Publications by authors named "Yiwen He"

18 Publications

  • Page 1 of 1

CO introduced the coagulation-flocculation of oil acidized wastewater: pollutant removal and cost analysis.

Water Sci Technol 2021 Mar;83(5):1108-1117

School of Civil Engineering, Chang'an University, Xi'an 710054, China E-mail:

It is difficult to adjust the pH of oil acidized wastewater rich in Ca, thus hindering the polyacrylamide (PAM) flocculation. This study aims at accelerating the flocculation process by introducing CO into the water to induce the formation of CaCO nuclei. The order in which CO and NaOH were added affected the floc structures. Compared with CO-NaOH-PAM, the flocs of NaOH-CO-PAM were more compact and more CaCO crystals were formed. The aqueous Ca involved in the reaction reached 20%, and CO utilization was enhanced. The settling time was shortened by half (from 20 to 3 min), and NaOH consumption was reduced by one-tenth (from 0.03 to 0.003 mol), hence significantly reducing the costs. Due to the higher settling rate and shorter contact time, the NaOH-CO-PAM flocs adsorbed less so that the residual oil was 124 mg·L, while in the case of CO-NaOH-PAM it was 88 mg·L. As a promising coagulation aid, CO can also be used to mineralize pollutants in wastewater.
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http://dx.doi.org/10.2166/wst.2021.054DOI Listing
March 2021

PIWI-interacting RNA sequencing profiles in maternal plasma-derived exosomes reveal novel non-invasive prenatal biomarkers for the early diagnosis of nonsyndromic cleft lip and palate.

EBioMedicine 2021 Mar 24;65:103253. Epub 2021 Feb 24.

Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang, PR China. Electronic address:

Background: Congenital malformations are common birth defects with high neonatal morbidity and mortality. It is essential to find simpler and more efficient biomarkers for early prenatal diagnosis. Therefore, we investigated PIWI-interacting RNAs (piRNAs) as potential prenatal biomarkers in plasma-derived exosomes from pregnant women carrying foetuses with congenital malformations.

Methods: Small RNA sequencing was used to screen piRNA biomarkers in plasma-derived exosomes of five pregnant women carrying foetuses with nonsyndromic cleft lip and palate (nsCLP) and five women carrying normal foetuses. Differentially expressed piRNAs were verified in 270 pregnant women, including 111 paired women carrying foetuses with congenital malformations and normal foetuses (at 24 gestational weeks), 10 paired women carrying foetuses with nsCLP and normal foetuses (at 15-19 gestational weeks), and 28 women at different stages of normal pregnancy. piRNA biomarkers were also verified in placentas, umbilical cords, fetal medial calf muscles, and lip tissues of nsCLP and normal foetuses.

Findings: We identified a biomarker panel of three pregnancy-associated exosomal piRNAs (hsa-piR-009228, hsa-piR-016659, and hsa-piR-020496) could distinguish nsCLP foetuses from normal foetuses. These three piRNAs had better diagnostic accuracy for nsCLP at the early gestational stage, at which time typical malformations were not detected upon prenatal ultrasound screening, and had diagnostic value for neural tube defects (NTDs) and congenital heart defects (CHDs).

Interpretation: Our work revealed the potential clinical applications of piRNAs for predicting nsCLP, NTDs, and CHDs.

Funding: National Key Research and Development Program, National Natural Science Foundation of China, and LiaoNing Revitalization Talents Program .
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http://dx.doi.org/10.1016/j.ebiom.2021.103253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921467PMC
March 2021

Effect of high-pressure pre-soaking on texture and retrogradation properties of parboiled rice.

J Sci Food Agric 2021 Jan 8. Epub 2021 Jan 8.

Engineering Research Center of Bio-Process of Ministry of Education, School of Food and Biological Engineering, Hefei University of Technology, Hefei, P. R. China.

Background: The poor palatability, low digestibility, and unpleasant color of parboiled rice (PR) have severely hampered its acceptance by consumers. It is hence necessary and urgent to develop a new method for producing high-quality PR. In the current study, the effect of high hydrostatic pressure (HHP) pre-soaking on the color, textural properties, and the degree of retrogradation of PR was investigated.

