Publications by authors named "Wenjian Li"

69 Publications

Association between VPS13C rs2414739 polymorphism and Parkinson's disease risk: A meta-analysis.

Neurosci Lett 2021 May 7;754:135879. Epub 2021 Apr 7.

Department of Neurology, Affiliated Hospital of Qingdao University, Qingdao, China. Electronic address:

Objective: We aimed to estimate the role of vacuolar protein sorting 13C (VPS13C) gene single nucleotide polymorphism (SNP) rs2414739 variant in the risk of PD by meta-analysis.

Methods: Five eligible case-control studies including 2796 PD cases and 4138 health controls involved in this meta-analysis. The fixed or random effect model was selected based on the heterogeneity of the included studies which detected by I and Q tests. The association between rs2414739 polymorphism and the risk of PD was evaluated using the pooled odds ratios (OR) and 95 % confidence interval (95 %CI). Sensitivity analysis was used to test the stability of the results. Funnel plot and Begg's test were employed to verified publication bias.

Results: The results of our meta-analysis showed a significant correlation between VPS13C rs2424739 gene polymorphism and PD susceptibility in Allele model (A versus vs. G: OR = 1.14, 95 %CI = 1.05-1.23, p = 0.002), dominant model (GG + AG vs. AA: OR = 0.86, 95 %CI = 0.78-0.95, p = 0.004), heterozygote model (AG vs. AA: OR = 0.87, 95 %CI = 0.77-0.99, p = 0.04), homozygote model (GG vs. AA: OR = 0.76, 95 %CI = 0.60-0.96, p = 0.02). Surprisingly, we did not find a significant statistical difference between VPS13C rs2414739 polymorphism and PD risk in Chinese cohort in the regional stratified analysis.

Conclusions: This meta-analysis suggests that VPS13C rs2414739 polymorphism might act as a genetic predisposition factor for PD, whereas does not include Chinese population.
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http://dx.doi.org/10.1016/j.neulet.2021.135879DOI Listing
May 2021

Structural characterization of a polysaccharide from Lycium barbarum and its neuroprotective effect against β-amyloid peptide neurotoxicity.

Int J Biol Macromol 2021 Apr 4;176:352-363. Epub 2021 Feb 4.

Biophysics Laboratory, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, Gansu 730000, China. Electronic address:

A water-soluble polysaccharide, designated as LBP-3, was isolated and purified from Lycium barbarum. Chemical analysis indicated that LBP-3 was composed of arabinose and galactose at a molar ratio of 1.00:1.56. The average molecular weight of LBP-3 was 6.74 × 104 Da. The structural features of LBP-3 were investigated by Fourier-transform infrared spectroscopy (FT-IR), methylation, and nuclear magnetic resonance (NMR). LBP-3 is a highly branched polysaccharide with a backbone of 1, 3-linked β-Galp, which is partially substituted at C-6. The branches contain 1, 5-linked α-Araf, 1, 6-linked β-Galp, 1, 3-linked α-Araf, and 1, 4-linked α-Araf. In vitro studies revealed that LBP-3 induced a concentration-dependent decrease in the levels of Aβ42/Aβ40 in N2a/APP695 cells. Proteomic analysis was conducted to investigate the potential molecular mechanism underlying the neuroprotective effect of LBP-3, and the results suggested that LBP-3 might have the potential for the treatment of AD.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.02.016DOI Listing
April 2021

Effects of Carbon Ion Beam Irradiation on Butanol Tolerance and Production of .

Front Microbiol 2020 18;11:602774. Epub 2020 Dec 18.

Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, China.

() has considerable potential for use in bioenergy development. Owing to the repeated use of traditional mutagenesis methods, the strains have developed a certain tolerance. The rheology of the bioprocess and the downstream processing of the product heavily depend on the ability of mutants to produce butanol. Carbon ion beam irradiation has advantages over traditional mutation methods for fermentative production because of its dose conformity and superb biological effectiveness. However, its effects on the specific productivity of the strains have not been clearly understood. In this study, we screened five mutants through carbon ion beam irradiation; mutant Y217 achieved a butanol-production level of 13.67 g/L, exceeding that of wild-type strain ATCC 824 (i.e., 9.77 g/L). In addition, we found that the mutant maintained normal cell membrane integrity under the stimulation of 15 g/L butanol, whereas the intracellular macromolecules of wild-type strain ATCC 824 leaked significantly. Subsequently, we used the response surface methodology (RSM) to determine if the mutant cell membrane integrity improved the butanol tolerance. We verified that with the addition of butanol, the mutant could be fermented to produce 8.35 g/L butanol, and the final butanol concentration in the fermentation broth could reach 16.15 g/L. In this study, we proved that under butanol stress, mutant Y217 features excellent butanol production and tolerance and cell membrane integrity and permeability; no prior studies have attempted to do so. This will serve as an interesting and important illustration of the complexity of genetic control of the irradiation mutation of strains. It may also prove to be useful in the bioengineering of strains of the mutant for use in the predevelopment stage.
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http://dx.doi.org/10.3389/fmicb.2020.602774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775398PMC
December 2020

Calibration for Camera-Projector Pairs Using Spheres.

IEEE Trans Image Process 2021 4;30:783-793. Epub 2020 Dec 4.

A newly developed calibration algorithm for camera-projector system using spheres is presented in this paper. Previous studies have exploited image conics of sphere to calibrate the camera, whereas this approach can be strengthened to apply in the projector and ultimately achieve the overall calibration for single or multiple pairs of camera-projector. Following the concept of taking the projector as an inverse camera, we retrieve the image conic of the sphere on the projector plane based on a pole-polar relationship we found. At least 3 image conics on the image plane of each device are required to calculate the intrinsic parameters of the device. The extrinsic parameters for all devices in the system are determined by the position of sphere centers in each coordinates frame of the device. Based on the isotropy of the calibration object (sphere), this work is mainly interested in accomplishing the entire calibration for multiple camera-projector systems in which sensors surround a central observation volume. Experiments are conducted on both synthetic and real datasets to evaluate its performance.
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http://dx.doi.org/10.1109/TIP.2020.3038514DOI Listing
December 2020

Point mutation screening of tumor neoantigens and peptide-induced specific cytotoxic T lymphocytes using The Cancer Genome Atlas database.

Oncol Lett 2020 Nov 19;20(5):123. Epub 2020 Aug 19.

Guangdong Province Key Laboratory for Biotechnology Drug Candidates, School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510006, P.R. China.

