Publications by authors named "Zhonghua Liu"

490 Publications

Glucose-Lipopeptide Conjugates Reveal the Role of Glucose Modification Position in Complexation and the Potential of Malignant Melanoma Therapy.

J Med Chem 2021 Jul 20. Epub 2021 Jul 20.

The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China.

Glycosylation and fatty acid modification are promising strategies to improve peptide performance. We previously studied glycosylation and fatty acid modification of the anticancer peptide R-lycosin-I. In this study, we further investigated the co-modification of fatty acids and monosaccharides in R-lycosin-I. A glucose derivative was covalently coupled to the ε-amino group of the Lys residues of the lipopeptide R-C, which was derived from R-lycosin-I modified with dodecanoic acid, and obtained seven glycolipid peptides. They exhibited different cytotoxicity profiles, which may be related to the changes in physicochemical properties and binding ability to glucose transporter 1 (GLUT1). Among them, R-C-4 exhibited the highest cytotoxicity and improved selectivity. A further study demonstrated that R-C-4 showed significant cytotoxicity and antimetastasis activity in murine melanoma cells, melanoma spheroids, and animal models. Our results indicated that the glucose derivative modification position plays important roles in glucose-lipopeptide conjugates, and R-C-4 might be a promising lead for developing anticancer drugs.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00805DOI Listing
July 2021

Pheochromocytoma: A Clinicopathologic and Molecular Study of 390 Cases From a Single Center.

Am J Surg Pathol 2021 Jul 19. Epub 2021 Jul 19.

Departments of Pathology Biostatistics Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, TX.

Pheochromocytomas are rare neuroendocrine tumors arising from chromaffin cells in the adrenal medulla. They may occur sporadically or in the context of hereditary syndromes. All pheochromocytomas are considered to have malignant potential (defined as risk of metastasis, not local invasion). The use of grading systems with incorporated clinical and histopathologic parameters can help but not definitively predict the metastatic potential of pheochromocytomas. The recent discovery of susceptibility genes provided new insights into the pathogenesis and introduced additional approaches to estimate the metastatic risk of pheochromocytoma. However, the prevalence of these genetic signatures in pheochromocytomas has yet to be fully addressed. Therefore, in the present study, we retrospectively reviewed cases of pheochromocytoma from 1980 to 2018 in the archives of our institution. Three hundred ninety cases were identified, and their clinicopathologic characteristics and genetic statuses were analyzed. About 25% of the cases had metastases, which were more common in older patients (median, 49 y) than in younger ones. Univariate and multivariate analyses revealed that older age, Hispanic ethnicity, metastasis, and large primary tumor size were markedly associated with poor overall survival. In contrast, family history of pheochromocytoma, lack of symptoms, and bilateral adrenal involvement were associated with better survival. About 37% of the pheochromocytomas were associated with inherited syndromes. About 52% of tested patients had pathogenic mutations of pheochromocytoma susceptibility genes. Of these, succinate dehydrogenase B gene mutation had the strongest association with metastasis. These data support that genetic testing should be offered to all patients with pheochromocytoma.
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http://dx.doi.org/10.1097/PAS.0000000000001768DOI Listing
July 2021

Causal mediation analysis with latent subgroups.

Stat Med 2021 Jul 15. Epub 2021 Jul 15.

Department of Statistics and Actuarial Science, University of Hong Kong, Pokfulam, Hong Kong SAR, China.

In biomedical studies, the causal mediation effect might be heterogeneous across individuals in the study population due to each study subject's unique characteristics. While individuals' mediation effects may differ from each other, it is often reasonable and more interpretable to assume that individuals belong to several distinct latent subgroups with similar attributes. In this article, we first show that the subgroup-specific mediation effect can be identified under the group-specific sequential ignorability assumptions. Then, we propose a simple mixture modeling approach to account for the latent subgroup structure where each mixture component corresponds to one latent subgroup in the linear structural equation model framework. Model parameters can be estimated using the standard expectation-maximization (EM) algorithm. Each individual's subgroup membership can be inferred based on the posterior probability. We propose to use the singular Bayesian information criterion to consistently select the number of latent subgroups by recognizing that the Fisher information matrix for mixture models might be singular. We then propose to use nonparametric bootstrap method to compute standard errors and confidence intervals. We conducted simulation studies to evaluate the empirical performance of our proposed method named iMed. Finally, we reanalyzed a DNA methylation data set from the Normative Aging Study and found that the mediation effects of two well-documented DNA methylation CpG sites are heterogeneous across two latent subgroups in the causal pathway from smoking behavior to lung function. We also developed an R package iMed for public use.
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http://dx.doi.org/10.1002/sim.9144DOI Listing
July 2021

Theaflavin Promotes Mitochondrial Abundance and Glucose Absorption in Myotubes by Activating the CaMKK2-AMPK Signal Axis via Calcium-Ion Influx.

J Agric Food Chem 2021 Jul 14. Epub 2021 Jul 14.

Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha 410128, Hunan, China.