Results: With HHP from 100 to 500 MPa, the water adsorption rate increased and cooking time decreased. Parboiled rice samples presented higher lightness scores (L) and had lower color intensity (B). Compared with a control group, PR samples treated with high-pressure pre-soaking showed a reduction of hardness values from 0.69% to 32.99%, and gumminess values also decreased from 8.58% to 33.62%. The differential scanning calorimetry (DSC) results indicated that the enthalpy values of PR samples decreased after high pressure pre-soaking. The molecular structure of PR characterized by Fourier transform infrared spectrometry confirmed that HHP pre-soaking could decrease the retrogradation level.

Conclusion: The findings outlined above suggest that the texture and retrogradation properties of PR were improved after high-pressure pre-soaking. © 2021 Society of Chemical Industry.
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http://dx.doi.org/10.1002/jsfa.11058DOI Listing
January 2021

Complement factors and alpha-fetoprotein as biomarkers for noninvasive prenatal diagnosis of neural tube defects.

Ann N Y Acad Sci 2020 10 5;1478(1):75-91. Epub 2020 Aug 5.

Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang, China.

Neural tube defects (NTDs) are serious congenital malformations. In this study, we aimed to identify more specific and sensitive maternal serum biomarkers for noninvasive NTD screenings. We collected serum from 37 pregnant women carrying fetuses with NTDs and 38 pregnant women carrying normal fetuses. Isobaric tags for relative and absolute quantitation were conducted for differential proteomic analysis, and an enzyme-linked immunosorbent assay was used to validate the results. We then used a support vector machine (SVM) classifier to establish a disease prediction model for NTD diagnosis. We identified 113 differentially expressed proteins; of these, 23 were either up- or downregulated 1.5-fold or more, including five complement proteins (C1QA, C1S, C1R, C9, and C3); C3 and C9 were downregulated significantly in NTD groups. The accuracy rate of the SVM model of the complement factors (including C1QA, C1S, and C3) was 62.5%, with 60% sensitivity and 67% specificity, while the accuracy rate of the SVM model of alpha-fetoprotein (AFP, an established biomarker for NTDs) was 62.5%, with 75% sensitivity and 50% specificity. Combination of the complement factor and AFP data resulted in the SVM model accuracy of 75%, and receiver operating characteristic curve analysis showed 75% sensitivity and 75% specificity. These data suggest that a disease prediction model based on combined complement factor and AFP data could serve as a more accurate method of noninvasive prenatal NTD diagnosis.
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http://dx.doi.org/10.1111/nyas.14443DOI Listing
October 2020

Characterization of a Sulfhydryl Oxidase From as a Target for Blocking Parasite Transmission.

Front Cell Infect Microbiol 2020 26;10:311. Epub 2020 Jun 26.

Department of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, China.

Quiescin sulfhydryl oxidase (QSOX), present in a wide variety of eukaryotic species, catalyzes the insertion of disulfide bonds into unfolded, reduced proteins. Here we characterized the QSOX protein from the rodent malaria parasite (PbQSOX), which is conserved in all sequenced malaria parasite species. The PbQSOX protein was not expressed in asexual erythrocytic stages, but was most abundantly expressed in ookinetes. Indirect immunofluorescence assays revealed PbQSOX was not only localized in cytoplasm of gametocytes, gametes and ookinetes, but also expressed on the surface of gametes and ookinetes. Western blot identified extracellular presence of PbQSOX in the culture medium of ookinetes suggestive of secretion. deletion (Δ) did not affect asexual intraerythrocytic development, but reduced exflagellation of male gametocytes as well as formation and maturation of ookinetes. deletion also led to a significant increase in the reduced thiol groups of ookinete surface proteins, suggesting that it may play a role in maintaining the integrity of disulfide bonds of surface proteins, which might be needed for ookinete development. Mosquitoes that fed on Δ-infected mice showed a significant reduction in ookinete and oocyst numbers compared to those fed on wild-type parasite-infected mice. Further, both polyclonal mouse antisera and a monoclonal antibody against the recombinant PbQSOX exhibited substantial transmission-blocking activities in and mosquito feeding assays, suggesting QSOX is a potential target for blocking parasite transmission.
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http://dx.doi.org/10.3389/fcimb.2020.00311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332561PMC
June 2020

A novel frameshift variant in SON causes Zhu-Tokita-Takenouchi-Kim Syndrome.

J Clin Lab Anal 2020 Aug 14;34(8):e23326. Epub 2020 Apr 14.

Department of Obstetrics and Gynecology, Peking University International Hospital, Beijing, China.

