Publications by authors named "Yunfeng Ma"

41 Publications

RAG enhances BCR-ABL1-positive leukemic cell growth through its endonuclease activity in vitro and in vivo.

Cancer Sci 2021 May 4. Epub 2021 May 4.

Department of Pathogenic Biology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, China.

BCR-ABL1 gene fusion associated with additional DNA lesions involves the pathogenesis of chronic myelogenous leukemia (CML) from a chronic phase (CP) to a blast crisis of B lymphoid (CML-LBC) lineage and BCR-ABL1 acute lymphoblastic leukemia (BCR-ABL1 ALL). The recombination-activating gene RAG1 and RAG2 (collectively, RAG) proteins that assemble a diverse set of antigen receptor genes during lymphocyte development are abnormally expressed in CML-LBC and BCR-ABL1 ALL. However, the direct involvement of dysregulated RAG in disease progression remains unclear. Here, we generate human wild-type (WT) RAG and catalytically inactive RAG-expressing BCR-ABL1 and BCR-ABL1 cell lines, respectively, and demonstrate that BCR-ABL1 specifically collaborates with RAG recombinase to promote cell survival in vitro and in xenograft mice models. WT RAG-expressing BCR-ABL1 cell lines and primary CD34 bone marrow cells from CML-LBC samples maintain more double-strand breaks (DSB) compared to catalytically inactive RAG-expressing BCR-ABL1 cell lines and RAG-deficient CML-CP samples, which are measured by γ-H2AX. WT RAG-expressing BCR-ABL1 cells are biased to repair RAG-mediated DSB by the alternative non-homologous end joining pathway (a-NHEJ), which could contribute genomic instability through increasing the expression of a-NHEJ-related MRE11 and RAD50 proteins. As a result, RAG-expressing BCR-ABL1 cells decrease sensitivity to tyrosine kinase inhibitors (TKI) by activating BCR-ABL1 signaling but independent of the levels of BCR-ABL1 expression and mutations in the BCR-ABL1 tyrosine kinase domain. These findings identify a surprising and novel role of RAG in the functional specialization of disease progression in BCR-ABL1 leukemia through its endonuclease activity.
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http://dx.doi.org/10.1111/cas.14939DOI Listing
May 2021

Corrigendum: Previous Radiotherapy Increases the Efficacy of IL-2 in Malignant Pleural Effusion: Potential Evidence of a Radio-Memory Effect?

Front Immunol 2021 23;12:649620. Epub 2021 Mar 23.

Department of Radiation Oncology, Shandong Cancer Hospital affiliated to Shandong University, Jinan, China.

[This corrects the article DOI: 10.3389/fimmu.2018.02916.].
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http://dx.doi.org/10.3389/fimmu.2021.649620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8023273PMC
March 2021

Involvement of Blnk and Foxo1 in tumor suppression in BCR‑ABL1‑transformed pro‑B cells.

Oncol Rep 2021 02 8;45(2):693-705. Epub 2020 Dec 8.

Department of Pathogenic Biology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, P.R. China.

Oncogenic Bcr‑Abl kinase mimics pre‑B cell receptor (pre‑BCR) survival signals in BCR‑ABL1‑positive B‑cell acute lymphoblastic leukemia (BCR‑ABL1+ B‑ALL), driving B‑cell progenitor malignant transformation; thus, defining a particularly unfavorable prognosis for patients. During B‑cell development, pre‑BCR differentiation signaling components terminate proliferative expansion and promote B‑cell maturation. To study whether pre‑BCR differentiation signaling components regulate the initiation and development of BCR‑ABL1+ B‑ALL, the tumor suppression mechanism of differentiation‑related signaling molecules in BCR‑ABL1‑transformed pro‑B cells were analyzed. The results demonstrated that Bcr‑Abl kinase activated the PI3K/Akt pathway, promoting cell growth, and upregulated Aid expression, increasing genomic instability in pro‑B cells. These findings suggest that Bcr‑Abl kinase mediates pro‑B cell malignant transformation. Furthermore, the present data revealed that BCR‑ABL1 oncogenic stress triggered enhanced expression of B‑cell differentiation components B‑cell linker (Blnk) and forkhead box protein O1 (Foxo1) in BCR‑ABL1 transformed pro‑B cells. Using the CRISPR/Cas9‑mediated Blnk or Foxo1 knockout BCR‑ABL1‑transformed pro‑B cells, it was identified that, in BCR‑ABL1‑transformed pro‑B cells, Blnk and Foxo1 reduced Bcr‑Abl kinase activity to induce cell cycle arrest and decrease genomic instability. In addition, Blnk suppressed the PI3K/Akt pathway to reduce Foxo1 phosphorylation and heighten the Foxo1 activity, indicating that, in BCR‑ABL1‑transformed pro‑B cells, Foxo1 participated in the regulation of Bcr‑Abl kinase by Blnk. The present data highlighted the antitumor mechanisms of Blnk and Foxo1 in the regulation of Bcr‑Abl kinase, and thus, may offer an alternative therapeutic strategy to Bcr‑Abl kinase regulation in BCR‑ABL1+ B‑ALL.
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http://dx.doi.org/10.3892/or.2020.7888DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757083PMC
February 2021

Air pollutant emission characteristics and HYSPLIT model analysis during heating period in Shenyang, China.

Environ Monit Assess 2020 Dec 14;193(1). Epub 2020 Dec 14.

Shenyang Neusoft System Integration Technology Co., Ltd., Shenyang, 110179, China.