The aim of the present study was to use The Cancer Genome Atlas (TCGA) database to identify tumor neoantigens, combined with a bioinformatics analysis to design and analyze antigen epitope peptides. Epitopes were screened using immunogenicity tests to identify the ideal epitope peptides to target tumor neoantigens, which can specifically activate the immune response of T cells. The high-frequency mutation loci (top 10) of colorectal, lung and liver cancer genes were screened using TCGA database. The antigenic epitope peptides with high affinity for major histocompatibility complex molecules were selected and synthesized using computer prediction algorithms, and were subsequently detected using flow cytometry. The cytotoxicity of specific cytotoxic T lymphocytes (CTLs) on peptide-loaded T2 cells was initially verified using interferon IFN-γ detection and a calcein-acetoxymethyl (Cal-AM) release assay. Tumor cell lines expressing point mutations in and genes were constructed respectively, and the cytotoxicity of peptide-induced specific CTLs on wild-type and mutant tumor cells was verified using a Cal-AM release assay and carboxyfluorescein succinimidyl ester-propidium iodide staining. The high-frequency gene mutation loci of KRAS proto-oncogene (KRAS) G12V, tumor protein p53 (TP53) R158L and catenin β1 (CTNNB1) K335I were identified in TCGA database. A total of 3 groups of wild-type and mutant peptides were screened using a peptide prediction algorithm. The CTNNB1 group had a strong affinity for the human leukocyte antigen-A2 molecule, as determined using flow cytometry. The IFN-γ secretion of specific CTLs in the CTNNB1 group was the highest, followed by the TP53 and the KRAS groups. The killing rate of mutant peptide-induced specific CTLs on peptide-loaded T2 cells in the CTNNB1 group was higher compared with that observed in the other groups. The killing rate of specific CTLs induced by mutant peptides present on tumor cells was higher compared with that induced by wild-type peptides. However, when compared with the TP53 and KRAS groups, specific CTLs induced by mutant peptides in the CTNNB1 group had more potent cytotoxicity towards mutant and wild-type tumor cells. In conclusion, point mutant tumor neoantigens screened in the three groups improved the cytotoxicity of specific T cells, and the mutant peptides in the CTNNB1 group were more prominent, indicating that they may activate the cellular immune response more readily.
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http://dx.doi.org/10.3892/ol.2020.11986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471748PMC
November 2020

Intrinsically Stretchable Organic-Tribotronic-Transistor for Tactile Sensing.

Research (Wash D C) 2020 24;2020:1398903. Epub 2020 Jun 24.

CAS Center for Excellence in Nanoscience, Beijing Key Laboratory of Micro-Nano Energy and Sensor, Beijing Institute of Nanoenergy and Nanosystems, Chinese Academy of Sciences, Beijing 100083, China.

Stretchable electronics are of great significance for the development of the next-generation smart interactive systems. Here, we propose an intrinsically stretchable organic tribotronic transistor (SOTT) without a top gate electrode, which is composed of a stretchable substrate, silver nanowire electrodes, semiconductor blends, and a nonpolar elastomer dielectric. The drain-source current of the SOTT can be modulated by external contact electrification with the dielectric layer. Under 0-50% stretching both parallel and perpendicular to the channel directions, the SOTT retains great output performance. After being stretched to 50% for thousands of cycles, the SOTT can survive with excellent stability. Moreover, the SOTT can be conformably attached to the human hand, which can be used for tactile signal perception in human-machine interaction and for controlling smart home devices and robots. This work has realized a stretchable tribotronic transistor as the tactile sensor for smart interaction, which has extended the application of tribotronics in the human-machine interface, wearable electronics, and robotics.
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http://dx.doi.org/10.34133/2020/1398903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7333181PMC
June 2020

Effects of AKT1 E17K mutation hotspots on the biological behavior of breast cancer cells.

Int J Clin Exp Pathol 2020 1;13(3):332-346. Epub 2020 Mar 1.

Guangdong Province Key Laboratory for Biotechnology Drug Candidates, School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University Guangzhou 510006, China.

Objective: To investigate the effect of the AKT1 gene mutation hotspot E17K on the growth, proliferation, survival, and migration of breast cancer cells, based on the survival and prognosis of breast cancer patients with the AKT1 E17K mutation shown in TCGA database.

Methods: The survival and incidence rates of AKT1 E17K mutation hotspots in breast cancer and other cancers were extracted from the Cancer Genome Atlas (TCGA). The recombinant eukaryotic expression plasmid AKT1 E17K-pIRES2-EGFP was constructed and transfected into breast cancer MCF-7, and MDA-MB-231 cell lines. MCF-7 and MDA-MB-231 cell lines were randomly divided into blank control groups, empty plasmid groups, and recombinant plasmid groups. The growth curve was drawn using the cell counting method. The proliferation and division of breast cancer cells were detected by CFSE fluorescent dye tracking. Apoptosis was detected by Annexin V/PI double labeling and cell vitality was detected using MTT assays, and cell migratory ability was detected by cell scratch and transwell chamber tests.

Results: In breast cancer, and other cancers, the overall survival rate of patients with an AKT E17K mutation was higher than that of patients with non-point mutation, and this mutation was the most common found in breast cancer. Compared with the wild type, the growth function of mutant MCF-7 cells was inhibited (P < 0.05), as was the proliferation of MCF-7 cells expressing the AKT1 E17K mutation gene (P < 0.001). The late apoptosis rate of mutant breast cancer cells increased (P < 0.05) and the viability was lower than that of wild-type cells (P < 0.05). Mutant MDA-MB-231 cells showed increased migration ability when compared to wild-type MDA-MB-231 cells (P < 0.05).

Conclusions: The expression of the AKT1 E17K mutation hotspot can inhibit the growth, proliferation, and survival ability of breast cancer cells, and promote apoptosis, while it also improves their migratory ability. The survival and prognosis of breast cancer patients with this mutation are good, which may be related to the inhibition of the PI3K/AKT/mTOR signaling pathway.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7137002PMC
March 2020

Repair characteristics and time-dependent effects in response to heavy-ion beam irradiation in Saccharomyces cerevisiae: a comparison with X-ray irradiation.

Appl Microbiol Biotechnol 2020 May 6;104(9):4043-4057. Epub 2020 Mar 6.

Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, 730000, China.