Background: Zhu-Tokita-Takenouchi-Kim syndrome is a severe multisystem developmental disorder characterized by intellectual disability, developmental delay, malformations of the cerebral cortex, epilepsy, vision problems, musculoskeletal abnormalities, and congenital malformations. This syndrome is caused by heterozygous pathogenic variants in the SON gene at chromosome 21q22.1.

Objectives: The aim of this study was to investigate the pathogenesis of a 4-year-old Chinese child who displayed severe intellectual disability, delayed psychomotor development, and facial dysmorphism.

Methods: A sequential detection including chromosome karyotyping, chromosome microarray analysis (CMA), and whole-exome sequencing (WES) was performed on this child. The familial verification of WES result was conducted by Sanger sequencing.

Results: A de novo frameshift variant SON: c.5230delC (p.Arg1744ValfsTer29) was identified in the proband. The identical variant was not found in his family members. The frequencies of this variant in gnomAD/gnomAD_EAS databases were both none.

Conclusions: This study substantiates that SON: c.5230delC (p.Arg1744ValfsTer29) is a pathogenic variant of Zhu-Tokita-Takenouchi-Kim syndrome and it is the first time to report Zhu-Tokita-Takenouchi-Kim syndrome in China.
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http://dx.doi.org/10.1002/jcla.23326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7439338PMC
August 2020

Theoretical design, preparation, and evaluation of Ginkgolide B molecularly imprinted polymers.

J Sep Sci 2020 Jan 21;43(2):514-523. Epub 2019 Nov 21.

Engineering Research Center of Bio-Process of Ministry of Education, School of Food and Biological Engineering, Hefei University of Technology, Hefei, P. R. China.

Ginkgolide B is in great demand worldwide on account of its extensive and excellent pharmacological effects, however, it is difficult to separate and purify ginkgolide B. In this study, ginkgolide B molecularly imprinted polymers were prepared by combining software simulation and molecular imprinting technique, and its characterization and adsorption performed evaluation were performed to understand the adsorption behavior of the polymers. The adsorption equilibrium concentration of molecularly imprinted polymers was 0.70 mg/mL, and the adsorption equilibrium time was 4 h. Meanwhile, the adsorption isotherm of the polymers for ginkgolide B fitted well with the Langmuir model, and the adsorption kinetics was in line with the pseudo-second-order kinetics. In contrast, the adsorption capacity of molecularly imprinted polymers on ginkgolide B was higher than that of non-molecular imprinted polymers, with better selectivity and better adsorption after repeated use for six times. The application experiments showed that molecular imprinted polymers have a good adsorption effect in low purity samples. Therefore, the polymers reported herein can be expected to apply in the adsorption and separation of ginkgolide B samples.
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http://dx.doi.org/10.1002/jssc.201900675DOI Listing
January 2020

Genome-wide discovery of somatic coding and noncoding mutations in pediatric endemic and sporadic Burkitt lymphoma.

Blood 2019 03 7;133(12):1313-1324. Epub 2019 Jan 7.

Lymphoid Malignancies Branch, Center for Cancer Research and.

Although generally curable with intensive chemotherapy in resource-rich settings, Burkitt lymphoma (BL) remains a deadly disease in older patients and in sub-Saharan Africa. Epstein-Barr virus (EBV) positivity is a feature in more than 90% of cases in malaria-endemic regions, and up to 30% elsewhere. However, the molecular features of BL have not been comprehensively evaluated when taking into account tumor EBV status or geographic origin. Through an integrative analysis of whole-genome and transcriptome data, we show a striking genome-wide increase in aberrant somatic hypermutation in EBV-positive tumors, supporting a link between EBV and activation-induced cytidine deaminase (AICDA) activity. In addition to identifying novel candidate BL genes such as , , and , we demonstrate that EBV-positive tumors had significantly fewer driver mutations, especially among genes with roles in apoptosis. We also found immunoglobulin variable region genes that were disproportionally used to encode clonal B-cell receptors (BCRs) in the tumors. These include IGHV4-34, known to produce autoreactive antibodies, and IGKV3-20, a feature described in other B-cell malignancies but not yet in BL. Our results suggest that tumor EBV status defines a specific BL phenotype irrespective of geographic origin, with particular molecular properties and distinct pathogenic mechanisms. The novel mutation patterns identified here imply rational use of DNA-damaging chemotherapy in some patients with BL and targeted agents such as the CDK4/6 inhibitor palbociclib in others, whereas the importance of BCR signaling in BL strengthens the potential benefit of inhibitors for PI3K, Syk, and Src family kinases among these patients.
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http://dx.doi.org/10.1182/blood-2018-09-871418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6428665PMC
March 2019

Tebuconazole induces triazole-resistance in Aspergillus fumigatus in liquid medium and soil.

