Publications by authors named "Tingting Guo"

208 Publications

Brain Function Network: Higher Order vs. More Discrimination.

Front Neurosci 2021 23;15:696639. Epub 2021 Aug 23.

School of Biomedical Engineering, ShanghaiTech University, Shanghai, China.

Brain functional network (BFN) has become an increasingly important tool to explore individual differences and identify neurological/mental diseases. For estimating a "good" BFN (with more discriminative information for example), researchers have developed various methods, in which the most popular and simplest is Pearson's correlation (PC). Despite its empirical effectiveness, PC only encodes the low-order (second-order) statistics between brain regions. To model high-order statistics, researchers recently proposed to estimate BFN by conducting two sequential PCs (denoted as in this paper), and found that -based BFN can provide additional information for group difference analysis. This inspires us to think about (1) what will happen if continuing the correlation operation to construct much higher-order BFN by (>2), and (2) whether the higher-order correlation will result in stronger discriminative ability. To answer these questions, we use -based BFNs to predict individual differences (Female vs. Male) as well as identify subjects with mild cognitive impairment (MCI) from healthy controls (HCs). Through experiments, we have the following findings: (1) with the increase of n, the discriminative ability of -based BFNs tends to decrease; (2) fusing the -based BFNs (>1) with the -based BFN can generally improve the sensitivity for MCI identification, but fail to help the classification accuracy. In addition, we empirically find that the sequence of BFN adjacency matrices estimated by ( = 1,2,3,⋯ ) will converge to a binary matrix with elements of ± 1.
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http://dx.doi.org/10.3389/fnins.2021.696639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419271PMC
August 2021

Process optimization and characterization of arachidonic acid oil degumming using ultrasound-assisted enzymatic method.

Ultrason Sonochem 2021 Aug 17;78:105720. Epub 2021 Aug 17.

Oil Crops Research Institute, Chinese Academy of Agricultural Sciences, Wuhan, China; Hubei Key Laboratory of Lipid Chemistry and Nutrition, Wuhan, China; Oil Crops and Lipids Process Technology National & Local Joint Engineering Laboratory, Wuhan, China.

Ultrasound assisted enzymatic method was applied to the degumming of arachidonic acid (ARA) oil produced by Mortierella alpina. The conditions of degumming process were optimized by response surface methodology with Box- Behnken design. A dephosphorization rate of 98.82% was achieved under optimum conditions of a 500 U/kg of Phospholipase A (PLA) dosage, 2.8 mL/100 g of water volume, 120 min of ultrasonic time, and 135 W of ultrasonic power. The phosphorus content of ultrasonic assisted enzymatic degumming oil (UAEDO) was 4.79 mg/kg, which was significantly lower than that of enzymatic degumming oil (EDO, 17.98 mg/kg). Crude Oil (CO), EDO and UAEDO revealed the similar fatty acid compositions, and ARA was dominated (50.97 ~ 52.40%). The oxidation stability of UAEDO was equivalent to EDO and weaker than CO, while UAEDO presented the strongest thermal stability, followed by EDO and CO. Furthermore, aldehydes, acids and alcohols were identified the main volatile flavor components for the three oils. The proportions of major contributing components such as hexanal, nonanal, (E)-2-nonanal, (E, E)-2,4-decadienal, (E)-2-nonenal and aldehydes in UAEDO and EDO were all lower than CO. Overall, Ultrasound assisted enzymatic degumming proved to be an efficient and superior method for degumming of ARA oil.
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http://dx.doi.org/10.1016/j.ultsonch.2021.105720DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8408658PMC
August 2021

Micelle nanovehicles for co-delivery of Lepidium meyenii Walp. (maca) polysaccharide and chloroquine to tumor-associated macrophages for synergistic cancer immunotherapy.

Int J Biol Macromol 2021 Aug 25;189:577-589. Epub 2021 Aug 25.

School of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China; Key Laboratory of Sustainable Utilization of Panax Notoginseng Resources of Yunnan, Province, Kunming 650500, China. Electronic address:

Here, we fabricated amphiphilic polysaccharide micelles for synergistic cancer immunotherapy targeting tumor-associated macrophages (TAMs). Lepidium meyenii Walp. (maca) polysaccharide (MP), a naturally derived macromolecule with a strong TAM-remodeling effect, was grafted on a hydrophobic poly(lactic-co-glycolic acid) (PLGA) segment, with a disulfide bond for redox-sensitive linkage. The amphiphilic polysaccharide derivatives could self-assemble into core (PLGA)-shell (MP)-structured micelles and encapsulate chloroquine (CQ) into the hydrophobic core. By using a 4T1-M2 macrophage co-culture model and a 4T1 tumor xenograft mouse model, we showed that the prepared micelles could co-deliver MP and CQ to the tumor sites and selectively accumulate at TAMs because of the specific properties of MP. Furthermore, the nanoparticles exerted synergistic tumor immunotherapeutic and antimetastatic effects, which might be attributable to the enhanced cell internalization of the micelles and the multiple regulatory mechanisms of MP and CQ. Thus, immunomodulatory MP may be a promising biomaterial for cancer immunotherapy.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.08.155DOI Listing
August 2021

Assessment on the lung injury of mice posed by airborne PM collected from developing area in China and associated molecular mechanisms by integrated analysis of mRNA-seq and miRNA-seq.

Ecotoxicol Environ Saf 2021 Aug 17;224:112661. Epub 2021 Aug 17.

Center of Precision Medicine, Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu 610041, China; Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China. Electronic address:

Some epidemiological evidences showed exposure of airborne fine particulate matter (PM) was associated with lung dysfunction. However, the adverse effects of PM from mid-scale city of China on the respiratory system were unknown. Correspondingly, the mechanisms, especially the epigenetic mechanism regulated by miRNAs, involved in PM-induced lung injury has not been fully understood. In this study, male Balb/C mice were exposed to PM collected from mid-scale city (Baoji), China for 8 weeks (mean concentration 298.52 ± 25.86 μg/m at exposure chamber) using a whole-body exposure system. The carbon component was the main ingredient (45.80%) of PM2.5 followed by ions (43.19%). Meanwhile, the sum concentrations of polycyclic aromatic hydrocarbons (PAHs) and n-alkanes (C18-C33) were 570.48 and 2029.13 ng/m in the exposure chamber, respectively. Obvious lung injury including pulmonary inflammation and fibrosis (p < 0.05 compared with the control) were found from PM exposure group determined by micro-CT and histopathological assays, respectively, suggesting the health risk posed by PM from mid-scale city of China should be concerned. The integrated analysis between mRNA-seq and miRNA-seq revealed the differentially expression genes in lung tissues were enriched in immune pathways including B cell receptor signaling (p = 0.078) and cell adhesion molecules (CAMs) (p = 0.0068). The expression profiles of the genes and corresponding mRNAs involved into the immune pathways determined by RT-qPCR analysis were consistent with them conducted by transcriptome. Moreover, the expression levels of the proteins (i.e., CD19, CD81, PIK3CD, and CD22) involved into B cell receptor signaling pathway from exposure group were 1.71- to 6.948- folds compared with the control, validating the results of the genes expression profiles. Further, canonical correlation analysis (CCA) and multiple correlation analysis between the target genes and components of PM documented the organic compounds (i.e., Benzo(a)pyrene (p = 0.012) and octadecane (p = 0.05)) and inorganic elements (i.e., Cl, Ti, Al, and Zn) was the key environmental factors. Cd19, Pik3cd, and Cd8b1 might be the key genes for lung dysfunction induced by PM illuminated using interactive analysis (p < 0.05). This work for the first time showed the adverse effects of PM in mid-scale city in China on respiratory system should be concerned, and the associated epigenetic mechanism regulated by miRNA were revealed. These results may provide new insight into the development of future assessment on the air pollution associated respiratory disease.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112661DOI Listing
August 2021

Development of a nomogram for predicting survival of patients with ovarian serous cystadenocarcinoma after based on SEER database.

Zhejiang Da Xue Xue Bao Yi Xue Ban 2021 Jun;50(3):369-374

Department of Obstetrics and Gynecology.

To develop a survival time prediction model for patients with ovarian serous cystadenocarcinoma after surgery. A retrospective analysis of 5906 postoperative patients with ovarian serous cystadenocarcinoma in the surveillance, epidemiology, and end results (SEER) database from 2010 to 2015 was performed. The independent risk factors for long-term survival were analyzed with multivariate Cox proportional hazard regression model. The nomogram of 3-year and 5-year survival was developed by using R language. The receiver operator characteristic (ROC) curve and were used to test the discrimination of the model and the calibration diagram was used to evaluate the degree of calibration of the prediction model. The survival curves was conducted by the risk factors. Cox proportional hazard regression model showed that age, race, histological grade (poorly differentiated and undifferentiated), stage T (T2a, T2b, T2c, T3a, T3b and T3c), and stage M (M1) were independent factors for the prognosis of patients with ovarian serous cystadenocarcinoma after surgery. A nomogram was developed by the R language tool for predicting the 3-year and survival of patients through age, race, histological classification, stage T and stage M. The C-index was 0.688 and the areas under ROC curve of the nomogram for predicting 3-year and 5-year survival were 0.708 and 0.716, respectively. The results of the calibration indicated that the predicted values were consistent with the actual values in the prediction models. The survival time of patients with high-risk factors was shorter than that of patients with low-risk factors (<0.05). The developed nomogram in this study can be used to predict 3-year and 5-year survival of postoperative patients with ovarian serous cystadenocarcinoma, and it may be beneficial to guide clinical treatment.
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http://dx.doi.org/10.3724/zdxbyxb-2021-0188DOI Listing
June 2021

De novo assembly, annotation, and comparative analysis of 26 diverse maize genomes.

Science 2021 08;373(6555):655-662

USDA-ARS Corn Insects and Crop Genetics Research Unit, Iowa State University, Ames, IA 50011, USA.

We report de novo genome assemblies, transcriptomes, annotations, and methylomes for the 26 inbreds that serve as the founders for the maize nested association mapping population. The number of pan-genes in these diverse genomes exceeds 103,000, with approximately a third found across all genotypes. The results demonstrate that the ancient tetraploid character of maize continues to degrade by fractionation to the present day. Excellent contiguity over repeat arrays and complete annotation of centromeres revealed additional variation in major cytological landmarks. We show that combining structural variation with single-nucleotide polymorphisms can improve the power of quantitative mapping studies. We also document variation at the level of DNA methylation and demonstrate that unmethylated regions are enriched for cis-regulatory elements that contribute to phenotypic variation.
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http://dx.doi.org/10.1126/science.abg5289DOI Listing
August 2021

A qPCR-based method for rapid quantification of six intestinal homeostasis-relevant bacterial genera in feces.

Future Microbiol 2021 Aug 3. Epub 2021 Aug 3.

State Key Laboratory of Microbial Technology, Shandong University, Qingdao, 266237, China.

Developing efficient methods for monitoring the complex microbial community to rapidly assess the health status. The qPCR-based method was developed, verified and applied in fecal samples. Six primer pairs with high specificity were designed to perform qPCR assays under a unified reaction condition within 2.5 h. The limits of detection, amplification efficiency and feasibility of the qPCR-based method established here were verified. application of 18 fecal samples showed that the amounts of , and in colorectal cancer patient feces were obviously lower than those of healthy volunteers. This qPCR-based method was a reliable tool for rapid quantification of the six intestinal homeostasis relevant bacterial genera in feces.
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http://dx.doi.org/10.2217/fmb-2020-0269DOI Listing
August 2021

Research Progress on the Antiviral Activity of Glycyrrhizin and its Derivatives in Liquorice.

Front Pharmacol 2021 6;12:680674. Epub 2021 Jul 6.

Institutes of Agricultural Science and Technology Development, College of Veterinary Medicine, Yangzhou University, Yangzhou, China.

Liquorice is a traditional medicine. Triterpenoids such as glycyrrhizin and glycyrrhetinic acid are the main active constituents of liquorice. Studies have revealed that these compounds exert inhibitory effects on several viruses, including SARS-CoV-2. The main mechanisms of action of these compounds include inhibition of virus replication, direct inactivation of viruses, inhibition of inflammation mediated by HMGB1/TLR4, inhibition of β-chemokines, reduction in the binding of HMGB1 to DNA to weaken the activity of viruses, and inhibition of reactive oxygen species formation. We herein review the research progress on the antiviral effects of glycyrrhizin and its derivatives. In addition, we emphasise the significance of exploring unknown antiviral mechanisms, structural modifications, and drug combinations in future studies.
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http://dx.doi.org/10.3389/fphar.2021.680674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290359PMC
July 2021

The anion of choline-based ionic liquids tailored interactions between ionic liquids and bovine serum albumin, MCF-7 cells, and bacteria.