Heavy-ion beam (HIB) irradiation has been widely used in microbial mutation breeding. However, a global cellular response to such radiation remains mostly uncharacterised. In this study, we used transcriptomics to analyse the damage repair response in Saccharomyces cerevisiae following a semi-lethal HIB irradiation (80 Gy), which induced a significant number of DNA double-strand breaks. Our analysis of differentially expressed genes (DEGs) from 50 to 150 min post-irradiation revealed that upregulated genes were significantly enriched for gene ontology and Kyoto encyclopaedia of genes and genomes terms related to damage repair response. Based on the number of DEGs, their annotation, and their relative expression, we established that the peak of the damage repair response occurred 75 min post-irradiation. Moreover, we exploited the data from our recent study on X-ray irradiation-induced repair to compare the transcriptional patterns induced by semi-lethal HIB and X-ray irradiations. Although these two radiations have different properties, we found a significant overlap (> 50%) for the DEGs associated with five typical DNA repair pathways and, in both cases, identified homologous recombination repair (HRR) as the predominant repair pathway. Nevertheless, when we compared the relative enrichment of the five DNA repair pathways at the key time point of the repair process, we found that the relative enrichment of HRR was higher after HIB irradiation than after X-ray irradiation. Additionally, the peak stage of HRR following HIB irradiation was ahead of that following X-ray irradiation. Since mutations occur during the DNA repair process, uncovering detailed repair characteristics should further the understanding of the associated mutagenesis features.
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http://dx.doi.org/10.1007/s00253-020-10464-8DOI Listing
May 2020

Effects of microbial inoculants on the fermentation characteristics and microbial communities of sweet sorghum bagasse silage.

Sci Rep 2020 01 21;10(1):837. Epub 2020 Jan 21.

Institute of Modern Physics, Chinese Academy of Sciences, 509 Nanchang Rd., Lanzhou, Gansu, 730000, P.R. China.

Sweet sorghum bagasse (SSB) is a promising raw material for silage fermentation due to its high residual nutritive, but the efficient fermentation strategy of SSB has not been reported yet. This study evaluated the effects of microbial inoculant on the fermentation quality, chemical composition and microbial community of SSB silage. The silage inoculated with isolated lactic acid bacteria (LpE) achieved better fermentation than that of commercial inoculant A, B (CIA, CIB) and untreatment, including low pH value, high levels of lactic acid and water soluble carbohydrates (WSC) content, which demonstrated that the LpE inoculant could contribute to the preservation of nutrition and the manipulation of fermentation process of SSB. In addition, the results of microbial community analysis indicated that the LpE inoculant significantly changed the composition and diversity of bacteria in SSB silage. After ensiling, the LpE inoculated silage were dominated by Lactobacillus(95.71%), Weissella(0.19%). These results were of great guiding significance aiming for high-quality silage production using SSB materials on the basis of target-based regulation methods.
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http://dx.doi.org/10.1038/s41598-020-57628-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6972861PMC
January 2020

Genome-Wide Comparisons of Mutations Induced by Carbon-Ion Beam and Gamma-Rays Irradiation in Rice Resequencing Multiple Mutants.

Front Plant Sci 2019 28;10:1514. Epub 2019 Nov 28.

National Engineering Research Center of Plant Space Breeding, South China Agricultural University, Guangzhou, China.

Physical mutagens, such as carbon-ion beams (CIBs) and gamma rays (GRs), induce mutations with high frequency at a relatively low dose and are more user-friendly and environment-friendly in mutation breeding. Previous studies showed that CIBs induced large sized deletions and insertions, and chromosomal rearrangements, whereas GRs induce shorter deletions and insertions, and more frequent base substitutions. However, the difference on the genomic level between CIB- and GR-induced mutations remains to be clarified. In the present study, we re-sequence six mutagenized lines derived from CIB irradiation and four mutagenized lines derived from GRs. A total of 283 and 381 variations are induced in these mutants by CIBs and GRs, respectively, including single base substitutions (SBSs), small insertion and deletions (InDels), multiple nucleotide variants (MNVs). SBSs are the most abundant type of mutation and single base transition is the main form for SBSs. CIB-induced InDels accounted for 25.44% of the total variations, while GR-induced InDels accounted for 17.85%. On the contrary, the frequency of MNVs induced by GRs was approximately 2.19 times that induced by CIBs, which indicates CIBs induced increased InDels, whereas GRs induced increased MNVs. Notably, multiple base deletions (≥5 bp) were induced at a much higher frequency by CIBs than by GRs. We also find mutations induced by CIBs and GRs are unevenly distributed on chromosomes. Unusual high-frequency (HF) and low-frequency (LF) mutation regions are discovered by analyzing mutations per 1Mb along the genome. The mutation frequency within the HF regions were significantly higher than the LF regions ( < 0.05). A large majority of SBSs, InDels, and MNVs induced by CIBs and GRs occurred in upstream and downstream regions. Our study compares difference of mutation profiles induced by the CIB irradiation and GR on rice genomes, and give some clues for understanding the mutagenesis mechanism of physical radiation and improving the mutagenesis efficiency.
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http://dx.doi.org/10.3389/fpls.2019.01514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6892775PMC
November 2019

Quantitative multi-omics analysis of the effects of mitochondrial dysfunction on lipid metabolism in Saccharomyces cerevisiae.

Appl Microbiol Biotechnol 2020 Feb 12;104(3):1211-1226. Epub 2019 Dec 12.

Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, 730000, China.

In this study, combined genome, transcriptome, and metabolome analysis was performed for eight Saccharomyces cerevisiae mitochondrial respiration-deficient mutants. Each mutant exhibited a unique nuclear genome mutation pattern; the nuclear genome mutations, and thus potentially affected genes and metabolic pathways, showed a co-occurrence frequency of ≤ 3 among the eight mutants. For example, only a lipid metabolism-related pathway was likely to be affected by the nuclear genome mutations in one of the mutants. However, large deletions in the mitochondrial genome were the shared characteristic among the eight mutants. At the transcriptomic level, lipid metabolism was the most significantly enriched Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway for differentially expressed genes (DEGs) co-occurring in both ≥ 4 and ≥ 5 mutants. Any identified DEG enriched in lipid metabolism showed the same up-/down-regulated pattern among nearly all eight mutants. Further, 126 differentially expressed lipid species (DELS) were identified, which also showed the same up-/down-regulated pattern among nearly all investigated mutants. It was conservatively demonstrated that the similar change pattern of lipid metabolism in the entire investigated mutant population was attributed to mitochondrial dysfunction. The change spectrum of lipid species was presented, suggesting that the number and change degree of up-regulated lipid species were higher than those of down-regulated lipid species. Additionally, energy storage lipids increased in content and plasma-membrane phospholipid compositions varied in the relative proposition. The results for the genome, transcriptome, and lipidome were mutually validated, which provides quantitative data revealing the roles of mitochondria from a global cellular perspective.
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http://dx.doi.org/10.1007/s00253-019-10260-zDOI Listing
February 2020

Induced pluripotent stem cell (iPSC) line (HEBHMUi002-A) from a healthy female individual and neural differentiation.

