Publications by authors named "Shan He"

423 Publications

Microbulbifer hainanensis sp. nov., a moderately halopilic bacterium isolated from mangrove sediment.

Antonie Van Leeuwenhoek 2021 Apr 12. Epub 2021 Apr 12.

College of Food and Pharmaceutical Sciences, Li Dak Sum Yip Yio Chin Kenneth Li Marine Biopharmaceutical Research Center, Ningbo University, Ningbo, 315800, People's Republic of China.

A new bacterium was successfully isolated from a mangrove sediment sample in Haikou City, Hainan Province, China. The organism is a Gram-negative, rod-shaped, non-motile and strictly aerobic bacterium, named NBU-8HK146. Strain NBU-8HK146 was able to grow at temperatures of 10-40 °C, at salinities of 0-11% (w/v) and at pH 5.5-9.5. Veoges-Proskauer, methyl red reaction and hydrolysis of Tween 20 were negative. Catalase and oxidase activities, HS production, hydrolysis of starch, casein, Tweens 40, 60 and 80 were positive. The major cellular fatty acids were C, iso-C and summed feature 9. The major respiratory quinone was ubiquinone-8 (Q-8). The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol and two unidentified glycolipids. According to 16S rRNA gene sequence similarities, strain NBU-8HK146 shared 98.0%, 97.9%, 97.7%, 97.6% and 97.3% similarities to the species with validated name Microbulbifer taiwanensis CC-LN1-12, Microbulbifer rhizosphaerae Cs16b, Microbulbifer marinus Y215, Microbulbifer donghaiensis CN85 and Microbulbifer aggregans CCB-MM1, respectively. Phylogenetic analyses indicated that strain NBU-8HK146 formed a distinct lineage with strains Microbulbifer taiwanensis CC-LN1-12 and Microbulbifer marinus Y215. Both digital DNA-DNA hybridization values (19.5-22.7%) and average nucleotide identity values (73.2-78.9%) between strain NBU-8HK146 and related species of genus Microbulbifer were below the species delineation cutoffs. The DNA G+C content was 58.9 mol%. Many proteins involving in the adaption of osmotic stress in the salt environment of mangrove were predicted in genome of strain NBU-8HK146. From phenotypic, genotypic, phylogenetic and chemotaxonomic characteristics, strain NBU-8HK146 can be regarded as a new Microbulbifer species for which the name Microbulbifer hainanensis. The type strain is NBU-8HK146 (= KCTC 82226 = MCCC 1K04737).
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http://dx.doi.org/10.1007/s10482-021-01574-yDOI Listing
April 2021

Anti-tumor activities of saponins and potential biomarkers in prostate cancer.

J Ginseng Res 2021 Mar 7;45(2):273-286. Epub 2020 Jan 7.

Department of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology & Immunology, Vienna General Hospital, Medical University of Vienna, Vienna, Austria.

Background: Prostate carcinoma is the second most common cancer among men worldwide. Developing new therapeutic approaches and diagnostic biomarkers for prostate cancer (PC) is a significant need. The Chinese herbal medicine saponins (PQS) have been reported to show anti-tumor effects. We hypothesized that PQS exhibits anti-cancer activity in human PC cells and we aimed to search for novel biomarkers allowing early diagnosis of PC.

Methods: We used the human PC cell line DU145 and the prostate epithelial cell line PNT2 to perform cell viability assays, flow cytometric analysis of the cell cycle, and FACS-based apoptosis assays. Microarray-based gene expression analysis was used to display specific gene expression patterns and to search for novel biomarkers. Western blot and quantitative real-time PCR were performed to demonstrate the expression levels of multiple cancer-related genes.

Results: Our data showed that PQS inhibited the viability of DU145 cells and induced cell cycle arrest at the G1 phase. A significant decrease in DU145 cell invasion and migration were observed after 24 h treatment by PQS. PQS up-regulated the expression levels of p21, p53, TMEM79, ACOXL, ETV5, and SPINT1 while it down-regulated the expression levels of bcl2, STAT3, FANCD2, DRD2, and TMPRSS2.

Conclusion: PQS promoted cells apoptosis and inhibited the proliferation of DU145 cells, which suggests that PQS may be effective for treating PC. TMEM79 and ACOXL were expressed significantly higher in PNT2 than in DU145 cells and could be novel biomarker candidates for PC diagnosis.
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http://dx.doi.org/10.1016/j.jgr.2019.12.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020356PMC
March 2021

Electron Donor-Acceptor Effect-Induced Organic/Inorganic Nanohybrids with Low Energy Gap for Highly Efficient Photothermal Therapy.

ACS Appl Mater Interfaces 2021 Apr 7. Epub 2021 Apr 7.

School of Light Industry, Beijing Technology and Business University, 11 Fucheng Road, Haidian District, Beijing 100048, P. R. China.

For the design and optimization of near-infrared photothermal nanohybrids, tailoring the energy gap of nanohybrids plays a crucial role in attaining a satisfactory photothermal therapeutic efficacy for cancer and remains a challenge. Herein, we report an electron donor-acceptor effect-induced organic/inorganic nanohybrid with a low energy gap (denoted as ICG/Ag/LDH) by the deposition of Ag nanoparticles onto the CoAl-LDH surface, followed by the coupling of ICG. A combination study verifies that the supported Ag nanoparticles as the electron donor (D) push electrons into the conjugated system of ICG by the electronic interaction between ICG and Ag, while OH groups of LDHs as the electron acceptor (A) pull electrons from the conjugated system of ICG by hydrogen bonding (NH-O). This induces the formation of the D-A conjugated π-system and has a strong influence on the π-conjugated system of ICG, thus leading to a prominent decrease toward the energy gap and correspondingly an ultra-long redshift (∼115 nm). The resulting ICG/Ag/LDHs show an enhanced photothermal conversion efficiency (∼45.5%) at 808 nm laser exposure, which is ∼1.6 times larger than that of ICG (∼28.4%). Such a high photothermal performance is attributed to the fact that ICG/Ag/LDHs possess a D-π-A hybrid structure and a resulting lower energy gap, thus effectively promoting nonradiative transitions and leading to enhancement of the photothermal effect. Both and results confirm the good biocompatible properties and capability of the ICG/Ag/LDHs for NIR-triggered cancer treatment. This research demonstrates a successful paradigm for the rational design and preparation of new nanohybrids through the modulation of electron donor-acceptor effect, which offers a new avenue to achieve efficient phototherapeutic agent for improving the cancer therapeutic outcomes.
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http://dx.doi.org/10.1021/acsami.1c00554DOI Listing
April 2021

Cytotoxic Polyketide Metabolites from a Marine Mesophotic Zone Chalinidae Sponge-Associated Fungus sp. NBUF144.