Drinking tea has been proven to have a positive biological effect in regulating human glucose and lipid metabolism and preventing type 2 diabetes (T2D). Skeletal muscle (SkM) is responsible for 70% of the sugar metabolism in the human body, and its dysfunction is an important factor leading to the development of obesity, T2D, and muscle diseases. As one of the four known theaflavins (TFs) in black tea, the biological role of theaflavin (TF1) in regulating SkM metabolism has not been reported. In this study, mature myotubes induced by C2C12 cells in vitro were used as models. The results showed that TF1 (20 μM) promoted mitochondrial abundance and glucose absorption in myotubes by activating the CaMKK2-AMPK signaling axis via Ca influx. Moreover, it promoted the expression of slow muscle fiber marker genes (Myh7, Myl2, Tnnt1, and Tnnc1) and PGC-1α/SIRT1, as well as enhanced the oxidative phosphorylation capacity of myotubes. In conclusion, this study preliminarily clarified the potential role of TF1 in regulating SkM glucose absorption as well as promoting SkM mitochondrial biosynthesis and slow muscle fiber formation. It has potential research and application values for the prevention/alleviation of SkM-related T2D and Ca-related skeletal muscle diseases through diet.
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http://dx.doi.org/10.1021/acs.jafc.1c02892DOI Listing
July 2021

An Aspergillus nidulans endo-β-1,3-glucanase exhibited specific catalytic features and was used to prepare 3-O-β-cellobiosyl-d-glucose and 3-O-β-gentiobiosyl-d-glucose with high antioxidant activity from barley β-glucan and laminarin, respectively.

Int J Biol Macromol 2021 Jul 9;186:424-432. Epub 2021 Jul 9.

Jiangsu Key Laboratory for Microbes and Microbial Functional Genomics, Jiangsu Engineering and Technology Research Center for Industrialization of Microbial Resources, College of Life Science, Nanjing Normal University, 1 Wenyuan Road, Nanjing, Jiangsu 210023, PR China. Electronic address:

An endo-β-1,3(4)-glucanase AnENG16A from Aspergillus nidulans shows distinctive catalytic features for hydrolysis of β-glucans. AnENG16A hydrolyzed Eisenia bicyclis laminarin to mainly generate 3-O-β-gentiobiosyl-d-glucose and hydrolyzed barley β-glucan to mainly produce 3-O-β-cellobiosyl-d-glucose. Using molecular exclusion chromatography, we isolated and purified 3-O-β-cellobiosyl-d-glucose and 3-O-β-gentiobiosyl-d-glucose, respectively, from AnENG16A-hydrolysate of barley β-glucan and E. bicyclis laminarin. Further study reveals that 3-O-β-cellobiosyl-d-glucose had 8.99-fold higher antioxidant activity than barley β-glucan and 3-O-β-gentiobiosyl-d-glucose exhibited 43.0% higher antioxidant activity than E. bicyclis laminarin. Notably, 3-O-β-cellobiosyl-d-glucose and 3-O-β-gentiobiosyl-d-glucose exhibited 148.9% and 116.0% higher antioxidant activity than laminaritriose, respectively, indicating that β-1,4-linkage or -1,6-linkage at non-reducing end of β-glucotrioses had enhancing effect on antioxidant activity compared to β-1,3-linkage. Furthermore, 3-O-β-cellobiosyl-d-glucose showed 237.9% higher antioxidant activity than cellotriose, and laminarin showed 5.06-fold higher antioxidant activity than barley β-glucan, indicating that β-1,4-linkage at reducing end of β-glucans or oligosaccharides resulted in decrease of antioxidant activity compared to β-1,3-linkage.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.07.053DOI Listing
July 2021

Associations of GWAS-Supported Non-MHC Genes with Autoimmune Thyroiditis in Patients with Type 1 Diabetes.

Diabetes Metab Syndr Obes 2021 1;14:3017-3026. Epub 2021 Jul 1.

Department of Rehabilitation, Zhongshan People's Hospital, Zhongshan, 528403, Guangdong, People's Republic of China.

Purpose: A genome-wide association study (GWAS) in Caucasian population identified five non-MHC genes (, and ) associated with risk of the co-occurrence of autoimmune thyroid diseases (AITD) and type 1 diabetes (T1D). The aim of this study is to replicate these associations with AITD in patients with T1D in Chinese Han population.

Patients And Methods: A case-control study was designed. Five single-nucleotide polymorphisms (SNPs) rs1111695, rs1217407, rs2153977, rs2358994, and rs7679475 were genotyped in 489 patients with T1D. Associations between genotypes and AITD risk were analyzed with logistic regression model.

Results: AITD occurred in 159 (32.5%) patients. When adjusting multiple factors by logistic regression, rs7679475 was significantly associated with an increased risk of AITD in T1D patients in codominant model (G/G vs A/A, OR 2.93; 95% CI 1.44-5.96; = 0.003), dominant model (G/A-G/G vs A/A, OR 1.81; 95% CI 1.17-2.79; = 0.007) and recessive model (G/G vs A/A-G/A, OR 2.28; 95% CI 1.17-4.43; = 0.015). Furthermore, we found a significant interaction between rs7679475 and female ( = 0.005). In silico analysis indicated that rs7679475 is located in histone modification marked region and can change the binding of regulatory motifs.

Conclusion: Our results suggested that rs7679475 may influence the risk of AITD in patients with T1D in Chinese Han population, and this effect may be modulated by sex.
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http://dx.doi.org/10.2147/DMSO.S319630DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257024PMC
July 2021

5,6,7,8-Tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine derivative attenuates lupus nephritis with less effect to thymocyte development.

