Publications by authors named "Zhihua Wu"

85 Publications

Heat stress interferes with formation of double-strand breaks and homolog synapsis.

Plant Physiol 2021 Jan 25. Epub 2021 Jan 25.

College of Life Sciences, South-Central University for Nationalities, Wuhan 430074, China.

Meiotic recombination (MR) drives novel combinations of alleles and contributes to genomic diversity in eukaryotes. In this study, we showed that heat stress (36°C-38°C) over the fertile threshold fully abolished crossover formation in Arabidopsis (Arabidopsis thaliana). Cytological and genetic studies in wild-type plants and syn1 and rad51 mutants suggested that heat stress reduces generation of SPO11-dependent double-strand breaks (DSBs). In support, the abundance of recombinase DMC1, which is required for MR-specific DSB repair, was significantly reduced under heat stress. In addition, high temperatures induced disassembly and/or instability of the ASY4- but not the SYN1-mediated chromosome axis. At the same time, the ASY1-associated lateral element of the synaptonemal complex (SC) was partially affected, while the ZYP1-dependent central element of SC was disrupted, indicating that heat stress impairs SC formation. Moreover, expression of genes involved in DSB formation; e.g. SPO11-1, PRD1, 2, and 3 was not impacted; however, recombinase RAD51 and chromosome axis factors ASY3 and ASY4 were significantly downregulated under heat stress. Taken together, these findings revealed that heat stress inhibits MR via compromised DSB formation and homolog synapsis, which are possible downstream effects of the impacted chromosome axis. Our study thus provides evidence shedding light on how increasing environmental temperature influences MR in Arabidopsis.
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http://dx.doi.org/10.1093/plphys/kiab012DOI Listing
January 2021

The chromosome-scale reference genome of safflower (Carthamus tinctorius) provides insights into linoleic acid and flavonoid biosynthesis.

Plant Biotechnol J 2021 Mar 25. Epub 2021 Mar 25.

Hubei Provincial Key Laboratory for Protection and Application of Special Plant Germplasm in Wuling Area of China, Key Laboratory of State Ethnic Affairs Commission for Biological Technology, College of Life Sciences, South-Central University for Nationalities, Wuhan, China.

Safflower (Carthamus tinctorius L.), a member of the Asteraceae, is a popular crop due to its high linoleic acid (LA) and flavonoid (such as hydroxysafflor yellow A) contents. Here, we report the first high-quality genome assembly (contig N50 of 21.23 Mb) for the 12 pseudochromosomes of safflower using single-molecule real-time sequencing, Hi-C mapping technologies and a genetic linkage map. Phyloge nomic analysis showed that safflower diverged from artichoke (Cynara cardunculus) and sunflower (Helianthus annuus) approximately 30.7 and 60.5 million years ago, respectively. Comparative genomic analyses revealed that uniquely expanded gene families in safflower were enriched for those predicted to be involved in lipid metabolism and transport and abscisic acid signalling. Notably, the fatty acid desaturase 2 (FAD2) and chalcone synthase (CHS) families, which function in the LA and flavonoid biosynthesis pathways, respectively, were expanded via tandem duplications in safflower. CarFAD2-12 was specifically expressed in seeds and was vital for high-LA content in seeds, while tandemly duplicated CarFAD2 genes were up-regulated in ovaries compared to CarFAD2-12, which indicates regulatory divergence of FAD2 in seeds and ovaries. CarCHS1, CarCHS4 and tandem-duplicated CarCHS5~CarCHS6, which were up-regulated compared to other CarCHS members at early stages, contribute to the accumulation of major flavonoids in flowers. In addition, our data reveal multiple alternative splicing events in gene families related to fatty acid and flavonoid biosynthesis. Together, these results provide a high-quality reference genome and evolutionary insights into the molecular basis of fatty acid and flavonoid biosynthesis in safflower.
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http://dx.doi.org/10.1111/pbi.13586DOI Listing
March 2021

Prognostic significance of family in multiple myeloma.

J Cancer 2021 30;12(7):1936-1944. Epub 2021 Jan 30.

Department of Hematology, The Second Affiliated Hospital, Guangzhou Medical University, 510260 Guangzhou, China.

Multiple myeloma (MM) is a hematologic tumor with monoclonal proliferation of malignant plasma cells in the bone marrow. Fascin (FSCN) is an actin-binding protein that plays a crucial role in cell migration and invasion, contributing to tumor metastasis. There are three members () in family However, the prognostic role of family in MM remains unclear. In this study, we used four independent Gene Expression Omnibus (GEO) datasets to explore the relationships between expression profiles and patient survival in MM. We found that was dramatically down-regulated in MM compared to normal donors ( < 0.001) and monoclonal gammopathy of undetermined significance (MGUS) ( = 0.032). Patients with high expression of and had significantly longer OS ( = 0.023 and 0.028, respectively). Univariate and multivariate analysis showed that ( = 0.003, 0.002) and ( = 0.018, 0.013) were independent favorable prognostic factors for OS in MM. Moreover, the combination of high expression of and could effectively predict both longer EFS ( = 0.046) and OS ( = 0.015). Our study suggested that and can be used as favorable biomarkers for predicting clinical outcomes in MM.
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http://dx.doi.org/10.7150/jca.53675DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7974516PMC
January 2021

Prognostic Value of MicroRNA-20b in Acute Myeloid Leukemia.

Front Oncol 2020 18;10:553344. Epub 2021 Feb 18.

Department of Hematology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Acute myeloid leukemia (AML) is a highly heterogeneous disease that requires fine-grained risk stratification for the best prognosis of patients. As a class of small non-coding RNAs with important biological functions, microRNAs play a crucial role in the pathogenesis of AML. To assess the prognostic impact of miR-20b on AML in the presence of other clinical and molecular factors, we screened 90 AML patients receiving chemotherapy only and 74 also undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) from the Cancer Genome Atlas (TCGA) database. In the chemotherapy-only group, high miR-20b expression subgroup had shorter event-free survival (EFS) and overall survival (OS, both  < 0.001); whereas, there were no significant differences in EFS and OS between high and low expression subgroups in the allo-HSCT group. Then we divided all patients into high and low expression groups based on median miR-20b expression level. In the high expression group, patients treated with allo-HSCT had longer EFS and OS than those with chemotherapy alone (both < 0.01); however, there were no significant differences in EFS and OS between different treatment subgroups in the low expression group. Further analysis showed that miR-20b was negatively correlated with genes in "ribosome," "myeloid leukocyte mediated immunity," and "DNA replication" signaling pathways. , the gene with the strongest correlation with miR-20b, also had significant prognostic value in patients undergoing chemotherapy but not in the allo-HSCT group. In conclusion, our findings suggest that high miR-20b expression is a poor prognostic indicator for AML, but allo-HSCT may override its prognostic impact.
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http://dx.doi.org/10.3389/fonc.2020.553344DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930740PMC
February 2021

Suramin Targets the Conserved Ligand-Binding Pocket of Human Raf1 Kinase Inhibitory Protein.

