 to be among 118 proteins that interact with endogenous chromatin-bound Fra-1 in TNBC cells. PARP1 inhibitor (olaparib) is currently in clinical use for treatment of BRCA-mutated TNBC breast cancer. Here, we demonstrate that the Fra-1-PARP1 interaction impacts the efficacy of olaparib treatment. We show that PARP1 interacts with and downregulates Fra-1, thereby reducing AP-1 transcriptional activity. Olaparib treatment, or silencing of PARP1, consequently, increases Fra-1 levels and enhances its transcriptional activity. Increased Fra-1 can have adverse effect, including treatment resistance. We also found that a large fraction of PARP1-regulated genes was dependent on Fra-1. We show that by inhibiting Fra-1/AP-1, non-BRCA-mutated TNBC cells can become sensitized to olaparib treatment. We identify that high PARP1 expression is indicative of a poor clinical outcome in breast cancer patients overall (P = 0.01), but not for HER-2 positive patients. In conclusion, by exploring the functionality of the Fra-1 and PARP1 interaction, we propose that targeting Fra-1 could serve as a combinatory therapeutic approach to improve olaparib treatment outcome for TNBC patients.
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http://dx.doi.org/10.1016/j.canlet.2021.02.018DOI Listing
May 2021

Effect of short-chain chlorinated paraffins (SCCPs) on lipid membranes: Combination of molecular dynamics and membrane damage experiments.

Sci Total Environ 2021 Jun 3;775:144906. Epub 2021 Feb 3.

School of Pharmacy, Lanzhou University, Lanzhou 730000, China. Electronic address:

In recent years, more attention has been paid to the biological effects of short-chain chlorinated paraffin (SCCP). Studies have shown that SCCPs exposure could cause metabolic damage and lipid metabolic damage. In the present work, based on E. coli membrane damage experiments and molecular dynamics (MD) simulation, the effects of SCCPs on the membrane structure and membrane properties were studied to explore the possible toxic damage effects of SCCPs on cell membrane. Experiments results showed that SCCPs had a significant inhibitory effect on E. coli. The E. coli cell membrane of the bacteria was broken and the macromolecules of the cell flowed out when exposed to SCCPs. SCCPs would lead to the decrease and depolarization of cell membrane potential, and then affect the integrity and permeability of cell membrane. The further molecular dynamic simulation revealed that SCCP molecules can easily enter the lipid DPPC membranes from the aqueous phase and tended to aggregate inside bilayer stably. The bound of SCCPs could lead to significant variations in DPPC bilayer with a less dense, more disorder and rougher layer, which thus made the damage of cell membrane. In a word, although the overall toxicity of SCCPs to cell was relatively weak, the damage to the cell membrane may be one of the mechanisms of its toxicity. MAIN FINDING OF THE WORK: The exposure of SCCPs could cause structural change of cell membrane in E. coli, which verified the damage to the cell membrane may be one of the mechanisms of its toxicity.
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http://dx.doi.org/10.1016/j.scitotenv.2020.144906DOI Listing
June 2021

Echinacoside Suppresses Amyloidogenesis and Modulates F-actin Remodeling by Targeting the ER Stress Sensor PERK in a Mouse Model of Alzheimer's Disease.

Front Cell Dev Biol 2020 19;8:593659. Epub 2020 Nov 19.

Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China.

Endoplasmic reticulum stress (ERS) plays a vital and pathogenic role in the onset and progression of Alzheimer's disease (AD). Phosphorylation of PKR-like endoplasmic reticulum kinase (PERK) induced by ERS depresses the interaction between actin-binding protein filamin-A (FLNA) and PERK, which promotes F-actin accumulation and reduces ER-plasma membrane (PM) communication. Echinacoside (ECH), a pharmacologically active component purified from , exhibits multiple neuroprotective activities, but the effects of ECH on ERS and F-actin remodeling remain elusive. Here, we found ECH could inhibit the phosphorylation of PERK. Firstly ECH can promote PERK-FLNA combination and modulate F-actin remodeling. Secondly, ECH dramatically decreased cerebral Aβ production and accumulation by inhibiting the translation of BACE1, and significantly ameliorated memory impairment in 2 × Tg-AD mice. Furthermore, ECH exhibited high affinity to either mouse PERK or human PERK. These findings provide novel insights into the neuroprotective actions of ECH against AD, indicating that ECH is a potential therapeutic agent for halting and preventing the progression of AD.
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http://dx.doi.org/10.3389/fcell.2020.593659DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717986PMC
November 2020

Differential genetic mutations of ectoderm, mesoderm, and endoderm-derived tumors in TCGA database.

Cancer Cell Int 2020 Dec 11;20(1):595. Epub 2020 Dec 11.

Department of Biochemistry and Molecular Biology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Heping District Qixiangtai Road No.22, Tianjin, 300070, People's Republic of China.

Background: In terms of biological behavior, gene regulation, or signaling pathways, there is a certain similarity between tumorigenesis and embryonic development of humans. Three germ layer structure exhibits the distinct ability to form specific tissues and organs.