Stem Cell Res 2020 01 23;42:101669. Epub 2019 Nov 23.

Hebei Medical University-National University of Ireland Galway Stem Cell Research Center, Hebei Medical University, Hebei Province 050017, China; Hebei Research Center for Stem Cell Medical Translational Engineering, Hebei Province 050017, China; Human Anatomy Department, Hebei Medical University, Hebei Province 050017, China. Electronic address:

Induced pluripotent stem cells (iPSCs) can be used to generate different types of somatic cells in vitro, including neuronal cells. Here, a human iPSC line was generated from the peripheral blood mononuclear cells of a healthy 39-year-old individual. The resulting iPSCs were integration-free, maintained the normal karyotype, expressed pluripotency stem cell markers, and were demonstrated to be capable of differentiating into cells representative of the three embryonic germ layers. Furthermore, we showed that this iPSC line could be differentiated into neural stem cells. Taken together, this generated iPSC line could be useful to test multiple differentiation protocols, and also serve as a control for investigating drug development and disease mechanisms.
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http://dx.doi.org/10.1016/j.scr.2019.101669DOI Listing
January 2020

Pretreatment of sweet sorghum straw and its enzymatic digestion: insight into the structural changes and visualization of hydrolysis process.

Biotechnol Biofuels 2019 23;12:276. Epub 2019 Nov 23.

1Institute of Modern Physics, Chinese Academy of Sciences, 509 Nanchang Rd., Lanzhou, 730000 Gansu People's Republic of China.

Background: The efficient utilization of lignocellulosic biomass for biofuel production has received increasing attention. Previous studies have investigated the pretreatment process of biomass, but the detailed enzymatic hydrolysis process of pretreated biomass remains largely unclear. Thus, this study investigated the pretreatment efficiency of dilute alkali, acid, hydrogen peroxide and its ultimate effects on enzymatic hydrolysis. Furthermore, to better understand the enzymatic digestion process of alkali-pretreated sweet sorghum straw (SSS), multimodal microscopy techniques were used to visualize the enzymatic hydrolysis process.

Result: After pretreatment with alkali, an enzymatic hydrolysis efficiency of 86.44% was obtained, which increased by 99.54% compared to the untreated straw (43.23%). The FTIR, XRD and SEM characterization revealed a sequence of microstructural changes occurring in plant cell walls after pretreatment, including the destruction of lignin-polysaccharide interactions, the increase of porosity and crystallinity, and reduction of recalcitrance. During the course of hydrolysis, the cellulase dissolved the cell walls in the same manner and the digestion firstly occurred from the middle of cell walls and then toward the cell wall corners. The CLSM coupled with fluorescent labeling demonstrated that the sclerenchyma cells and vascular bundles in natural SSS were highly lignified, which caused the nonproductive bindings of cellulase on lignin. However, the efficient delignification significantly increased the accessibility and digestibility of cellulase to biomass, thereby improving the saccharification efficiency.

Conclusion: This work will be helpful in investigating the biomass pretreatment and its structural characterization. In addition, the visualization results of the enzymatic hydrolysis process of pretreated lignocellulose could be used for guidance to explore the lignocellulosic biomass processing and large-scale biofuel production.
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http://dx.doi.org/10.1186/s13068-019-1613-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6874820PMC
November 2019

Genetic polymorphisms in mutagenesis progeny of irradiated by carbon-ion beams and γ-rays irradiations.

Int J Radiat Biol 2020 02 18;96(2):267-275. Epub 2019 Nov 18.

Department of Biophysics, Biomedical Center, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, China.

Heavy-ion beams and γ-rays are popular physical mutagenesis to generate mutations in higher plants. It has been found that they show different mutation frequencies and spectrums of phenotype induction, however, the characteristics of heavy-ion beams on genetic polymorphism have not been clarified by comparing with γ-rays. In the present study, seeds of were exposed to carbon-ion beams (with linear energy transfer (LET) of 50 keV/μm) and γ-rays (with average LET of 0.2 keV/μm) irradiation. By using inter-simple sequence repeat (ISSR) and random amplified polymorphic DNA (RAPD) analysis, the genetic polymorphism of both M and M plants were investigated, respectively. Carbon-ion beams induced relatively higher polymorphism rate in both M and M generation than γ-rays: the polymorphism rates of M plants derived from carbon-ion beams irradiation are 12.87% (ISSR-C) and 9.01% (RAPD-C), while are 7.67% (ISSR-γ) and 1.45% (RAPD-γ) of plants derived from γ-rays. In M generation, the polymorphism rates of ISSR-C, RAPD-C, ISSR-γ, and RAPD-γ are 17.64%, 22.79%, 12.10%, and 2.82%, respectively. In summary, the exposure to carbon-ion beams and γ-rays lead to the change of genomic DNA of , which could be tested in M plants and M plants by ISSR and RAPD technology. So, both carbon-ion beams and γ-rays can induce variations of genetic polymorphisms in M plants and M plants. The genetic polymorphisms of M plants and M plants induced by carbon-ion beams are higher than γ-rays, indicating that heavy-ion beams irradiations mutation breeding is more advantageous than conventional ionizing radiations. Average molecular polymorphism of M plants is lower than M mutants, by nearly 4.77% (ISSR-C), 13.78% (RAPD-C), 4.43% (ISSR-γ), and 1.37% (RAPD-γ). We hope our study will provide basic information for understanding the effects of carbon-ion beams and γ-rays for plant mutation breeding.
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http://dx.doi.org/10.1080/09553002.2020.1688412DOI Listing
February 2020

Enhancing enzymatic hydrolysis yield of sweet sorghum straw polysaccharides by heavy ion beams irradiation pretreatment.

Carbohydr Polym 2019 Oct 8;222:114976. Epub 2019 Jun 8.

Institute of Modern Physics, Chinese Academy of Sciences, 509 Nanchang Rd., Lanzhou, Gansu 730000, PR China; University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, PR China.