Colloids Surf B Biointerfaces 2021 Oct 9;206:111971. Epub 2021 Jul 9.

Department of Chemistry, College of Sciences, Northeastern University, Shenyang, 110819, China. Electronic address:

Choline-based ionic liquids (ILs) have been widely applied because of their good biocompatibility. Herein, the toxicity of choline-based ILs containing different anions was studied by UV-vis absorption spectra, fluorescence spectra, MTT assays and antibacterial experiments. The results explained that choline chloride ([Ch][Cl]) had no obvious effect on the conformation of bovine serum albumin (BSA), while the conformation could be slightly changed by choline bromide ([Ch][Br]). In the presence of choline iodide ([Ch][I]), choline bitartrate ([Ch][Bit]) and choline dihydrogen citrate ([Ch][Dhc]), the conformation of BSA changed significantly. The quenching mechanisms of [Ch][Bit] and [Ch][Dhc] were static quenching procedure, while there were charge transfer quenching and static quenching for [Ch][I]. ILs combined with BSA in spontaneous manner driven by hydrogen bond and van der Waals force, which was proved by thermodynamic constants and molecular docking. The toxicity of the five ILs to mammalian cells and bacteria came to a similar conclusion. [Ch][Cl] had little toxicity to cells, which was less than [Ch][Br] and [Ch][I]. [Ch][Bit] and [Ch][Dhc] were more toxic. These results provide more information to understand the effect of anions on choline-based ILs, in order to find low toxic choline-based ILs that can be used in biological and pharmaceutical fields.
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http://dx.doi.org/10.1016/j.colsurfb.2021.111971DOI Listing
October 2021

Whole-genome re-sequencing association study on yearling wool traits in Chinese fine-wool sheep.

J Anim Sci 2021 Sep;99(9)

Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Sciences, Sheep Breeding Engineering Technology Research Center, Lanzhou, 730050, China.

To investigate single nucleotide polymorphism (SNP) loci associated with yearling wool traits of fine-wool sheep for optimizing marker-assisted selection and dissection of the genetic architecture of wool traits, we conducted a genome-wide association study (GWAS) based on the fixed and random model circulating probability unification (FarmCPU) for yearling staple length (YSL), yearling mean fiber diameter (YFD), yearling greasy fleece weight (YGFW), and yearling clean fleece rate (YCFR) by using the whole-genome re-sequenced data (totaling 577 sheep) from the following four fine-wool sheep breeds in China: Alpine Merino sheep (AMS), Chinese Merino sheep (CMS), Qinghai fine-wool sheep (QHS), and Aohan fine-wool sheep (AHS). A total of 16 SNPs were detected above the genome-wise significant threshold (P = 5.45E-09), and 79 SNPs were located above the suggestive significance threshold (P = 5.00E-07) from the GWAS results. For YFD and YGFW traits, 7 and 9 SNPs reached the genome-wise significance thresholds, whereas 10 and 12 SNPs reached the suggestive significance threshold, respectively. For YSL and YCFR traits, none of the SNPs reached the genome-wise significance thresholds, whereas 57 SNPs exceeded the suggestive significance threshold. We recorded 14 genes located at the region of ±50-kb near the genome-wise significant SNPs and 59 genes located at the region of ±50-kb near the suggestive significant SNPs. Meanwhile, we used the Average Information Restricted Maximum likelihood algorithm (AI-REML) in the "HIBLUP" package to estimate the heritability and variance components of the four desired yearling wool traits. The estimated heritability values (h2) of YSL, YFD, YGFW, and YCFR were 0.6208, 0.7460, 0.6758, and 0.5559, respectively. We noted that the genetic parameters in this study can be used for fine-wool sheep breeding. The newly detected significant SNPs and the newly identified candidate genes in this study would enhance our understanding of yearling wool formation, and significant SNPs can be applied to genome selection in fine-wool sheep breeding.
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http://dx.doi.org/10.1093/jas/skab210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418636PMC
September 2021

Genetic tools for the development of recombinant lactic acid bacteria.

Microb Cell Fact 2021 Jun 19;20(1):118. Epub 2021 Jun 19.

State Key Laboratory of Microbial Technology, Shandong University, Qingdao, 266237, People's Republic of China.

Lactic acid bacteria (LAB) are a phylogenetically diverse group with the ability to convert soluble carbohydrates into lactic acid. Many LAB have a long history of safe use in fermented foods and are recognized as food-grade microorganisms. LAB are also natural inhabitants of the human intestinal tract and have beneficial effects on health. Considering these properties, LAB have potential applications as biotherapeutic vehicles to delivery cytokines, antigens and other medicinal molecules. In this review, we summarize the development of, and advances in, genome manipulation techniques for engineering LAB and the expected future development of such genetic tools. These methods are crucial for us to maximize the value of LAB. We also discuss applications of the genome-editing tools in enhancing probiotic characteristics and therapeutic functionalities of LAB.
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http://dx.doi.org/10.1186/s12934-021-01607-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214781PMC
June 2021

Establishment of a 3D model of tumor-driven angiogenesis to study the effects of anti-angiogenic drugs on pericyte recruitment.

Biomater Sci 2021 Sep 14;9(18):6064-6085. Epub 2021 Sep 14.

Laboratory of Stem Cells and Translational Medicine, Institutes for Life Sciences, School of Medicine, South China University of Technology, Guangzhou 510006, P. R. China.

Hepatocellular carcinoma (HCC), as a well-vascularized tumor, has attracted increasing attention in antiangiogenic therapies. Notably, emerging studies reveal that the long-term administration of antiangiogenic drugs induces hypoxia in tumors. Pericytes, which play a vital role in vascular stabilization and maturation, have been documented to be associated with antiangiogenic drug-induced tumor hypoxia. However, the role of antiangiogenic agents in regulating pericyte behavior still remains elusive. In this study, by using immunostaining analysis, we first demonstrated that tumors obtained from HCC patients were highly angiogenic, in which vessels were irregularly covered by pericytes. Therefore, we established a new 3D model of tumor-driven angiogenesis by culturing endothelial cells, pericytes, cancer stem cells (CSCs) and mesenchymal stem cells (MSCs) with microcarriers in order to investigate the effects and mechanisms exerted by antiangiogenic agents on pericyte recruitment during tumor angiogenesis. Interestingly, microcarriers, as supporting matrices, enhanced the interactions between tumor cells and the extracellular matrix (ECM), promoted malignancy of tumor cells and increased tumor angiogenesis within the 3D model, as determined by qRT-PCR and immunostaining. More importantly, we showed that zoledronic acid (ZA) reversed the inhibited pericyte recruitment, which was induced by sorafenib (Sora) treatment, through fostering the expression and activation of ErbB1/ErbB2 and PDGFR-β in pericytes, in both an 3D model and an xenograft HCC mouse model. Hence, our model provides a more pathophysiologically relevant platform for the assessment of therapeutic effects of antiangiogenic compounds and identification of novel pharmacological targets, which might efficiently improve the benefits of antiangiogenic treatment for HCC patients.
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http://dx.doi.org/10.1039/d0bm02107eDOI Listing
September 2021

LncRNA PCNAP1 Promotes Hepatoma Cell Proliferation through Targeting miR-340-5p and is Associated with Patient Survival.