Mar Drugs 2021 Mar 26;19(4). Epub 2021 Mar 26.

Department of Marine Pharmacy, Li Dak Sum Marine Biopharmaceutical Research Center, College of Food and Pharmaceutical Sciences, Ningbo University, Ningbo, Zhejiang 315800, China.

Two new polyketide natural products, globosuxanthone F (), and 2'-hydroxy bisdechlorogeodin (), were isolated from the fungus sp. NBUF144, which was derived from a 62 m deep Chalinidae family sponge together with four known metabolites, 3,4-dihydroglobosuxanthone A (), 8-hydroxy-3-methylxanthone-1-carboxylate (), crosphaeropsone C (), and 4-megastigmen-3,9-dione (). The structures of these compounds were elucidated on the basis of extensive spectroscopic analysis, including 1D and 2D NMR and high-resolution electrospray ionization mass spectra (HRESIMS) data. The absolute configuration of was further established by single-crystal X-ray diffraction studies. Compounds - were evaluated for cytotoxicity towards CCRF-CEM human acute lymphatic leukemia cells, and it was found that had an IC value of 0.46 µM.
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http://dx.doi.org/10.3390/md19040186DOI Listing
March 2021

Human breast milk-derived exosomes may help maintain intestinal epithelial barrier integrity.

Pediatr Res 2021 Mar 17. Epub 2021 Mar 17.

Department of Neonatology, Children's Hospital of Soochow University, Suzhou, China.

Background: This study explores the functions of exosomes derived from human breast milk (HBM) in vivo and in vitro.

Methods: HBM-derived exosomes were collected from healthy lactating mothers. In vitro analysis were divided into five groups: (1) a control with no added agents, (2) exosomes added, (3) stimulated with lipopolysaccharide (LPS), (4) pretreated with exosomes and stimulated with LPS, and (5) pretreated with exosome-free HBM and stimulated with LPS. For in vivo analysis, mouse pups were randomly assigned to four groups: (1) a control group of breastfed pups, (2) necrotizing enterocolitis-induced (NEC) pups, (3) pups pretreated with HBM-derived exosomes 6 h before being induced by NEC, and (4) pups pretreated with exosome-free HBM 6 h before NEC induction.

Results: Expression of zonula occludens-1 (ZO-1), claudin-1, and occludin were decreased in groups 3 and 5. In the animal model, mice pups in group 3 showed milder intestinal tissue injury than those in group 2 or 4 and had lower levels of the proinflammatory cytokines and higher levels of epithelial tight-junction proteins than groups 2 and 4.

Conclusions: HBM-derived exosomes exert beneficial effects in preventing NEC by reducing inflammation and injury to the intestinal epithelium as well as by restoring intestinal tight-junction proteins.

Impact: HBM-derived exosomes can help protect the epithelial tight-junction proteins ZO-1, claudin, and occludin from inflammatory attack. This study sought (1) to analyze whether there were differences in exosome levels between the human breast milk (HBM) of mothers who had delivered preterm or at term and (2) to investigate whether these exosomes could help sustain the intestinal epithelial tight-junction proteins ZO-1, claudin-1, and occludin in the presence of NEC in vitro and in vivo.
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http://dx.doi.org/10.1038/s41390-021-01449-yDOI Listing
March 2021

Discovery of Cymopolyphenols A-F From a Marine Mesophotic Zone Sponge-Associated Fungus sp. NBUF082.

Front Microbiol 2021 22;12:638610. Epub 2021 Feb 22.

Li Dak Sum Marine Biopharmaceutical Research Center, Department of Marine Pharmacy, College of Food and Pharmaceutical Sciences, Ningbo University, Ningbo, China.

Mesophotic coral ecosystems (MCEs) have complex but understudied biodiversity, especially for natural products discovery. Untargeted metabolomics research on 80 extracts prepared from marine sponge-associated fungi, half from shallow reefs (<30 m) and half from MCEs (30-150 m), facilitated prioritization for further study a fungus from a 103 m deep sponge. LC-MS target-directed isolation yielded a series of new compounds, cymopolyphenols A-F (-), and two known phenylspirodrimanes, F1839-I () and stachybotrylactone (). This is the first report of natural products from the recently described genus, . Compounds - and contain a dihydroisobenzofuran moiety, and - are low-order polymers of with novel scaffolds. The structures of the compounds were established by spectroscopic and spectrometric data interpretation, with further support from X-ray crystallography studies of and . Compound undergoes facile racemization in solution and was found to crystalize as a racemic mixture. Compound was also obtained in racemic form, and after chiral chromatography, both separated enantiomers racemized in solution by a presumed keto-enol tautomerization. Compounds and - were found to be weakly antimicrobial (MIC 16-64 μg/ml) against several Gram-positive and Gram-negative human or aquatic pathogens, compound was shown to chelate iron at 10 μM, and activated plant disease resistance in a transgenic model organism.
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http://dx.doi.org/10.3389/fmicb.2021.638610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937805PMC
February 2021

The Structural Understanding of Transthyretin Misfolding and the Inspired Drug Approaches for the Treatment of Heart Failure Associated With Transthyretin Amyloidosis.

Front Pharmacol 2021 18;12:628184. Epub 2021 Feb 18.

Department of Cardiology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.

Substantial controversies exist in the exploration of the molecular mechanism of heart failure (HF) and pose challenges to the diagnosis of HF and the discovery of specific drugs for the treatment. Recently, cardiac transthyretin (TTR) amyloidosis is becoming recognized as one of major causes of underdiagnosed HF. The investigation and modulation of TTR misfolding and amyloidal aggregation open up a new revenue to reveal the molecular mechanisms of HF and provide new possibilities for the treatment of HF. The aim of this review is to briefly introduce the recent advances in the study of TTR native and misfolding structures, discuss the correlation between the genotype and phenotype of cardiac TTR amyloidosis, and summarize the therapeutic applications of TTR structural stabilizers in the treatment of TTR amyloidosis-associated HF.
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http://dx.doi.org/10.3389/fphar.2021.628184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930814PMC
February 2021

Toroidal polar topology in strained ferroelectric polymer.

Science 2021 03;371(6533):1050-1056

State Key Lab of New Ceramics and Fine Processing, School of Materials Science and Engineering, Tsinghua University, Beijing 100084, China.