Molecules 2021 Feb 21;26(4). Epub 2021 Feb 21.

Key Laboratory of Chemical Biology of Fujian Province, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China.

Suramin was initially used to treat African sleeping sickness and has been clinically tested to treat human cancers and HIV infection in the recent years. However, the therapeutic index is low with numerous clinical side-effects, attributed to its diverse interactions with multiple biological macromolecules. Here, we report a novel binding target of suramin, human Raf1 kinase inhibitory protein (hRKIP), which is an important regulatory protein involved in the Ras/Raf1/MEK/ERK (MAPK) signal pathway. Biolayer interference technology showed that suramin had an intermediate affinity for binding hRKIP with a dissociation constant of 23.8 µM. Both nuclear magnetic resonance technology and molecular docking analysis revealed that suramin bound to the conserved ligand-binding pocket of hRKIP, and that residues K113, W173, and Y181 play crucial roles in hRKIP binding suramin. Furthermore, suramin treatment at 160 µM could profoundly increase the ERK phosphorylation level by around 3 times. Our results indicate that suramin binds to hRKIP and prevents hRKIP from binding with hRaf1, thus promoting the MAPK pathway. This work is beneficial to both mechanistically understanding the side-effects of suramin and efficiently improving the clinical applications of suramin.
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http://dx.doi.org/10.3390/molecules26041151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926937PMC
February 2021

Discovery of A031 as effective proteolysis targeting chimera (PROTAC) androgen receptor (AR) degrader for the treatment of prostate cancer.

Eur J Med Chem 2021 Apr 23;216:113307. Epub 2021 Feb 23.

State Key Laboratory of Applied Organic Chemistry, Department of Chemistry, Lanzhou University, 222 S. Tianshui Rd, Lanzhou, 730000, PR China. Electronic address:

Androgen receptor (AR) is an effective therapeutic target for the treatment of prostate cancer. We report herein the design, synthesis, and biological evaluation of highly effective proteolysis targeting chimeras (PROTAC) androgen receptor (AR) degraders, such as compound A031. It could induce the degradation of AR protein in VCaP cell lines in a time-dependent manner, achieving the IC 50 value of less than 0.25 μM. The A031 is 5 times less toxic than EZLA and works with an appropriate half-life (t 1/2) or clearance rate (Cl). Also, it has a significant inhibitory effect on tumor growth in zebrafish transplanted with human prostate cancer (VCaP). Therefore, A031 provides a further idea of developing novel drugs for prostate cancer.
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http://dx.doi.org/10.1016/j.ejmech.2021.113307DOI Listing
April 2021

Prognostic role of Wnt and Fzd gene families in acute myeloid leukaemia.

J Cell Mol Med 2021 Feb 8;25(3):1456-1467. Epub 2021 Jan 8.

Department of Hematology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Wnt-Fzd signalling pathway plays a critical role in acute myeloid leukaemia (AML) progression and oncogenicity. There is no study to investigate the prognostic value of Wnt and Fzd gene families in AML. Our study screened 84 AML patients receiving chemotherapy only and 71 also undergoing allogeneic haematopoietic stem cell transplantation (allo-HSCT) from the Cancer Genome Atlas (TCGA) database. We found that some Wnt and Fzd genes had significant positive correlations. The expression levels of Fzd gene family were independent of survival in AML patients. In the chemotherapy group, AML patients with high Wnt2B or Wnt11 expression had significantly shorter event-free survival (EFS) and overall survival (OS); high Wnt10A expressers had significantly longer OS than the low expressers (all P < .05), whereas, in the allo-HSCT group, the expression levels of Wnt gene family were independent of survival. We further found that high expression of Wnt10A and Wnt11 had independent prognostic value, and the patients with high Wnt10A and low Wnt11 expression had the longest EFS and OS in the chemotherapy group. Pathway enrichment analysis showed that genes related to Wnt10A, Wnt11 and Wnt 2B were mainly enriched in 'cell morphogenesis involved in differentiation', 'haematopoietic cell lineage', 'platelet activation, signalling and aggregation' and 'mitochondrial RNA metabolic process' signalling pathways. Our results indicate that high Wnt2B and Wnt11 expression predict poor prognosis, and high Wnt10A expression predicts favourable prognosis in AML, but their prognostic effects could be neutralized by allo-HSCT. Combined Wnt10A and Wnt11 may be a novel prognostic marker in AML.
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http://dx.doi.org/10.1111/jcmm.16233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875934PMC
February 2021

Demographic and social correlates and indicators for behavioural compliance with personal protection among Chinese community-dwellers during COVID-19: a cross-sectional study.

BMJ Open 2021 01 6;11(1):e041453. Epub 2021 Jan 6.

School of Public Health, and Department of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, Zhejiang, China

Objectives: Examine compliance with personal protective measures in communities for the prevention and control of local transmission of the COVID-19, and explore indicators for such behavioural compliance.

Design: Cross-sectional design with a self-selecting sample. Data collected in February 2020.

Setting: Community dwellers in China.

Participants: 2956 participants aged 16 and above completed the study and were included in the analysis.

Outcome Measures: Nationwide COVID-19 survey. Demographics and self-reported compliance with four personal protective measures-home quarantine, mask-wearing, temperature-taking and hand-sanitising were collected. Outbreak severity and timeliness of personal protection order were obtained from the China Center for Disease Control and Prevention website. Logistic regression models were employed to examine the association between demographic and social indicators and behavioural compliance.

Results: Compliance with home quarantine was only associated with gender (men, OR=0.61 (0.51-0.73), inverse association) but no other indicators. In contrast, men had higher compliance with mask-wearing (OR=1.79 (1.49-2.16)) and temperature-taking (OR=1.27 (1.05-1.53)). Compared with younger adults (≤20 years), the middle-age groups (31-40 and 41-50 years of age) were more compliant with all protective behaviours, except for home quarantine (OR=0.71 (0.54-0.93) and 0.67 (0.46-0.97), respectively).

Conclusion: Male gender was associated with lower compliance with home quarantine yet higher compliance with mask-wearing and temperature-taking. The middle-age participants (31-50 years) had lower compliance with home quarantine but higher with other measures. These findings may be supported by the economic considerations and the long-inherited Confucian values among Chinese. In light of the ongoing COVID-19 pandemic, public health authorities should tailor policy implementation to disparities in psychosocial indicators.
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http://dx.doi.org/10.1136/bmjopen-2020-041453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789200PMC
January 2021

Challenges and growth opportunities: the landscape of Chinese medical publication professionals in the global context: a questionnaire-based survey.