To find out the characteristics and sources of atmospheric pollutants during heating period in Shenyang, the study investigated the temporal and spatial distribution of pollutants, using data of six typical atmospheric pollutants (SO, NO, PM, PM, O, and CO) from November 2017 to March 2018 in 11 monitoring stations in Shenyang. These features were combined with the HYSPLIT model for backward trajectory simulation of heavily polluted weather. PM and PM are the main pollutants during heating period in Shenyang, with average concentrations of 90.26 μg/m and 56.92 μg/m, respectively. The concentrations of various types of contaminants at the Taiyuan Street station were relatively high. PM and PM were relatively high in the southwestern area of Shenyang, gradually decreasing to the northeast. Only one heavy pollution event occurred during heating period in 2018. The results of the backward trajectory analysis of this heavy pollution event using HYSPLIT show that air masses from inland areas such as the southwest and northwest brought some particulate matter and atmospheric pollutants, which exacerbated Shenyang Air pollution in the city.
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http://dx.doi.org/10.1007/s10661-020-08767-4DOI Listing
December 2020

Emission and migration of PCDD/Fs and major air pollutants from co-processing of sewage sludge in brick kiln.

Chemosphere 2021 Feb 27;265:129120. Epub 2020 Nov 27.

State Key Laboratory of Clean Energy Utilization, National Engineering Laboratory of Waste Incineration Technology and Equipment, Institute of Thermal Power Engineering of Zhejiang University, Hangzhou, 310027, Zhejiang, China. Electronic address:

The annual output of sewage in China is increasing rapidly and continues to grow, so there is an urgent need for a treatment other than landfills. Among various treatment methods, brick production coprocessing of sewage sludge is technically and economically advantageous. The emission characteristics of typical brick kiln coprocessing of sewage sludge with an annual production of 60 million bricks were studied. The major air pollutants and PCDD/Fs in gas and soil were determined. Particulate matter and SO contributed most before treatment, with concentrations of (1.017 ± 0.089) × 10 mg/Nm and (2.770 ± 0.251) × 10 mg/Nm, respectively. After cleaning, the average emitted concentrations of major air pollutants were permissive and homogeneous: 58.13 ± 5.51 mg/Nm for NO, 30.15 ± 9.12 mg/Nm for HCl, 28.63 ± 14.33 mg/Nm for SO, 23.76 ± 3.31 mg/Nm for particulate matter, and 356.8 ± 99.1 for odor. The PCDD/Fs in the exhaust gas and ambient air showed similar distributions and fingerprint characteristics. The annual emission amounts of the PCDD/Fs were 0.265 g/year and 0.0393 g TEQ/year. Moreover, correlation analysis indicated that PCDD/Fs were most relevant to HCl, and particulate matter might be important to SO and fluoride. Further relativity studies showed that the brick kiln was a source of PCDD/Fs but not a main source of major air pollutants to the surrounding environment. All the above pollutants from the brick kiln were permissive with relevant national standards. The results could help with pollution inventories for the brick and tile industry and sewage sludge disposal process.
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http://dx.doi.org/10.1016/j.chemosphere.2020.129120DOI Listing
February 2021

Formation and inhibition of Polychlorinated-ρ-dibenzodioxins and dibenzofurans from mechanical grate municipal solid waste incineration systems.

J Hazard Mater 2021 02 5;403:123812. Epub 2020 Sep 5.

State Key Laboratory for Clean Energy Utilization, Institute for Thermal Power Engineering, Zhejiang University, Hangzhou 310027, China.

This study is carried out in two full-scale (300 t/d) municipal solid waste incinerators (MSWI), focusing on the inhibition effect on polychlorinated-ρ-dibenzodioxins and dibenzofurans (PCDD/F) formation by the Sulfur-, Phosphorus-, and Nitrogen-containing inhibitors. The inhibition efficiencies of total PCDD/F range from 45.77 % to 58.55 %, meanwhile, from 50.1 % to 57.6 % for toxic PCDD/F. X-ray photoelectron spectroscopy results conduct the inhibition effect on the three key factors of PCDD/F formation: catalytic metal, carbon source and chlorine source. Inhibitors can increase the proportion of inorganic chlorine form at the ash surface. The changes of sulfur and phosphorus forms support the inhibition mechanisms of PCDD/F. De novo synthesis is the stable inhibition pathway in this study, meanwhile, the chlorophenols-route and dibenzodioxin and dibenzofuran chlorination also work in some tests. The results are the basics for further industrial application of PCDD/F inhibitors and benefit in controlling the PCDD/F emission from MSWI.
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http://dx.doi.org/10.1016/j.jhazmat.2020.123812DOI Listing
February 2021

Effect of different air pollution control devices on the gas/solid-phase distribution of PCDD/F in a full-scale municipal solid waste incinerator.

Environ Pollut 2020 Oct 29;265(Pt B):114888. Epub 2020 May 29.

State Key Laboratory for Clean Energy Utilization, Institute for Thermal Power Engineering, Zhejiang University, Hangzhou, 310027, China.

The emission of polychlorinated dibenzo-p-dioxins and -furans (PCDD/F) from full-scale municipal solid waste incinerators (MSWI) is harmful to human and environmental health. This study analyzes the effect of different units of an air pollution control devices (APCDs), i.e. the semi-dry scrubber, fabric filter (FF), selective catalytic reduction (SCR), and wet scrubber (WS), on the removal characteristics and gas- and solid-phase distributions of PCDD/F in MSWI flue gas. APCDs reduce PCDD/F concentrations from 24.9 ng Nm to 0.979 ng Nm (2.16 ng I-TEQ Nm to 0.0607 ng I-TEQ Nm), with a total removal efficiency (RE) of 96.1% (97.2% I-TEQ). Specifically, APCDs remove more than 95% of both gas- and solid-phase PCDD/F. The FF coupled with active carbon injection (FF + ACI) substantially reduces both gas- and solid-phase PCDD/F concentrations with an RE of 97.2% (98.7% I-TEQ). Additionally, FF + ACI exhibits a better RE of PCDF (98.9%) than PCDD (94.6%) and leads to PCDD congeners dominating the gas-phase. Both desorption and destruction of PCDD/F occur in the SCR, which favors removal of gas-phase PCDD/F but increases solid-phase PCDD/F. Therefore, SCR only decreases PCDD/F with a low RE of 27.6% (16.9% I-TEQ). However, SCR reduces NO with a high RE of 82.3%, which could inhibit the RE of PCDD/F because of their different reaction mechanisms. WS increases PCDD/F in both the gas and solid-phase by 1.95 times (2.57 times for I-TEQ) due to the memory effect, which typically increases the total mass concentration of PCDD/F and the proportions of lower-chlorinated gas-phase PCDD/F. Migration of gas- and solid-phase PCDD/F are also analyzed according to temperature. The results of this study can contribute to the optimized design of industrial APCDs for controlling PCDD/F emissions from MSWI.
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http://dx.doi.org/10.1016/j.envpol.2020.114888DOI Listing
October 2020