Polar topological texture has become an emerging research field for exotic phenomena and potential applications in reconfigurable electronic devices. We report toroidal topological texture self-organized in a ferroelectric polymer, poly(vinylidene fluoride--trifluoroethylene) [P(VDF-TrFE)], that exhibits concentric topology with anticoupled chiral domains. The interplay among the elastic, electric, and gradient energies results in continuous rotation and toroidal assembly of the polarization perpendicular to polymer chains, whereas relaxor behavior is induced along polymer chains. Such toroidal polar topology gives rise to periodic absorption of polarized far-infrared (FIR) waves, enabling the manipulation of the terahertz wave on a mesoscopic scale. Our observations should inform design principles for flexible ferroic materials toward complex topologies and provide opportunities for multistimuli conversions in flexible electronics.
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http://dx.doi.org/10.1126/science.abc4727DOI Listing
March 2021

Progress in the Development of Eukaryotic Elongation Factor 2 Kinase (eEF2K) Natural Product and Synthetic Small Molecule Inhibitors for Cancer Chemotherapy.

Int J Mol Sci 2021 Feb 27;22(5). Epub 2021 Feb 27.

Li Dak Sum Yip Yio Chin Kenneth Li Marine Biopharmaceutical Research Center, College of Food and Pharmaceutical Sciences, Ningbo University, Ningbo 315800, China.

Eukaryotic elongation factor 2 kinase (eEF2K or Ca2+/calmodulin-dependent protein kinase, CAMKIII) is a new member of an atypical α-kinase family different from conventional protein kinases that is now considered as a potential target for the treatment of cancer. This protein regulates the phosphorylation of eukaryotic elongation factor 2 (eEF2) to restrain activity and inhibit the elongation stage of protein synthesis. Mounting evidence shows that eEF2K regulates the cell cycle, autophagy, apoptosis, angiogenesis, invasion, and metastasis in several types of cancers. The expression of eEF2K promotes survival of cancer cells, and the level of this protein is increased in many cancer cells to adapt them to the microenvironment conditions including hypoxia, nutrient depletion, and acidosis. The physiological function of eEF2K and its role in the development and progression of cancer are here reviewed in detail. In addition, a summary of progress for in vitro eEF2K inhibitors from anti-cancer drug discovery research in recent years, along with their structure-activity relationships (SARs) and synthetic routes or natural sources, is also described. Special attention is given to those inhibitors that have been already validated in vivo with the overall aim to provide reference context for the further development of new first-in-class anti-cancer drugs that target eEF2K.
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http://dx.doi.org/10.3390/ijms22052408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957638PMC
February 2021

Widely targeted metabolomics analysis reveals new biomarkers and mechanistic insights on chestnut (Castanea mollissima Bl.) calcification process.

Food Res Int 2021 Mar 9;141:110128. Epub 2021 Jan 9.

Department of Food Science, School of Chemistry and Chemical Engineering, Guangzhou University, Guangzhou 510006, PR China.

Chestnut calcification is a quality deterioration due to fast water loss, which has been of deep concern for chestnut quality control because its mechanism is unclear. In order to find out the different key metabolites and metabolic pathways related to the occurrence of chestnut calcification, in this study, liquid chromatography-tandem mass spectrometry (LC-MS/MS) based widely targeted metabolomics analysis was performed on chestnuts that were stored at 50%-55% (low relative humidity, LRH) at 25 °C and 85%-90% (high relative humidity, HRH) at 25 °C. A total of 611 metabolites were detected, and 55 differentially accumulated metabolites were identified as key metabolites involved in chestnut calcification process. The decrease in some monosaccharides accompanied with the increase in some unsaturated fatty acids indicated the degradation of chestnut cell wall and cell membrane during calcification process. As a stress response, amino acid metabolism related to membrane stability was significantly activated. In addition, the enhancement of phenylpropanoid biosynthesis pathway and flavonoid biosynthesis pathway characterized by the accumulation of lignin precursors and antioxidants suggested that lignification process was triggered in calcified chestnut. Therefore, the degradation and hardening of the cell wall and membrane damage were proposed to be associated with the calcification occurrence of chestnut. The metabolic profile of chestnut characterized in this study provided new insights into chestnut calcification process and laid a foundation for further chestnut quality control.
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http://dx.doi.org/10.1016/j.foodres.2021.110128DOI Listing
March 2021

Heparinization and hybridization of electrospun tubular graft for improved endothelialization and anticoagulation.

Mater Sci Eng C Mater Biol Appl 2021 Mar 7;122:111861. Epub 2021 Jan 7.

Jiangxi Key Laboratory of Nanobiomaterials, Institute of Advanced Materials, East China Jiaotong University, Nanchang 330013, China; School of Materials Science and Engineering, Tianjin University, Tianjin 300072, China. Electronic address:

Constructing biomimetic structure and immobilizing antithrombus factors are two effective methods to ensure rapid endothelialization and long-term anticoagulation for small-diameter vascular grafts. However, few literatures are available regarding simultaneous implementation of these two strategies. Herein, a nano-micro-fibrous biomimetic graft with a heparin coating was prepared via a step-by-step in situ biosynthesis method to improve potential endothelialization and anticoagulation. The 4-mm-diameter tubular graft consists of electrospun cellulose acetate (CA) microfibers and entangled bacterial nanocellulose (BNC) nanofibers with heparin coating on dual fibers. The hybridized and heparinized graft possesses suitable pore structure that facilitates endothelia cells adhesion and proliferation but prevents infiltration of fibrous tissue and blood leakage. In addition, it shows higher mechanical properties than those of bare CA and hybridized CA/BNC grafts, which match well with native blood vessels. Moreover, this dually modified graft exhibits improved blood compatibility and endothelialization over the counterparts without hybridization or heparinization according to the testing results of platelet adhesion, cell morphology, and protein expression of von Willebrand Factor. This novel graft with dual modifications shows promising as a new small-diameter vascular graft. This study provides a guidance for promoting endothelialization and blood compatibility by dual modifications of biomimetic structure and immobilized bioactive molecules.
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http://dx.doi.org/10.1016/j.msec.2020.111861DOI Listing
March 2021

Altered circular RNA expression profiles in an ovalbumin-induced murine model of allergic rhinitis.

Allergol Immunopathol (Madr) 2021 1;49(2):94-103. Epub 2021 Mar 1.

Department of Otorhinolaryngology - Head and Neck Surgery, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, PR China.

Background: Emerging evidence shows that circular RNAs (circRNAs) participate in the pathogenesis of multiple immune diseases. However, few studies have focused on the mechanisms of circRNAs involved in allergic rhinitis (AR).

Methods: This study performed an RNA sequence (RNA-seq) profiling to identify the expression of circRNAs in nasal mucosa from ovalbumin-induced AR murine models and normal controls. Quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR) was then conducted to validate the differential expression of circRNAs. Bioinformatics analysis was applied to demonstrate the biological functions of the dysregulated circRNAs.