Sci Total Environ 2019 Jan 19;648:1237-1243. Epub 2018 Aug 19.

Institute of Pesticide and Environmental Toxicology, College of Agricultural and Biotechnology, Zhejiang University, Hangzhou 310058, China. Electronic address:

Aspergillus fumigatus is the mainly leading cause of invasive aspergillosis associated with significant morbidity and mortality in immunocompromised patients. However, triazole resistance in A. fumigatus has increased dramatically throughout the world nowadays. The emergence of triazole resistance has aroused growing concern. This research was conducted to assess if the resistance in A. fumigatus and its associated mutations in the cpy51A gene could be induced during its exposure to tebuconazole in liquid medium and in soil. The results indicated that the resistance in A. fumigatus with mutations of TR46/Y121F/T289A could be induced by tebuconazole in liquid medium. Nine resistant strains without any mutation in cyp51A were isolated in soil treated with tebuconazole at levels of 0.5-5.0 mg kg after incubation for 120 d. The two (HI-30 and HI-36) of the nine resistant isolates were caused by overexpression of AtrF, AfuMDR1, cyp51A and cyp51B and hereditary stability. This strongly implies that conventional application of tebuconazole for plant protection will cause resistance of A. fumigatus to triazole medicals in agricultural soils.
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http://dx.doi.org/10.1016/j.scitotenv.2018.08.247DOI Listing
January 2019

Chiral triazole fungicide tebuconazole: enantioselective bioaccumulation, bioactivity, acute toxicity, and dissipation in soils.

Environ Sci Pollut Res Int 2018 Sep 27;25(25):25468-25475. Epub 2018 Jun 27.

Institute of Pesticide and Environmental Toxicology, College of Agriculture and Biotechnology, Zhejiang University, Hangzhou, 310029, China.

Enantioselectivity in environmental behavior and toxic effect of chiral pesticides has been received much attention. In this study, enantioselective bioactivity towards target organism Botrytis cinerea, acute toxicity and bioaccumulation in Eisenia fetida, and degradation in five kinds of soil under laboratory conditions regarding triazole fungicide tebuconazole were investigated. The results showed that fungicidal activity to Botrytis cinerea of R-(-)-tebuconazole was 44 times higher than S-(+)-tebuconazole with an order of R-(-)-tebuconazole > rac-tebuconazole > S-(+)-tebuconazole. No significant difference was found in acute toxicity of rac-, R-, and S-tebuconazole to E. fetida with 48-h EC of 10.78, 10.48, and 10.84 μg/cm, respectively. Dissipation of tebuconazole in the five tested soils varied upon soil characteristics with half-life ranging from 32.2 to 216.6 days. Enantioselective and rapid dissipation of tebuconazole were observed in soils Hainan and Huajiachi, compared to the other soils. Enantioselective accumulation of tebuconazole in E. fetida was found with a preferential of S-(+)-tebuconazole although no significant difference in acute toxicity to E. fetida between rac-tebuconazole and enantiomers. The results indicated that S-(+)-tebuconazole with less fungicidal activity may be more likely to be accumulated in earthworm E. fetida. This research is helpful to better evaluate the environmental and ecological risk of tebuconazole on enantiomeric level.
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http://dx.doi.org/10.1007/s11356-018-2587-9DOI Listing
September 2018

Characterization of Plasmodium berghei Pbg37 as Both a Pre- and Postfertilization Antigen with Transmission-Blocking Potential.

Infect Immun 2018 08 23;86(8). Epub 2018 Jul 23.