Immunol Res 2021 Jul 4. Epub 2021 Jul 4.

Institute of Human Virology, Sun Yat-Sen University, Guangzhou, China.

Retinoic‑acid‑receptor‑related orphan nuclear hormone receptor gamma t (RORγt), a critical transcriptional factor of Th17 cells, is a potential therapeutic target for Th17-mediated autoimmune diseases. In addition, RORγt is essential for thymocyte survival and lymph node development, and RORγt inhibition or deficiency causes abnormal thymocyte development, thymus lymphoma, and lymph node defect. Recent study demonstrated that specific regulation of Th17 differentiation related to the hinge region of RORγt. In this research, we investigated the effect of RORγt inhibitor, 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine derivative (TTP), in the therapy of lupus nephritis and its safety on thymocyte development. We demonstrated that TTP repressed the development of Th17 cells and ameliorated the autoimmune disease manifestation in the pristane-induced lupus nephritis mice model. The treatment of TTP in the mice did not interfere with thymocyte development, including total thymocyte number and proportion of CD4CD8 double-positive populations in the thymus, and had no substantial effects on the pathogenesis of thymoma. The TTP had a stronger affinity with full-length RORγt protein compared with the truncated RORγt LBD region via surface plasmon resonance, which indicated TTP binding to RORγt beyond LBD region. Molecular docking computation showed that the best binding pocket of TTP to RORγt is located in the hinge region of RORγt. In summary, as a RORγt inhibitor, TTP had a potential to develop the clinical medicine for treating Th17-mediated autoimmune diseases with low safety risk for thymocyte development.
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http://dx.doi.org/10.1007/s12026-021-09204-5DOI Listing
July 2021

Genome-wide identification and characterization of phosphate transporter gene family members in tea plants (Camellia sinensis L. O. kuntze) under different selenite levels.

Plant Physiol Biochem 2021 Jun 26;166:668-676. Epub 2021 Jun 26.

Key Laboratory of Tea Science of Ministry of Education, National Research Center of Engineering and Technology for Utilization of Botanical Functional Ingredients & Co-Innovation Center of Education Ministry for Utilization of Botanical Functional Ingredients, Hunan Agricultural University, Changsha, Hunan, 410128, China. Electronic address:

Selenium (Se) is an essential element for human health and an important nutrient for plant growth. Selenite is the main form of Se available to plants in acidic soils. Previous studies have shown that phosphate transporters (PTHs) participate in selenite uptake in plants. Research on the PHT gene family is therefore vital for production of Se-rich products. Here, 23 CsPHT genes were identified in the tea (Camellia sinensis) genome and renamed based on homology with AtPHT genes in Arabidopsis thaliana. The CsPHT genes were divided into four subfamilies: PHT1, PHT3, PHT4, and PHO, containing nine, three, six, and five genes, respectively. Phylogenetic analysis indicated that fewer duplication events occurred in tea plants than in A. thaliana, rice, apple, and poplar. Genes in the same subfamily tended to share similar gene structures, conserved motifs, and potential functions. CsPHT genes were differentially expressed in various tissues and in roots under different Se levels, suggesting key roles in selenite uptake, translocation, and homeostasis. The results illuminate the contributions of CsPHT genes to selenite supply in tea plants, and lay a foundation for follow-up studies on their potential functions in this plant species.
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http://dx.doi.org/10.1016/j.plaphy.2021.06.038DOI Listing
June 2021

Metabolomic Analysis and Identification of Sperm Freezability-Related Metabolites in Boar Seminal Plasma.

Animals (Basel) 2021 Jun 29;11(7). Epub 2021 Jun 29.

Key Laboratory of Animal Cellular and Genetics Engineering of Heilongjiang Province, College of Life Science, Northeast Agricultural University, Harbin 150030, China.

Some potential markers of boar sperm freezability have been found in spermatozoa, but little attention has been paid to seminal plasma. The seminal plasma is composed of secretions from the testis, epididymis, and accessory sex glands. The exposure of spermatozoa to small molecules such as metabolites can affect sperm function. However, details and significance of the seminal plasma metabolome related to boar sperm freezability are unknown. Therefore, the main aim of this study was to explore the differences in the metabolic level of seminal plasma between boars with differential freezability and to explore the candidate biomarkers of semen freezability. A total of 953 metabolites were identified in boar semen plasma by UHPLC-qTOF-MS analysis, and 50 metabolites showed significant change between the GFE group and PFE group. Further, twelve metabolites were subjected to metabolic target analysis, and three metabolites (D-aspartic acid, N-acetyl-L-glutamate (NAG), and inosine) showed differences. In conclusion, there is significant difference in the metabolome of seminal plasma between GFE and PFE individuals. D-aspartic acid, NAG, and inosine in seminal plasma may be potential markers for assessing sperm cryopreservation resistance in boars.
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http://dx.doi.org/10.3390/ani11071939DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8300243PMC
June 2021

Theanine Improves High-Dose Epigallocatechin-3-Gallate-Induced Lifespan Reduction in .

Foods 2021 Jun 17;10(6). Epub 2021 Jun 17.

National Research Center of Engineering and Technology for Utilization of Botanical Functional Ingredients from Botanicals, Hunan Agricultural University, Changsha 410128, China.