Results: A total of 86 distinct circRNA candidates were sequenced, of which 51 were upregulated and 35 were downregulated. The T cell receptor, B cell receptor, and calcium signaling pathways may be involved in the pathology of AR. Furthermore, a circRNA-miRNA interaction network was constructed via miRNA response elements analysis. Some circRNAs were correlated with miRNAs that are involved in T cell polarization and activation, thereby highlighting their potential role in the pathogenesis of AR.

Conclusions: This study demonstrates a number of aberrantly expressed circRNAs related to AR, and offers a novel perspective into AR pathogenesis and future therapeutic strategies.
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http://dx.doi.org/10.15586/aei.v49i2.33DOI Listing
March 2021

Accessing previously uncultured marine microbial resources by a combination of alternative cultivation methods.

Microb Biotechnol 2021 Feb 27. Epub 2021 Feb 27.

Li Dak Sum Yip Yio Chin Kenneth Li Marine Biopharmaceutical Research Center, College of Food and Pharmaceutical Sciences, Ningbo University, Ningbo, China.

Few microbes can grow under laboratory conditions, highlighting the fact that the majority of microbes in environment are still uncultured and untapped resources. This study used alternative cultivation methods, diffusion chambers (DC), dilution-to-extinction culture (DTE) and modified agar preparation step (PS media) to cultivate previously uncultured marine bacterial species. These methods were applied to samples from a coastal intertidal zone, and the results were compared with those from standard direct plating (SDP) cultivation. Among the strains isolated with DC, DTE and PS media methods, 28%, 48% and 33% were novel species, respectively, while the SDP method resulted in the isolation of only 9% of novel species. Most isolates were unique to the method used for their cultivation. This implies that each method is selective in its own way, which is different from SDP, thus able to access species that are difficult to obtain using conventional approaches. Comparing the diversity showed that 75 genera were recovered by the alternative methods, 2.7 times higher than that of the SDP cultivation, which constituted 45% of total diversity from culture-independent sequencing. We conclude that combining alternative cultivation methods represents a highly promising key for accessing 'microbial dark matter'.
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http://dx.doi.org/10.1111/1751-7915.13782DOI Listing
February 2021

Transcriptome sequencing and metabolome analysis of food habits domestication from live prey fish to artificial diets in mandarin fish (Siniperca chuatsi).

BMC Genomics 2021 Feb 22;22(1):129. Epub 2021 Feb 22.

College of Fisheries, Chinese Perch Research Center, Huazhong Agricultural University, 1 Shizishan Street, Wuhan, 430070, Hubei, China.

Background: As economical traits, food habits domestication can reduce production cost in aquaculture. However, the molecular mechanism underlying food habits domestication has remained elusive. Mandarin fish (Siniperca chuatsi) only feed on live prey fish and refuse artificial diets. In the present study, we domesticated mandarin fish to feed on artificial diets. The two groups were obtained, the fish did not eat artificial diets or ate artificial diets during all of the three domestication processes, named Group W or X, respectively.

Results: Using transcriptome and metabolome analysis, we investigated the differentially expressed genes and metabolites between the two groups, and found three common pathways related to food habit domestication, including retinol metabolism, glycerolipid metabolism, and biosynthesis of unsaturated fatty acids pathways. Furthermore, the western blotting and bisulfite sequencing PCR analysis were performed. The gene expression of TFIIF and histone methyltransferase ezh1 were significantly increased and decreased in the fish of Group X, respectively. The total DNA methylation levels of TFIIF gene and tri-methylation of histone H3 at lysine 27 (H3K27me3) were significantly higher and lower in the fish of Group X, respectively.

Conclusion: It was speculated that mandarin fish which could feed on artificial diets, might be attributed to the lower expression of ezh1, resulting in the decreased level of H3K27me3 and increased level of DNA methylation of TFIIF gene. The high expression of TFIIF gene might up-regulate the expression of genes in retinol metabolism, glycerolipid metabolism and glycerophosphoric metabolism pathways. Our study indicated the relationship between the methylation of DNA and histone and food habits domestication, which might be a novel molecular mechanism of food habits domestication in animals.
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http://dx.doi.org/10.1186/s12864-021-07403-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898776PMC
February 2021

A high-density genetic linkage map for Chinese perch (Siniperca chuatsi) using 2.3K genotyping-by-sequencing SNPs.

Anim Genet 2021 Feb 18. Epub 2021 Feb 18.

College of Fisheries, Key Lab of Freshwater Animal Breeding, Ministry of Agriculture, Engineering Research Center of Green development for Conventional Aquatic Biological Industry in the Yangtze River Economic Belt, Ministry of Education, Huazhong Agricultural University, Wuhan, China.

Chinese perch, Siniperca chuatsi (Basilewsky), is one of the most commercially important cultured fishes in China. In the present study, a high-density genetic linkage map of Chinese perch was constructed by genotyping-by-sequencing technique with an F1 mapping panel containing 190 progenies. A total of 2328 SNPs were assigned to 24 linkage groups (LGs), agreeing with the chromosome haploid number in this species (n = 24). The sex-averaged map covered 97.9% of the Chinese perch genome, with the length of 1694.3 cM and a marker density of 0.7 cM/locus. The number of markers per LG ranged from 57 to 222, with a mean of 97. The length of LGs varied from 43.2 to 108.2 cM, with a mean size of 70.6 cM. The recombination rate of females was 1.5:1, which was higher than that of males. To better understand the distribution pattern of segregation distortion between the two sexes of Chinese perch, the skewed markers were retained and used to reconstruct the sex-specific maps. The 16 segregation distortion regions were identified on 10 LGs of the female map, while 12 segregation distortion regions on eight LGs of the male map. Among these LGs, six LGs matched between the sex-specific maps. This high-density linkage map could provide a solid basis for identifying QTL associated with economically important traits, and for implementing marker-assisted selection breeding of Chinese perch.
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http://dx.doi.org/10.1111/age.13046DOI Listing
February 2021

Hepatocellular carcinoma cells-derived exosomal microRNA-378b enhances hepatocellular carcinoma angiogenesis.

Life Sci 2021 May 10;273:119184. Epub 2021 Feb 10.

Department of Gastroenterology, Xiangyang No.1 People's Hospital, Hubei University of Medicine, Xiangyang 3420272, Hubei, China.

Objective: It has been already accepted that hepatocellular carcinoma (HCC) cells-derived exosomes mediate HCC development partially through transferring microRNAs (miRNAs). Illuminated by that, this work pivoting on HCC specifically starts from miR-378b in HepG2 cells-derived exosomes, involving with transforming growth factor β receptor III (TGFBR3).