A deeper understanding of the pretreatment process of lignocellulosic biomass could enhance the production efficiency of biofuels. Sweet sorghum straws (SSS) were subjected to heavy ion beams irradiation (HIBI) pretreatment and then hydrolyzed with 2.4 FPU of cellulase. Notably, the pretreatment has been proved to increase enzymatic digestibility of SSS. The reducing sugar yield and hydrolysis yield of SSS pretreated by 600 Gray (Gy) of HIBI reached to 7.23 mg/mL and 34.43% for 36 h, respectively, which was significantly higher than that of the untreated SSS (4.93 mg/mL of reducing sugar and 23.47% of hydrolysis yield). Additionally, the analysis of pretreated SSS showed that the destruction of amorphous region and surface ultrastructure as well as the transformation of polymorphs (I →I) of cellulose I were major effects on SSS by HIBI pretreatment. The results demonstrated that HIBI could be chosen as an effective physical pretreatment process for enhancing enzymatic hydrolysis yield of lignocellulosic biomass.
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http://dx.doi.org/10.1016/j.carbpol.2019.114976DOI Listing
October 2019

Plasma Osteoprotegerin Correlates with Stroke Severity and the Occurrence of Microembolic Signals in Patients with Acute Ischemic Stroke.

Dis Markers 2019 2;2019:3090364. Epub 2019 May 2.

Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao 266000, China.

Background: Instability of atherosclerotic plaques is associated with the occurrence of stroke. Microembolic signals (MESs) are an indicator of unstable plaque. A relationship between plasma osteoprotegerin (OPG) and ischemic stroke has already been identified. The aim of this study was to investigate whether plasma OPG levels have a relationship with MESs and to evaluate the feasibility of OPG as a biomarker of stroke severity and occurrence of MESs.

Methods: Our study consisted of 127 patients with large artery atherosclerosis stroke and 56 controls. Patients were classified into subgroups based on stroke severity and the occurrence of MESs. MES-monitoring was performed for 60 min using transcranial Doppler within 72 h of stroke onset. Stroke severity at admission was assessed by the National Institutes of Health Stroke Scale.

Results: Plasma OPG levels were significantly associated with stroke, MESs, and stroke severity at admission (adjusted OR [95% CI]: 1.002 [1.001-1.003] < 0.001; 1.002 [1.001-1.003] = 0.001; 1.001 [1.000-1.002] = 0.028). When plasma OPG levels were used to determine the stroke severity, the area under the receiver-operating characteristic curve (AUC) was 0.734 (95% CI: 0.625-0.843) based on a cutoff value of 1998.44 pg/ml; the sensitivity and specificity of this test were 80.6% and 65.6%, respectively. Furthermore, when the levels of OPG were used to distinguish the presence of MESs, the AUC was 0.766 (95% CI: 0.672-0.860); the cutoff value was 2107.91 pg/ml. The sensitivity of this cutoff value was 68.8% and the specificity was 73.7%.

Conclusions: Plasma OPG levels correlate with stroke severity and the occurrence of MESs.
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http://dx.doi.org/10.1155/2019/3090364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6525837PMC
December 2019

Tribotronic bipolar junction transistor for mechanical frequency monitoring and use as touch switch.

Microsyst Nanoeng 2018 5;4:25. Epub 2018 Nov 5.

1CAS Center for Excellence in Nanoscience, Beijing Key Laboratory of Micro-nano Energy and Sensor, Beijing Institute of Nanoenergy and Nanosystems, Chinese Academy of Sciences, 100083 Beijing, China.

Tribotronics, a new field that involves the coupling of triboelectricity and semiconductors, has attracted great interest in the nanoenergy and nanoelectronics domains. This paper proposes a tribotronic bipolar junction transistor (TBJT) that incorporates a bipolar junction transistor and a triboelectric nanogenerator (TENG) in the single-electrode mode. When the mobile triboelectric layer slides on the device surface for electrification, a bias voltage is created and applied to the emitter junction, and then the base current from the TENG is amplified. Based on the fabricated TBJT, a mechanical frequency monitoring sensor with high sensitivity and excellent stability and a finger-triggered touch switch were developed. This work demonstrated for the first time a tribotronic device with simultaneously controlled voltage and current voltage/current simultaneously controlled tribotronic device, which has promising potential applications in micro/nano-sensors, human-machine interactions, intelligent instrumentation, wearable electronics, and other applications.
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http://dx.doi.org/10.1038/s41378-018-0026-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6220156PMC
November 2018

RSV recombinant candidate vaccine G1F/M2 with CpG as an adjuvant prevents vaccine-associated lung inflammation, which may be associated with the appropriate types of immune memory in spleens and lungs.

Hum Vaccin Immunother 2019 29;15(11):2684-2694. Epub 2019 Apr 29.

Department of Immunology, Hebei Medical University, Shijiazhuang, Hebei, PR China.

Respiratory syncytial virus (RSV) is a major respiratory pathogen in infants. The early formalin-inactivated RSV not only failed to protect infants against infection, but also was associated with enhanced pulmonary inflammatory disease upon natural infection. A safe and effective vaccine should prevent the inflammatory disease and provide protection. Immune memory is the cornerstone of vaccines. In this study, we evaluated three types of immune memory T cells, antibodies, and lung inflammation of a vaccine candidate G1F/M2, which includes a neutralizing epitope fragment of RSV G protein and a cytotoxic T lymphocyte epitope of M2 protein, with toll-like receptor 9 agonist CpG2006 as an adjuvant by intranasal (i.n.) and intraperitoneal (i.p.) immunization protocols. The results indicated that immunization of mice with G1F/M2 + CpG i.p. induced significantly higher level of CD4 or CD8 central memory (TCM), Th1-type effector memory (TEM), and balanced ratio of IgG1/IgG2a, but lower level of lung tissue-resident memory (TRM), compared with immunization with G1F/M2 + CpG i.n., G1F/M2 i.n., or G1F/M2 i.p. Following RSV challenge, the mice immunized with G1F/M2 + CpG i.p. showed higher level of Th1-type responses, remarkably suppressed inflammatory cytokines and histopathology in lungs, compared with mice immunized with G1F/M2 + CpG i.n., G1F/M2 i.n., or G1F/M2 i.p. These results suggested that high level of TCM and Th1 type of TEM in spleens may contribute to inhibition of lung inflammation, while high level of TRM in lungs and lack of or weak Th1-type immune memory in spleens may promote lung inflammation following RSV challenge.
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http://dx.doi.org/10.1080/21645515.2019.1596710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6930060PMC
May 2020

The mechanisms for the radioprotective effect of beta-d-glucan on high linear-energy-transfer carbon ion irradiated mice.

Int J Biol Macromol 2019 Jun 12;131:282-292. Epub 2019 Mar 12.