J Oncol 2021 28;2021:6627173. Epub 2021 Apr 28.

Department of Critical Care Medicine, Chongqing Traditional Chinese Medicine Hospital, Chongqing 400011, China.

Hepatocellular carcinoma (HCC) is one of the most common malignancies and causes poor outcome. Dysregulation of long noncoding RNA (lncRNA) is involved in HCC. Upregulation of the lncRNA PCNAP1 has been reported to promote HBV-infectious HCC growth, but its clinical significance and underlying mechanisms in HCC development remain unclear. Here, we report that PCNAP1 expression is increased in both HBV-infectious and noninfectious HCC tissues compared with matched normal tissues, and its upregulation correlates with poor survival rates of HCC patients. Furthermore, we found that PCNAP1 promotes HCC cell proliferation through acting as a competitive endogenous RNA (ceRNA) to sponge miR-340-5p, which has been reported to directly inhibit ATF7 expression in HCC cells. Moreover, the PCNAP1/miR-340-5p/ATF7 signaling associates with the poor survival rates of HCC patients. Collectively, our findings suggest that the PCNAP1/miR-340-5p/ATF7 signaling may be a potential biomarker for the prognosis of HCC patients and a potential therapeutic target for HCC.
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http://dx.doi.org/10.1155/2021/6627173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100385PMC
April 2021

Identifying Genomic Alterations in Small Cell Lung Cancer Using the Liquid Biopsy of Bronchial Washing Fluid.

Front Oncol 2021 26;11:647216. Epub 2021 Apr 26.

Department of Respiratory Ward One, Shanxi Provincial Cancer Hospital, Taiyuan, China.

With the rapid development of cancer genomics and immunomics, some new treatments of small cell lung cancer (SCLC) are emerging. However, there are limitations to the clinical use of tumor tissue. Our study aimed to evaluate the potential use of bronchial washing fluid (BWF) in the liquid biopsy of SCLC. Twenty-one extensive SCLC (ES-SCLC) patients were enrolled in this study. For all patients, four sample types, BWF supernatant (BWFs), BWF precipitate (BWFp), plasma and tumor tissue, were collected before receiving chemotherapy, and one type, plasma, was collected after chemotherapy. All samples were conducted to NGS using the 1021-gene panel. The concordance rates of genomic profiling using NGS in the four types of samples were evaluated. Multiple clinical information was analyzed for correlation. We successfully tested 20 BWFs samples, 21 BWFp samples, 21 tumor tissue samples, 20 pre-treatment plasma, and 13 post-treatment plasma of these 21 patients. The detectability of somatic mutations was 100% for BWFs, BWFp, tumor tissues, and post-treatment plasma, and only one pre-treatment plasma was absent with any mutation. Matched tumor tissue, BWFs, BWFp, and pre-treatment plasma samples were subsistent for 19 patients. For these patients, 204 genomic alterations were identified in tissue samples, while 189 (92.6%), 175 (85.5%), and 163 (79.9%) alterations were detected in the matched BWFs, BWFp, and pre-treatment plasma, respectively. Moreover, we found that the three tumor markers associated with SCLC have a lower sensitivity than genomic alterations. The endocrine resistance pathway was found enriched in hyponatremia patients which may be related to the hyponatremia. The TMBs of BWF, BWFp, and pre-treatment plasma samples all had a strong correlation with that of tissue samples. Both the VAF and the MVAF of mutations in post-treatment plasma were less than those in pre-treatment plasma, which was in accordance with the evaluation of curative effect. For ES-SCLC patients, the liquid biopsy of BWF showed a highly potential advantage to identify DNA alterations, which suggested that genomic analysis of BWF liquid biopsy may have clinical value as a supplement for tissue and blood detection. Through the restricted validation, it can be widely used in routine clinical practice.
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http://dx.doi.org/10.3389/fonc.2021.647216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110515PMC
April 2021

The TCM prescription Ma-xing-shi-gan-tang inhibits Streptococcus pneumoniae pathogenesis by targeting pneumolysin.

J Ethnopharmacol 2021 Jul 20;275:114133. Epub 2021 Apr 20.

Changchun University of Chinese Medicine, Changchun, Jilin, 130117, China. Electronic address:

Ethnopharmacological Relevance: Ma-xing-shi-gan-tang (MXSGT), which is documented in the Treatise on Febrile Diseases and is a therapeutic drug, is a well-known classic prescription in China and has been widely studied. Previous studies have shown that MXSGT has various pharmacological activities, including anti-influenza virus activity, and ameliorates microvascular hyperpermeability and inflammatory reactions. However, no study has reported the effect of MXSGT in the treatment of bacterial pneumonia.

Aim Of The Study: In this study, the potential inhibition of MXSGT against the virulence of S. pneumoniae by targeting PLY was investigated.

Materials And Methods: First, HPLC analysis was used to determine the main components of MXSGT. Then PLY protein was constructed and used for hemolysis assay and western blot to test the ability of MXSGT to inhibit PLY activity, production and widowed characteristics. The growth curve of S. pneumoniae was drawled with or without MXSGT treatment. In addition, the inhibition of MXSGT against PLY-mediated A549 cell death was examined by cytotoxicity assay. Finally, the mouse experiment was used to verify the effect of MXSGT on mouse lungs.

Results: This work has discovered that MXSGT, a TCM prescription, is an effective inhibitor of PLY, an important virulence factor that is essential for S. pneumoniae pathogenicity. MXSGT inhibits the oligomerization of PLY without affecting S. pneumoniae growth and PLY production. In addition, experimental MXSGT treatment was effective against S. pneumoniae infection both in vitro and in vivo.