Methods: HCC tissue and normal tissue specimens were resected, in which miR-378b and TGFBR3 expression were tested. The connection between miR-378b and TGFBR3 was assessed. HepG2 cells were transfected with miR-378b and TGFBR3-related sequences to explore their functions in HCC cell progression. The extracted exosomes from HepG2 cells were identified and co-cultured with human umbilical vein endothelial cells to explore their roles in HCC cell progression and angiogenesis. Tumorigenesis in mice was conducted for further validation of the findings in cells.

Results: Up-regulated miR-378b and down-regulated TGFBR3 presented in HCC, and miR-378b targeted TGFBR3. Depleted miR-378b disturbed HCC cell migration and promoted apoptosis. Knockdown of TGFBR3 reversed the effects of down-regulated miR-378b on HCC cells. HepG2 cells-derived exosomes promoted angiogenesis in vitro and tumor growth in vivVo, which would be further enhanced by miR-378b overexpression while impaired by miR-378b down-regulation.

Conclusion: It is elucidated that HepG2 cells-derived exosomal miR-378b enhances HCC cell progression and angiogenesis, which may be linked with TGFBR3, providing therapeutic agents for HCC curing.
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http://dx.doi.org/10.1016/j.lfs.2021.119184DOI Listing
May 2021

First complete-genome documentation of HIV-1 intersubtype superinfection with transmissions of diverse recombinants over time to five recipients.

PLoS Pathog 2021 Feb 12;17(2):e1009258. Epub 2021 Feb 12.

NHC Key Laboratory of AIDS Immunology (China Medical University), National Clinical Research Center for Laboratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang, China.

Human immunodeficiency virus type 1 (HIV-1) recombinants in the world are believed to be generated through recombination between distinct HIV-1 strains among coinfection or superinfection cases. However, direct evidence to support transmission of HIV-1 recombinants from a coinfected/superinfected donor to putative recipient is lacking. Here, we report on the origin and evolutionary relationship between a set of recombinants from a CRF01_AE/CRF07_BC superinfected putative donor and diverse CRF01_AE/CRF07_BC recombinants from five putative recipients. Interviews on sociodemographic characteristics and sexual behaviors for these six HIV-1-infected men who have sex with men showed that they had similar ways of partner seeking: online dating sites and social circles. Phylogenetic and recombination analyses demonstrated that the near-full-length genome sequences from six patients formed a monophyletic cluster different from known HIV-1 genotypes in maximum likelihood phylogenetic trees, were all composed of CRF01_AE and CRF07_BC fragments with two common breakpoints on env, and shared 4-7 breakpoints with each other. Moreover, 3' half-genomes of recombinant strains from five recipients had identical/similar recombinant structures with strains at longitudinal samples from the superinfected donor. Recombinants from the donor were paraphyletic, whereas five recipients were monophyletic or polyphyletic in the maximum clade credibility tree. Bayesian analyses confirmed that the estimated time to the most recent common ancestor (tMRCA) of CRF01_AE and CRF07_BC strains of the donor was 2009.2 and 2010.7, respectively, and all were earlier than the emergence of recombinants from five recipients. Our results demonstrated that the closely related unique recombinant forms of HIV-1 might be the descendent of a series of recombinants generated gradually in a superinfected patient. This finding highlights the importance of early initiation of antiretroviral therapy as well as tracing and testing of partners in patients with multiple HIV-1 infection.
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http://dx.doi.org/10.1371/journal.ppat.1009258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906459PMC
February 2021

Controllable Cell Deformation Using Acoustic Streaming for Membrane Permeability Modulation.

Adv Sci (Weinh) 2021 Feb 21;8(3):2002489. Epub 2020 Dec 21.

State Key Laboratory of Precision Measuring Technology & Instruments Tianjin University Tianjin 300072 China.

Hydrodynamic force loading platforms for controllable cell mechanical deformation play an essential role in modern cell technologies. Current systems require assistance from specific microstructures thus limiting the controllability and flexibility in cell shape modulation, and studies on real-time 3D cell morphology analysis are still absent. This article presents a novel platform based on acoustic streaming generated from a gigahertz device for cell shape control and real-time cell deformation analysis. Details in cell deformation and the restoration process are thoroughly studied on the platform, and cell behavior control at the microscale is successfully achieved by tuning the treating time, intensity, and wave form of the streaming. The application of this platform in cell membrane permeability modulation and analysis is also exploited. Based on the membrane reorganization during cell deformation, the effects of deformation extent and deformation patterns on membrane permeability to micro- and macromolecules are revealed. This technology has shown its unique superiorities in cell mechanical manipulation such as high flexibility, high accuracy, and pure fluid force operation, indicating its promising prospect as a reliable tool for cell property study and drug therapy development.
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http://dx.doi.org/10.1002/advs.202002489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856903PMC
February 2021

Hsa_circ_0025202 suppresses cell tumorigenesis and tamoxifen resistance via miR-197-3p/HIPK3 axis in breast cancer.

World J Surg Oncol 2021 Feb 3;19(1):39. Epub 2021 Feb 3.

Department of Laboratory Medicine, Jingmen No.1 People's Hospital, Jingmen, 448000, Hubei, China.

Background: The involvement of circular RNAs (circRNAs) in tamoxifen (TAM) resistance has been identified. Herein, we aimed to identify the role and novel mechanisms of hsa_circ_0025202 in tamoxifen resistance in breast cancer (BC).

Methods: The levels of hsa_circ_0025202, microRNA (miR)-197-3p, and homeodomain-interacting protein kinase 3 (HIPK3) were tested using quantitative real-time polymerase chain reaction and western blot. IC value of TAM, cell proliferation, cell cycle, cell invasion, migration, apoptosis, western blot, and mouse xenograft assays was used to demonstrate the effects of hsa_circ_0025202, miR-197-3p, and HIPK3 on BC cell tumorigenesis and TAM resistance. Dual-luciferase report and RNA immunoprecipitation assays were applied to explore the potential interaction between miR-197-3p and hsa_circ_0025202 or HIPK3.

Results: Hsa_circ_0025202 was decreased in BC tissues and TAM resistant BC cells, and knockdown of hsa_circ_0025202 elevated the IC value of cells to TAM, led to the promotion of cell proliferation, invasion and migration, mediated cell cycle progression, and inhibited cell apoptosis in BC in vitro. Besides, the upregulation of hsa_circ_0025202 hindered tumor growth and promoted TAM sensitivity in vivo. In a mechanical study, hsa_circ_0025202 targeted miR-197-3p, and silencing of miR-197-3p reversed the regulatory effects of hsa_circ_0025202 knockdown on TAM resistance and malignant phenotypes. Additionally, HIPK3 was a target of miR-197-3p, and miR-197-3p overexpression enhanced TAM resistance and promoted cell malignant biological behaviors in BC by targeting HIPK3.