Curr Med Res Opin 2021 Feb 14;37(2):261-267. Epub 2021 Jan 14.

Sanofi (China) Investment Co., Ltd, Shanghai, China.

Objective: The Chinese healthcare industry has immense potential for innovation and requires competent publication professionals for global reach. Changes in regulatory landscape of China necessitates pharmaceutical industries to collaborate with medical professionals who are capable of keeping up with both changes in regulations and innovative medicine.

Methods: We initiated an online questionnaire-based survey WeChat from August 3 to August 14, 2019 which focused on experience level, challenges, career development, and training requirements of survey participants.

Results: A total of 53 medical publication professionals participated in this survey. Contrary to global trends, 77% of participants had <5 years of professional experience in publication, although only 36% of participants had <5 years of experience in healthcare industry. In all, 63% of respondents spent <50% of their time in publication-related activities, contributing to <10 manuscripts per year. Their expertise in manuscripts spanned clinical studies (68%), post-marketing studies (62%), and reviews (38%). Poor research design and data quality, limited medical writing skill, and inefficient communication with authors were major challenges for developing high-quality publications. Awareness of good publication practices guidelines was high (49%) and 15% of respondents were Certified Medical Publication Professionals. Strategic publication planning (72%), industry trends (66%), and best practices (55%) were some of training requirements identified to increase competencies among respondents.

Conclusions: Although the Chinese medical publication professional industry is at a nascent stage, an attempt is being made to provide opportunities for its publication professionals to develop their competencies to match global standards.
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http://dx.doi.org/10.1080/03007995.2020.1867523DOI Listing
February 2021

Transcriptome analyses reveals the dynamic nature of oil accumulation during seed development of Plukenetia volubilis L.

Sci Rep 2020 11 24;10(1):20467. Epub 2020 Nov 24.

China Eucalypt Research Centre (CERC), Zhanjiang, 524022, Guangdong, China.

Sacha inchi (Plukenetia volubilis L.) is a shrub native to Amazon rainforests that's of commercial interest as its seeds contain 35-60% edible oil (dry weight). This oil is one of the healthiest vegetable oils due to its high polyunsaturated fatty acid content and favourable ratio of omega-6 to omega-3 fatty acids. De novo transcriptome assembly and comparative analyses were performed on sacha inchi seeds from five stages of seed development in order to identifying genes associated with oil accumulation and fatty acid production. Of 30,189 unigenes that could be annotated in public databases, 20,446 were differentially expressed unigenes. A total of 14 KEGG pathways related to lipid metabolism were found, and 86 unigenes encoding enzymes involved in α-linolenic acid (ALA) biosynthesis were obtained including five unigenes encoding FATA (Unigene0008403), SAD (Unigene0012943), DHLAT (Unigene0014324), α-CT (Unigene0022151) and KAS II (Unigene0024371) that were significantly up-regulated in the final stage of seed development. A total of 66 unigenes encoding key enzymes involved in the synthesis of triacylglycerols (TAGs) were found, along with seven unigenes encoding PDCT (Unigene0000909), LPCAT (Unigene0007846), Oleosin3 (Unigene0010027), PDAT1 (Unigene0016056), GPDH (Unigene0022660), FAD2 (Unigene0037808) and FAD3 (Unigene0044238); these also proved to be up-regulated in the final stage of seed development.
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http://dx.doi.org/10.1038/s41598-020-77177-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686490PMC
November 2020

Multifunctional tumor-targeted PLGA nanoparticles delivering Pt(IV)/siBIRC5 for US/MRI imaging and overcoming ovarian cancer resistance.

Biomaterials 2021 Feb 12;269:120478. Epub 2020 Nov 12.

State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200032, China. Electronic address:

Cisplatin (Pt(II)) resistance is an important factor in the high mortality rates of ovarian cancer. Herein, we synthesized multifunctional tumor-targeted poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs-cRGD) for monitoring therapeutic effects by dual-mode imaging and overcoming cisplatin resistance. Uniformly sized NPs-cRGD demonstrated controlled and sustained release of drugs and genes, excellent gene loading and gene protection capacity, good storage stability and no serum-induced aggregation in vitro. NPs-cRGD demonstrated clear, targeting and prolonged ultrasound imaging and magnetic resonance imaging (MRI) in vivo. The targeting of NPs-cRGD combined with ultrasound facilitated nanoparticle penetrattion into cells; entry was time-dependent. NPs-cRGD escaped from lysosomes, thereby preventing siBIRC5 degradation, which enabled siBIRC5 to efficiently inhibit the antiapoptosis effects of BIRC5 in SKO3-DDP to overcome the antiapoptosis properties of resistant cells. Furthermore, Pt(IV) in NPs-cRGD exhausted glutathione (GSH), thereby increasing drug accumulation to effectively increase Pt(II) levels. The subsequent combination of Pt(II) with DNA prevented the expressions of genes and upregulated the expression of p53 to induce the mitochondria apoptosis pathway. The reduced GSH activity and the generation of Pt(II) further promoted high levels of reactive oxygen species (ROS) to induce cell apoptosis. Therefore, NPs-cRGD with ultrasound promoted the apoptosis of resistant ovarian cancer cells by multiple mechanisms, including increased cellular drug accumulation, reversed antiapoptotic effects by siBIRC5, and enhanced ROS levels. In a tumor-bearing nude mice model, NPs-cRGD with US demonstrated excellent tumor-targeting, high efficiency tumor inhibition and low systemic toxicity. Therefore, NPs-cRGD provides a means to monitor treatment processes and can be combined with ultrasound treatment to overcome ovarian cancer resistance in vitro and in vivo.
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http://dx.doi.org/10.1016/j.biomaterials.2020.120478DOI Listing
February 2021

Comprehensive Identification and Expression Profiling of Circular RNAs During Nodule Development in .

Front Plant Sci 2020 28;11:587185. Epub 2020 Oct 28.

Hubei Provincial Key Laboratory for Protection and Application of Special Plant Germplasm in Wuling Area of China, College of Life Sciences, South-Central University for Nationalities, Wuhan, China.