Department of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning, China

Transmission-blocking vaccines (TBVs) interrupting malaria transmission are an integrated tool for malaria eradication. We characterized a sexual-stage-specific gene (PBANKA_060330) from and studied its potential for use as a TBV. This gene, referred to as , encodes a protein of 37 kDa with a signal peptide and multiple transmembrane domains and is preferentially expressed in gametocytes. A recombinant Pbg37 (rPbg37) protein targeting the N-terminal 63 amino acids (amino acids 26 to 88) expressed in bacteria elicited strong antibody responses in mice. Western blotting demonstrated Pbg37 expression in gametocytes, zygotes, and, to a lesser extent, ookinetes and its predominant association with the membranes of gametocytes. Indirect immunofluorescence assay showed an abundant surface localization of Pbg37 on gametes and zygotes but reduced amounts on retorts and ookinetes. Knockout of (Δ) led to a considerable reduction in gametocytemia, which translated into a ~92.1% decrease in the oocyst number in mosquitoes. Deletion of had a more substantial influence on the development and maturation of microgametocytes. As a result, the Δ lines exhibited a higher female/male gametocyte ratio, fewer mature male gametocytes, and defects in the exflagellation of mature microgametocytes. To test the transmission-blocking potential of Pbg37, an ookinete assay showed that the major inhibitory effects of anti-Pbg37 antiserum were on the exflagellation and fertilization processes. Direct feeding of mosquitoes on mice immunized with rPbg37 or a control protein showed that rPbg37-immunized and -infected mice had a significant reduction (49.1%) in oocyst density compared to the controls. The conservation of this gene in warrants further investigations in human malaria parasites.
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http://dx.doi.org/10.1128/IAI.00785-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6056874PMC
August 2018

Characterization of Pb51 in Plasmodium berghei as a malaria vaccine candidate targeting both asexual erythrocytic proliferation and transmission.

Malar J 2017 Nov 13;16(1):458. Epub 2017 Nov 13.

Department of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, 110001, Liaoning, China.

Background: A vaccine that targets multiple developmental stages of malaria parasites would be an effective tool for malaria control and elimination.

Methods: A conserved gene in Plasmodium, the Plasmodium berghei gene (PBANKA_020570) encoding a 51 kDa protein (pb51 gene), was identified through search of the PlasmoDB database using a combination of expression and protein localization criteria. A partial domain of the Pb51 protein was expressed in a prokaryotic expression system (rPb51) and used for immunization in mice. The protein expression profile and localization were studied by Western blot and indirect immunofluorescence assay (IFA), respectively. The inhibitory effect of the anti-rPb51 antibodies on parasite proliferation was evaluated in erythrocytes in vivo. The transmission-blocking activity of the immune sera was determined by in vitro ookinete conversion assay and by direct mosquito feeding assay (DFA).

Results: The rPb51 elicited specific antibodies in mice. Western blot confirmed Pb51 expression in schizonts, gametocytes and ookinetes. IFA showed localization of Pb51 on the outer membranes of schizonts, gametocytes, zygotes, retorts, ookinetes and sporozoites of P. berghei. Mice immunized with the rPb51 protein significantly reduced parasite proliferation and gametocyte conversion in vivo. Moreover, the rPb51 antisera also significantly reduced the in vitro ookinete conversion when added into the ookinete culture medium. In DFA, mice immunized with the rPb51 reduced the prevalence of mosquito infection by 21.3% and oocyst density by 54.8%.

Conclusions: In P. berghei, P51 was expressed in both asexual erythrocytic and sexual stages and localized on the surface of these stages with the exception of the ring stage. The anti-rPb51 antibodies inhibited both P. berghei proliferation in mice and transmission of the parasite to mosquitoes.
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http://dx.doi.org/10.1186/s12936-017-2107-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5683326PMC
November 2017

Ultra-sensitive near-infrared graphene photodetectors with nanopillar antennas.

Nanoscale 2017 Nov;9(44):17459-17464

SUNY College of Nanoscale Science and Engineering, State University of New York, Albany, New York 12203, USA.

Graphene has been demonstrated as a candidate for optoelectronic devices due to its broad absorption spectrum and ultra-high carrier mobility. However, graphene is essentially transparent in visible and near-infrared regimes with an absorptivity of 2.3%, which largely limits its application in photodetection. Here, we show that metallic nanopillar antennas could improve light absorption in graphene detectors. The coupled antennas help to concentrate a free space electromagnetic wave around the nanopillars by localized surface plasmon resonance, strongly impacted by geometrical design. It is found that spectral selectivity can be realized by tuning key geometrical parameters such as period, radius, and height of the metallic nanopillar, leading to wavelength-tunable photodetectors within a broad range from 0.6 μm to 1.2 μm. With the optimized design, the detector exhibits an excellent photoresponsivity of 7 A W at a wavelength of 0.82 μm.
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http://dx.doi.org/10.1039/c7nr06009bDOI Listing
November 2017

Functional characterization of Plasmodium berghei PSOP25 during ookinete development and as a malaria transmission-blocking vaccine candidate.