CD19-targeting fusion protein combined with PD1 antibody enhances anti-tumor immunity in mouse models.

Oncoimmunology 2020 21;9(1):1747688. Epub 2020 Apr 21.

Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, China.

In our previous studies, using a B cell vaccine (scFv-Her2), the targeting of tumor-associated antigen Her2 (human epidermal growth factor receptor-2) to B cells via the anti-CD19 single chain variable fragment (scFv) was shown to augment tumor-specific immunity, which enhanced tumor control in the prophylactic and therapeutic setting. However, the fusion protein displayed limited activity against established tumors, and local relapses often occurred following scFv-Her2 treatment, indicating that scFv-Her2-induced responses are inadequate to maintain anti-tumor immunity. In this study, targeting the IV region (D4) of the extracellular region of Her2 to B cells via CD19 molecules (scFv-Her2) was found to enhance IFN-γ-producing-CD8 T cell infiltration in tumor tissues and reduced the number of tumor-infiltrating myeloid-derived suppressor cells (MDSCs). However, negative co-stimulatory molecules such as programmed cell death protein-1 (PD-1), CD160, and LAG-3 on T cells and programmed death protein ligand-1 (PD-L1) on tumor cells were upregulated in the tumor microenvironment after scFv-Her2 treatment. Further, anti-PD1 administration enhanced the efficacy of scFv-Her2 and anti-tumor immunity, as evidenced by the reversal of tumor-infiltrating CD8 T cell exhaustion and the reduction of MDSCs and Treg cells, which suppress T cells and alter the tumor immune microenvironment. Moreover, combining this with anti-PD1 antibodies promoted complete tumor rejection. Our data provide evidence of a close interaction among tumor vaccines, T cells, and the PD-L1/PD-1 axis and establish a basis for the rational design of combination therapy with immune modulators and tumor vaccine therapy.
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http://dx.doi.org/10.1080/2162402X.2020.1747688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7185221PMC
April 2020

Effects of azithromycin on feeding behavior and nutrition accumulation of Daphnia magna under the different exposure pathways.

Ecotoxicol Environ Saf 2020 Jul 9;197:110573. Epub 2020 Apr 9.

Department of Physiology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, 430030, China. Electronic address:

Antibiotics had been paid more and more attention to their toxicity to non-target aquatic organisms in the aquatic environment. As azithromycin (AZI) was an important antibiotic pollutant in water, its toxicity to aquatic organisms had been investigated. In this study, the potential aquatic ecological risk of AZI was identified by assessing the toxicity on the feeding behavior and physiological function of Daphnia magna (D. magna) under the different exposure pathways (aqueous phase exposure vs. food phase exposure). For the food Chlorella pyrenoidosa (C. pyrenoidosa), AZI could inhibit the growth and nutrition accumulation with concentration- and time-response relationship. For D. magna, the feeding behavior was inhibited by AZI under the aqueous phase exposure pathway. However, the feeding behavior was inhibited firstly and then reversed into promotion in the low and medium concentration groups and was continually promoted in the high concentration group under the food phase exposure pathway. The accumulation of polysaccharides and total protein were decreased in D. magna n the high concentration group under the aqueous phase exposure pathway, while the accumulation of polysaccharides and crude fat were decreased in the high concentration group under the food phase exposure pathway. The activity of amylase (AMS) and trypsin in D. magna were decreased after exposure to AZI under the aqueous phase exposure pathway. On the other hand, the activity of AMS in the medium and high concentration groups was decreased under the food phase exposure pathway, but the activity of trypsin was decreased in the medium concentration group and increased in the high concentration group. The levels of ROS in D. magna were also measured and increased in both exposure pathways except in the low concentration group under the food phase exposure pathway, indicating the oxidative stress injury of D. magna. Our results showed that AZI could affect the digestive enzyme activities and oxidative stress-antioxidative system, ultimately leading to the change of D. magna's feeding behavior and nutrition accumulation. These results also provided a comprehensive perspective to evaluate the toxic effects of non-lethal dose antibiotics to non-target aquatic organisms via different exposure pathways.
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http://dx.doi.org/10.1016/j.ecoenv.2020.110573DOI Listing
July 2020

AID assists DNMT1 to attenuate BCL6 expression through DNA methylation in diffuse large B-cell lymphoma cell lines.

Neoplasia 2020 03 12;22(3):142-153. Epub 2020 Feb 12.