Epigallocatechin-3-gallate (EGCG) is the most abundant polyphenol in green tea. Our previous report showed that induced hormesis was a critical determinant for the promotion of a healthy lifespan in . In the present study, we investigated the anti-aging effects of the main active ingredients in green tea. We found that galloylated catechins (EGCG and epicatechin gallate) could extend the lifespan of , while their metabolites (gallic acid, epicatechin, and epigallocatechin) could not. Interestingly, the combination with theanine, not caffeine, could alleviate the adverse effects induced by high-dose EGCG, including the promotion of lifespan and locomotor ability. This was due to the attenuation of the excess production of reactive oxygen species and the activation of DAF-16. These findings will facilitate further studies on the health benefits of tea active components and their interactions.
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http://dx.doi.org/10.3390/foods10061404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235257PMC
June 2021

Assessment of causality between modifiable factors and heart failure: A Mendelian randomization analysis.

Asia Pac J Clin Nutr 2021 Jun;30(2):340-347

Department of Epidemiology & Biostatistics, School of Public Health, Peking University, Beijing, China. Email:

Background And Objectives: Observational studies have associated lifestyle, dietary, adiposity, biochemical and clinical measures with heart failure. Whether the associations are causal remains unclear. We aimed to determine the causal associations between modifiable risk factors and incidence or mortality of heart failure.

Methods And Study Design: Using single-nucleotide polymorphism (SNP) as genetic instruments, we conducted a two-sample Mendelian randomization (MR) analysis to estimate the causal effects of 27 modifiable risk factors on incident heart failure (2526 cases; 20926 participants) and mortality of heart failure (1798 deaths; 2828 patients).

Results: None of 27 modifiable risk factors were significantly associated with incidence or mortality of heart failure after the Bonferroni correction (p<0.0019). However, there was suggestive evidence for genetically predicted educational attainment (odds ratio [OR] per educational year increase: 0.57, 95% CI 0.33-0.99, p=0.049), circulating mono-unsaturated fatty acid concentrations (OR per 1-SD increase [ORSD] : 1.50, 1.10-2.04, p=0.011), C-reactive protein (CRP) (1.53, 1.04-2.25, p=0.031), high-density lipoprotein (HDL) (0.84, 0.72-0.99, p=0.036), triglycerides (1.24, 1.00-1.52, p=0.045), and systolic blood pressure (SBP) (1.06, 1.01-1.11, p=0.017) with incident heart failure.

Conclusions: Our findings provide supporting evidence for prioritizing certain modifiable risk factors such as education, lipids, and blood pressure for primary prevention of heart failure, suggesting important clues for further mechanism research.
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http://dx.doi.org/10.6133/apjcn.202106_30(2).0019DOI Listing
June 2021

Recognition of Fetal Facial Ultrasound Standard Plane Based on Texture Feature Fusion.

Comput Math Methods Med 2021 3;2021:6656942. Epub 2021 Jun 3.

Biomedical Ultrasound Laboratory, The University of Southern California (USC), Los Angeles, USA.

In the process of prenatal ultrasound diagnosis, accurate identification of fetal facial ultrasound standard plane (FFUSP) is essential for accurate facial deformity detection and disease screening, such as cleft lip and palate detection and Down syndrome screening check. However, the traditional method of obtaining standard planes is manual screening by doctors. Due to different levels of doctors, this method often leads to large errors in the results. Therefore, in this study, we propose a texture feature fusion method (LH-SVM) for automatic recognition and classification of FFUSP. First, extract image's texture features, including Local Binary Pattern (LBP) and Histogram of Oriented Gradient (HOG), then perform feature fusion, and finally adopt Support Vector Machine (SVM) for predictive classification. In our study, we used fetal facial ultrasound images from 20 to 24 weeks of gestation as experimental data for a total of 943 standard plane images (221 ocular axial planes, 298 median sagittal planes, 424 nasolabial coronal planes, and 350 nonstandard planes, OAP, MSP, NCP, N-SP). Based on this data set, we performed five-fold cross-validation. The final test results show that the accuracy rate of the proposed method for FFUSP classification is 94.67%, the average precision rate is 94.27%, the average recall rate is 93.88%, and the average 1 score is 94.08%. The experimental results indicate that the texture feature fusion method can effectively predict and classify FFUSP, which provides an essential basis for clinical research on the automatic detection method of FFUSP.
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http://dx.doi.org/10.1155/2021/6656942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8195636PMC
June 2021

Variation of Two S3b Residues in K4.1-4.3 Channels Underlies Their Different Modulations by Spider Toxin κ-LhTx-1.

Front Pharmacol 2021 10;12:692076. Epub 2021 Jun 10.

The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, China.