School of Life Science and Engineering, Lanzhou University of Technology, Lanzhou 730000, China.

S. cerevisiae-derived-beta-d-glucan (S. cerevisiae-BG) is a natural polysaccharide with various biological effects. The present study was to investigate the protective effect of S. cerevisiae-BG on the injury induced by high linear-energy-transfer (LET) carbon ion irradiation and to reveal the protective mechanisms. Female mice were orally administrated with S. cerevisiae-BG before irradiation. 30-day survival of 6 Gy irradiated-mice was monitored. The damage and recovery of hematopoietic system were evaluated after 2 Gy irradiation, cytokines in plasma were detected, transcriptomics of bone marrow mononuclear cells (BMMNCs) were detected and analyzed. The mortality results showed that S. cerevisiae-BG could prolong the survival of mice exposed to 6 Gy. The results of BMMNCs injury analysis showed that S. cerevisiae-BG could reduce the ROS level, mitigate DNA damage and apoptosis. S. cerevisiae-BG increased the plasma radioprotective cytokines level in irradiated mice. Transcriptomics analysis revealed that S. cerevisiae-BG modulated the gene expression in BMMNCs of irradiated mice, 256 genes were significantly up-regulated and 97 genes were significantly down-regulated. Gene function and Gene Ontology analysis indicated the key genes related to hematopoiesis and immunity. Pathway analysis revealed that these up-regulated genes mainly focus on PI3K-Akt pathway and down-regulated genes mainly focus on MAPK pathway. These data contribute to understanding the molecular mechanisms of the radioprotective effect of S. cerevisiae-BG.
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http://dx.doi.org/10.1016/j.ijbiomac.2019.03.073DOI Listing
June 2019

Transcriptional response of murine bone marrow cells to total-body carbon-ion irradiation.

Mutat Res Genet Toxicol Environ Mutagen 2019 Mar 26;839:49-58. Epub 2019 Jan 26.

School of Life Science and Engineering, Lanzhou University of Technology, Lanzhou, 730000, China.

The need to understand the health effects of heavy ion irradiation is motivated by the use of this modality in radiotherapy and by the potential for exposure during space missions. We have studied the effects of carbon-ion total-body irradiation on the hematopoietic system of the mouse and, in particular, the transcriptional response of bone marrow (BM) cells. Carbon-ion irradiation caused BM cell DNA damage, apoptosis, elevated ROS, and myelosuppression. Transcriptomic analysis showed that overall gene expression in irradiated BM cells differed significantly from the controls. Of 253 genes that were modulated, 192 were up-regulated and 61 down-regulated. Gene ontology analysis showed that the modulated genes are involved in DNA damage response signaling, DNA repair, apoptosis, and the immune response. Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that these functions are regulated by the p38 MAPK, TNF, and apoptosis pathways. These findings indicate pathways that may be involved in protection against carbon ion radiation injury.
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http://dx.doi.org/10.1016/j.mrgentox.2019.01.014DOI Listing
March 2019

Pyrolyzed municipal sewage sludge ensured safe grain production while reduced C emissions in a paddy soil under rice and wheat rotation.

Environ Sci Pollut Res Int 2019 Mar 5;26(9):9244-9256. Epub 2019 Feb 5.

Institute of Resource, Ecosystem and Environment of Agriculture, Nanjing Agricultural University, 1 Weigang, Nanjing, 210095, Jiangsu, China.

Safe recycling of the growing amounts of municipal sewage sludge containing toxic metals had been critically challenged with the fast urbanization. In this study, we investigated soil amendment of municipal wastewater treatment (MSS) converted biochar for its recycling in agricultural soils. In a field experiment, unpyrolyzed (USS) and pyrolyzed municipal sewage sludge (PSS) was amended at 20 t ha on dry base to a rice paddy before rice plantation, with a control without amendment. Grain yield and emission of non-CO potent greenhouse gases were examined as well as topsoil metal mobility and plant uptake determined throughout a rice-wheat rotation year. Compared to USS treatment, addition of PSS caused a significantly increased grain yield of rice by 35% but no change in grain yield of wheat following the rice season. No distinct difference was observed in grain concentration of major nutrients of N, P, and K between USS and PSS treatments. Compared to USS treatment, PSS treatment reduced CH emissions by 91.6% from soil and by 78.5% from ecosystem during rice-growing season. Whereas, PSS treatment led to a reduction of ecosystem NO emissions by 70.8% relative to USS treatment during wheat-growing season. While both USS and PSS treatments slightly but insignificantly increased soil total content of heavy metals, PSS treatment reduced CaCl-extractable Cd pool by 33~40% over USS treatment. Grain contents of Cd and Pb and Cd/Zn were markedly reduced under PSS over USS, without exceeding the Chinese state guideline limit. Carbon emission intensity was considerably (by over 20%) reduced for soil and ecosystem but unchanged for wheat soil, under PSS over USS. Thus, soil amendment of pyrolyzed sewage sludge could be a measure for climate smart soil and for safe grain production in rice agriculture. It deserves further study if repeated amendment could exert sustainable impacts on soil health and food security in the paddy.
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http://dx.doi.org/10.1007/s11356-019-04417-6DOI Listing
March 2019

A genome-wide view of mutations in respiration-deficient mutants of Saccharomyces cerevisiae selected following carbon ion beam irradiation.

Appl Microbiol Biotechnol 2019 Feb 19;103(4):1851-1864. Epub 2019 Jan 19.

Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, 730000, China.

Mitochondrial dysfunction in Saccharomyces cerevisiae was selected as a marker of ion penetration following carbon ion beam (CIB) irradiation. Respiration-deficient mutants were screened. Following confirmation of negligible spontaneous mutation, eight genetically stable S. cerevisiae respiration-deficient mutant strains and a control strain were resequenced with ~ 200-fold read depth. Strategies were established to identify and validate the particular mutations induced by CIB irradiation. In the nuclear genome, CIB irradiation mainly caused base substitutions and some small (< 100 bp) insertions/deletions (indels), which were widely distributed across the chromosomes. Although mitochondrial dysfunction was selected as a screening marker, variants in the nuclear genome were detected at a high frequency (10) relative to spontaneous mutations (10). The transition to transversion ratio for base substitutions was 0.746, which was less than that of spontaneous mutations. In the mitochondrial genome, there were very large deletions including substantial gene areas, resulting in extremely low read coverage. Meanwhile, every mutant possessed a distinctive mutation pattern, for both the nuclear and the mitochondrial genome. Nuclear genomes contained scanty mitochondrial respiration-related genes that were potentially affected by verified mutations, suggesting that variants in the mitochondrial genome may be the main drivers of respiratory deficiencies. Our study confirmed the previous finding that heavy ion beam (HIB) irradiation mainly induces substantial base substitutions and some small indels but also yielded some novel findings, in particular, novel structural variants in the mitochondrial genomes. These data will enhance the understanding of HIB-induced damage and mutations and aid in the HIB-based microbial mutation breeding.
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http://dx.doi.org/10.1007/s00253-019-09626-0DOI Listing
February 2019

Repair characteristics and time-dependent effects in Saccharomyces cerevisiae cells after X-ray irradiation.