Department of Pathogenic Biology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Centre, Xi'an, Shaanxi, China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education of China, Xi'an, Shaanxi, China. Electronic address:

The BCL6 proto-oncogene encodes a transcriptional repressor, which is required for germinal centers (GCs) formation and lymphomagenesis. Previous studies have been reported that the constitutive expression of BCL6 leads to diffuse large B cell lymphoma (DLBCL) through activation-induced cytidine deaminase (AID) mediated chromosomal translocations and mutations. However, other DLBCLs (45%) without structural variants were characterized by abnormally high level of BCL6 expression through an unknown mechanism. Herein, we report that deficiency in AID or methyltransferase 1 (DNMT1) triggers high level of BCL6 expression. AID-DNMT1 complex binds to -0.4 kb -0 kb region of BCL6 promoter and contributes to generate BCL6 methylation which results in inhibition of BCL6 expression. The proteasome pathway inhibitor MG132 induces accumulation of AID and DNMT1, causes decreased BCL6 expression, and leads to cell apoptosis and tumor growth inhibition in DLBCL cell xenograft mice. These findings propose mechanistic insight into an alternative cofactor role of AID in assisting DNMT1 to maintain BCL6 methylation, thus suppress BCL6 transcription in DLBCL. This novel mechanism will provide a new drug selection in the therapeutic approach to DLBCL in the future.
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http://dx.doi.org/10.1016/j.neo.2020.01.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7021553PMC
March 2020

Influence factors and mass balance of memory effect on PCDD/F emissions from the full-scale municipal solid waste incineration in China.

Chemosphere 2020 Jan 22;239:124614. Epub 2019 Aug 22.

State Key Laboratory for Clean Energy Utilization, Institute for Thermal Power Engineering, Zhejiang University, Hangzhou, 310027, China.

Studies are carried out in two wet scrubbing systems (WSSs) subordinated to two similar full-scale (30 t h) municipal solid waste (MSW) incinerators to explore the influence factors and mass balance of memory effect on polychlorinated-ρ-dibenzodioxins and dibenzofurans (PCDD/Fs) emissions. The results show that the memory effect on two WSSs notably increases the TEQ concentrations by 13.6 and 3 times, respectively, through increase in the total mass concentration and the proportions of low-chlorinated PCDD/Fs, directly resulting in the PCDD/F emissions of 1# MSW incinerator over the national standard. PCDD/F adsorption/desorption in WSSs is the reasonable acting mechanisms of memory effect. In addition, memory effect mainly influences gaseous PCDD/F emissions by elevating the percentage of PCDFs, while slightly affects PCDD/Fs in residuals. A mass balance of PCDD/Fs is established to further analyze the influence factors of memory effect on WSSs, indicating filling as the largest potential source discharging PCDD/Fs into outlet flue gas. The results pave the way for further industrial optimization of WSSs design, such as the filling materials with less adsorption capacity on PCDD/Fs and more reasonable operation.
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http://dx.doi.org/10.1016/j.chemosphere.2019.124614DOI Listing
January 2020

Identification and characterization of a murine model of BCR‑ABL1+ acute B‑lymphoblastic leukemia with central nervous system metastasis.

Oncol Rep 2019 Aug 3;42(2):521-532. Epub 2019 Jun 3.

Department of Pathogenic Biology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Centre, Xi'an, Shaanxi 710061, P.R. China.

Breakpoint cluster region (BCR)‑Abelson murine leukemia (ABL)1+ acute B‑lymphoblastic leukemia (B‑ALL) is a disease associated with a dismal prognosis and a high incidence of central nervous system (CNS) metastasis. However, BCR‑ABL1+ B‑ALL with CNS infiltration has not been previously characterized, at least to the best of our knowledge. In the present study, a murine model of BCR‑ABL1+ B‑ALL with CNS metastasis was established using retroviral transduction. The vast majority of BCR‑ABL1+ leukemic cells were found to be immature B cells with a variable proportion of pro‑B and pre‑B populations. The present results indicated that the BCR‑ABL1+ B‑leukemic cells expressed high levels integrin subunit alpha 6 (Itga6) and L‑selectin adhesion molecules, and have an intrinsic ability to disseminate and accumulate in CNS tissues, predominantly in meninges. On the whole, these results provide an approach for addressing the mechanisms of BCR‑ABL1+ B‑ALL with CNS metastasis and may guide the development of novel therapeutic strategies.
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http://dx.doi.org/10.3892/or.2019.7184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6610040PMC
August 2019

Influences of P-N-containing inhibitor and memory effect on PCDD/F emissions during the full-scale municipal solid waste incineration.

Chemosphere 2019 Aug 24;228:495-502. Epub 2019 Apr 24.

State Key Laboratory for Clean Energy Utilization, Institute for Thermal Power Engineering, Zhejiang University, Hangzhou, 310027, China.

Influence of inhibition and memory effect on PCDD/Fs are carried out in a full-scale (23 t h) municipal solid waste (MSW) incinerator under three conditions. Ammonium dihydrogen phosphate (ADP) is injected into the post combustion zone of incinerator. The results show that the inhibition efficiency of PCDD/Fs in flue gas was 53.34% (71% for TEQ), and ADP possibly also didn't have effect on the chlorination reaction of PCDD/F formation. The memory effect phenomenon, PCDD/F adsorption/desorption, is clearly discovered in the wet scrubber system (WSS), resulting in PCDD/F concentration increased by 6.2-19.9 times. Memory effect also changes the distribution of PCDD/Fs by increasing the proportions of low-chlorinated PCDD/Fs, which is easily to be desorbed because of their higher vapor pressure comparing with the high-chlorinated PCDD/Fs. After renewing the scrubbing solution and cleaning the bottom sludge in WSS, the PCDD/F TEQ concentrations decreases from 0.51 to 0.24 ng I-TEQ Nm, further mitigating but still not enough to eliminate the memory effect because the PCDD/F desorption of wall and scrubber fillings in the WSS. The results are paving the way for further industrial optimized design of WSS and assist in controlling the PCDD/F emissions from MSWI.
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http://dx.doi.org/10.1016/j.chemosphere.2019.04.161DOI Listing
August 2019

Previous Radiotherapy Increases the Efficacy of IL-2 in Malignant Pleural Effusion: Potential Evidence of a Radio-Memory Effect?