The naturally occurred peptide toxins from animal venoms are valuable pharmacological tools in exploring the structure-function relationships of ion channels. Herein we have identified the peptide toxin κ-LhTx-1 from the venom of spider (the Lichen huntsman spider) as a novel selective antagonist of the K4 family potassium channels. κ-LhTx-1 is a gating-modifier toxin impeded K4 channels' voltage sensor activation, and mutation analysis has confirmed its binding site on channels' S3b region. Interestingly, κ-LhTx-1 differently modulated the gating of K4 channels, as revealed by toxin inhibiting K4.2/4.3 with much more stronger voltage-dependence than that for K4.1. We proposed that κ-LhTx-1 trapped the voltage sensor of K4.1 in a much more stable resting state than that for K4.2/4.3 and further explored the underlying mechanism. Swapping the non-conserved S3b segments between K4.1(FVPK) and K4.3(VMTN) fully reversed their voltage-dependence phenotypes in inhibition by κ-LhTx-1, and intensive mutation analysis has identified P282 in K4.1, D281 in K4.2 and N278 in K4.3 being the key residues. Furthermore, the last two residues in this segment of each K4 channel (P282/K283 in K4.1, T280/D281 in K4.2 and T277/N278 in K4.3) likely worked synergistically as revealed by our combinatorial mutations analysis. The present study has clarified the molecular basis in K4 channels for their different modulations by κ-LhTx-1, which have advanced our understanding on K4 channels' structure features. Moreover, κ-LhTx-1 might be useful in developing anti-arrhythmic drugs given its high affinity, high selectivity and unique action mode in interacting with the K4.2/4.3 channels.
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http://dx.doi.org/10.3389/fphar.2021.692076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222713PMC
June 2021

In vitro and in vivo study on angiogenesis of porcine induced pluripotent stem cell-derived endothelial cells.

Differentiation 2021 Jun 4;120:10-18. Epub 2021 Jun 4.

College of Life Science, Northeast Agricultural University, Harbin, 150030, PR China. Electronic address:

Pluripotent stem cells (PSCs) are a promising source of endothelial cells (ECs) for the treatment of cardiovascular diseases. Since clinical application of embryo stem cells (ESCs) involves issues of medical ethics and risk of immune rejection, induced pluripotent stem cells (iPSCs) will facilitate cell transplantation therapy for the cardiovascular diseases. Swine is identified as an ideal large-animal model for human, because of its similar organ size and physiological characteristics. However, there are very few studies on EC differentiation of porcine iPSCs (piPSCs). In recent study, we provided an efficient protocol to differentiate piPSCs into ECs with the purity of 19.76% CD31 positive cells within 16 days. Passaging of these cells yielded a nearly pure population, which also expressed other endothelial markers such as CD144, eNOS and vWF. Besides, these cells exhibited functions of ECs such as uptake of low-density lipoprotein and formation of tubes in vitro or blood vessels in vivo. Our study successfully obtained ECs from piPSCs via a feeder- and serum-free monolayer system and demonstrated their angiogenic function in vivo and in vitro. piPSC-ECs derivation is not only potential for the autologous cell transplantation and cardiovascular drug screening, but also for the mechanistic studies on EC differentiation and endothelial dysfunction.
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http://dx.doi.org/10.1016/j.diff.2021.05.003DOI Listing
June 2021

INI1-Deficient Thyroid Carcinoma is an Aggressive Disease with Epithelioid and Rhabdoid Phenotype. A Case Report, Survey of INI1 Expression in Thyroid Lesions and Literature Review.

Head Neck Pathol 2021 May 31. Epub 2021 May 31.

Department of Pathology, University at Buffalo, Buffalo, NY, USA.

Integrase interactor 1 (INI1)-deficient carcinomas, recently described in several sites including the head and neck, are associated with basaloid or rhabdoid histology and aggressive behavior irrespective of origin. INI1-deficient thyroid carcinoma is extremely rare. We present here the phenotype and genotype of an INI1-deficient thyroid carcinoma and report on the INI1 protein expression in various thyroid lesions. Case report with clinicopathologic and molecular characterization and INI1 assessment in 184 thyroid lesions. A 67-year-old woman presented with globus sensation due to a large thyroid mass with extrathyroid extension, focal necrosis and cervical and mediastinal nodal involvement. Histologically, tumor cells had a solid, alveolar and pseudopapillary architecture in a myxoid stroma, exhibited monomorphic epithelioid and focal rhabdoid/plasmacytoid morphology and lacked glandular, squamous or follicular cell differentiation. Tumor cells were positive for AE1/AE3 and CK18 but negative for TTF1, thyroglobulin and PAX8. INI1 nuclear expression was absent. A frameshift SMARCB1/INI1 mutation was detected. In addition, TET2 and Notch1 mutations were present but alterations of BRAF, RET, PAX8/PPAR8 or RAS were not identified. Patient death occurred 14 months after diagnosis from post-therapeutic complications. None of the 184 benign and malignant thyroid lesions tested, including 12 poorly and undifferentiated thyroid carcinomas, were INI1-deficient. INI1-deficient thyroid carcinoma shares the phenotype, genotype and biology of other INI1-deficient tumors. Epithelioid and plasmacytoid/rhabdoid changes are most frequent whereas basaloid morphology is not reported, in contrast with sinonasal tumors. Poorly differentiated and undifferentiated thyroid tumors with epithelioid or rhabdoid morphology should be tested for INI1 protein expression to better characterize these aggressive neoplasms and identify patients eligible for targeted therapy.
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http://dx.doi.org/10.1007/s12105-021-01338-0DOI Listing
May 2021

Histone demethylase complexes KDM3A and KDM3B cooperate with OCT4/SOX2 to define a pluripotency gene regulatory network.