Conclusion: Hsa_circ_0025202 repressed cell tumorigenesis and TAM resistance via miR-197-3p/HIPK3 axis in BC, suggesting a potential therapeutic strategy to overcome chemoresistance in BC patients.
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http://dx.doi.org/10.1186/s12957-021-02149-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7860040PMC
February 2021

Nampt promotes osteogenic differentiation and lipopolysaccharide-induced interleukin-6 secretion in osteoblastic MC3T3-E1 cells.

Aging (Albany NY) 2021 02 1;13(4):5150-5163. Epub 2021 Feb 1.

Department of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.

The Nicotinamide phosphoribosyltransferase (Nampt)-NAD-Sirt1 pathway modulates processes involved in the pathogenesis of multiple diseases by influencing inflammation. This study aimed to explore the effect of Nampt in osteogenic differentiation and inflammatory response of osteoblastic MC3T3-E1 cells. We developed an model of lipopolysaccharide (LPS)-induced inflammation and showed that Nampt and Sirt1 were significantly upregulated in LPS-treated MC3T3-E1 cells. LPS induced secretion of the proinflammatory cytokine interleukin-6 (IL-6) and attenuated osteogenic differentiation. Then we transfected cells with adenoviruses to knock down or over express Nampt. Nampt promoted the expression of IL-6, TAK1 and phospho-NF-κB p65 after LPS treatment. Overexpression of Nampt overrode the effect of LPS and rescued LPS-induced inhibition on osteogenic differentiation. FK866, a Nampt inhibitor, had the same inhibitory effect as Nampt knockdown. In addition, Sirt1 suppression by EX527 decreased IL-6 secretion and NF-κB activation without changing the level of Nampt. EX527 also decreased osteogenic differentiation. Incubation with NMN or SRT 1720 also counteract the inhibitory effect of LPS and rescued osteoblast differentiation. Therefore, we demonstrated that Nampt acted both in promoting osteoblast differentiation and in enhancing inflammatory response, mediated by Sirt1 in MC3T3-E1 cells.
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http://dx.doi.org/10.18632/aging.202434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7950263PMC
February 2021

Data-driven Boolean Network Inference Using a Genetic Algorithm with Marker-based Encoding.

IEEE/ACM Trans Comput Biol Bioinform 2021 Jan 29;PP. Epub 2021 Jan 29.

The inference of Boolean networks is crucial for analyzing the topology and dynamics of gene regulatory networks. Many data-driven approaches using evolutionary algorithms have been proposed based on time-series data. However, the ability to infer both network topology and dynamics is restricted by their inflexible encoding schemes. To address this problem, we propose a novel Boolean network inference algorithm for inferring both network topology and dynamics simultaneously. The main idea is that, we use a marker-based genetic algorithm to encode both regulatory nodes and logical operators in a chromosome. By using the markers and introducing more logical operators, the proposed algorithm can infer more diverse candidate Boolean functions. The proposed algorithm is applied to five networks, including two artificial Boolean networks and three real-world gene regulatory networks. Compared with other algorithms, the experimental results demonstrate that our proposed algorithm infers more accurate topology and dynamics.
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http://dx.doi.org/10.1109/TCBB.2021.3055646DOI Listing
January 2021

Inhibition of Dot1L Alleviates Fulminant Hepatitis Through Myeloid-Derived Suppressor Cells.

Cell Mol Gastroenterol Hepatol 2021 Jan 23. Epub 2021 Jan 23.

Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address:

Background & Aims: Fulminant hepatitis (FH) is a clinical syndrome characterized by sudden and severe liver dysfunction. Dot1L, a histone methyltransferase, is implicated in various physiologic and pathologic processes, including transcription regulation and leukemia. However, the role of Dot1L in regulating inflammatory responses during FH remains elusive.

Methods: Propionibacterium acnes (P. acnes)-primed, lipopolysaccharides (LPS)-induced FH was established in C57BL/6 mice and was treated with the Dot1L inhibitor EPZ-5676. Myeloid derived suppressor cells (MDSCs) were depleted by anti-Gr-1 antibody to evaluate their therapeutic roles in Dot1L treatment of FH. Moreover, peripheral blood of patients suffered with FH and healthy controls was collected to determine the expression profile of Dot1L-SOCS1-iNOS axis in their MDSCs.

Results: Here we identified that EPZ-5676, pharmacological inhibitor of Dot1L, attenuated the liver injury of mice subjected to FH. Dot1L inhibition led to decreased T helper 1 cell response and expansion of regulatory T cells (Tregs) during FH. Interestingly, Dot1L inhibition didn't directly target T cells, but dramatically enhanced the immunosuppressive function of MDSCs. Mechanistically, Dot1L inhibition epigenetically suppressed SOCS1 expression, thus inducing inducible nitric oxide synthase (iNOS) expression in a STAT1-dependent manner. Moreover, in human samples, the levels of Dot1L and SOCS1 expression were upregulated in MDSCs, accompanied by decreased expression of iNOS in patients with FH, compared with healthy controls.

Conclusions: Altogether, our findings established Dot1L as a critical regulator of MDSC immunosuppressive function for the first time, and highlighted the therapeutic potential of Dot1L inhibitor for FH treatment.
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http://dx.doi.org/10.1016/j.jcmgh.2021.01.013DOI Listing
January 2021

Molecular characterization and expression profiles of six genes involved in vitellogenic deposition and hydrolysis of Chinese sturgeon (Acipenser sinensis) suggesting their transcriptional regulation on ovarian development.

Theriogenology 2021 Mar 4;162:59-66. Epub 2021 Jan 4.

College of Fisheries, Huazhong Agricultural University/Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture/Hubei Collaborative Innovation Center for Freshwater Aquaculture/Hubei Provincial Engineering Laboratory for Pond Aquaculture, Wuhan 430070, China. Electronic address:

Ovary development of Chinese sturgeon (Acipenser sinensis) in controlled breeding has been reported to respond to dietary lipid levels. However, the corresponding molecular regulatory mechanism about ovary development of Chinese sturgeon is still unclear. To elucidate the molecular mechanism of vitellogenic deposition and hydrolysis, six key genes, namely, vtgr (vitellogenin receptor), atp6v1c1 (Vacuolar H-ATPase subunit c1), atp6v1h (Vacuolar H-ATPase subunit h), ctsb (cathepsin B), ctsd (cathepsin D) and ctsl (cathepsin L) involved in vitellogenic deposition and hydrolysis of Chinese sturgeon were cloned and characterized, and their spatio-temporal mRNA expression profiles as well as transcriptional responses to dietary lipid level were investigated. The full-length cDNA sequences of these six genes showed similar domain structure to their respective orthologous genes from other vertebrates. Tissue-specific expression patterns of these genes were observed in ovary, liver, muscle, spleen, brain, gill, intestine, heart, stomach and kidney. Ovarian expression level of vtgr was the highest in stage II, and ctsl expression was the highest in stage IV, while the mRNA expressions of other 4 genes were the highest in stage III. The increase of dietary lipid level promoted ovary development and elevated the expressions of vtgr, atp6v1c1, atp6v1h, ctsb and ctsd in the ovary. The results of the present study indicated that these genes are crucial for vitellogenic deposition, and provided a preliminary understanding on the molecular regulation of vitellogenic deposition and hydrolysis during ovary development of Chinese sturgeon.
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http://dx.doi.org/10.1016/j.theriogenology.2020.12.023DOI Listing
March 2021

Vortex fluidics mediated non-covalent physical entanglement of tannic acid and gelatin for entrapment of nutrients.