Symbiotic nitrogen fixation by legume nodules provides an abundant nitrogen source for plants, and understanding this process is key for developing green agriculture. Circular RNA (circRNA), a type of endogenous RNA produced by reverse splicing of mRNA precursors, plays important regulatory roles in plants at the transcriptional and post-transcriptional levels. However, the relationship between circRNAs and legume-rhizobium is unknown. Here, we performed comprehensive identification and expression profiling of circRNAs during nodulation in common bean () compared to uninoculated roots of corresponding ages by constructing circRNA-seq and mRNA-seq libraries. We identified 8,842 high-confident circRNAs, 3,448 of which were specifically produced during symbiosis, with the highest number at the nitrogen-fixing stage. Significantly, more circRNAs were derived from exons than from intergenic regions or introns in all samples. The lengths and GC contents of the circRNAs were similar in roots and nodules. However, circRNAs showed specific spatiotemporal expression patterns during nodule and root development. GO and other functional annotation of parental genes of differentially expressed circRNAs indicated their potential involvement in different biological processes. The expression of major circRNAs during symbiosis is independent of parental genes' expression to a certain degree, while expression of the remaining minor circRNAs showed positive correlation to parental genes. Functional annotation of the targeted mRNAs in the circRNA-miRNA-mRNA network showed that circRNAs may be involved in transmembrane transport and positive regulation of kinase activity during nodulation and nitrogen fixation as miRNA sponges. Our comprehensive analysis of the expression profile of circRNAs and their potential functions suggests that circRNAs may function as new post-transcriptional regulators in legume-rhizobium symbiosis.
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http://dx.doi.org/10.3389/fpls.2020.587185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7655914PMC
October 2020

Efficient Treatment of Atherosclerosis by Dexamethasone Acetate and Rapamycin Co-Loaded mPEG-DSPE Calcium Phosphate Nanoparticles.

J Biomed Nanotechnol 2020 Jun;16(6):810-826

Atherosclerosis (AS) is one of the leading causes of vascular disease, producing high morbidity and mortality in many countries. Autophagy plays an important role when cells are facing serious circumstances, such as oxidative stress induced by Ox-LDL (oxidized low-density lipoprotein). Recent studies have revealed that DEX (dexamethasone acetate) and RAPA (rapamycin) exhibit efficient AS therapeutic ability by protecting endothelial cells and killing foam cells, respectively. Herein, we hypothesize that combining DEX and RAPA together in a specific nanocarrier system can achieve better AS therapy while limiting harmful effects. As a proof of concept, DEX and RAPA coloaded mPEG-DSPE calcium phosphate (CaP) nanoparticles (DR-NPs) were prepared by using a biomineralization method. DR-NPs increased HUVEC survival and induced foam cell apoptosis , which were correlated with autophagy activity. DR-NPs efficiently aggregated at AS plaques in the carotid artery and abdominal artery in ApoE mice 24 h after i.v. injection. Moreover, DR-NPs exhibited excellent plaque regression ability, with smaller necrotic cores and lipid core areas observed after treatment. Furthermore, the function of vascular endothelial cells was largely promoted, as evidenced by the dramatically decreased expression levels of adhesion factors, such as MMP-2, MMP-9 and ICAM-1. Consequently, DR-NPs can act as an effective AS therapeutic agent and broaden the AS therapeutic approach by inducing autophagy.
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http://dx.doi.org/10.1166/jbn.2020.2936DOI Listing
June 2020

Skeletal screening IMPC/KOMP using μCT and computer automated cryohistology: Application to the Efna4 KO mouse line.

Bone 2021 Mar 14;144:115688. Epub 2020 Oct 14.

Regenerative Medicine and Skeletal Development, Department of Reconstructive Sciences, Biomaterials and Skeletal Development, School of Dental Medicine, University of Connecticut Health, Farmington, CT 06030, United States of America.

The IMPC/KOMP program provides the opportunity to screen mice harboring well defined gene-inactivation mutations in a uniform genetic background. The program performs a global tissue phenotyping survey that includes skeletal x-rays and bone density measurements. Because of the relative insensitivity of the two screening tests for detecting variance in bone architecture, we initiated a secondary screen based on μCT and a cryohistolomorphological workflow that was performed on the femur and vertebral compartments on 220 randomly selected knockouts (KOs) and 36 control bone samples over a 2 1/2 year collection period provided by one of the production/phenotyping centers. The performance of the screening protocol was designed to balance throughput and cost versus sensitivity and informativeness such that the output would be of value to the skeletal biology community. Here we report the reliability of this screening protocol to establish criteria for control skeletal variance at the architectural, dynamic and cellular histomorphometric level. Unexpected properties of the control population include unusually high variance in BV/TV in male femurs and greater bone formation and bone turnover rates in the female femur and vertebral trabeculae bone compartments. However, the manner for maintaining bone formation differed between these two bone sites. The vertebral compartment relies on maintaining a greater number of bone forming surfaces while the femoral compartment utilized more matrix production per cell. The comparison of the architectural properties obtained by μCT and histomorphology revealed significant differences in values for BV/TV, Tb.Th and Tb.N which is attributable to sampling density of the two methods. However, as a screening tool, expressing the ratio of KO to the control line as obtained by either method was remarkably similar. It identified KOs with significant variance which led to a more detailed histological analysis. Our findings are exemplified by the Efna4 KO, in which a high BV/TV was identified by μCT and confirmed by histomorphometry in the femur but not in the vertebral compartment. Dynamic labeling showed a marked increase in BFR which was attributable to increased labeling surfaces. Cellular analysis confirmed partitioning of osteoblast to labeling surfaces and a marked decrease in osteoclastic activity on both labeling and quiescent surfaces. This pattern of increased bone modeling would not be expected based on prior studies of the Ephrin-Ephrin receptor signaling pathways between osteoblasts and osteoclasts. Overall, our findings underscore why unbiased screening is needed because it can reveal unknown or unanticipated genes that impact skeletal variation.
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http://dx.doi.org/10.1016/j.bone.2020.115688DOI Listing
March 2021

Genome-Wide Identification, Characterization, and Regulation of RWP-RK Gene Family in the Nitrogen-Fixing Clade.

Plants (Basel) 2020 Sep 11;9(9). Epub 2020 Sep 11.

Hubei Provincial Key Laboratory for Protection and Application of Special Plant Germplasm in Wuling Area of China & Key Laboratory of State Ethnic Affairs Commission for Biological Technology, College of Life Sciences, South-Central University for Nationalities, Wuhan 430074, China.