Front Immunol 2018 11;9:2916. Epub 2018 Dec 11.

Department of Radiation Oncology, Shandong Cancer Hospital affiliated to Shandong University, Jinan, China.

Preclinical and clinical studies have shown that prior receipt of radiotherapy enhances antitumor immune responses, a phenomenon we call the "radio-memory effect." However, all of the evidence regarding this effect to date comes from work with PD1/PDL1 inhibitors. Here we explored whether this effect also occurs with other forms of immune therapy, specifically interleukin-2 (IL-2). We retrospectively assessed outcomes in patients with malignant pleural effusion (MPE) who had previously received radiotherapy for non-small-cell lung cancer (NSCLC) within 18 months before the intrapleural infusion of IL-2 or cisplatin. Radiotherapy sites included lungs, thoracic lymph nodes, and intracranial. All patients received intrapleural infusion of IL-2 or cisplatin, and most had had several cycles of standard chemotherapy for NSCLC. We identified 3,747 patients with MPE (median age 64 years [range 29-88)) treated at one of several institutions from August 2009 through February 2015; 642 patients had been treated with IL-2 and 1102 with cisplatin and had survived for at least 6 months afterward. Among those who received IL-2, 288 had no radiotherapy, 324 had extracranial (i.e., thoracic) radiotherapy, and 36 had intracranial radiotherapy. The median follow-up time for surviving patients was 38 months. Patients who had received extracranial radiotherapy followed by IL-2 had significantly longer PFS than patients who had not received extracranial radiotherapy (i.e., either no radiotherapy or intracranial radiotherapy). Patients who had received intracranial or extracranial radiotherapy followed by IL-2 had significantly longer OS than did other patients. No survival advantage was noted for prior radiotherapy among patients who received intrapleural cisplatin. We speculate that previous radiotherapy could enhance the efficacy of subsequent intrapleural infusion of IL-2, a "radio-memory" effect that could be beneficial in future studies.
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http://dx.doi.org/10.3389/fimmu.2018.02916DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6297715PMC
October 2019

Transcription factor c-Maf is essential for IL-10 gene expression in B cells.

Scand J Immunol 2018 Sep 16;88(3):e12701. Epub 2018 Aug 16.

Department of Orthopaedics, Renmin Hospital, Wuhan University, Wuhan City, China.

Interleukin (IL)-10 is an essential anti-inflammatory cytokine that plays important roles as a negative regulator of immune responses to microbial antigens. c-Maf has been suggested as an essential transcriptional factor for IL-10 production in CD4 T cells and macrophages. However, it remains unclear whether c-Maf participates in IL-10 expression in B cells. In this study, we investigated the role of c-Maf in the transcriptional regulation of IL-10 in regulatory B cells, as well as the underlying molecular mechanism. We found that c-Maf was constitutively expressed in resting B cells. c-Maf expression was upregulated in the presence of LPS and dose-dependently enhanced IL-10 production following binding to the IL-10 promoter. Moreover, a lower expression of c-Maf and decreased production of regulatory B (Breg) cells were detected in mice with collagen-induced arthritis (CIA), which may contribute to the pathological changes. Taken together, these data demonstrate that c-Maf is an indispensable yet constitutive transcription factor for IL-10 gene expression in LPS-activated B cells.
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http://dx.doi.org/10.1111/sji.12701DOI Listing
September 2018

Association of serum interleukin-10, interleukin-17A and transforming growth factor-α levels with human benign and malignant breast diseases.

Exp Ther Med 2018 Jun 30;15(6):5475-5480. Epub 2018 Apr 30.

Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, P.R. China.

Interleukin-10 (IL-10), interleukin-17A (IL-17A) and transforming growth factor α (TGF-α) have been implicated in the progression of breast cancer. However, the diagnostic and prognostic roles of these cytokines in ductal carcinoma remain unclear. The present study therefore aimed to determine the serum levels of IL-10, IL-17 and TGF-α in subjects with benign and malignant breast diseases and to evaluate the clinical significance of these cytokines in ductal carcinoma. Pre-operative serum samples were collected from 378 patients with breast disease and 70 healthy subjects. IL-10, IL-17A and TGF-α levels were measured using ELISA. Serum levels of these cytokine in patients with different breast diseases were evaluated. Furthermore, correlations between levels of these cytokines and the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) in ductal carcinoma were determined. The results demonstrated that serum levels of IL-10 and IL-17A were significantly increased in subjects with atypical hyperplasia and ductal carcinoma. Furthermore, IL-10 and IL-17A levels were increased in patients with a more serious clinical tumor stage and tumors that were ER and PR. Furthermore, high serum levels of TGF-α were associated with HER2 tumors. A strong positive correlation was identified between TGF-α and IL-17A levels. Therefore, the results of the current study revealed that elevated serum IL-10, IL-17A and TGF-α levels are strongly associated with ductal carcinoma, specifically with tumor stage. High serum levels of IL-10 and IL-17A were also associated with the negative expression of ER and PR in ductal carcinoma, and high serum levels of TGF-α were associated with the positive expression of HER2 in ductal carcinoma. Thus, serum cytokine levels may be measured to identify patients with a poor prognosis who may benefit from more aggressive management and treatment.
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http://dx.doi.org/10.3892/etm.2018.6109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5996718PMC
June 2018

Fabrication of Semiconductor ZnO Nanostructures for Versatile SERS Application.

Nanomaterials (Basel) 2017 Nov 19;7(11). Epub 2017 Nov 19.

Ceramics and Biomaterials Research Group, Ton Duc Thang University, Ho Chi Minh City 800010, Vietnam.