Methods: The present study set out to investigate the genetic mutation characteristics of germ layer differentiation-related genes using the tumor cases of the cancer genome atlas (TCGA) database.

Results: These tumor samples were divided into three groups, including the ectoderm, mesoderm, and endoderm. Children cases less than 9 years old accounted for a larger proportion for the cases in the ectoderm and mesoderm groups; whereas the middle-aged and elderly individuals (from 50 to 89 years old) were more susceptible to tumors of endoderm. There was a better prognosis for the cases of mesoderm, especially the male with the race of White, compared with the other groups. A missense mutation was frequently detected for the cases of ectoderm and endoderm, while deletion mutation was common for that of mesoderm. We could not identify the ectoderm, mesoderm, or endoderm-specific mutated genes or variants with high mutation frequency. However, there was a relatively higher mutation incidence of endoderm markers (GATA6, FOXA2, GATA4, AFP) in the endoderm group, compared with the groups of ectoderm and mesoderm. Additionally, four members (SMO, GLI1, GLI2, GLI3) within the Hedgehog signaling pathway genes showed a relatively higher mutation rate in the endoderm group than the other two groups.

Conclusions: TCGA tumors of ectoderm, mesoderm, and endoderm groups exhibit the distinct subject distribution, survival status, and genomic alteration characteristics. The synergistic mutation effect of specific genes closely related to embryonic development may contribute to the tumorigenesis of tissues or organs derived from the specific germ layers. This study provides a novel reference for exploring the functional connection between embryogenesis and tumorigenesis.
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http://dx.doi.org/10.1186/s12935-020-01678-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730784PMC
December 2020

Sargassum blooms in the East China Sea and Yellow Sea: Formation and management.

Mar Pollut Bull 2021 Jan 19;162:111845. Epub 2020 Nov 19.

College of Marine Ecology and Environment, Shanghai Ocean University, No. 999, Huchenghuan Road, Pudong New District, 201306 Shanghai, China. Electronic address:

Large-scale Sargassum blooms, known as golden tides, have been occurring along the coast of the Yellow Sea in recent years, resulting in an enormous loss of Pyropia yezoensis production. To locate the source of the blooms, we performed large-scale spatio-temporal sampling in the South Yellow Sea, East China Sea, and Jeju Island, South Korea. Based on morphology and molecular traits, the attached and floating Sargassum samples collected from the three regions were all identified as Sargassum horneri, although slight differences were observed in morphology among samples. Genetic distance and automatic barcode gap discovery analysis revealed very low genetic diversity among the three regions. The 33 samples from 12 sites were divided into six haplotypes, and the samples from the ECS shared more haplotypes than samples from other two regions. Our results suggested that S. horneri in the ECS was responsible for the formation of blooms in the Yellow Sea.
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http://dx.doi.org/10.1016/j.marpolbul.2020.111845DOI Listing
January 2021

The ZiBuPiYin recipe regulates proteomic alterations in brain mitochondria-associated ER membranes caused by chronic psychological stress exposure: Implications for cognitive decline in Zucker diabetic fatty rats.

Aging (Albany NY) 2020 11 18;12(23):23698-23726. Epub 2020 Nov 18.

Department of Emergency Medicine, Zhongshan Hospital, Dalian University, Dalian 116001, China.

Chronic psychological stress (PS) cumulatively affects memory performance through the deleterious effects on hypothalamic-pituitary-adrenal axis regulation. Several functions damaged in cognitive impairment-related diseases are regulated by mitochondria-associated ER membranes (MAMs). To elucidate the role of ZiBuPiYin recipe (ZBPYR) in regulating the MAM proteome to improve PS-induced diabetes-associated cognitive decline (PSD), differentially expressed MAM proteins were identified among Zucker diabetic fatty rats, PSD rats, and PS combined with ZBPYR administration rats via iTRAQ with LC-MS/MS. Proteomic analysis revealed that the expressions of 85 and 33 proteins were altered by PS and ZBPYR treatment, respectively. Among these, 21 proteins were differentially expressed under both PS and ZBPYR treatments, whose functional categories included energy metabolism, lipid and protein metabolism, and synaptic dysfunction. Furthermore, calcium signaling and autophagy-related proteins may play roles in the pathogenesis of PSD and the mechanism of ZBPYR, respectively. Notably, KEGG pathway analysis suggested that 'Alzheimer's disease' and 'oxidative phosphorylation' pathways may be impaired in PSD pathogenesis, while ZBPYR could play a neuroprotective role through regulating the above pathways. Overall, exposure to chronic PS contributes to the evolution of diabetes-associated cognitive decline and ZBPYR might prevent and treat PSD by regulating the MAM proteome.
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http://dx.doi.org/10.18632/aging.103894DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762487PMC
November 2020

A polyoxometalate-encapsulated nanocage cluster organic framework built from {CuP} units and its efficient bifunctional electrochemical performance.

Chem Commun (Camb) 2020 Dec;56(96):15177-15180

College of Materials Science and Engineering, Key Laboratory of Polymeric Composite Materials of Heilongjiang Province, Qiqihar University, Qiqihar 161006, P. R. China.