RWP-RK is a plant-specific family of transcription factors, involved in nitrate response, gametogenesis, and nodulation. However, genome-wide characterization, phylogeny, and the regulation of RWP-RK genes in the nodulating and non-nodulating plant species of nitrogen-fixing clade (NFC) are widely unknown. Therefore, we identified a total of 292 RWP-RKs, including 278 RWP-RKs from 25 NFC species and 14 RWP-RKs from the outgroup, . We classified the 292 RWP-RKs in two subfamilies: the NIN-like proteins (NLPs) and the RWP-RK domain proteins (RKDs). The transcriptome and phylogenetic analysis of RWP-RKs suggested that, compared to genes, the genes were just upregulated in nitrate response and nodulation. Moreover, nodule-specific genes of some nodulating NFC species may have a common ancestor (OG0002084) with genes in . Further, co-expression networks of under N-starvation and N-supplementation conditions revealed that there is a higher correlation between expression of genes and symbiotic genes during N-starvation. In , we confirmed that N-starvation stimulated nodulation by regulating expression of , closely related to and with another common origin (OG0004041). Taken together, we concluded that different origins of the genes involved in both N-starvation response and specific expression of nodulation would contribute to the evolution of nodulation in NFC plant species. Our results shed light on the phylogenetic relationships of genes and their differential regulation in nitrate response of and nodulation of NFC.
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http://dx.doi.org/10.3390/plants9091178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7569760PMC
September 2020

Gliadin Nanoparticles Pickering Emulgels for β-Carotene Delivery: Effect of Particle Concentration on the Stability and Bioaccessibility.

Molecules 2020 Sep 12;25(18). Epub 2020 Sep 12.

State Key Laboratory of Food Science and Technology, Nanchang University, No. 235 Nanjing East Road, Nanchang 330047, China.

β-carotene is a promising natural active ingredient for optimum human health. However, the insolubility in water, low oral bioavailability, and instability in oxygen, heat, and light are key factors to limit its application as incorporation into functional foods. Therefore, gliadin nanoparticles (GNPs) Pickering emulgels were chosen as food-grade β-carotene delivery systems. The objectives of the present study were to investigate the influence of GNPs concentration on the rheological properties, stability, and simulated gastrointestinal fate of β-carotene of Pickering emulgels. The formulations of Pickering emulgels at low GNPs concentration had better fluidity, whereas at high GNPs concentration, they had stronger gel structures. Furthermore, the thermal stability of β-carotene loaded in Pickering emulgels after two pasteurization treatments was significantly improved with the increase of GNPs concentration. The Pickering emulgels stabilized with higher GNPs concentration could improve the protection and bioaccessibility of β-carotene after different storage conditions. This study demonstrated the tremendous potential of GNPs Pickering emulgels to carry β-carotene.
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http://dx.doi.org/10.3390/molecules25184188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7570780PMC
September 2020

Analysis of six chloroplast genomes provides insight into the evolution of Chrysosplenium (Saxifragaceae).

BMC Genomics 2020 Sep 10;21(1):621. Epub 2020 Sep 10.

Hubei Provincial Key Laboratory for Protection and Application of Special Plant Germplasm in Wuling Area of China, Key Laboratory of State Ethnic Affairs Commission for Biological Technology, College of Life Sciences, South-Central University for Nationalities, Wuhan, 430074, Hubei, China.

Background: Chrysosplenium L. (Saxifragaceae) is a genus of plants widely distributed in Northern Hemisphere and usually found in moist, shaded valleys and mountain slopes. This genus is ideal for studying plant adaptation to low light conditions. Although some progress has been made in the systematics and biogeography of Chrysosplenium, its chloroplast genome evolution remains to be investigated.

Results: To fill this gap, we sequenced the chloroplast genomes of six Chrysosplenium species and analyzed their genome structure, GC content, and nucleotide diversity. Moreover, we performed a phylogenetic analysis and calculated non-synonymous (Ka) /synonymous (Ks) substitution ratios using the combined protein-coding genes of 29 species within Saxifragales and two additional species as outgroups, as well as a pair-wise estimation for each gene within Chrysosplenium. Compared with the outgroups in Saxifragaceae, the six Chrysosplenium chloroplast genomes had lower GC contents; they also had conserved boundary regions and gene contents, as only the rpl32 gene was lost in four of the Chrysosplenium chloroplast genomes. Phylogenetic analyses suggested that the Chrysosplenium separated to two major clades (the opposite group and the alternate group). The selection pressure estimation (Ka/Ks ratios) of genes in the Chrysosplenium species showed that matK and ycf2 were subjected to positive selection.

Conclusion: This study provides genetic resources for exploring the phylogeny of Chrysosplenium and sheds light on plant adaptation to low light conditions. The lower average GC content and the lacking gene of rpl32 indicated selective pressure in their unique habitats. Different from results previously reported, our selective pressure estimation suggested that the genes related to photosynthesis (such as ycf2) were under positive selection at sites in the coding region.
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http://dx.doi.org/10.1186/s12864-020-07045-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488271PMC
September 2020

Raman-tag labelled Au@ZIF-8 for cell metabolism monitoring in vitro.

Clin Hemorheol Microcirc 2020 ;75(4):489-498

State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, International Joint Laboratory for Advanced Fiber and Low-Dimension Materials, College of Materials Science and Engineering, Donghua University, Shanghai, China.

 Cell metabolism decides the state of cells in division, differentiation and growth, maintaining intracellular balance. Monitoring the metabolic behavior of cells is of great significance to study the development of diseases in cell levels. Surface-enhanced Raman spectroscopy (SERS) is a powerful technique to detect and quantify analytes in extremely low concentration. Combined with SRES technology, we can monitor the concentration of metabolites in live cells and thus study the biological behavior of cells. In this work, Raman-tag labelled Au@ZIF-8 nanoparticles were used to monitor the distribution of reactive oxygen species (ROS) in SKOV3 cells. With the help of the ultrasensitive Raman enhancement material, the distribution of ROS in SKOV3 cells was mapped, the results were further confirmed in the fluorescent images. The SERS platform provides an ultrasensitive monitoring method of ROS distribution, which may offer an opportunity for real-time monitoring the cell metabolism in the cell biology applications.
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http://dx.doi.org/10.3233/CH-200861DOI Listing
November 2020

Facile synthesis of 3D hierarchical micro-/nanostructures in capillaries for efficient capture of circulating tumor cells.

J Colloid Interface Sci 2020 Sep 21;575:108-118. Epub 2020 Apr 21.