Conclusion: These findings directly demonstrate the potential mechanism of the Chinese herbal formula MXSGT in the treatment of pneumococcal disease and provide additional evidence for promotion of the wide use of MXSGT in the clinic.
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http://dx.doi.org/10.1016/j.jep.2021.114133DOI Listing
July 2021

Real-world data combined with studies on Regulatory B Cells for newly diagnosed Multiple Myeloma from a tertiary referral Hospital in South-Western China.

J Cancer 2021 5;12(9):2633-2642. Epub 2021 Mar 5.

Department of Hematology, West China Hospital, Sichuan University, China.

Multiple myeloma (MM) is a heterogeneous disease that remains incurable with significant interpatient variability in outcomes. Regulatory B cells (Bregs) were observed to be involved into specific defects in MM. Here, we provide our risk-adapted approach to newly diagnosed MM (NDMM), combining with the fundamental dysfunction of Bregs. We reported one hundred consecutive patients with NDMM from South-Western China, primarily treated with bortezomib plus dexamethasone with or without a 3 agent, were enrolled from 2017. Bone marrow aspirates were obtained and flow cytometry (FCM) was used to quantify the percentage of Bregs from the bone marrow. The correlation between Bregs and clinical characters were further analyzed. This study found using bortezomib plus dexamethasone as backbone showed promising efficacy with acceptable tolerability in NDMM. The relatively compromised progression free survival (PFS) points to the essential synergy of bortezomib and lenalidomide here. This study also found that altered proportions of Bregs were closely correlated with treatment efficacy and prognosis in MM. Further understanding of Bregs biology might provide new opportunities to develop immunotherapy, which could prove beneficial in treating MM.
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http://dx.doi.org/10.7150/jca.53209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040702PMC
March 2021

Effect of 4-chloro-2-methylphenoxy acetic acid on tomato gene expression and rhizosphere bacterial communities under inoculation with phosphate-solubilizing bacteria.

J Hazard Mater 2021 08 27;416:125767. Epub 2021 Mar 27.

Institute of Horticulture, Anhui Academy of Agricultural Sciences, Hefei 230031, Anhui Province, China; Key Laboratory of Genetic Improvement and Ecophysiology of Horticultural Crops, Hefei 230031, Anhui Province, China.

The herbicide 4-chloro-2-methylphenoxy acetic acid (MCPA) is widely used to control the spread of broad-leaved weeds in agricultural soils, though it remains unclear how tomato plants cope with the phytotoxic effects of MCPA at the molecular level. In this study, RNA-seq and Illumina MiSeq were used to sequence bacterial communities in tomato rhizosphere soils treated with MCPA and the phosphate-solubilizing bacterial strain N3. The results showed that MCPA induced abnormal growth of lateral roots in tomato seedlings and reduced uptake of the nutrients N, P, and K as well as the hormone (ABA and GA3) levels. Inoculation with strain N3 increased nutrient uptake by roots and increased levels of the hormones ABA, ZEA, and JA in tomato seedlings and also increased the abundance of the phyla Proteobacteria and Gemmatimonadetes in soil under MCPA treatment. GO functional groups in which differentially expressed genes (DEGs) are involved included DNA binding transcription factor activity, transcriptional regulator activity, enzyme inhibitor activity, and cell wall biogenesis. The highest numbers of DEGs are annotated to ribosome, photosynthesis, and carbon metabolism categories. Our findings provide valuable information for the application of strain N3, which is beneficial for reducing the toxic effect of MCPA on vegetable plants.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125767DOI Listing
August 2021

Homoharringtonine synergizes with quizartinib in FLT3-ITD acute myeloid leukemia by targeting FLT3-AKT-c-Myc pathway.

Biochem Pharmacol 2021 06 6;188:114538. Epub 2021 Apr 6.

Hematology Research Laboratory, Department of Hematology, West China Hospital of Sichuan University, Chengdu, China. Electronic address:

Acute myeloid leukemia (AML) with FLT3 internal tandem duplication (FLT3-ITD) has a dismal prognosis. FLT3 inhibitors have been developed to treat patients with FLT3-ITD AML; however, when used alone, their efficacy is insufficient. FLT3 inhibitors combined with chemotherapy may be a promising treatment for FLT3-ITD AML. Homoharringtonine (HHT) is a classical anti-leukaemia drug with high sensitivity to FLT3-ITD AML cells. Here, we showed that HHT synergizes with a selective next-generation FLT3 inhibitor, quizartinib, to inhibit cell growth/viability and induce cell-cycle arrest and apoptosis in FLT3-ITD AML cells in vitro, significantly inhibit acute myeloid leukemia progression in vivo, and substantially prolong survival of mice-bearing human FLT3-ITD AML. Mechanistically, HHT and quizartinib cooperatively inhibit FLT3-AKT and its downstream targets GSK3β, c-Myc, and cyclin D1, cooperatively up-regulate the pro-apoptosis proteins Bim and Bax, and down-regulate the anti-apoptosis protein Mcl1. Most strikingly, HHT and quizartinib cooperatively reduce the numbers of side-population (SP) and aldehyde dehydrogenase (ALDH)-positive cells, which reportedly are rich in LSCs. In conclusion, HHT combined with quizartinib may be a promising treatment strategy for patients with FLT3-ITD AML.
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http://dx.doi.org/10.1016/j.bcp.2021.114538DOI Listing
June 2021

The URL1-ROC5-TPL2 transcriptional repressor complex represses the ACL1 gene to modulate leaf rolling in rice.

Plant Physiol 2021 04;185(4):1722-1744

National Key Facility for Crop Gene Resources and Genetic Improvement, Institute of Crop Sciences, Chinese Academy of Agricultural Sciences, Beijing 100081, China.