The first polyoxometalate (POM)-encapsulated twenty-four-nucleus organophosphorus-copper nanocage cluster organic framework has been constructed. Here, the phosphomolybdate POMs were incorporated into an octahedral nanocage cluster organic framework, and the resulting material exhibited highly efficient bifunctional electrochemical performance. The crystalline material showed a high specific capacitance of 366.3 F g-1 at a current density of 3 A g-1.
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http://dx.doi.org/10.1039/d0cc06665fDOI Listing
December 2020

Characterization and Genomic Analysis of Escherichia coli O157:H7 Bacteriophage FEC14, a New Member of Genus Kuttervirus.

Curr Microbiol 2021 Jan 13;78(1):159-166. Epub 2020 Nov 13.

Department of Pathogenobiology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin, People's Republic of China.

Escherichia coli O157:H7 is an important foodborne pathogen that has become a major worldwide factor affecting the public safety of food. Bacteriophage has gradually attracted attention because of its ability to kill specific pathogens. In this study, a lytic phage of E. coli O157:H7, named FEC14, was isolated from hospital sewage. Transmission electron microscopy analysis showed that phage FEC14 had an isometric head 80 ± 5 nm in diameter and a contractile tail whose terminal spikes present an umbrella-like structure. Phage FEC14 revealed 158,639 bp double-stranded DNA, with the G+C content of 44.6%, 209 ORFs and four tRNAs. Genome DNA of FEC14 could not be digested by some endonucleases. Many of the features of phage FEC14 are very similar to those of the newly classified genus "Kuttervirus", including morphology, genome size and organization, etc. Phage FEC14 is proposed to be a new isolate of genus "Kuttervirus" within the family Ackermannviridae, moreover, the endonuclease resistance of phage FEC14, has priority over other genera of bacteriophages for its use in biocontrol of foodborne pathogens.
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http://dx.doi.org/10.1007/s00284-020-02283-xDOI Listing
January 2021

Growth arrest-specific 2 protein family: Structure and function.

Cell Prolif 2021 Jan 25;54(1):e12934. Epub 2020 Oct 25.

Department of Biochemistry and Molecular Biology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.

Members of the growth arrest-specific 2 (GAS2) protein family consist of a putative actin-binding (CH) domain and a microtubule-binding (GAR) domain and are considered miniversions of spectraplakins. There are four members in the GAS2 family, viz. GAS2, GAS2L1, GAS2L2 and GAS2L3. Although GAS2 is defined as a family of growth arrest-specific proteins, the significant differences in the expression patterns, interaction characteristics and biological issues or diseases among the different GAS2 family members have not been systemically reviewed to date. Therefore, we summarized the available evidence on the structures and functions of GAS2 family members. This review facilitates a comprehensive molecular understanding of the involvement of the GAS2 family members in an array of biological processes, including cytoskeleton reorganization, cell cycle, apoptosis and cancer development.
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http://dx.doi.org/10.1111/cpr.12934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791176PMC
January 2021

Interaction of BDE-47 with nuclear receptors (NRs) based on the cytotoxicity: In vitro investigation and molecular interaction.

Ecotoxicol Environ Saf 2021 Jan 10;208:111390. Epub 2020 Oct 10.

POPs Lab, Shenzhen Center for Disease Control and Prevention, Shenzhen 518055, China. Electronic address:

Polybrominated diphenyl ethers (PBDEs) are endocrine-disrupting chemicals that possess neuroendocrine and reproductive toxicity to humans and disturb thyroid hormone homeostasis, neurobehavior, and development. The most predominant congener of PBDEs in humans and other organisms is 2,2',4,4'-tetrabromodiphenyl ether (BDE-47); however, the molecular mechanisms underlying its cytotoxicity remain largely unknown. Here, we evaluated the toxic effect and underlying mechanism of nuclear receptors (NRs) induced by BDE-47 in SK-N-SH human neuroblastoma cells. The CCK-8 cell viability assay showed that the proliferation of human SK-N-SH cells exposed to BDE-47 was significantly inhibited in time- and dose-dependent manners, and flow cytometry showed that cell cycle was arrested at the S phase after BDE-47 exposure. Moreover, compared with the control group, the expression of retinoic acid receptor alpha (RXRα), pregnane X receptor (PXR), thyroid hormone receptors (TRs), and peroxisome proliferator-activated receptors (PPARs) at the mRNA and protein levels was significantly increased, as determined by quantitative PCR and western blot analysis, demonstrating that BDE-47 activated the NRs in vitro. Moreover, BDE-47 could bind to all four NRs in the affinity order of PPARγ > PXR > TRβ > RXRα under molecular dynamics. Because RXR is the promiscuous dimerization partner for a large number of NRs, ZDock was used to calculate its interaction with other three NRs. Taking the number of hydrogen bonds and ZDock scores into account, the rank of docking ability between RXRα and the NRs was PXR > TRβ > PPARγ. Further analysis of the interaction between BDE-47 and dimerized-NRs, the affinity order was RXRα > TRβ > PXR > PPARγ via Glide. The results of this study demonstrated that BDE-47 interfered the cross-talk among NRs, especially the promiscuous RXRα, which might be critical for the harmonized re-adjustment of cytotoxicity and biological regulation. Our findings provide a better understanding of the mechanisms underlying toxic effects and intermolecular interaction induced by BDE-47.
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http://dx.doi.org/10.1016/j.ecoenv.2020.111390DOI Listing
January 2021

The peptidyl-prolyl isomerases FKBP15-1 and FKBP15-2 negatively affect lateral root development by repressing the vacuolar invertase VIN2 in Arabidopsis.