Since the initial discovery of surface-enhanced Raman scattering (SERS) in the 1970s, it has exhibited a huge potential application in many fields due to its outstanding advantages. Since the ultra-sensitive noble metallic nanostructures have increasingly exposed themselves as having some problems during application, semiconductors have been gradually exploited as one of the critical SERS substrate materials due to their distinctive advantages when compared with noble metals. ZnO is one of the most representative metallic oxide semiconductors with an abundant reserve, various and cost-effective fabrication techniques, as well as special physical and chemical properties. Thanks to the varied morphologies, size-dependent exciton, good chemical stability, a tunable band gap, carrier concentration, and stoichiometry, ZnO nanostructures have the potential to be exploited as SERS substrates. Moreover, other distinctive properties possessed by ZnO such as biocompatibility, photocatcalysis and self-cleaning, and gas- and chemo-sensitivity can be synergistically integrated and exerted with SERS activity to realize the multifunctional potential of ZnO substrates. In this review, we discuss the inevitable development trend of exploiting the potential semiconductor ZnO as a SERS substrate. After clarifying the root cause of the great disparity between the enhancement factor (EF) of noble metals and that of ZnO nanostructures, two specific methods are put forward to improve the SERS activity of ZnO, namely: elemental doping and combination of ZnO with noble metals. Then, we introduce a distinctive advantage of ZnO as SERS substrate and illustrate the necessity of reporting a meaningful average EF. We also summarize some fabrication methods for ZnO nanostructures with varied dimensions (0-3 dimensions). Finally, we present an overview of ZnO nanostructures for the versatile SERS application.
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http://dx.doi.org/10.3390/nano7110398DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5707615PMC
November 2017

IL-6, IL-8 and TNF-α levels correlate with disease stage in breast cancer patients.

Adv Clin Exp Med 2017 May-Jun;26(3):421-426

Department of Pathogenic Microbiology and Immunology, Xi'an Jiaotong University Health Science Center, Xi'an, China.

Background: Breast cancer is the most common cancer in Chinese women. Inflammation contributes to tumor progression and can be induced by excessive production of pro-inflammatory cytokines such as interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α). However, how their levels relate to the expression of estrogen receptors (ER), progesterone receptors (PR) and human epidermal growth factor receptor 2 (HER2) by the tumor has not been investigated.

Objectives: The aim of the study is to more fully understand the significance of serum IL-6, IL-8 and TNF-α in breast cancers with different ER, PR and HER2 status.

Material And Methods: Preoperative serum samples were collected from 110 patients diagnosed with ductal carcinoma and 30 healthy control subjects. IL-6, IL-8 and TNF-α levels were determined by enzyme-linked immunosorbent assay (ELISA). Associations of cytokine levels with clinical tumor stage were evaluated, and correlations of serum cytokine levels with ER, PR and HER2 expression were determined using the Pearson correlation coefficient.

Results: Serum levels of IL-6 and IL-8 were significantly higher in the subjects with ductal carcinoma than in the controls, and strongly correlated with clinical tumor stage, lymph node metastasis, and ER and HER2 antigen expression (p < 0.05). TNF-α levels in stage III carcinoma patients were significantly higher than in the controls (p < 0.01) and were associated with lymph node metastasis (p < 0.01). A strong positive correlation was found between IL-8 and TNF-α levels in the cancer patients (p < 0.0001).

Conclusions: The study showed that IL-6, IL-8 and TNF-α levels correlated with clinical disease stage and lymph node metastasis as well as with ER and HER2 antigen expression. Specifically, IL-6 and IL-8 seem to have significant potential as prognostic cancer biomarkers. Analyzing serum cytokine levels might help identify patients with a poor prognosis who may benefit from more aggressive disease management.
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http://dx.doi.org/10.17219/acem/62120DOI Listing
October 2017

RAG2 involves the Igκ locus demethylation during B cell development.

Mol Immunol 2017 08 20;88:125-134. Epub 2017 Jun 20.

Department of Pathogenic Biology and Immunology, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education of China, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, No.76 Yanta West Road, Xi'an, Shaanxi,710061, China. Electronic address:

The genes encoding the immunoglobulin κ light chain are assembled during B cell development by V(D)J recombination. For efficient rearrangement, the Igκ locus must undergo a series of epigenetic changes. One such epigenetic mark is DNA methylation. The mechanism that the Igκ locus is selectively demethylated at the pre-B cell stage has not previously been characterized. Here, we employed bisulfite DNA-modification assays to analyze the methylation status of the Igκ locus in primary pre-B cells from RAG-deficient mice with pre-rearranged Igh knock-in allele. We observed that the Igκ locus was hypermethylated in RAG2-deficient pre-B cells but hypomethylated in RAG1-deficient pre-B cells, indicating that wild-type (WT) RAG2 involves the Igκ locus demethylation in a RAG1-independent manner prior to rearrangement. We generated a series of RAG2 mutants between residue 350 and 383. We showed that these mutants mediated the Igκ rearrangement but failed to regulate the Igκ gene demethylation. We further analyzed that these mutants could increase RAG recombinase activity in vivo. We conclude that residues 350-383 region are responsible for endogenous Igκ locus demethylation at pre-B cells. We propose that WT RAG2 has an intrinsic function to regulate the Igκ locus demethylation.
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http://dx.doi.org/10.1016/j.molimm.2017.06.026DOI Listing
August 2017

Dual-core antiresonant hollow core fibers.