World J Microbiol Biotechnol 2018 Dec 10;35(1). Epub 2018 Dec 10.

Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, 730000, China.

In this study, we examined the dynamics of phenotypic and transcriptional profiles in Saccharomyces cerevisiae following semi-lethal X-ray irradiation. Post-irradiation, reproductive death was revealed as the predominant form of death in S. cerevisiae and almost all the irradiated cells were physically present and intact. In addition, cell cycle arrest reached its peak and cell division was at its valley at 2 h. Cell cycle arrest, cell division potential, DNA damage, and mitochondrial transmembrane potential (MTP) showed significant recovery at 4 h (P > 0.05 vs. control). The improvements of DNA damage and MTP decrease were evaluated as at least 77% and 84% for the original irradiated cells at 4 h, respectively. In the transcriptional profile, the amount of differentially expressed genes (DEGs) and the fold change in the repair-related DEGs were highest at 1 h post-irradiation and then decreased. The DEGs at 1 h (but not 2 h or 3 h) were significantly enriched in gene ontology (GO) categories of detoxification (up) and antioxidant activity (up). Although the transcriptional profile supported the repair time frame observed in the phenotypic profile, the complete repair may take a longer duration as the transcriptional levels of several important repair-related DEGs did not show a decrease and the DNA repair-related pathways (up) were the major enriched pathway in Kyoto Encyclopaedia of Genes and Genomes pathway analysis throughout the whole course of the study. These results provide an important reference for the selection of key time points in further studies.
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http://dx.doi.org/10.1007/s11274-018-2566-9DOI Listing
December 2018

Chlorine migration mechanisms during torrefaction of fermentation residue from food waste.

Bioresour Technol 2019 Jan 25;271:9-15. Epub 2018 Aug 25.

School of Mechanical and Power Engineering, Nanjing Technology University, Nanjing 211816, China; Guangzhou Institute of Energy Conversion, Chinese Academy of Sciences, Guangzhou 510640, China; CAS Key Laboratory of Renewable Energy, Guangzhou 510640, China; Guangdong Provincial Key Laboratory of New and Renewable Energy Research and Development, Guangzhou 510640, China; School of Materials and Energy, Guangdong University of Technology, Guangzhou 510006, China.

Fermentation residue from food waster (FRFW) has a large amount of residual chlorine (Cl), and the high-salt of FRFW is either landfilled or treated as a fertilizer. The transfer of chlorine to the atmosphere and soil can cause pollution and soil salinization. This work primarily investigated the combined forms and migration mechanisms of Cl during the torrefaction of FRFW from 250 to 400 °C. The results showed that the form and amount of Cl released during the torrefaction of FRFW depended on temperature. The absolute content of soluble Cl and total Cl in torrefied solid products decreased, and the absolute content of insoluble Cl reached a maximum at 350 °C, which indicated that some soluble Cl was transferred to the insoluble Cl (CCl forms). The Cl-containing products in non-condensable gas was too little to be detected, so the majority of the reduced Cl was in liquids with different organic compounds.
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http://dx.doi.org/10.1016/j.biortech.2018.08.098DOI Listing
January 2019

Wearable Wire-Shaped Symmetric Supercapacitors Based on Activated Carbon-Coated Graphite Fibers.

ACS Appl Mater Interfaces 2018 Oct 27;10(40):34302-34310. Epub 2018 Sep 27.

CAS Center for Excellence in Nanoscience, Beijing Key Laboratory of Micro-nano Energy and Sensor, Beijing Institute of Nanoenergy and Nanosystems , Chinese Academy of Sciences , Beijing 100083 , P. R. China.

With the advantages of being lightweight, flexible, and wearable, wire-shaped supercapacitors have received tremendous attention in wearable and portable power sources in recent years. Considering the demands for large-scale applications, it is necessary to explore a facile and convenient preparation approach for wire-shaped supercapacitors. Herein, we reported a simple approach to fabricate wire-shaped electrodes by a dipping method, which possessed a nitric acid-activated graphite fiber core and an activated carbon-coating layer structure. Parallel and symmetric all-solid-state wire-shaped supercapacitors (PWSCs) based on the electrodes were fabricated. The as-fabricated PWSC showed high energy density (6.60 W h/kg, 8.08 mW h/cm, and 1 mV/s) and power density (253 mW/kg, 0.31 mW/cm, and 100 mV/s) and excellent flexibility. Furthermore, this wire-shaped supercapacitor may bring broader application prospects for energy storage devices in future wearable electronic areas.
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http://dx.doi.org/10.1021/acsami.8b12279DOI Listing
October 2018

Effects of heavy-ion beam irradiation on avermectin B1a and its analogues production by .

Eng Life Sci 2018 Oct 12;18(10):711-720. Epub 2018 Sep 12.

Institute of Modern Physics Chinese Academy of Sciences Lanzhou Gansu P. R. China.

The biggest challenge in anabolism research is to improve the stability and safety of microbial metabolite production on an industrial scale. One class of metabolites, avermectins, are produced by . In this study, an avermectin B1a-high-producing mutant was produced using heavy ion mutagenesis and selected based on LTQ-MS and HPLC-UV method. The mutants ZJAV-Y-147 and ZJAV-Y-HS, obtained after subjecting the spores of to 70 Gy of C heavy ion irradiation, were found to best improve the avermectin B1a production (4822.23 μg/mL and 4632.17 μg/mL, respectively). These two mutants' yielded of avermectin B1a were 2-fold high than the original strains. The DNA of the original and mutant strains were analyzed by RAPD technique with four random primers after irradiated with ion beam irradiation. The results show that different high-titer strains contain different genetic modifications. In addition, the mutation position, mutation type and sequence context of all mutations of gene in two mutants were researched, and the production of avermectin B1a and its analogues of wild-type and mutants were analyzed by fermenting 240 h, which was suggested that the partial base deletion of aveI gene may be the key sites for increasing avermectin B1a production after the C-ion irradiation. All these modifications promote increased avermectin biosynthesis, leading to multiple high-titer strains. The results demonstrate that this is an effective approach to engineer as a host for the biological production of commercial analogs.
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http://dx.doi.org/10.1002/elsc.201800094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6999553PMC
October 2018

Determining survival fractions of Saccharomyces cerevisiae in response to ionizing radiation in liquid culture.