Planta 2020 Sep 18;252(4):52. Epub 2020 Sep 18.

Department of Plant Science, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, 200240, China.

Main Conclusion: The peptidyl-prolyl isomerases FKBP15-1 and FKBP15-2 negatively modulate lateral root development by repressing vacuolar invertase VIN2 activity. Lateral root (LR) architecture greatly affects the efficiency of nutrient absorption and the anchorage of plants. Although the internal phytohormone regulatory mechanisms that control LR development are well known, how external nutrients influence lateral root development remains elusive. Here, we characterized the function of two FK506-binding proteins, namely, FKBP15-1 and FKBP15-2, in Arabidopsis. FKBP15-1/15-2 genes were expressed prominently in the vascular bundles of the root basal meristem region, and the FKBP15-1/15-2 proteins were localized to the endoplasmic reticulum of the cells. Using IP-MS, Co-IP, and BiFC assays, we demonstrated that FKBP15-1 and FKBP15-2 interacted with vacuolar invertase 2 (VIN2). Compared to Col-0 and the single mutants, the fkbp15-1fkbp15-2 double mutant had more LRs, and presented higher sucrose catalytic activity. Moreover, genetic analysis showed genetic epistasis of VIN2 over FKBP15-1/FKBP15-2 in controlling LR development. Our results indicate that FKBP15-1 and FKBP15-2 participate in the control of LR number by inhibiting the catalytic activity of VIN2. Owing to the conserved peptidylprolyl cis-trans isomerase activity of FKBP family proteins, our results provide a clue for further analysis of the interplay between lateral root development and protein modification by FKBPs.
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http://dx.doi.org/10.1007/s00425-020-03459-2DOI Listing
September 2020

Arabidopsis NRT1.2 interacts with the PHOSPHOLIPASE Dα1 (PLDα1) to positively regulate seed germination and seedling development in response to ABA treatment.

Biochem Biophys Res Commun 2020 11 12;533(1):104-109. Epub 2020 Sep 12.

Plant Biotechnology Research Center, School of Agriculture and Life Sciences, Shanghai Jiao Tong University, Shanghai, 200240, China. Electronic address:

NRT1.2 has been characterized as a low-affinity nitrate transporter and an abscisic acid (ABA) transporter in Arabidopsis. In this study, we demonstrate that NRT1.2 positively regulated the ABA response during germination and seedling development. The transgenic Arabidopsis NRT1.2-over-expressionors showed increased sensitivity to ABA during these processes. qRT-PCR assays indicated that NRT1.2 over-production in 7-days-old seedlings up-regulated the expression of ABA-responsive genes: ABI1, ABI2, ABI3, ABI4, ABI5, RAB18, RD29A, and RD29B and PHOSPHOLIPASE Dα1 (PLDα1). The expression of these genes was suppressed in the nrt1.2 mutant in comparison with the wild type following ABA treatment. Importantly, bimolecular fluorescence complementation assays indicated that NRT1.2 interacts with PLDα1 at the plasma membrane. Their interaction was further confirmed by using yeast two hybrid (Y2H) experiments with the mating-based split ubiquitin system (MbSUS). Moreover, genetic assays indicated that PLDα1 acts epistatically on NRT1.2 to affect ABA signaling. Taken together, our results provide detailed mechanisms of NRT1.2 in ABA-mediated seed germination and seedling development.
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http://dx.doi.org/10.1016/j.bbrc.2020.08.025DOI Listing
November 2020

Effect of inlet temperature on the physicochemical properties of spray-dried seed-watermelon seed protein powder.

J Food Sci 2020 Oct 14;85(10):3442-3449. Epub 2020 Sep 14.

College of Food Science, Shenyang Agricultural University, Shenyang, 110866, P. R. China.