FASEB J 2021 06;35(6):e21664

College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering & Technology, Northwest A&F University, Yangling, China.

The pluripotency gene regulatory network of porcine induced pluripotent stem cells(piPSCs), especially in epigenetics, remains elusive. To determine the biological function of epigenetics, we cultured piPSCs in different culture conditions. We found that activation of pluripotent gene- and pluripotency-related pathways requires the erasure of H3K9 methylation modification which was further influenced by mouse embryonic fibroblast (MEF) served feeder. By dissecting the dynamic change of H3K9 methylation during loss of pluripotency, we demonstrated that the H3K9 demethylases KDM3A and KDM3B regulated global H3K9me2/me3 level and that their co-depletion led to the collapse of the pluripotency gene regulatory network. Immunoprecipitation-mass spectrometry (IP-MS) provided evidence that KDM3A and KDM3B formed a complex to perform H3K9 demethylation. The genome-wide regulation analysis revealed that OCT4 (O) and SOX2 (S), the core pluripotency transcriptional activators, maintained the pluripotent state of piPSCs depending on the H3K9 hypomethylation. Further investigation revealed that O/S cooperating with histone demethylase complex containing KDM3A and KDM3B promoted pluripotency genes expression to maintain the pluripotent state of piPSCs. Together, these data offer a unique insight into the epigenetic pluripotency network of piPSCs.
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http://dx.doi.org/10.1096/fj.202100230RDOI Listing
June 2021

L-Theanine regulates glutamine metabolism and immune function by binding to cannabinoid receptor 1.

Food Funct 2021 Jul;12(13):5755-5769

Key Lab of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha, Hunan 410128, China. and National Research Center of Engineering Technology for Utilization of Botanical Functional Ingredients, Hunan Agricultural University, Changsha, Hunan 410128, China and Hunan Agricultural University, Co-Innovation Center of Education Ministry for Utilization of Botanical Functional Ingredients, Changsha, Hunan 410128, China.

l-Theanine is a characteristic amino acid in tea with various effects including antioxidant and anti-inflammatory effects. Previously, most studies had reported that l-theanine regulates the immune function in vivo by inhibiting the expression of the inflammatory factors, but how l-theanine regulates the inflammatory factors' pathway is not known. In this study, we innovatively found the binding target of l-theanine in vivo-cannabinoid receptor 1, and demonstrated that l-theanine regulated the immune function and glutamine metabolism by competitively binding cannabinoid receptor 1. Mechanistically, l-theanine competitively binds cannabinoid receptor 1, leading to inhibition of cannabinoid receptor 1 activity, and regulates glutamine metabolism and immune function in normal and E44813-stressed rats. In normal rats, l-theanine inhibits ERK1/2 phosphorylation through Gβy by antagonizing cannabinoid receptor 1, thus affecting GS expression. From the point of view of immune signaling, after LTA antagonizes the activity of cannabinoid receptor 1, it relieves the inhibition of cannabinoid receptor 1 on COX-2 expression, downregulates Pdcd4 expression and NFκB, and ultimately enhances the expression of the anti-inflammatory factor IL-10. In E44813-stressed rats, l-theanine promotes the nuclear translocation of p-ERK1/2 by inhibiting the activity of cannabinoid receptor 1, and finally acts on GS. At the same time, it decreases the expression of the pro-inflammatory factor TNF-α and increases the expression of the anti-inflammatory factor IL-10 in stressed rats through the COX2-Pdcd4-NFκB-IL10 and TNFα pathways. In summary, these results demonstrate that l-theanine regulates glutamine metabolism and immune function by competitively binding to cannabinoid receptor 1.
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http://dx.doi.org/10.1039/d1fo00505gDOI Listing
July 2021

Functional Genomic and Biochemical Analysis Reveals Pleiotropic Effect of Congo Red on Aspergillus fumigatus.

mBio 2021 05 18;12(3). Epub 2021 May 18.

Unité des Aspergillus, Institut Pasteur, Paris, France

Inhibition of fungal growth by Congo red (CR) has been putatively associated with specific binding to β-1,3-glucans, which blocks cell wall polysaccharide synthesis. In this study, we searched for transcription factors (TFs) that regulate the response to CR and interrogated their regulon. During the investigation of the susceptibility to CR of the TF mutant library, several CR-resistant and -hypersensitive mutants were discovered and further studied. Abnormal distorted swollen conidia called Quasimodo cells were seen in the presence of CR. Quasimodo cells in the resistant mutants were larger than the ones in the sensitive and parental strains; consequently, the conidia of the resistant mutants absorbed more CR than the germinating conidia of the sensitive or parental strains. Accordingly, this higher absorption rate by Quasimodo cells resulted in the removal of CR from the culture medium, allowing a subset of conidia to germinate and grow. In contrast, all resting conidia of the sensitive mutants and the parental strain were killed. This result indicated that the heterogeneity of the conidial population is essential to promote the survival of in the presence of CR. Moreover, amorphous surface cell wall polysaccharides such as galactosaminogalactan control the influx of CR inside the cells and, accordingly, resistance to the drug. Finally, long-term incubation with CR led to the discovery of a new CR-induced growth effect, called drug-induced growth stimulation (DIGS), since the growth of one of them could be stimulated after recovery from CR stress. The compound Congo red (CR) has been historically used for coloring treatment and histological examination as well to inhibit the growth of yeast and filamentous fungi. It has been thought that CR binds to β-1,3-glucans in the fungal cell wall, disrupting the organization of the cell wall structure. However, other processes have been implicated in affecting CR sensitivity. Here, we explore CR susceptibility through screening a library of genetic null mutants. We find several previously uncharacterized genetic regulators important for CR susceptibility. Through biochemical and molecular characterization, we find cell membrane permeability to be important. Additionally, we characterize a novel cell type, Quasimodo cells, that occurs upon CR exposure. These cells take up CR, allowing the growth of the remaining fungi. Finally, we find that priming with CR can enhance long-term growth in one mutant.
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http://dx.doi.org/10.1128/mBio.00863-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262895PMC
May 2021