Opt Express 2016 Jul;24(15):17453-8

In this work, dual-core antiresonant hollow core fibers (AR-HCFs) are numerically demonstrated, based on our knowledge, for the first time. Two fiber structures are proposed. One is a composite of two single-core nested nodeless AR-HCFs, exhibiting low confinement loss and a circular mode profile in each core. The other has a relatively simple structure, with a whole elliptical outer jacket, presenting a uniform and wide transmission band. The modal couplings of the dual-core AR-HCFs rely on a unique mechanism that transfers power through the air. The core separation and the gap between the two cores influence the modal coupling strength. With proper designs, both of the dual-core fibers can have low phase birefringence and short modal coupling lengths of several centimeters.
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http://dx.doi.org/10.1364/OE.24.017453DOI Listing
July 2016

The crystal structure of Cpf1 in complex with CRISPR RNA.

Nature 2016 Apr 20;532(7600):522-6. Epub 2016 Apr 20.

School of Life Science and Technology, Harbin Institute of Technology, Harbin 150080, China.

The CRISPR-Cas systems, as exemplified by CRISPR-Cas9, are RNA-guided adaptive immune systems used by bacteria and archaea to defend against viral infection. The CRISPR-Cpf1 system, a new class 2 CRISPR-Cas system, mediates robust DNA interference in human cells. Although functionally conserved, Cpf1 and Cas9 differ in many aspects including their guide RNAs and substrate specificity. Here we report the 2.38 Å crystal structure of the CRISPR RNA (crRNA)-bound Lachnospiraceae bacterium ND2006 Cpf1 (LbCpf1). LbCpf1 has a triangle-shaped architecture with a large positively charged channel at the centre. Recognized by the oligonucleotide-binding domain of LbCpf1, the crRNA adopts a highly distorted conformation stabilized by extensive intramolecular interactions and the (Mg(H2O)6)(2+) ion. The oligonucleotide-binding domain also harbours a looped-out helical domain that is important for LbCpf1 substrate binding. Binding of crRNA or crRNA lacking the guide sequence induces marked conformational changes but no oligomerization of LbCpf1. Our study reveals the crRNA recognition mechanism and provides insight into crRNA-guided substrate binding of LbCpf1, establishing a framework for engineering LbCpf1 to improve its efficiency and specificity for genome editing.
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http://dx.doi.org/10.1038/nature17944DOI Listing
April 2016

TIGIT overexpression diminishes the function of CD4 T cells and ameliorates the severity of rheumatoid arthritis in mouse models.

Exp Cell Res 2016 Jan 9;340(1):132-8. Epub 2015 Dec 9.

Department of Immunology and Pathogenic Biology, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi Province, 710061, China. Electronic address:

Rheumatoid arthritis (RA) is an immune-mediated disease with a pathogenesis that involves CD4 T cell activation. Multiple immune regulatory molecules expressed on CD4(+) T cells were involved in RA pathogenesis. In this study, we investigated the role of T cell immunoglobulin and ITIM (immunoreceptor tyrosine-based inhibition motif) domain (TIGIT) in RA. The frequency of TIGIT-positive CD4(+) T cells in the synovial fluid (SF) of active RA patients was lower than that of inactive RA patients. And a negative correlation between RA disease activity and TIGIT expression was found. In CD4(+) T cells isolated from SF of active RA patients, TIGIT upregulation significantly decreased cell proliferation, as shown by MTT assay. TIGIT overexpression also significantly decreased the production of IFN-γ and IL-17, and increased that of IL-10, as determined by ELISA and qRT-PCR. In CD4(+) T cells isolated from SF of inactive RA patients, TIGIT was silenced by siRNA transfection. As expected, TIGIT knockdown resulted in an opposite effect on cell proliferation and the production of cytokines, including IFN-γ, IL-17 and IL-10. A RA mouse model was established using type II collagen induction. TIGIT was upregulated in RA mouse by lentivector infection. As expected, TIGIT overexpression in vivo significantly alleviated the disease severity and deceased the levels of anti-collagen II antibodies. TIGIT upregulation in the early stage was more effective to alleviate disease severity. Our data suggested the potential therapeutic role of TIGIT in RA patients.
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http://dx.doi.org/10.1016/j.yexcr.2015.12.002DOI Listing
January 2016

Intracranial malignant melanoma: A report of 7 cases.

Oncol Lett 2015 Oct 24;10(4):2171-2175. Epub 2015 Jul 24.

Department of Psychology, Chinese PLA General Hospital, Beijing 100853, P.R. China.

The aim of the present study was to investigate the clinical diagnosis and treatment of intracranial malignant melanoma. For this purpose, the clinical manifestation, signs, cerebrospinal fluid (CSF) contents, imageology, pathological features, treatment and prognosis of 7 cases of intracranial malignant melanoma were analyzed in The Chinese PLA General Hospital (Beijing, China) from 1996 to 2013. All the melanoma cases were confirmed by histopathology, and CSF cytopathology demonstrated that there were 5 cases of primary malignant melanoma and 2 cases of secondary malignant melanoma. Among the patients, 4 presented with >1 pigmented nevus in the skin, and 1 presented with skin melanoma. Intracranial malignant melanoma mostly affects middle-aged males. CSF cytopathology and imageology (particularly enhanced magnetic resonance), are important tools in the diagnosis of the disease. Particularly, when a patient presents with a pigmented nevus in the skin and an abnormal lesion in the brain, a diagnosis of intracranial malignant melanoma should be considered.
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http://dx.doi.org/10.3892/ol.2015.3537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4579826PMC
October 2015

Two types of isolated epileptic nystagmus: case report.

Int J Clin Exp Med 2015 15;8(8):13500-7. Epub 2015 Aug 15.

Department of Neurology, Chinese PLA General Hospital 28 Fuxing Road, Beijing, China.