State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, International Joint Laboratory for Advanced Fiber and Low-Dimension Materials, College of Materials Science and Engineering, Donghua University, Shanghai 201620, China. Electronic address:

The efficient capture of rare circulating tumor cells (CTCs) with high viability is of great importance in cancer diagnosis. The integration of three-dimensional (3D) nanobiointerfaces with capillary flow channel platforms can efficiently improve CTC capture performance by providing abundant binding sites and increasing the likelihood of contact as samples flow through the microchannels. However, due to the complex preparation processes, facile synthesis of nanostructures for use as substrates in flow channels for biomedical applications is still challenging. To reduce the encapsulation steps in the fabricating of nanostructured flow channel devices, we chose the enclosed glass capillaries as flow channels and accomplished all the experiments in the microchannels, including 3D nanostructure synthesis, surface modification and capture/release of CTCs. In this work, we constructed a novel 3D Zn(OH)F/ZnO nanoforest array in capillaries for CTC isolation via a facile microfluidic wet chemistry method. Because of the abundant binding sites of the 3D Zn(OH)F/ZnO nanoforest array, the capture efficiency was remarkably enhanced compared with that of vertical nanowires (90.3% vs 69.1%). In addition, a high release efficiency and cell viability of released cells were achieved by grafting poly(N-isopropylacrylamide) (PNIPPAm). These results may provide evidence for a novel method to fabricate hierarchical 3D substrates with a combination of biomolecule recognition and topographical interaction for biomedical applications.
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http://dx.doi.org/10.1016/j.jcis.2020.04.087DOI Listing
September 2020

Structure and allergenicity assessments of bovine β-lactoglobulin treated by sonication-assisted irradiation.

J Dairy Sci 2020 May 26;103(5):4109-4120. Epub 2020 Feb 26.

State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China; School of Food Science and Technology, Nanchang University, Nanchang 330031, China. Electronic address:

Bovine β-lactoglobulin (β-LG) is recognized as a major allergen in milk. This study aimed to investigate ultrasound-assisted irradiation for reducing the allergenicity of β-LG, since irradiation can reduce the allergenicity of cow milk proteins and ultrasound can improve the quality of milk. The structural changes induced in high purity β-LG, treated by irradiation, with or without sonication, were characterized by native PAGE, circular dichroism spectroscopy, and fluorescence spectroscopy. The changes in allergenicity were measured by IgE binding capacity to, and inflammatory mediator secretion by, human basophil KU812 cells. Surface hydrophobicity was reduced and aggregation of β-LG increased after treatment by irradiation, both with and without sonication. The IgE binding capacity and release of inflammatory mediators were reduced significantly and the reduction induced by irradiation before sonication was the greatest, suggesting that irradiation after sonication can be a safe and effective method to reduce the allergenicity of β-LG in dairy processing.
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http://dx.doi.org/10.3168/jds.2019-17070DOI Listing
May 2020

Influence of heat treatment and egg matrix on the physicochemical and allergenic properties of egg custard.

J Food Sci 2020 Mar 20;85(3):789-799. Epub 2020 Feb 20.

State Key Laboratory of Food Science and Technology, Nanchang Univ., Nanchang, 330047, P. R. China.

To investigate the influence of heat treatment and egg matrix on egg custard (EC) proteins, 12 different kinds of ECs with different egg/water ratios (1:1, 1:1.5, 1:2, or 1:3, v/v) and different heating temperatures (80, 90, or 100 °C) and times (10, 15, or 20 min) were prepared and evaluated for the digestibility, structure, eliciting capacity and sensitizing capacity using SDS-PAGE, fluorescence spectra, ELISA, and a BALB/c mouse model, respectively. The physicochemical properties of EC proteins were significantly affected by heat treatment and egg matrix, which showed the increased digestibility and partially unfolded structure. The eliciting capacity of EC evaluated by IgE binding to sera from egg-allergic patients was reduced after heat treatment, and the EC made by heating at 100 °C for 20 min with a whole egg/water ratio of 1:2 (v/v) was the weakest. The sensitizing capacity of EC was also reduced in the BALB/c mouse model, which showed the significantly decreased levels of specific IgE, IgG, IgG1 and IgG2a, mMCP-1 and histamine in the mouse sera, as well as cytokine secretions of IL-4, IL-5, and IL-13, compared with the raw egg (RE) group. Results demonstrate that heat treatment and egg matrix significantly reduced the eliciting and sensitizing capacity of EC by changing the tertiary structure and increasing the digestibility of EC proteins. PRACTICAL APPLICATION: Egg custard (EC) is one kind of savory food suitable for all ages, and is also a traditional supplementary food for infants and young children in China. However, limited information is available on the allergenicity of egg custard. In this work, we evaluated how the structure, digestibility, and allergenic potential of egg allergens in EC were altered by the degree of thermal treatment and egg matrix, and elucidated the links between the physicochemical properties and allergenic potential of EC affected by heat treatment and egg matrix. Our results demonstrate that heat treatment and egg matrix significantly reduced the eliciting and sensitizing capacity of EC by changing the tertiary structure and increasing the digestibility of EC proteins.
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http://dx.doi.org/10.1111/1750-3841.15065DOI Listing
March 2020

Structural analysis and allergenicity assessment of an enzymatically cross-linked bovine α-lactalbumin polymer.

Food Funct 2020 Jan;11(1):628-639

State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, P.R. China.

Enzymatic cross-linking is frequently used in bio-processing of dairy products since it could change the physiochemical and functional characterization. In our study, bovine α-lactalbumin was cross-linked by polyphenol oxidase from Agaricus bisporus and the changes in the structure, digestibility and allergenicity of α-lactalbumin were explored after cross-linking, and the structural alterations of the polymers were analyzed by circular dichroism spectroscopy, ultraviolet absorption spectroscopy and fluorescence spectroscopy. The digestibility of cross-linked α-lactalbumin was evaluated by simulated digestion in vitro. After that, the allergenicity of α-lactalbumin polymers was evaluated by detection of the specific IgE binding ability using an animal model. The results showed that the secondary and tertiary structures of various α-lactalbumin polymers exhibited a significant variation compared with those of untreated α-lactalbumin, and the cross-linked α-lactalbumin was relatively less susceptible to digestion. Moreover, the allergenicity of cross-linked polymers decreased significantly. These results suggested that there was a direct correlation between a loss of an α-helix and IgE binding to α-lactalbumin, which indicated that enzymatic cross-linking might be an efficient approach to reduce the allergenicity of bovine α-lactalbumin.
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http://dx.doi.org/10.1039/c9fo02238dDOI Listing
January 2020

Effect of transglutaminase cross-linking on the allergenicity of tofu based on a BALB/c mouse model.

Food Funct 2020 Jan;11(1):404-413

State Key Laboratory of Food Science and Technology, Nanchang University, Nanjing Dong Lu 235, Nanchang 330047, China.