Dynamic changes of metabolic profile and taste quality during the long-term aging of Qingzhuan Tea: The impact of storage age.

Food Chem 2021 Oct 26;359:129953. Epub 2021 Apr 26.

Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha, Hunan 410128, PR China. Electronic address:

Qingzhuan tea (QZT) with longer aging year is usually believed to have higher quality and commercial value. In this study, a 20 years sequence of aged QZT were subjected to an electronic tongue and liquid chromatography-mass spectrometry to investigate the effect of storage age on its metabolic profile and taste quality. The changes in both taste quality and metabolic profile exhibited a parabolic trend in the 20 years of QZT aging and reached the maximum at the 10th year. A total of 47 compounds were identified as critical metabolites responsible for the age variation of QZT quality, with the methylation of catechins, glycosylation of flavonoids, degradation of flavoalkaloids, biosynthesis of triterpenoids, and formation of theabrownins. These results suggested that the taste of QZT was improved after 10 years of storage, with the reduction of bitterness and astringency and a general increase of key quality-related compounds.
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http://dx.doi.org/10.1016/j.foodchem.2021.129953DOI Listing
October 2021

Interspecies cell fusion between mouse embryonic stem cell and porcine pluripotent cell.

Reprod Domest Anim 2021 May 15. Epub 2021 May 15.

College of Life Science, Northeast Agricultural University, Harbin, China.

In the area of stem cell research, fusion of somatic cells into pluripotent cells such as mouse embryonic stem (ES) cells induces reprogramming of the somatic nucleus and can be used to study the effect of trans-acting factors from the pluripotent cell on the pluripotent state of somatic nucleus. As many other groups, we previously established a porcine pluripotent cell line at a low potential. Therefore, here, we performed experiments to investigate if the fusion with mouse ES cell could improve the pluripotent state of porcine pluripotent cell. Our data showed that resultant mouse-porcine interspecies fused cells are AP positive, and could be passaged up to 20 passages. Different degrees of increases in expression of porcine pluripotent genes proved that pig-origin gene network can be programmed by mouse ES. Further differentiation study also confirmed these fused cells' potential to form three germ layers. However, unexpectedly, we found that chromosome loss and aberrant (especially in porcine chromosomes) is severe after the cell fusion, implying that interspecies cell fusion may be not suitable to study porcine pluripotency without additional supportive conditions for genome stabilization.
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http://dx.doi.org/10.1111/rda.13952DOI Listing
May 2021

Sensing of mycobacterial arabinogalactan by galectin-9 exacerbates mycobacterial infection.

EMBO Rep 2021 Jul 13;22(7):e51678. Epub 2021 May 13.

Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.

Mycobacterial arabinogalactan (AG) is an essential cell wall component of mycobacteria and a frequent structural and bio-synthetical target for anti-tuberculosis (TB) drug development. Here, we report that mycobacterial AG is recognized by galectin-9 and exacerbates mycobacterial infection. Administration of AG-specific aptamers inhibits cellular infiltration caused by Mycobacterium tuberculosis (Mtb) or Mycobacterium bovis BCG, and moderately increases survival of Mtb-infected mice or Mycobacterium marinum-infected zebrafish. AG interacts with carbohydrate recognition domain (CRD) 2 of galectin-9 with high affinity, and galectin-9 associates with transforming growth factor β-activated kinase 1 (TAK1) via CRD2 to trigger subsequent activation of extracellular signal-regulated kinase (ERK) as well as induction of the expression of matrix metalloproteinases (MMPs). Moreover, deletion of galectin-9 or inhibition of MMPs blocks AG-induced pathological impairments in the lung, and the AG-galectin-9 axis aggravates the process of Mtb infection in mice. These results demonstrate that AG is an important virulence factor of mycobacteria and galectin-9 is a novel receptor for Mtb and other mycobacteria, paving the way for the development of novel effective TB immune modulators.
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http://dx.doi.org/10.15252/embr.202051678DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256295PMC
July 2021

Regulating Twisted Skeleton to Construct Organ-Specific Perylene for Intensive Cancer Chemotherapy.

Angew Chem Int Ed Engl 2021 07 14;60(29):16215-16223. Epub 2021 Jun 14.

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology (NCNST), Beijing, 100190, China.