Moderate leaf rolling is beneficial for leaf erectness and compact plant architecture. However, our understanding regarding the molecular mechanisms of leaf rolling is still limited. Here, we characterized a semi-dominant rice (Oryza sativa L.) mutant upward rolled leaf 1 (Url1) showing adaxially rolled leaves due to a decrease in the number and size of bulliform cells. Map-based cloning revealed that URL1 encodes the homeodomain-leucine zipper (HD-Zip) IV family member RICE OUTERMOST CELL-SPECIFIC 8 (ROC8). A single-base substitution in one of the two conserved complementary motifs unique to the 3'-untranslated region of this family enhanced URL1 mRNA stability and abundance in the Url1 mutant. URL1 (UPWARD ROLLED LEAF1) contains an ethylene-responsive element binding factor-associated amphiphilic repression motif and functions as a transcriptional repressor via interaction with the TOPLESS co-repressor OsTPL2. Rather than homodimerizing, URL1 heterodimerizes with another HD-ZIP IV member ROC5. URL1 could bind directly to the promoter and suppress the expression of abaxially curled leaf 1 (ACL1), a positive regulator of bulliform cell development. Knockout of OsTPL2 or ROC5 or overexpression of ACL1 in the Url1 mutant partially suppressed the leaf-rolling phenotype. Our results reveal a regulatory network whereby a transcriptional repression complex composed of URL1, ROC5, and the transcriptional corepressor TPL2 suppresses the expression of the ACL1 gene, thus modulating bulliform cell development and leaf rolling in rice.
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http://dx.doi.org/10.1093/plphys/kiaa121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133684PMC
April 2021

An integrated framework reinstating the environmental dimension for GWAS and genomic selection in crops.

Mol Plant 2021 Jun 10;14(6):874-887. Epub 2021 Mar 10.

Department of Agronomy, Iowa State University, Ames, IA 50011, USA. Electronic address:

Identifying mechanisms and pathways involved in gene-environment interplay and phenotypic plasticity is a long-standing challenge. It is highly desirable to establish an integrated framework with an environmental dimension for complex trait dissection and prediction. A critical step is to identify an environmental index that is both biologically relevant and estimable for new environments. With extensive field-observed complex traits, environmental profiles, and genome-wide single nucleotide polymorphisms for three major crops (maize, wheat, and oat), we demonstrated that identifying such an environmental index (i.e., a combination of environmental parameter and growth window) enables genome-wide association studies and genomic selection of complex traits to be conducted with an explicit environmental dimension. Interestingly, genes identified for two reaction-norm parameters (i.e., intercept and slope) derived from flowering time values along the environmental index were less colocalized for a diverse maize panel than for wheat and oat breeding panels, agreeing with the different diversity levels and genetic constitutions of the panels. In addition, we showcased the usefulness of this framework for systematically forecasting the performance of diverse germplasm panels in new environments. This general framework and the companion CERIS-JGRA analytical package should facilitate biologically informed dissection of complex traits, enhanced performance prediction in breeding for future climates, and coordinated efforts to enrich our understanding of mechanisms underlying phenotypic variation.
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http://dx.doi.org/10.1016/j.molp.2021.03.010DOI Listing
June 2021

Precise regulation of the properties of hydrophobic carbon dots by manipulating the structural features of precursor ionic liquids.

Biomater Sci 2021 Apr 12;9(8):3127-3135. Epub 2021 Mar 12.

Department of Chemistry, College of Sciences, Northeastern University, Shenyang, 110819, China.

To prepare carbon dots (CDs), there are numerous protocols that use a wide variety of carbon sources, which results in properties of CDs that are unpredictable and highly variable. Therefore, the development of reliable approaches for precisely regulating the nature of CDs is urgently required. Herein, a series of organophilic/hydrophobic CDs (OCDs) were prepared under microwave agitation with ionic liquid 1-alkyl-3-methylimidazolium dicyanamide as the precursor, by varying the alkyl chain linked in the cationic imidazolium moiety. The physicochemical, optical and biological properties, and imaging performance of OCDs were exploited to elucidate the structure-activity relationship, and it was discovered that the alkyl chain plays key roles in governing the properties of OCDs. The increase in the alkyl chain length, from ethyl, butyl, hexyl, and octyl to decyl, led to a remarkable variation in the properties of the OCDs, i.e., a reduction in nitrogen doping from 40.71 to 20.75%, a decrease in binding affinity with bovine serum albumin (BSA), and an increase in cytotoxicity. The interaction of OCDs with BSA and the formation of a 'protein corona' substantially increased the biocompatibility of the OCDs. The OCDs penetrated into MCF-7 human breast cancer cells in 10 min and demonstrated bright fluorescence imaging.
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http://dx.doi.org/10.1039/d1bm00090jDOI Listing
April 2021

Selective Sweeps Uncovering the Genetic Basis of Horn and Adaptability Traits on Fine-Wool Sheep in China.

Front Genet 2021 23;12:604235. Epub 2021 Feb 23.

Animal Science Department, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou, China.

Long-term natural and artificial selection leads to change in certain regions of the genome, resulting in selection signatures that can reveal genes associated with selected traits, such as horns (i.e., polled/horned), high-quality wool traits, and high-altitude hypoxia adaptability. These are complex traits determined by multiple genes, regulatory pathways, and environmental factors. A list of genes with considerable effects on horn and adaptability traits has not been found, although multiple quantitative trait loci (QTL) have been identified. Selection signatures could be identified using genetic differentiation (F ), polymorphism levels θπ, and Tajima's D. This study aimed to identify selection signatures in fine-wool sheep and to investigate the genes annotated in these regions, as well as the biological pathways involved in horn and adaptability traits. For this purpose, the whole-genome sequence of 120 individuals from four breeds, which come from different elevations and habitats in China, was used to analyze selection signatures for horn and adaptability traits. Annotation of the consensus regions of F and θπ ratios revealed a list of identified genes associated with polled/horned and high-altitude hypoxia adaptability traits, such as , EE, , , , , , and . Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis identified genes related primarily to mismatch repair, metabolism, vascular smooth muscle contraction, and cardiac muscle contraction. This is the first study to demonstrate that selection signatures play an important role in the polled/horned and high-altitude hypoxia adaptability traits of fine-wool sheep breeds that have undergone high-intensity selection and adapted to different ecological environments in China. Changes observed in the genome of fine-wool sheep may have acted on genomic regions that affect performance traits and provide a reference for genome design and breeding.
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http://dx.doi.org/10.3389/fgene.2021.604235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940688PMC
February 2021

Epigallocatechin-3-Gallate, the Main Polyphenol in Green Tea, Inhibits Porcine Epidemic Diarrhea Virus .

Front Pharmacol 2021 22;12:628526. Epub 2021 Feb 22.

Institutes of Agricultural Science and Technology Development, College of Veterinary Medicine, Yangzhou University, Yangzhou, China.