Parasit Vectors 2017 01 5;10(1). Epub 2017 Jan 5.

Department of Entomology, The Pennsylvania State University, University Park, PA, 16802, USA.

Background: Plasmodium ookinete surface proteins as post-fertilization target antigens are potential malaria transmission-blocking vaccine (TBV) candidates. Putative secreted ookinete protein 25 (PSOP25) is a highly conserved ookinete surface protein, and has been shown to be a promising novel TBV target. Here, we further investigated the TBV activities of the full-length recombinant PSOP25 (rPSOP25) protein in Plasmodium berghei, and characterized the potential functions of PSOP25 during the P. berghei life-cycle.

Methods: We expressed the full-length P. berghei PSOP25 protein in a prokaryotic expression system, and developed polyclonal mouse antisera and a monoclonal antibody (mAb) against the recombinant protein. Indirect immunofluorescence assay (IFA) and Western blot were used to test the specificity of antibodies. The transmission-blocking (TB) activities of antibodies were evaluated by the in vitro ookinete conversion assay and by direct mosquito feeding assay (DFA). Finally, the function of PSOP25 during Plasmodium development was studied by deleting the psop25 gene.

Results: Both polyclonal mouse antisera and anti-rPSOP25 mAb recognized the PSOP25 proteins in the parasites, and IFA showed the preferential expression of PSOP25 on the surface of zygotes, retorts and mature ookinetes. In vitro, these antibodies significantly inhibited ookinetes formation in an antibody concentration-dependent manner. In DFA, mice immunized with the rPSOP25 and those receiving passive transfer of the anti-rPSOP25 mAb reduced the prevalence of mosquito infection by 31.2 and 26.1%, and oocyst density by 66.3 and 63.3%, respectively. Genetic knockout of the psop25 gene did not have a detectable impact on the asexual growth of P. berghei, but significantly affected the maturation of ookinetes and the formation of midgut oocysts.

Conclusions: The full-length rPSOP25 could elicit strong antibody response in mice. Polyclonal and monoclonal antibodies against PSOP25 could effectively block the formation of ookinetes in vitro and transmission of the parasites to mosquitoes. Genetic manipulation study indicated that PSOP25 is required for ookinete maturation in P. berghei. These results support further testing of the PSOP25 orthologs in human malaria parasites as promising TBV candidates.
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http://dx.doi.org/10.1186/s13071-016-1932-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5217559PMC
January 2017

Neuroprotective Effects of Clostridium butyricum against Vascular Dementia in Mice via Metabolic Butyrate.

Biomed Res Int 2015 7;2015:412946. Epub 2015 Oct 7.

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

Probiotics actively participate in neuropsychiatric disorders. However, the role of gut microbiota in brain disorders and vascular dementia (VaD) remains unclear. We used a mouse model of VaD induced by a permanent right unilateral common carotid arteries occlusion (rUCCAO) to investigate the neuroprotective effects and possible underlying mechanisms of Clostridium butyricum. Following rUCCAO, C. butyricum was intragastrically administered for 6 successive weeks. Cognitive function was estimated. Morphological examination was performed by electron microscopy and hematoxylin-eosin (H&E) staining. The BDNF-PI3K/Akt pathway-related proteins were assessed by western blot and immunohistochemistry. The diversity of gut microbiota and the levels of butyrate in the feces and the brains were determined. The results showed that C. butyricum significantly attenuated the cognitive dysfunction and histopathological changes in VaD mice. C. butyricum not only increased the levels of BDNF and Bcl-2 and decreased level of Bax but also induced Akt phosphorylation (p-Akt) and ultimately reduced neuronal apoptosis. Moreover, C. butyricum could regulate the gut microbiota and restore the butyrate content in the feces and the brains. These results suggest that C. butyricum might be effective in the treatment of VaD by regulating the gut-brain axis and that it can be considered a new therapeutic strategy against VaD.
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http://dx.doi.org/10.1155/2015/412946DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4615854PMC
September 2016

Neuroprotective Effect of Sodium Butyrate against Cerebral Ischemia/Reperfusion Injury in Mice.

Biomed Res Int 2015 7;2015:395895. Epub 2015 May 7.

Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, China.