Food Funct 2021 Feb;12(3):1087-1096

Flinders Institute for Nanoscale Science and Technology, College of Science and Engineering, Flinders University, Bedford Park, South Australia, 5042, Australia.

We have developed a simple process for the entrapment of nutrients in shear stress induced non-covalent physically entangled tannic acid-gelatin gel in a thin film vortex fluidic device (VFD) operating under continuous flow. This allows control of the porosity and surface area of the pores in order to improve the nutrient entrapment capacity. The VFD microfluidic platform simplifies the processing procedure of physically entangled biopolymers, as a time and cost saving one-step process devoid of any organic solvents, in contrast to the conventional homogenization process, which is also inherently complex, involving multiple-step processing. Moreover, the use of homogenization (as a benchmark to entrap nutrients) afforded much larger porosity and surface area of pores, with lower entrapment capacity of nutrients. Overall, the VFD processing provides a new alternative, bottom-up approach for easy, scalable processing for materials with a high nutrient entrapment capacity.
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http://dx.doi.org/10.1039/d0fo02230fDOI Listing
February 2021

IFI27 may predict and evaluate the severity of respiratory syncytial virus infection in preterm infants.

Hereditas 2021 Jan 2;158(1). Epub 2021 Jan 2.

Department of Neonatology, Children's Hospital of Soochow University, NO.92 Zhongnan Street, Industrial Park, Suzhou, 215025, Jiangsu, China.

Background: Preterm infants are a special population that vulnerable to respiratory syncytial virus (RSV) infection and the lower respiratory tract infections (LRTIs) caused by RSV could be severe and even life-threating. The purpose of the present study was to identify candidate genes of preterm infants who are susceptible to RSV infection and provide a new insight into the pathogenesis of RSV infection.

Methods: Three datasets (GSE77087, GSE69606 and GSE41374) containing 183 blood samples of RSV infected patients and 33 blood samples of healthy controls from Gene Expression Omnibus (GEO) database were downloaded and the differentially expressed genes (DEGs) were screened out. The function and pathway enrichments were analyzed through Database for Annotation, Visualization and Integrated Discovery (DAVID) website. The protein-protein interaction (PPI) network for DEGs was constructed through Search Tool for the Retrieval of Interacting Genes (STRING). The module analysis was performed by Cytoscape software and hub genes were identified. Clinical verification was employed to verify the expression level of top five hub genes among 72 infants including 50 RSV infected patients and 22 non-RSV-infected patients hospitalized in our center. Further, the RSV infected infants with high-expression IFI27 and those with low-expression IFI27 were compared (defined as higher or lower than the median mRNA level). Finally, the gene set enrichment analysis (GSEA) focusing on IFI27 was carried out.

Results: Totally, 4028 DEGs were screened out and among which, 131 most significant DEGs were selected. Subsequently, 13 hub genes were identified, and function and pathway enrichments of hub genes mainly were: response to virus, defense response to virus, regulation of viral genome replication and regulation of viral life cycle. Furthermore, IFI27 was confirmed to be the most significantly expressed in clinical verification. Gene sets associated with calcium signaling pathway, arachidonic acid metabolism, extracellular matrix receptor interaction and so on were significantly enriched when IFI27 was highly expressed. Moreover, high-expression IFI27 was associated with more severe cases (p = 0.041), more requirements of mechanical ventilation (p = 0.034), more frequent hospitalization (p < 0.001) and longer cumulative hospital stay (p = 0.012).

Conclusion: IFI27 might serve to predict RSV infection and evaluate the severity of RSV infection in preterm infants.
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http://dx.doi.org/10.1186/s41065-020-00167-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778825PMC
January 2021

Automatically Explaining Machine Learning Prediction Results on Asthma Hospital Visits in Patients With Asthma: Secondary Analysis.

JMIR Med Inform 2020 Dec 31;8(12):e21965. Epub 2020 Dec 31.

Department of Pediatrics, University of Utah, Salt Lake City, UT, United States.

Background: Asthma is a major chronic disease that poses a heavy burden on health care. To facilitate the allocation of care management resources aimed at improving outcomes for high-risk patients with asthma, we recently built a machine learning model to predict asthma hospital visits in the subsequent year in patients with asthma. Our model is more accurate than previous models. However, like most machine learning models, it offers no explanation of its prediction results. This creates a barrier for use in care management, where interpretability is desired.

Objective: This study aims to develop a method to automatically explain the prediction results of the model and recommend tailored interventions without lowering the performance measures of the model.

Methods: Our data were imbalanced, with only a small portion of data instances linking to future asthma hospital visits. To handle imbalanced data, we extended our previous method of automatically offering rule-formed explanations for the prediction results of any machine learning model on tabular data without lowering the model's performance measures. In a secondary analysis of the 334,564 data instances from Intermountain Healthcare between 2005 and 2018 used to form our model, we employed the extended method to automatically explain the prediction results of our model and recommend tailored interventions. The patient cohort consisted of all patients with asthma who received care at Intermountain Healthcare between 2005 and 2018, and resided in Utah or Idaho as recorded at the visit.

Results: Our method explained the prediction results for 89.7% (391/436) of the patients with asthma who, per our model's correct prediction, were likely to incur asthma hospital visits in the subsequent year.

Conclusions: This study is the first to demonstrate the feasibility of automatically offering rule-formed explanations for the prediction results of any machine learning model on imbalanced tabular data without lowering the performance measures of the model. After further improvement, our asthma outcome prediction model coupled with the automatic explanation function could be used by clinicians to guide the allocation of limited asthma care management resources and the identification of appropriate interventions.
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http://dx.doi.org/10.2196/21965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808890PMC
December 2020

Novel Zn-Binding Peptide Isolated from Soy Protein Hydrolysates: Purification, Structure, and Digestion.

J Agric Food Chem 2021 Jan 28;69(1):483-490. Epub 2020 Dec 28.