Soybean products are limited in terms of safe consumption because of the sensitization of raw materials. In this study, the allergenicity of cross-linked tofu with microbial transglutaminase (MTG) was evaluated on the basis of a BALB/c mouse model. The mice were randomly divided into five groups. Cholera toxin was used as an adjuvant to sensitize the mice through intragastric administration, and tofu was given orally to investigate its sensitization effect on the mice. The allergy symptoms, body temperature, and weight of the mice were detected. The immunoglobulin E (IgE), immunoglobulin G (IgG), and spleen cytokines of the mice were determined through an enzyme-linked immunosorbent assay. The regulation of the differentiation balance of the different subsets of splenic T lymphocyte (Th1, Th2) and regulatory T cells (Tregs) in the mice was measured through flow cytometry. Results showed that the mice administered with MTG-cross-linked tofu had fewer allergic symptoms compared with those of the control group. The concentrations of serum-specific IgE and IgG, plasma histamine, and mast cell protease 1 (mMCP-1) significantly decreased. The Th2-related cytokine levels reduced, and the IFN-γ levels increased. The proportion of Th2 cells decreased, and the proportion of CD4+CD25+Foxp+ Tregs increased as the percentage of Th1 cells increased. Therefore, the sensitization of enzymatic cross-linked tofu decreased.
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http://dx.doi.org/10.1039/c9fo02376cDOI Listing
January 2020

Local delivery of arsenic trioxide nanoparticles for hepatocellular carcinoma treatment.

Signal Transduct Target Ther 2019;4:28. Epub 2019 Sep 6.

1State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 200032 Shanghai, China.

Hepatocellular carcinoma (HCC) is a malignancy with a poor prognosis. Surgery combined with chemotherapy has been recommended as a curative regimen for HCC. Nevertheless, the anticancer mechanisms of chemicals in hepatocellular carcinoma remain unclear. Pyroptosis is a type of programmed necrosis, and its mechanism in hepatocellular carcinoma is poorly understood. The efficacy and mechanism of arsenic trioxide nanoparticles in the treatment of HCC were explored in this research. Arsenic trioxide alone and arsenic trioxide nanoparticles were conveniently administered to mice intratumorally using a needle. Compared with AsO, AsO nanoparticles (AsO-NPs) showed better inhibition, promoted greater LDH release, and induced cell morphology indicative of pyroptosis in vitro. Compared with the free drug, AsO-NPs increased GSDME-N expression and decreased Dnmt3a, Dnmt3b, and Dnmt1 expression in Huh7 cells. In vivo, AsO-NPs induced a significant decrease in the expression of Dnmt3a, Dnmt3b and Dnmt1, but significantly upregulated the expression of GSDME-N (gasdermin E (GSDME) was originally found to be related to deafness; recently, it has been defined as a gasdermin family member associated with pyroptosis). AsO-NPs inhibited tumor growth more strongly than AsO or control, a finding likely attributed to the downregulation of PCNA and DNMT-related proteins and the upregulation of GSDME-N.
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http://dx.doi.org/10.1038/s41392-019-0062-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6799825PMC
January 2021

Polyphenol-oxidase-catalyzed cross-linking of Ara h 2: reaction sites and effect on structure and allergenicity.

J Sci Food Agric 2020 Jan 6;100(1):308-314. Epub 2019 Nov 6.

State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, China.

Background: Peanut is among the most common of food allergies, and one of its allergens is Ara h 2. A previous study revealed that this allergen was recognized by serum immunoglobulin E (IgE) in over 90% of a peanut-allergic patient population. Enzymatic cross-linking is a popular processing method used to tailor food functionality, such as antigenicity.

Result: The cross-linking reactions of Ara h 2 were catalyzed by polyphenol oxidase (PPO), and the relevant reaction sites were identified using mass spectrometry and StavroX software. Two pairs of intramolecular cross-linking peptides and two intermolecular cross-linking peptides were found. Intramolecular cross-linking was speculated to occur between ARG (amino acids 116-131) and TYR (amino acids 63-80) and between TYR (amino acids 56-62) and ARG (amino acids 92-102); the intermolecular cross-linking sites were ARG with TYR or TYR and TYR or TYR with ARG or ARG . Three out of four cross-linking peptides were found in α-helices, and destruction of this secondary structure resulted in a loose tertiary structure. Although seven linear allergen epitopes were involved in cross-linking, the IgE binding capacity of protein changed slightly, while its sensitization potential decreased in mouse model.

Conclusion: Exploring the structural change of Ara h 2 after cross-linking is beneficial in further understanding the influence of structure on sensitization. This result indicated the future possibility of precision processing on structure of proteins to improve their properties. © 2019 Society of Chemical Industry.
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http://dx.doi.org/10.1002/jsfa.10040DOI Listing
January 2020

Improvement on stability, loading capacity and sustained release of rhamnolipids modified curcumin liposomes.

Colloids Surf B Biointerfaces 2019 Nov 26;183:110460. Epub 2019 Aug 26.

State Key Laboratory of Food Science and Technology, Nanchang University, No. 235 Nanjing East Road, Nanchang 330047, Jiangxi, China. Electronic address:

A novel cholesterol-free curcumin delivery system was fabricated by rhamnolipids modified liposomes (RL-Lps). The incorporation of the rhamnolipids increased the sphericity, reduced the size, and decreased the polydispersity of the liposomes compared with pure liposomes (Lps). Analysis of the environmental stability of the RL-Lps showed they have good long-term stability over a wide range of pH (2-3 and 5-8), ionic strengths (0-200 mM), and accelerated centrifugal conditions. The curcumin-loaded rhamnolipids modified liposomes (Cur-RL-Lps) could be prepared with a relatively high loading efficiency (LE > 90%) and loading capacity (LC > 3.5%). The thermal and photochemical stability of the curcumin was improved after encapsulation in the Cur-RL-Lps. In vitro release studies indicated that the sustained release of the curcumin was prolonged when rhamnolipids were incorporated into the liposomes. This study shows that rhamnolipids have great potential for liposomal delivery system suitable for utilization in functional foods, dietary supplements, and pharmaceutical preparations.
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http://dx.doi.org/10.1016/j.colsurfb.2019.110460DOI Listing
November 2019

Effect of microbial transglutaminase cross-linking on the quality characteristics and potential allergenicity of tofu.

Food Funct 2019 Sep 14;10(9):5485-5497. Epub 2019 Aug 14.

State Key Laboratory of Food Science and Technology, Nanchang University, Nanjing Dong Lu 235, Nanchang 330047, China. and Sino-German Joint Research Institute, Nanchang University, Nanjing Dong Lu 235, Nanchang 330047, China.