Here, we studied the effects of inlet temperature on the physicochemical properties of the hydrolyzed protein (seed-watermelon seed hydrolyzed protein [SWSP]) powder in seed-watermelon seeds. The inlet temperature of the study was in the range of 150 to 180 °C, and the remaining experimental parameters remained constant, that is, the feed flow rate was 0.2 L/hr, the concentration of maltodextrin was 30%, and the outlet temperature was 80 °C. We studied the water activity and moisture content, bulk density, flowability (Carr index and Hausner ratio), angle of repose, solubility, color, hygroscopicity, powder morphology, particle size, crystallinity, and odor of the sample. Inlet temperature of 170 to 180 °C reduced the moisture content and increased the particle size. It was found that the value of measured water activity was less than 0.5, which helped in maintaining stability of the sample. Powders produced at the temperatures showed smoother particle surfaces, whereas higher inlet temperature showed spherical particles with some shrinkage as analyzed by scanning electron microscope. The inlet temperature affected the color of the sample, thus at high temperature, the sample had a brighter color. The sample was approximately 18% crystalline. At a preparation temperature of 160 °C, the sample showed significant antioxidant activity (P < 0.05).
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http://dx.doi.org/10.1111/1750-3841.15432DOI Listing
October 2020

Fecal microbiota transplantation alters the susceptibility of obese rats to type 2 diabetes mellitus.

Aging (Albany NY) 2020 Sep 12;12(17):17480-17502. Epub 2020 Sep 12.

Department of Emergency Medicine, Zhongshan Hospital, Dalian University, Dalian 116001, China.

Obesity is one of the susceptibility factors for type 2 diabetes (T2DM), both of which could accelerate the aging of the body and bring many hazards. A causal relationship is present between intestinal microbiota and body metabolism, but how the microbiota play a role in the progression of obesity to T2DM has not been elucidated. In this study, we transplanted healthy or obese-T2DM intestinal microbiota to ZDF and LZ rats, and used 16S rRNA and targeted metabonomics to evaluate the directional effect of the microbiota on the susceptibility of obese rats to T2DM. The glycolipid metabolism phenotype could be changed bidirectionally in obese rats instead of in lean ones. One possible mechanism is that the microbiota and metabolites alter the structure of the intestinal tract, and improve insulin and leptin resistance through JAK2 / IRS / Akt pathway. It is worth noting that 7 genera, such as , and can regulate 15 metabolites, such as 3-indolpropionic acid, acetic acid and docosahexaenoic acid, and have a significant improvement on glycolipid metabolism phenotype. Attention to intestinal homeostasis may be the key to controlling obesity and preventing T2DM.
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http://dx.doi.org/10.18632/aging.103756DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521520PMC
September 2020

Fluorodeoxyglucose-avid focal lesions and extramedullary disease on 18F-FDG PET/computed tomography predict the outcomes of newly diagnosed symptomatic multiple myeloma patients.

Nucl Med Commun 2020 Sep;41(9):950-958

Department of Nuclear Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, China.

Purpose: To investigate whether the number of fluorodeoxyglucose (FDG)-avid focal lesions and the presence of extramedullary disease (EMD) on F-FDG PET/computed tomography (PET/CT) can predict the outcomes of newly diagnosed symptomatic multiple myeloma patients.

Methods: We performed a meta-analysis to research the prognostic significance of focal lesions and EMD on F-FDG PET/CT for overall survival (OS) and progression-free survival (PFS) using a fix-effected model. The PubMed, EMBASE and Cochrane Library databases were searched. Manual searches were also conducted.

Results: Of the 398 citations identified in the original search, 13 original studies with a total of 2823 patients met the inclusion criteria. The pooled hazard ratios of focal lesions were 1.63 [95% confidence interval (CI) 1.41-1.86, P = 0.442, I= 0%] for PFS and 2.15 (95% CI 1.74-2.57, P = 0.615, I= 0%) for OS. The pooled hazard ratios of EMD were 1.89 (95% CI 1.44-2.34, P = 0.497, I= 0%) for PFS and 1.91 (95% CI 1.08-2.73, P = 0.182, I= 29.6%) for OS. The results of the subgroup analysis showed the same trend. No significant heterogeneity was observed among studies.

Conclusion: This meta-analysis demonstrated that patients with a higher number of FDG-avid focal lesions and EMD on PET/CT may experience a higher risk for progression and a shorter survival time than those with a few focal lesions and no EMD.
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http://dx.doi.org/10.1097/MNM.0000000000001242DOI Listing
September 2020

IL10-modified Human Mesenchymal Stem Cells inhibit Pancreatic Cancer growth through Angiogenesis Inhibition.

J Cancer 2020 9;11(18):5345-5352. Epub 2020 Jul 9.

Sicuhan Key Laboratory of Medical Imaging, Affiliated Hospital of North Sichuan Medical University 637000, Nanchong, Sichuan Province, China.