There are currently no licensed drugs against porcine epidemic diarrhea virus (PEDV), but vaccines are available. We identified a natural molecule, epigallocatechin-3-gallate (EGCG), the main polyphenol in green tea, which is effective against infection with PEDV. We used a variety of methods to test its effects on PEDV in Vero cells. Our experiments show that EGCG can effectively inhibit PEDV infections (with HLJBY and CV777 strains) at different time points in the infection using western blot analysis. We found that EGCG inhibited PEDV infection in a dose-dependent manner 24 h after the infection commenced using western blotting, plaque formation assays, immunofluorescence assays (IFAs), and quantitative reverse-transcriptase PCR (qRT-PCR). We discovered that EGCG treatment of Vero cells decreased PEDV attachment and entry into them by the same method analysis. Western blotting also showed that PEDV replication was inhibited by EGCG treatment. Whereas EGCG treatment was found to inhibit PEDV assembly, it had no effect on PEDV release. In summary, EGCG acts against PEDV infection by inhibiting PEDV attachment, entry, replication, and assembly.
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http://dx.doi.org/10.3389/fphar.2021.628526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937899PMC
February 2021

Genome-wide association studies detects candidate genes for wool traits by re-sequencing in Chinese fine-wool sheep.

BMC Genomics 2021 Feb 18;22(1):127. Epub 2021 Feb 18.

Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Sheep Breeding Engineering Technology Research Center of Chinese Academy of Agricultural Sciences, Lanzhou, 730050, China.

Background: The quality and yield of wool determine the economic value of the fine-wool sheep. Therefore, discovering markers or genes relevant to wool traits is the cornerstone for the breeding of fine-wool sheep. In this study, we used the Illumina HiSeq X Ten platform to re-sequence 460 sheep belonging to four different fine-wool sheep breeds, namely, Alpine Merino sheep (AMS), Chinese Merino sheep (CMS), Aohan fine-wool sheep (AHS) and Qinghai fine-wool sheep (QHS). Eight wool traits, including fiber diameter (FD), fiber diameter coefficient of variance (FDCV), fiber diameter standard deviation (FDSD), staple length (SL), greasy fleece weight (GFW), clean wool rate (CWR), staple strength (SS) and staple elongation (SE) were examined. A genome-wide association study (GWAS) was performed to detect the candidate genes for the eight wool traits.

Results: A total of 8.222 Tb of raw data was generated, with an average of approximately 8.59X sequencing depth. After quality control, 12,561,225 SNPs were available for analysis. And a total of 57 genome-wide significant SNPs and 30 candidate genes were detected for the desired wool traits. Among them, 7 SNPs and 6 genes are related to wool fineness indicators (FD, FDCV and FDSD), 10 SNPs and 7 genes are related to staple length, 13 SNPs and 7 genes are related to wool production indicators (GFW and CWR), 27 SNPs and 10 genes associated with staple elongation. Among these candidate genes, UBE2E3 and RHPN2 associated with fiber diameter, were found to play an important role in keratinocyte differentiation and cell proliferation. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment results, revealed that multitude significant pathways are related to keratin and cell proliferation and differentiation, such as positive regulation of canonical Wnt signaling pathway (GO:0090263).

Conclusion: This is the first GWAS on the wool traits by using re-sequencing data in Chinese fine-wool sheep. The newly detected significant SNPs in this study can be used in genome-selective breeding for the fine-wool sheep. And the new candidate genes would provide a good theoretical basis for the fine-wool sheep breeding.
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http://dx.doi.org/10.1186/s12864-021-07399-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893944PMC
February 2021

Quantitative proteomic analysis identified differentially expressed proteins with tail/rump fat deposition in Chinese thin- and fat-tailed lambs.

PLoS One 2021 2;16(2):e0246279. Epub 2021 Feb 2.

Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences (CAAS), Lanzhou, China.

Tail adipose as one of the important functional tissues can enhance hazardous environments tolerance for sheep. The objective of this study was to gain insight into the underlying development mechanisms of this trait. A quantitative analysis of protein abundance in ovine tail/rump adipose tissue was performed between Chinese local fat- (Kazakh, Hu and Lanzhou) and thin-tailed (Alpine Merino, Tibetan) sheep in the present study by using lable-free approach. Results showed that 3400 proteins were identified in the five breeds, and 804 were differentially expressed proteins, including 638 up regulated proteins and 83 down regulated proteins in the tail adipose tissues between fat- and thin-tailed sheep, and 8 clusters were distinguished for all the DEPs' expression patterns. The differentially expressed proteins are mainly associated with metabolism pathways and peroxisome proliferator activated receptor signaling pathway. Furthermore, the proteomics results were validated by quantitative real-time PCR and Western Blot. Our research has also suggested that the up-regulated proteins ACSL1, HSD17β4, FABP4 in the tail adipose tissue might contribute to tail fat deposition by facilitating the proliferation of adipocytes and fat accumulation in tail/rump of sheep. Particularly, FABP4 highly expressed in the fat-tail will play an important role for tail fat deposition. Our study might provide a novel view to understanding fat accumulation in special parts of the body in sheep and other animals.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246279PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7853479PMC
July 2021

(-)-Epigallocatechin-3-Gallate Inhibits the Life Cycle of Pseudorabies Virus and Protects Mice Against Fatal Infection.

Front Cell Infect Microbiol 2020 14;10:616895. Epub 2021 Jan 14.

College of Veterinary Medicine, Institutes of Agricultural Science and Technology Development, Yangzhou University, Yangzhou, China.

A newly emerged pseudorabies virus (PRV) variant with enhanced pathogenicity has been identified in many PRV-vaccinated swine in China since 2011. The PRV variant has caused great economic cost to the swine industry, and measures for the effective prevention and treatment of this PRV variant are still lacking. (-)-Epigallocatechin-3-gallate (EGCG) exhibits antiviral activity against diverse viruses and thus in this study, we investigated the anti-PRV activity of EGCG and . EGCG significantly inhibited infectivity of PRV Ra and PRV XJ5 strains in PK15 B6 cells and Vero cells. The anti-PRV activity of EGCG was dose-dependent, and 50 μM EGCG could completely block viral infection at different multiplicities of infection. We next revealed that EGCG blocked PRV adsorption and entry to PK15 B6 cells in a dose-dependent manner, but inhibition of PRV entry by EGCG was not as efficient as its inhibition of PRV adsorption. PRV replication was suppressed in PK15 B6 cells treated with EGCG post-infection. However, EGCG did not affect PRV assembly and could promote PRV release. Furthermore, 40 mg/kg EGCG provided 100% protection in BALB/c mice challenged with PRV XJ5, when EGCG was administrated both pre- and post-challenge. These results revealed that EGCG exhibits antiviral activity against PRV mainly by inhibiting virus adsorption, entry and replication . Meanwhile, EGCG increased the survival of mice challenged with PRV. Therefore, EGCG might be a potential antiviral agent against PRV infection.
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http://dx.doi.org/10.3389/fcimb.2020.616895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841300PMC
June 2021

A global analysis of CNVs in Chinese indigenous fine-wool sheep populations using whole-genome resequencing.