School of Chemistry and Chemical Engineering, Guangzhou University, Guangzhou 510006, China.

In this study, a novel Zn-binding peptide, Lys-Tyr-Lys-Arg-Gln-Arg-Trp (KYKRQRW), was purified and identified from soy protein isolate hydrolysates (SPIHs). The Zn-binding peptide exhibited improved Zn-binding capacity (83.21 ± 2.65%) than SPIH solutions. CD, NMR, and Fourier transform infrared spectroscopy were used to confirm the complexation between Zn and the peptide. The results showed that the Zn-binding peptide formed a folding structure with part of the β-sheet (29.3-13.4%) turning into random coils (41.7-57.6%) during complexation. It was further proved that the binding sites were located at the oxygen atoms on the carboxyl group of the Trp side chain and nitrogen atoms on the amino group of the Lys side chain. Moreover, the Zn-peptide complex exhibited increased solubility than ZnSO during simulated gastrointestinal digestion. This study highlighted that the novel soy peptide possessed a strong zinc chelate rate and had a positive effect on the gastrointestinal stability of Zn which could be utilized as a functional ingredient in future.
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http://dx.doi.org/10.1021/acs.jafc.0c05792DOI Listing
January 2021

CD74, a novel predictor for bronchopulmonary dysplasia in preterm infants.

Medicine (Baltimore) 2020 Nov;99(48):e23477

Department of Neonatology, Children's Hospital of Soochow University, Suzhou, Jiangsu.

Bronchopulmonary dysplasia (BPD) remains a major complication and accounts for high morbidity and mortality of preterm infants. The present study aimed to identify the key genes in the development of BPD and to provide some new insights into the pathogenesis of BPD. The GSE108754 dataset was downloaded from Gene Expression Omnibus database containing 5 samples of BPD patients and 6 of non-BPD infants. The differentially expressed genes (DEGs) between BPD and non-BPD patients were identified by R software. The pathway and function enrichment analyses were performed through Database for Annotation Visualization and Integrated Discovery website. The protein-protein interaction network for DEGs was established by Cytoscape software and the most highly connected module was selected through MCODE plugin. Furthermore, the clinical sample verification among 25 BPD patients and 10 non-BPD infants was carried out in our center. Finally, based on the results above, the gene set enrichment analysis focusing on CD74 upregulated status was employed. Totally, 189 DEGs including 147 upregulated genes and 42 downregulated genes between BPD and non-BPD patients were screened out. The pathway and function enrichments revealed these DEGs were mainly enriched in asthma, intestinal immune network for IgA production, antigen processing and presentation and immune response. Thirteen DEGs (CD74, HLA-DMA, HLA-DRA, HLA-DMB, HLA-DOB, HLA-DQA1, HLA-DRB5, HLA-DPA1, HLA-DOA, HLA-DPB1, HLA-DQB2, HLA-DQA2, and HLA-DQB1) were determined as hub genes. The mRNA expression levels of the 13 hub genes were tested by quantitative real-time polymerase chain reaction among our clinical samples. Eventually, CD74 was confirmed to be the most significant highly expressed in BPD samples (P < .001) and its expression level was negatively correlated with gestational age (r = -0.653) and birth weight (r = -0.675). The gene set enrichment analysis results showed the gene sets associated with lupus erythematosus, viral myocarditis, immune network for IgA production, graft versus host disease, cell adhesion molecules and so no were differentially enriched with the phenotype of high-expression CD74. In conclusion, CD74 may serve to predict the BPD development and provide a new therapeutic target for BPD.
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http://dx.doi.org/10.1097/MD.0000000000023477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710202PMC
November 2020

Exploiting Co Defects in CoFe-Layered Double Hydroxide (CoFe-LDH) Derivatives for Highly Efficient Photothermal Cancer Therapy.

ACS Appl Mater Interfaces 2020 Dec 24;12(49):54916-54926. Epub 2020 Nov 24.

Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, P. R. China.

Currently, two-dimensional materials are being actively pursued in catalysis and other fields due their abundance of defects, which results in enhanced performance relative to their bulk defect-free counterparts. To date, the exploitation of defects in two-dimensional materials to enhance photothermal therapies has received little attention, motivating a detailed investigation. Herein, we successfully fabricated a series of novel CoFe-based photothermal agents (CoFe-) by heating CoFe-layered double hydroxide (CoFe-LDH) nanosheets at different temperatures () between 200-800 °C under a Ar atmosphere. The CoFe- products differed in their particle size, cobalt defect concentration, and electronic structure, with the CoFe-500 product containing the highest concentration of Co defects and most efficient photothermal performance under near-infrared (NIR, 808 nm) irradiation. Experiments and density functional theory (DFT) calculations revealed that Co defects modify the electronic structure of CoFe-, narrowing the band gap and thus increasing the nonradiative recombination rate, thereby improving the NIR-driven photothermal properties. In vitro and in vivo results demonstrated that CoFe-500 was an efficient agent for photothermal cancer treatment and also near-infrared (NIR) thermal imaging, magnetic resonance (MR) imaging, and photoacoustic (PA) imaging. This work provides valuable new insights about the role of defects in the rational design of nanoagents with optimized structures for improved cancer therapy.
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http://dx.doi.org/10.1021/acsami.0c14147DOI Listing
December 2020

The structural basis of Rubisco phase separation in the pyrenoid.

Nat Plants 2020 12 23;6(12):1480-1490. Epub 2020 Nov 23.

Department of Molecular Biology, Princeton University, Princeton, NJ, USA.

Approximately one-third of global CO fixation occurs in a phase-separated algal organelle called the pyrenoid. The existing data suggest that the pyrenoid forms by the phase separation of the CO-fixing enzyme Rubisco with a linker protein; however, the molecular interactions underlying this phase separation remain unknown. Here we present the structural basis of the interactions between Rubisco and its intrinsically disordered linker protein Essential Pyrenoid Component 1 (EPYC1) in the model alga Chlamydomonas reinhardtii. We find that EPYC1 consists of five evenly spaced Rubisco-binding regions that share sequence similarity. Single-particle cryo-electron microscopy of these regions in complex with Rubisco indicates that each Rubisco holoenzyme has eight binding sites for EPYC1, one on each Rubisco small subunit. Interface mutations disrupt binding, phase separation and pyrenoid formation. Cryo-electron tomography supports a model in which EPYC1 and Rubisco form a codependent multivalent network of specific low-affinity bonds, giving the matrix liquid-like properties. Our results advance the structural and functional understanding of the phase separation underlying the pyrenoid, an organelle that plays a fundamental role in the global carbon cycle.
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http://dx.doi.org/10.1038/s41477-020-00811-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736253PMC
December 2020