In the present study, we constructed the recombinant plasmid IL10-PEGFP-C1 and successfully transfected into human mesenchymal stem cells. After culturing for 72 h, the levels of IL6 and TNF-α in the supernatant of the MSCs-IL10 group were significantly lower than the vector group and the control group (17.6 ± 0.68vs73.8 ± 0.8 and 74.4 ± 1.5) µg/L and (65.05 ± 3.8 vs 203.2 ± 2.4 and 201.3 ± 3.7) µg/L, respectively (p < 0.001) .The animal experiments showed that the volume of subcutaneous tumors in the MSCs-IL10 group was a significantly less level compared to that in MSC control and the blank control groups (76.84 ± 20.11) mm vs (518. 344 ± 48.66) mm, (576.99± 49.88) mm, (P < 0. 05) and they have a longer life time. Further we found the mass concentrations of IL6 and TNF-α in the blood serum of MSC-IL10 group were lower than the vector group and the control group (64.42 ± 10.9 vs120.83 ± 15.52 and 122.65 ± 13.71) and (40.05 ± 5.63 vs 126.78 ±1.89 and 105.83 ± 2.16) µg/L respectively (p < 0.001). CD31 immunohistochemistry and alginate encapsulation experiments showed tumor angiogenesis were inhibited in MSCs-IL10 group in comparison to the control and vector group (P < 0.001), FITC-labeled dextran intake was also lower than the other groups (P < 0.01). Collectively, this study suggested IL10 could inhibit the growth of the transplanted tumor and prolong survival of mice, and the primary mechanism may be the indirect inhibition of pro-inflammatory cytokines IL6 and TNF-α secretion and tumor angiogenesis formation.
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http://dx.doi.org/10.7150/jca.38062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7391191PMC
July 2020

Molecular dynamics exploring of atmosphere components interacting with lung surfactant phospholipid bilayers.

Sci Total Environ 2020 Nov 26;743:140547. Epub 2020 Jun 26.

School of Pharmacy, Lanzhou University, Lanzhou 730000, China. Electronic address:

Sulfur dioxide (SO), nitrogen oxide (NO) and ozone (O) in the atmosphere are significantly correlated with various respiratory and cardiovascular diseases. High doses of each of these gases or a mixture can change the physical and chemical properties of the lung membrane, thus leading to an increased pulmonary vascular permeability and structural failure of the alveolar cell membrane. In the present study, detailed molecular dynamic (MD) modeling was applied to investigate the effects of SO, NO, O and mixtures of these gases on the dipalmitoyl phosphatidylcholine (DPPC) phospholipid bilayer. The results showed that several key physical properties, including the mass density, lipid ordering parameter, lipid diffusion, and electrostatic potential of the cell membrane, have been changed by the binding of different compounds. This resulted in significant variations and more disorder in the DPPC bilayer. The multiple analyses of membrane properties proved the toxicity of NO, O, and SO to the DPPC bilayer, providing a theoretical basis for the experimental phenomenon that SO, NO and O can cause lung cell apoptosis. For the single systems, the damage to DPPC bilayer caused by O was more serious than NO and SO. More importantly, the MD simulations using the mixtures of SO, NO, and O showed a much greater decline of membrane fluidity and the aggravation of membrane damage than the single systems, indicating a synergistic effect when NO, SO, and O coexisted in the atmosphere, which could lead to much more severe damage and greater toxicities to the lung.
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http://dx.doi.org/10.1016/j.scitotenv.2020.140547DOI Listing
November 2020

The Interaction of Isoflavone Phytoestrogens with ERα and ERβ by Molecular Docking and Molecular Dynamics Simulations.

Curr Comput Aided Drug Des 2020 Jul 12. Epub 2020 Jul 12.

School of Pharmacy Lanzhou University, P.O. Box: 730000, Lanzhou. China.

Aim And Objective: Isoflavone phytoestrogens, which commonly present in natural plants, are closely related to human health. The combination of them with estrogen receptors in the body can play a more important role in the prevention and treatment of cardiovascular diseases, cancer, and menopausal diseases. This research is conducted for the wider application of isoflavone phytoestrogens in various fields.

Method: In this study, molecular docking studies and molecular dynamics simulations were performed to explore the affinities and interaction between three typical isoflavone phytoestrogens and estrogen receptors (ERα and ERβ), respectively.

Results And Conclusion: Molecular docking results showed that the affinity of genistein, daidzein and formononetin was different, and the ligand structures and hydrogen bonds force were the main factors affecting the binding abilities. The calculation of the binding free energy shows the stability of the complex and the contribution of various interactions to the binding free energy. The decomposition of binding free energy indicates that van der Waals interaction and electrostatic interaction promote the binding of the complex, which are in agreement with the docking studies.
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http://dx.doi.org/10.2174/1573409916666200712140245DOI Listing
July 2020

A pan-cancer analysis of the oncogenic role of staphylococcal nuclease domain-containing protein 1 (SND1) in human tumors.

Genomics 2020 11 6;112(6):3958-3967. Epub 2020 Jul 6.

Department of Biochemistry and Molecular Biology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China; Key Laboratory of Immune Microenvironment and Disease, Ministry of Education, Key Laboratory of Cellular and Molecular Immunology in Tianjin, Excellent Talent Project, Tianjin Medical University, Tianjin, China. Electronic address:

Although emerging cell- or animal-based evidence supports the relationship between SND1 and cancers, no pan-cancer analysis is available. We thus first explored the potential oncogenic roles of SND1 across thirty-three tumors based on the datasets of TCGA (The cancer genome atlas) and GEO (Gene expression omnibus). SND1 is highly expressed in most cancers, and distinct associations exist between SND1 expression and prognosis of tumor patients. We observed an enhanced phosphorylation level of S426 in several tumors, such as breast cancer or lung adenocarcinoma. SND1 expression was associated with the CD8T-cell infiltration level in colon adenocarcinoma and melanoma, and cancer-associated fibroblast infiltration was observed in other tumors, such as bladder urothelial carcinoma or testicular germ cell tumors. Moreover, protein processing- and RNA metabolism-associated functions were involved in the functional mechanisms of SND1. Our first pan-cancer study offers a relatively comprehensive understanding of the oncogenic roles of SND1 across different tumors.
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http://dx.doi.org/10.1016/j.ygeno.2020.06.044DOI Listing
November 2020

Whole-Body Bone Scintigraphy Helps to Detect Kidney Diseases.