BMC Genomics 2021 Jan 23;22(1):78. Epub 2021 Jan 23.

Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Sciences, Sheep Breeding Engineering Technology Research Center, Lanzhou, 730050, China.

Background: Copy number variation (CNV) is an important source of genetic variation that has a significant influence on phenotypic diversity, economically important traits and the evolution of livestock species. In this study, the genome-wide CNV distribution characteristics of 32 fine-wool sheep from three breeds were analyzed using resequencing.

Results: A total of 1,747,604 CNVs were detected in this study, and 7228 CNV regions (CNVR) were obtained after merging overlapping CNVs; these regions accounted for 2.17% of the sheep reference genome. The average length of the CNVRs was 4307.17 bp. "Deletion" events took place more frequently than "duplication" or "both" events. The CNVRs obtained overlapped with previously reported sheep CNVRs to variable extents (4.39-55.46%). Functional enrichment analysis showed that the CNVR-harboring genes were mainly involved in sensory perception systems, nutrient metabolism processes, and growth and development processes. Furthermore, 1855 of the CNVRs were associated with 166 quantitative trait loci (QTL), including milk QTLs, carcass QTLs, and health-related QTLs, among others. In addition, the 32 fine-wool sheep were divided into horned and polled groups to analyze for the selective sweep of CNVRs, and it was found that the relaxin family peptide receptor 2 (RXFP2) gene was strongly influenced by selection.

Conclusions: In summary, we constructed a genomic CNV map for Chinese indigenous fine-wool sheep using resequencing, thereby providing a valuable genetic variation resource for sheep genome research, which will contribute to the study of complex traits in sheep.
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http://dx.doi.org/10.1186/s12864-021-07387-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825165PMC
January 2021

Numerical modeling in arterial hemodynamics incorporating fluid-structure interaction and microcirculation.

Theor Biol Med Model 2021 01 19;18(1). Epub 2021 Jan 19.

Thrombosis Center, National Clinical Research Center for Cardiovascular Diseases, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China.

Background: The effects of arterial wall compliance on blood flow have been revealed using fluid-structure interaction in last decades. However, microcirculation is not considered in previous researches. In fact, microcirculation plays a key role in regulating blood flow. Therefore, it is very necessary to involve microcirculation in arterial hemodynamics.

Objective: The main purpose of the present study is to investigate how wall compliance affects the flow characteristics and to establish the comparisons of these flow variables with rigid wall when microcirculation is considered.

Methods: We present numerical modeling in arterial hemodynamics incorporating fluid-structure interaction and microcirculation. A novel outlet boundary condition is employed to prescribe microcirculation in an idealised model.

Results: The novel finding in this work is that wall compliance under the consideration of microcirculation leads to the increase of wall shear stress in contrast to rigid wall, contrary to the traditional result that wall compliance makes wall shear stress decrease when a constant or time dependent pressure is specified at an outlet.

Conclusions: This work provides the valuable study of hemodynamics under physiological and realistic boundary conditions and proves that wall compliance may have a positive impact on wall shear stress based on this model. This methodology in this paper could be used in real model simulations.
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http://dx.doi.org/10.1186/s12976-021-00136-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816504PMC
January 2021

Curcumin and Glu-GNPs Induce Radiosensitivity against Breast Cancer Stem-Like Cells.

Biomed Res Int 2020 28;2020:3189217. Epub 2020 Dec 28.

School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.

Breast cancer stem cells are an important cause of radiotherapy resistance in the clinical treatment of breast cancer patients. How to target breast cancer stem cells is the key to improving the efficacy of breast cancer radiotherapy. We proposed for the first time that curcumin combined with glucose nanogold particles (Glu-GNPs) targeted breast cancer stem cells to reduce radiotherapy resistance, which can significantly enhance the apoptosis level of MCF-7 and MDA-MB-231 breast cancer stem-like cells (BCSCs) after radiotherapy and antiproliferation and colony-forming. Under simulated hypoxic conditions, curcumin combined with Glu-GNPs can significantly improve the ROS level of MCF-7 and MDA-MB-231 mammospheres; reduce the expression of HIF-1 and HSP90, thereby inhibiting the tumor cells' own stress ability; promote the apoptosis of tumor stem cells; and enhance the sensitivity of radiotherapy. The current results indicate that the combination of curcumin and Glu-GNPs has great potential to relieve tumor hypoxia and increase radiosensitivity on BCSCs, providing scientific research data for developing a novel radiosensitizer with high efficiency and low toxicity.
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http://dx.doi.org/10.1155/2020/3189217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785366PMC
September 2021

Molecular dynamics simulation of lentinan and its interaction with the innate receptor dectin-1.

Int J Biol Macromol 2021 Feb 8;171:527-538. Epub 2021 Jan 8.

Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan, China; Hubei province clinical research center for precision medicine for critical illness, 430030 Wuhan, China. Electronic address:

Lentinan, a β-1,3-D-glucan, is clinically used as an immune enhancement drug for tumor therapy. Dectin-1 is a cell-surface immune receptor, which plays an important role in immunological defense against fungal pathogens and β-glucan-mediated immune modulation. Herein we attempted to study the advanced structure of lentinan and how lentinan interacts with dectin-1 for its immune enhancement effect. We firstly used MD simulation and rigid macromolecule docking, combining some spectral techniques, to uncover the complex 3D conformation of a typical polysaccharide - lentinan, and the detailed interaction mode of lentinan with dectin-1. We proved by computational simulation that lentinan can maintain its triple-helix through hydrogen network and disclosed some structural properties of lentinan. We also characterized the affinity of lentinan to dectin-1 by LSPR and binding free energy calculation, and we found out that hydrogen bonds and CH-π interaction are the major contributors for lentinan's binding to dectin-1. Besides, after bound with lentinan, dectin-1 might surprisingly go through a conformational change. In summary, our work provided insights into lentinan's advanced structure and β-glucan recognition by dectin-1.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.01.032DOI Listing
February 2021
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