Sodium butyrate (NaB) is a dietary microbial fermentation product of fiber and serves as an important neuromodulator in the central nervous system. In this study, we further investigated that NaB attenuated cerebral ischemia/reperfusion (I/R) injury in vivo and its possible mechanisms. NaB (5, 10 mg/kg) was administered intragastrically 3 h after the onset of reperfusion in bilateral common carotid artery occlusion (BCCAO) mice. After 24 h of reperfusion, neurological deficits scores were estimated. Morphological examination was performed by electron microscopy and hematoxylin-eosin (H&E) staining. The levels of oxidative stress and inflammatory cytokines were assessed. Apoptotic neurons were measured by TUNEL; apoptosis-related protein caspase-3, Bcl-2, Bax, the phosphorylation Akt (p-Akt), and BDNF were assayed by western blot and immunohistochemistry. The results showed that 10 mg/kg NaB treatment significantly ameliorated neurological deficit and histopathology changes in cerebral I/R injury. Moreover, 10 mg/kg NaB treatment markedly restored the levels of MDA, SOD, IL-1β, TNF-α, and IL-8. 10 mg/kg NaB treatment also remarkably inhibited the apoptosis, decreasing the levels of caspase-3 and Bax and increasing the levels of Bcl-2, p-Akt, and BDNF. This study suggested that NaB exerts neuroprotective effects on cerebral I/R injury by antioxidant, anti-inflammatory, and antiapoptotic properties and BDNF-PI3K/Akt pathway is involved in antiapoptotic effect.
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http://dx.doi.org/10.1155/2015/395895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4439479PMC
March 2016

The 15kDa selenoprotein and thioredoxin reductase 1 promote colon cancer by different pathways.

PLoS One 2015 17;10(4):e0124487. Epub 2015 Apr 17.

Molecular Biology of Selenium Section, Mouse Cancer Genetics Program, National Institutes of Health, Bethesda, Maryland, United States of America.

Selenoproteins mediate much of the cancer-preventive properties of the essential nutrient selenium, but some of these proteins have been shown to also have cancer-promoting effects. We examined the contributions of the 15kDa selenoprotein (Sep15) and thioredoxin reductase 1 (TR1) to cancer development. Targeted down-regulation of either gene inhibited anchorage-dependent and anchorage-independent growth and formation of experimental metastases of mouse colon carcinoma CT26 cells. Surprisingly, combined deficiency of Sep15 and TR1 reversed the anti-cancer effects observed with down-regulation of each single gene. We found that inflammation-related genes regulated by Stat-1, especially interferon-γ-regulated guanylate-binding proteins, were highly elevated in Sep15-deficient, but not in TR1-deficient cells. Interestingly, components of the Wnt/β-catenin signaling pathway were up-regulated in cells lacking both TR1 and Sep15. These results suggest that Sep15 and TR1 participate in interfering regulatory pathways in colon cancer cells. Considering the variable expression levels of Sep15 and TR1 found within the human population, our results provide insights into new roles of selenoproteins in cancer.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0124487PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4401539PMC
April 2016

E2F-3B is a physiological target of cyclin A.

J Biol Chem 2002 Jun 29;277(26):23493-9. Epub 2002 Apr 29.

Department of Biochemistry and Molecular Biology, University of South Florida, College of Medicine, Tampa 33612, USA.

The E2F family of transcription factors controls the expression of numerous genes that are required for the G(1)/S transition. Among the mechanisms that modulate the activity of the E2F proteins, cyclin A has been found to be important for the down-regulation of E2F-1, -2, and -3A activity after cells have progressed through G(1)/S. Specifically, phosphorylation of these E2F proteins by cyclin A/Cdk2 ultimately results in their necessary degradation as cells progress through S phase. E2F-3B was recently identified as an alternatively spliced form of E2F-3A that was predicted to lack a functional cyclin A binding domain. In this paper, we present considerable evidence that contradicts this prediction. First, we demonstrate binding of cyclin A to E2F-3B as bacterially expressed proteins in vitro. Second, we demonstrate binding of cyclin A to E2F-3B in mammalian cells in vivo. Third, we show that co-expression of cyclin A with E2F-3B significantly reduces E2F-3B-mediated transcriptional activity. Finally, in synchronized cells, we observe down-regulation of E2F-3B protein expression coincident with the up-regulation of cyclin A. We conclude that E2F-3B is a physiological target of cyclin A.
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http://dx.doi.org/10.1074/jbc.M202629200DOI Listing
June 2002