Microbial transglutaminase (MTGase) has been developed as a new tofu coagulant in recent years due to its good hydrophilicity, high catalytic activity, and strong thermal stability. This study aimed to investigate the effect of MTGase on the physicochemical properties and immunoreactivity of tofu relative to conventional coagulants [brine and glucono-δ-lactone (GDL)]. Structural changes of the MTGase cross-linked soymilk protein were characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), circular dichroism (CD) spectroscopy, ultraviolet (UV) absorption spectroscopy, and fluorescence spectroscopy. The IgE-binding capacity of MTGase cross-linked proteins was tested by enzyme-linked immunosorbent assay (ELISA). The physicochemical properties, quality characteristics, and surface microstructures of five different types of tofu were determined by the Kjeldahl nitrogen method, texture analysis, and scanning electron microscopy (SEM). The digestibility of tofu was evaluated in vitro by simulated gastrointestinal (GIS) digestion. A cell sensitization experiment was performed in vitro to evaluate the capability of tofu digestion products to induce the release of bioactive mediators from human basophil leukemia (KU812) cells. Results indicated that MTGase significantly changed the advanced structure of the soymilk protein. Compared with tofu without MTGase, the composite coagulant tofu containing MTGase exhibited better quality. MTGase improved the water-holding capacity (WHC) of the internal mesh structure and increased the yield of tofu. The digestion products of the composite coagulant tofu, especially the GDL plus MTGase tofu, induced KU812 cells to release fewer bioactive mediators compared with those of MTGase-free tofu. MTGase can not only improve the quality of conventional coagulant tofu but also reduce the potential allergenicity of tofu to a certain extent.
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http://dx.doi.org/10.1039/c9fo01118hDOI Listing
September 2019

Allergenicity reduction and rheology property of Lactobacillus-fermented soymilk.

J Sci Food Agric 2019 Dec 12;99(15):6841-6849. Epub 2019 Sep 12.

State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, China.

Background: This study aimed to investigate the reduction in the potential allergenicity of soymilk, and its rheological properties, after fermentation with Lactobacillus. Soymilk (SM) was fermented with Lactobacillus brevis and Lactobacillus sp. The molecular weight of fermented soymilk (FSM) was characterized using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and the potential allergenicity of FSM was analyzed using enzyme-linked immunosorbent assay in vitro and the BALB/c mouse model to detect changes in histamine, mouse mast cell protease-1 (mMCP-1), allergen-specific IgG/IgE, and cytokine levels and histomorphology of jejunum in vivo.

Results: The SDS-PAGE and enzyme linked immunosorbent assay (ELISA) showed that allergens of soybean (β-conglycinin and acidic subunit of glycinin) were almost degraded, and their immunoreactivity was decreased. In the BALB/c mouse model, the FSM group did not show anaphylactic shock symptoms compared with the SM group. Moreover, a tendency toward decreased serum allergen-specific IgG/IgE levels, plasma histamine levels, and mMCP-1 concentrations was observed in the FSM group. Furthermore, Th2-related cytokines were decreased, while IFN-γ production increased in spleen cell cultures. The intestinal villus was slightly damaged after the challenge. All these findings indicated that the Th1/Th2 balance in the FSM group shifted toward a Th1 response, ultimately reducing the potential allergenicity of FSM. Rheological assessment suggested that FSM has good viscous and pseudoplastic properties.

Conclusion: Fermentation might be a promising method for producing tasty, hypoallergenic soybean products. © 2019 Society of Chemical Industry.
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http://dx.doi.org/10.1002/jsfa.9969DOI Listing
December 2019

A global coexpression network of soybean genes gives insights into the evolution of nodulation in nonlegumes and legumes.

New Phytol 2019 09 25;223(4):2104-2119. Epub 2019 Jul 25.

National Key Laboratory of Crop Genetic Improvement, Center of Integrative Biology, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, Hubei Province, 430070, China.

A coexpression network is a powerful tool for revealing genes' relationship with many biological processes. Mass transcriptomic and genomic data from different plant species provide the foundation for understanding the evolution of nodulation across the Viridiplantae at a systematic level. We used weighted coexpression network analysis (WGCNA) to mine a nodule-related module (NRM) in Glycine max. Comparative genomic analysis of 78 green plant species revealed that NRM genes are recruited from different evolutionary nodes along with gene duplication events. A set of core coexpressed genes within legumes may play vital roles in regulating nodule environments essential for nitrogen fixation, including oxygen concentrations, sulfur transport, and iron homeostasis (such as GmCHY). The regulation of these genes occurred mainly at the transcription level, although some of them, such as sulfate transporters, may also undergo positive selection at protein level. We revealed that ancient orthologs and duplication events before the origin of legumes were preadapted for symbiosis. Conserved coregulated genes found within legumes paved the way for nodule formation and nitrogen fixation. These findings provide significant insights into the evolution of nodulation and indicate promising candidates for identifying other key components of legume nodulation and nitrogen fixation.
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http://dx.doi.org/10.1111/nph.15845DOI Listing
September 2019

GSH-sensitive Pt(IV) prodrug-loaded phase-transitional nanoparticles with a hybrid lipid-polymer shell for precise theranostics against ovarian cancer.

Theranostics 2019 30;9(4):1047-1065. Epub 2019 Jan 30.

State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200032, People's Republic of China.

: Platinum (II) (Pt(II))-based anticancer drugs dominate the chemotherapy field of ovarian cancer. However, the patient's quality of life has severely limited owing to dose-limiting toxicities and the advanced disease at the time of diagnosis. Multifunctional tumor-targeted nanosized ultrasound contrast agents (glutathione (GSH)-sensitive platinum (IV) (Pt(IV)) prodrug-loaded phase-transitional nanoparticles, Pt(IV) NP-cRGD) were developed for precise theranostics against ovarian cancer. : Pt(IV) NP-cRGD were composed of a perfluorohexane (PFH) liquid core, a hybrid lipid-polymer shell with PLGA-PEG and DSPE-PEG-Pt(IV), and an active targeting ligand, the cRGD peptide (PLGA: poly(lactic-co-glycolic acid), PEG: polyethylene glycol, DSPE: 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, cRGD: cyclic Arg-Gly-Asp). Pt(IV), a popular alternative to Pt(II), was covalently attached to DSPE-PEG to form the prodrug, which fine-tuned lipophilicity and improved cellular uptake. The potential of Pt(IV) NP-cRGD as contrast agents for ultrasound (US) imaging was assessed and . Moreover, studies on the antitumor efficiency and antitumor mechanism of Pt(IV) NP-cRGD assisted by US were carried out. : Pt(IV) NP-cRGD exhibited strong echogenic signals and excellent echo persistence under an US field. In addition, the GSH-sensitive and US-triggered drug delivery system maximized the therapeutic effect while reducing the toxicity of chemotherapy. The mechanistic studies confirmed that Pt(IV) NP-cRGD with US consumed GSH and enhanced reactive oxy gen species (ROS) levels, which further causes mitochondria-mediated apoptosis. : A multifunctional nanoplatform based on phase-transitional Pt(IV) NP-cRGD with US exhibited excellent echogenic signals, brilliant therapeutic efficacy and limited side effect, suggesting precise theranostics against ovarian cancer.
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http://dx.doi.org/10.7150/thno.29820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6401401PMC
January 2020