J Radiat Res 2018 Nov;59(6):760-764

Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, China.

Saccharomyces cerevisiae survival fractions (SFs) in response to X-ray radiation were determined by two new methods: an OD600-based method and a 96-well method. For the OD600-based method, cells were exposed to various X-ray doses and inoculated into fresh medium: a lower biomass accumulated, indicating fewer surviving cells within the investigated dose range (0-100 Gy). For the 96-well method, diluent containing ~0-100 cells was equally divided into 96 droplets and respectively inoculated into 96 wells containing 200 μl of broth: fewer wells without S. cerevisiae clones indicated more surviving cells after 48 h of incubation. Corresponding quantitative systems were established. Both methods were sensitive and reliable. The OD600-based method is simple and fast, and the 96-well method simplifies the counting process. SF estimates by the OD600-based method were lower than those by 96-well methods owing to cell cycle arrest. In addition, comparisons of newly proposed and plate-counting methods indicated a higher rate of repair in S. cerevisiae in liquid culture than on agar.
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http://dx.doi.org/10.1093/jrr/rry070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6251422PMC
November 2018

A Comet Assay for DNA Damage and Repair After Exposure to Carbon-Ion Beams or X-rays in .

Dose Response 2018 Jul-Sep;16(3):1559325818792467. Epub 2018 Aug 9.

Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, China.

Ionizing radiation (IR) can result in serious genomic instability and genotoxicity by causing DNA damage. Carbon ion (CI) beams and X-rays are typical IRs and possess high-linear energy transfer (LET) and low-LET, respectively. In this article, a comet assay that was optimized by decreasing the electrophoresis time (8 minutes) and voltage (0.5 V/cm) was performed to elucidate and quantify the DNA damage induced by CI or X-rays radiation. Two quantitative methods for the comet assay, namely, comet score and olive tail moment, were compared, and the appropriate means and parameter values were selected for the present assay. The dose-effect relationship for CI or X-rays radiation and the DNA repair process were studied in yeast cells. These results showed that the quadratic function fitted the dose-effect relationship after CI or X-rays exposure, and the trend for the models fitted the dose-effect curves for various repair times was precisely described by the cubic function. A kinetics model was also creatively used to describe the process of DNA repair, and equations were calculated within repairable ranges that could be used to roughly evaluate the process and time necessary for DNA repair.
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http://dx.doi.org/10.1177/1559325818792467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6088507PMC
August 2018

M Protein of Group a Streptococcus Plays an Essential Role in Inducing High Expression of A20 in Macrophages Resulting in the Downregulation of Inflammatory Response in Lung Tissue.

Front Cell Infect Microbiol 2018 11;8:131. Epub 2018 May 11.

Key Laboratory of Immune Mechanism and Intervention on Serious Disease in Hebei Province, Department of Immunology, Basic Medical College, Hebei Medical University, Shijiazhuang, China.

Group A streptococcus (GAS), a common pathogen, is able to escape host immune attack and thus survive for longer periods of time. One of the mechanisms used by GAS is the upregulated expression of immunosuppressive molecules, which leads to a reduction in the production of inflammatory cytokines in immune cells. In the present study, we found that macrophages produced lower levels of proinflammatory cytokines (IL-1β, TNF-α, IL-6) when challenged with GAS than they did when challenged with (). Simultaneously, in a mouse model of lung infection, GAS appeared to induce a weaker inflammatory response compared to . Our data also indicated that the expression of the A20 transcriptional regulator was higher in GAS-infected macrophages than that in macrophages infected with , and that high expression of A20 correlated with a reduction in the production of TRAF6. SiRNA targeting of A20 led to the increased production of TRAF6, IL-1β, TNF-α, and IL-6, suggesting that A20 inhibits synthesis of these key proinflammatory cytokines. We also investigated the pathway underlying A20 production and found that the synthesis of A20 depends on My88, and to a lower extent on TNFR1. Finally, we showed a significant reduction in the expression of A20 in macrophages stimulated by M protein-mutant GAS, however, a speB-GAS mutant, which is unable to degrade M protein, induced a greater level of A20 production than wild type GAS. Collectively, our data suggested that M protein of GAS was responsible for inducing A20 expression in macrophages, which in turn down-regulates the inflammatory cytokine response in order to facilitate GAS in evading immune surveillance and thus prolong survival in the host.
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http://dx.doi.org/10.3389/fcimb.2018.00131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5968387PMC
February 2019

Tumor Cell-Accelerated Senescence Is Associated With DNA-PKcs Status and Telomere Dysfunction Induced by Radiation.

Dose Response 2018 Apr-Jun;16(2):1559325818771527. Epub 2018 Apr 23.

Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, China.

Whether telomere structure integrity is related to radiosensitivity is not well investigated thus far. In this study, we investigated the relation between telomere instability and radiation-induced accelerated senescence. Partial knockdown of DNA-dependent catalytic subunit of protein kinase (DNA-PKcs) in human breast cancer cell line MCF-7 was established by small interfering RNA. Radiosensitivity of control and DNA-PKcs knockdown MCF-7 cells was analyzed by clonogenetic assay. Cell growth was measured by real-time cell electronic sensing. Senescence and apoptosis were evaluated by β-galactosidase histochemical staining and fluorescence-activated cell sorting, respectively. DNA damage was determined by long polymerase chain reaction (PCR). Telomere length and integrity were analyzed by real-time PCR and cytogenetic assay, respectively. DNA-PKcs knockdown MCF-7 cells were more sensitive to X-irradiation than control cells. Further investigation revealed that accelerated senescence is more pronounced than apoptosis in cells after radiation, particularly in DNA-PKcs knockdown cells. The cytogenetic assay and kinetics of DNA damage repair revealed that the role of telomere end-capping in DNA-PKcs, rather than DNA damage repair, was more relevant to radiosensitivity. To our knowledge, this is the first study to show that DNA-PKcs plays an important role in radiation-induced accelerated senescence via maintenance of telomere integrity in MCF-7 cells. These results could be useful for future understanding of the radiation-induced genome instability and its consequences.
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http://dx.doi.org/10.1177/1559325818771527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5944147PMC
April 2018