AJR Am J Roentgenol 2021 01 19;216(1):172-185. Epub 2020 Nov 19.

Department of Nuclear Medicine, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, 610041, PR China.

Objective: We conducted this retrospective study to explore whether abnormalities on renal images obtained using whole-body bone scintigraphy (WBS) can help detect renal diseases.

Materials And Methods: Patients who underwent WBS between June 2017 and October 2018 were screened and then underwent a minimum 6-month follow-up, during which their clinical information was tracked. The percentage of different renal abnormalities, diseases, and intervention considerations was calculated.

Results: We screened 4706 WBS examinations, and 486 (10.3%) patients exhibited abnormalities on renal images. The major types of abnormal renal images obtained via WBS included images of diffuse increased uptake (10.9% [53/486]), focal increased uptake (65.6% [319/486]), diffuse decreased uptake (8.0% [39/486]), focal decreased uptake (10.7% [52/486]), heterogeneous uptake (3.3% [16/486]), and small kidney size (1.4% [7/486]). After a 6-month follow-up period, 65.4% (318/486) of our included patients exhibited confirmed kidney abnormalities that included calculus, urine accumulation, cyst, atrophy, severe hydronephrosis, and tumors. Among these patients with confirmed kidney abnormalities, 27.4% (87/318) had newly identified renal abnormalities, 11.9% (38/318) underwent further examinations by clinicians, and 7.9% (25/318) received further intervention and treatment, including surgery and chemotherapy.

Conclusion: Although renal images obtained with WBS could not be used to accurately evaluate kidney conditions, abnormal renal images obtained with WBS may indicate that serious renal problems exist. Therefore, both nuclear medicine physicians and clinicians should pay more attention to renal abnormalities on WBS. Patients with renal abnormalities should undergo dedicated renal examinations with WBS, which may change clinical decision-making.
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http://dx.doi.org/10.2214/AJR.20.22834DOI Listing
January 2021

Determination of allosteric and active sites responsible for catalytic activity of delta 12 fatty acid desaturase from Geotrichum candidum and Mortierella alpina by domain swapping.

Enzyme Microb Technol 2020 Aug 22;138:109563. Epub 2020 Apr 22.

College of Food Science, Shenyang Agricultural University, Shenyang 110866, PR China. Electronic address:

Cheese lacks essential fatty acids (EFAs). Delta 12 fatty acid desaturase (FADS12) is a critical enzyme required for EFA biosynthesis in fermentation of the predominant strains of cheese. Previously, we identified the FADS12 gene and characterized its function for the first time in Geotrichum candidum, a dominant strain used to manufacture soft cheese with white rind. In this study, we analyzed the molecular mechanism of FADS12 function by swapping domains from Mortierella alpina and G. candidum that had, respectively, high and low oleic acid conversion rates. The results revealed three regions that are essential to this process, including regions from the end of the second transmembrane domain to the beginning of the third transmembrane domain, from the end of the third transmembrane domain to the beginning of the fourth transmembrane domain, and from the 30-amino acid from the end of the sixth transmembrane domain to the C-terminal end region. Based on our domain swapping analyses, nine pairs of amino acids including H112, S118, H156, Q161, K301, R306, E307, A309 and S323 in MaFADS12 (K123, A129, N167, M172, T302, D307, I308, E310 and D324 in GcFADS12) were identified as having a significantly effect on FADS12 catalytic efficiency, and linoleic acid and its analogues (12,13-cyclopropenoid fatty acid) were found to inhibit the catalytic activity of FADS12 and related recombinant enzymes. Furthermore, the molecular mechanism of FADS12 inhibition was analyzed. The results revealed two allosteric domains, including one domain from the N-terminal region to the beginning of the first transmembrane domain and another from the 31 amino acid from the end of the sixth transmembrane domain to the C terminus. Y4 and F398 amino acid residues from MaFADS12 and eight pairs of amino acids including G56, L60, L344, G10, Q13, S24, K326 and L344 in MaFADS12 (while Y66, F70, F345, F20, Y23, Y34, F327 and F345 in GcFADS12) played a pivotal role in FADS12 inhibition. Finally, we found that both allosteric and active sites were responsible for the catalytic activity of FADS12 at various temperatures, pH, and times. This study offers a solid theoretical basis to develop preconditioning methods to increase the rate at which GcFADS12 converts oleic and linoleic acids to produce higher levels of EFAs in cheese.
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http://dx.doi.org/10.1016/j.enzmictec.2020.109563DOI Listing
August 2020

Interaction of Coumarin Phytoestrogens with ER and ER: A Molecular Dynamics Simulation Study.