Epileptic nystagmus (EN) is a quick, repetitive jerky movement of the eyeball caused by seizure activity, unaccompanied by other ictal phenomena rare. Here, we described two cases, one characterized by binocular and the other by monocular isolated epileptic nystagmus (IEN), and we identified the characteristics of the etiology, clinical manifestations, electroencephalogram, imaging, treatment and prognosis in epileptic nystagmus through reviewing literature. We found IEN occurs more frequently in children than in adults. Etiological factors included trauma, cerebral vascular disease, tumor, and anoxia. The frequency of IEN was high, which varied from several to hundreds of times per day, and the duration of it was usually less than 1 minute. EN and its subtypes, such as epileptic monocular nystagmus, vertical epileptic nystagmus, epileptic skew deviation, periodic alternating nystagmus, and partial oculo-clonic status, are rare. The fast phase of the nystagmus was contralateral to the epileptogenic zone in most cases. Periodic lateralized epileptiform discharges (PLEDs) is a distinct EEG pattern in EN. Our findings suggested that the occipital lobe may plays a key role in the origin of EN.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4612972PMC
November 2015

Dectin-1 Activation by a Natural Product β-Glucan Converts Immunosuppressive Macrophages into an M1-like Phenotype.

J Immunol 2015 Nov 9;195(10):5055-65. Epub 2015 Oct 9.

Division of Hematology/Oncology, Department of Medicine, James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202; Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY 40202;

Tumor-associated macrophages (TAM) with an alternatively activated phenotype have been linked to tumor-elicited inflammation, immunosuppression, and resistance to chemotherapies in cancer, thus representing an attractive target for an effective cancer immunotherapy. In this study, we demonstrate that particulate yeast-derived β-glucan, a natural polysaccharide compound, converts polarized alternatively activated macrophages or immunosuppressive TAM into a classically activated phenotype with potent immunostimulating activity. This process is associated with macrophage metabolic reprograming with enhanced glycolysis, Krebs cycle, and glutamine utilization. In addition, particulate β-glucan converts immunosuppressive TAM via the C-type lectin receptor dectin-1-induced spleen tyrosine kinase-Card9-Erk pathway. Further in vivo studies show that oral particulate β-glucan treatment significantly delays tumor growth, which is associated with in vivo TAM phenotype conversion and enhanced effector T cell activation. Mice injected with particulate β-glucan-treated TAM mixed with tumor cells have significantly reduced tumor burden with less blood vascular vessels compared with those with TAM plus tumor cell injection. In addition, macrophage depletion significantly reduced the therapeutic efficacy of particulate β-glucan in tumor-bearing mice. These findings have established a new paradigm for macrophage polarization and immunosuppressive TAM conversion and shed light on the action mode of β-glucan treatment in cancer.
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http://dx.doi.org/10.4049/jimmunol.1501158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4637216PMC
November 2015

MicroRNA-24 Regulates Osteogenic Differentiation via Targeting T-Cell Factor-1.

Int J Mol Sci 2015 May 21;16(5):11699-712. Epub 2015 May 21.

Department of Immunology and Pathogenic Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China.

MicroRNAs (miRNAs) have been reported to have diverse biological roles in regulating many biological processes, including osteogenic differentiation. In the present study, we identified that miR-24 was a critical regulator during osteogenic differentiation. We found that overexpression of miR-24 significantly inhibited osteogenic differentiation, which decreased alkaline phosphatase activity, matrix mineralization and the expression of osteogenic differentiation markers. In contrast, inhibition of miR-24 exhibited an opposite effect. Furthermore, we delineated that miR-24 regulates post-transcriptionals of T-cell factor-1 (Tcf-1) via targeting the 3'-untranslated region (UTR) of Tcf-1 mRNA. MiR-24 was further found to regulate the protein expression of Tcf-1 in the murine osteoprogenitors cells and bone mesenchymal stem cells. Additionally, the positive effect of miR-24 suppression on osteoblast differentiation was apparently abrogated by Tcf-1 silencing. Taken together, our data suggest that miR-24 participates in osteogenic differentiation by targeting and regulating Tcf-1 expression in osteoblastic cells.
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http://dx.doi.org/10.3390/ijms160511699DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4463725PMC
May 2015

MiR-21 overexpression improves osteoporosis by targeting RECK.

Mol Cell Biochem 2015 Jul 17;405(1-2):125-33. Epub 2015 Apr 17.

Department of Orthopedics, The 1st Affiliated Hospital of Medical College, Xi'an Jiaotong University, 277 West Yanta Street, Xi'an, 710061, Shaanxi, China,

Osteoporosis is a kind of metabolic bone disorder. MicroRNA-21 (miR-21) has been proven to play an important role in bone formation, whereas its role in osteoporosis is unclear. In the present study, miR-21 expression was inhibited by TNF-α in mesenchymal stem cells (MSCs). TNF-α induced cell apoptosis, and inhibited cell proliferation and differentiation of MSCs. Whereas the effect was reversed by miR-21 mimics. Expression of reversion-inducing cysteine-rich protein with Kazal motifs (RECK) which is a predicted target of miR-21 was inhibited by miR-21 mimics. A luciferase reporter gene assay showed that miR-21 directly bound to RECK 3'-UTR. The effect of TNF-α on MSCs was reversed by RECK siRNA which was consistent with miR-21 mimics. The expression of MT1-MMP was inhibited by TNF-α and enhanced by RECK siRNA and miR-21 mimics. For the in vivo study, an osteoporosis model (OVX) was established by bilateral oophorectomy in mice. The expression of miR-21 decreased and RECK increased in the OVX mice. When treated with lentiviral RECK shRNA, the osteocalcin concentration and alkaline phosphate activity of the OVX mice decreased. The bone mineral density of the right femur mid-diaphysis was improved by RECK shRNA. Collectively, miR-21 modulated the osteoporosis by targeting RECK. These results emphasize the role of miR-21 during osteoporosis and suggest RECK might be a new medical target for osteoporosis.
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http://dx.doi.org/10.1007/s11010-015-2404-4DOI Listing
July 2015