Molecules 2020 Mar 5;25(5). Epub 2020 Mar 5.

LAQV/REQUIMTE, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal.

Coumarin phytoestrogens, as one of the important classes of phytoestrogens, have been proved to play an important role in various fields of human life. In this study, molecular simulation method including molecular docking and molecular dynamics methods were performed to explore the various effects between four classical coumarin phytoestrogens (coumestrol, 4-methoxycoumestrol, psoralen and isopsoralen), and estrogen receptors (ER ER), respectively. The calculated results not only proved that the four coumarin phytoestrogens have weaker affinity than 17β-estradiol to both ER and ER, but also pointed out that the selective affinity for ER is greater than ER. In addition, the binding mode indicated that the formation of hydrogen bond and hydrophobic interaction have an important effect on the stability of the complexes. Further, the calculation and decomposition of binding free energy explored the main contribution interactions to the total free energy.
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http://dx.doi.org/10.3390/molecules25051165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7179152PMC
March 2020

A Facile and Highly Efficient Route to Amphiphilic Star-Like Rod-Coil Block Copolymer via a Combination of Atom Transfer Radical Polymerization with Thiol-Ene Click Chemistry.

Macromol Rapid Commun 2020 Mar 24;41(5):e1900540. Epub 2020 Jan 24.

Institute of Advanced Synthesis, School of Chemistry and Molecular Engineering, Jiangsu National Synergetic Innovation Center for Advanced Materials, Nanjing Tech University, Nanjing, 211816, China.

With a combination of atom transfer radical polymerization (ATRP), quasi-living Grignard metathesis method, and thiol-ene click reaction, an amphiphilic star-like rod-coil diblock copolymer poly(acrylic acid)-block-poly(3-hexylthiophene) comprising 21-arm inner coil-like PAA blocks and outer rod-like conjugated polymer poly(3-hexylthiophene) (P3HT) blocks with well-defined molecular structures and narrow molecular weight distribution is synthesized. First, the bromide end-groups of 21-arm star-like ATRP coil polymers PtBA-Br are converted successfully into reactive thioacetate end groups by post-functionalization using potassium thioacetate. Subsequently, 21-arm star-like coil polymers PtBA-SCOCH react with rod-like vinyl-functionalized P3HT to yield functional star-like rod-coil diblock copolymers PtBA-b-P3HT via thiol-ene click reaction, followed by selective hydrolysis of inner PtBA block into PAA block. The present synthetic approach enables the construction of well-defined star-like conformation with few structural limitations in a facile and highly efficient manner due to the robust and orthogonal nature of the thiol-ene click reaction. It may be extended to produce block copolymers with other topologies, such as cylindrical, hyperbranched, and dendritic structures.
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http://dx.doi.org/10.1002/marc.201900540DOI Listing
March 2020

CD22 and CD72 contribute to the development of scleroderma in a murine model.

J Dermatol Sci 2020 Jan 13;97(1):66-76. Epub 2019 Dec 13.

Department of Dermatology, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Ishikawa, Japan. Electronic address:

Background: Systemic sclerosis (SSc) is a systemic autoimmune disease that is characterized by excessive fibrosis. CD22 and CD72 are B cell-specific cell surface molecules that negatively regulate B cell function.

Objective: The aim of the present study was to investigate the roles of CD22 and CD72 in a murine scleroderma model.

Methods: The experimental fibrosis model was generated by subcutaneous injection of bleomycin or hypochlorous acid (HOCL) into wild-type (WT), CD22-deficient (CD22), CD72-deficient (CD72) and CD22 and CD72 double-deficient (CD22/CD72) mice. We histologically assessed skin fibrosis and inflammatory cell infiltration. Cytokine and chemokine expression levels were measured by real-time polymerase chain reaction.

Results: The severity of fibrosis in the skin and lung was significantly less in CD22, CD72, and CD22/CD72 mice than in WT mice in the bleomycin-induced model. In the skin of bleomycin-treated mice, the numbers of CD3 T cells, CD8 T cells, and F4/80 macrophages were significantly lower in CD22, CD72, and CD22/CD72 mice than in WT mice. The expression levels of mRNAs for IL-6, TNF-α, TGF-β, CTGF, IL-1β, IL-13, CXCL2, and ICAM-1 were significantly lower in CD22, CD72, and CD22/CD72 mice than in WT mice. In the HOCL-induced model, both skin and lung fibrosis were ameliorated in CD22, CD72 and CD22/CD72 mice compared to WT mice.

Conclusion: These results indicate that CD22 and CD72 likely play crucial roles in skin and lung fibrosis. Moreover, the inhibition of CD22 and CD72 function has potential as a therapeutic approach to SSc.
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http://dx.doi.org/10.1016/j.jdermsci.2019.12.007DOI Listing
January 2020