The systemic use of pharmaceutical drugs for cancer patients is a compromise between desirable therapy and side effects because of the intrinsic shortage of organ-specific pharmaceutical drug. Design and construction of pharmaceutical drug to achieve the organ-specific delivery is thus desperately desirable. We herein regulate perylene skeleton to effect organ-specificity and present an example of lung-specific distribution on the basis of bay-twisted PDIC-NC. We further demonstrate that PDIC-NC can target into mitochondria to act as cellular respiration inhibitor, inducing insufficient production of adenosine triphosphate, promoting endogenous H O and OH burst, elevating calcium overload, efficiently triggering the synergistic apoptosis, autophagy and endoplasmic reticulum stress of lung cancer cells. The antitumor performance of PDIC-NC is verified on in vivo xenografted, metastasis and orthotopic lung cancer, presenting overwhelming evidences for potentially clinical application. This study contributes a proof-of-concept demonstration of twisted perylene to well attain lung-specific distribution, and meanwhile achieves intensive lung cancer chemotherapy.
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http://dx.doi.org/10.1002/anie.202105607DOI Listing
July 2021

Shared genetic etiology and causality between body fat percentage and cardiovascular diseases: a large-scale genome-wide cross-trait analysis.

BMC Med 2021 Apr 29;19(1):100. Epub 2021 Apr 29.

Department of Epidemiology & Biostatistics, School of Public Health, Peking University, China. 38 Xueyuan Road, Beijing, 100191, China.

Background: Accumulating evidences have suggested that high body fat percentage (BF%) often occurs in parallel with cardiovascular diseases (CVDs), implying a common etiology between them. However, the shared genetic etiology underlying BF% and CVDs remains unclear.

Methods: Using large-scale genome-wide association study (GWAS) data, we investigated shared genetics between BF% (N = 100,716) and 10 CVD-related traits (n = 6968-977,323) with linkage disequilibrium score regression, multi-trait analysis of GWAS, and transcriptome-wide association analysis, and evaluated causal associations using Mendelian randomization.

Results: We found strong positive genetic correlations between BF% and heart failure (HF) (Rg = 0.47, P = 1.27 × 10) and coronary artery disease (CAD) (Rg = 0.22, P = 3.26 × 10). We identified 5 loci and 32 gene-tissue pairs shared between BF% and HF, as well as 16 loci and 28 gene-tissue pairs shared between BF% and CAD. The loci were enriched in blood vessels and brain tissues, while the gene-tissue pairs were enriched in the nervous, cardiovascular, and exo-/endocrine system. In addition, we observed that BF% was causally related with a higher risk of HF (odds ratio 1.63 per 1-SD increase in BF%, P = 4.16 × 10-04) using a MR approach.

Conclusions: Our findings suggest that BF% and CVDs have shared genetic etiology and targeted reduction of BF% may improve cardiovascular outcomes. This work advances our understanding of the genetic basis underlying co-morbid obesity and CVDs and opens up a new way for early prevention of CVDs.
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http://dx.doi.org/10.1186/s12916-021-01972-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082910PMC
April 2021

Molecular engineering of diketopyrrolopyrrole-conjugated polymer nanoparticles by chalcogenide variation for photoacoustic imaging guided photothermal therapy.

J Mater Chem B 2021 04 25;9(14):3153-3160. Epub 2021 Mar 25.

Laboratory for NanoMedical Photonics, School of Basic Medical Science, Henan University, Kaifeng, 475004, P. R. China.

Photothermal therapy is promising for augmenting cancer therapeutic outcomes in cancer treatment. Diketopyrrolopyrrole (DPP)-conjugated polymer nanoparticles are in focus due to their dual photoacoustic imaging and photothermal therapy functions. Herein, the design and synthesis of three near-infrared absorbing conjugated polymers, named DPP-SO, DPP-SS and DPP-SSe, with heteroatom substitution of the thiophene moiety were developed for a photoacoustic imaging guided photothermal therapy. It was demonstrated that systematically changing only the heteroatom from O to S or Se could apparently adjust the absorption spectrum and energy gap of DPP-conjugated polymers to obtain the most suitable photothermal transduction agents (PTAs) for use in biomedicine. The characterization of photophysical properties proved that the photothermal conversion efficiency and absorption coefficient of DPP-SO nanoparticles under 808 nm irradiation was up to 79.3% and 66.51 L g cm, respectively, which were much higher than those of DPP-SS and DPP-SSe nanoparticles. Remarkably, the IC value of DPP-SO for killing A549 cells was half that of DPP-SS and DPP-SSe nanoparticles. Further in vivo works demonstrated efficient photothermal therapeutic effects of DPP-SO nanoparticles with the guidance of photoacoustic imaging. Thus, this is an efficient method to regulate the photothermal performance of DPP-conjugated polymers by changing the heteroatom in the molecular skeleton.
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http://dx.doi.org/10.1039/d1tb00193kDOI Listing
April 2021

Comprehensive analyses of m6A regulators and interactive coding and non-coding RNAs across 32 cancer types.

Mol Cancer 2021 04 13;20(1):67. Epub 2021 Apr 13.

State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, 211166, China.

N6-Methyladenosine (m6A) is an RNA modification that interacts with numerous coding and non-coding RNAs and plays important roles in the development of cancers. Nonetheless, the clinical impacts of m6A interactive genes on these cancers largely remain unclear since most studies focus only on a single cancer type. We comprehensively evaluated m6A modification patterns, including 23 m6A regulators and 83 interactive coding and non-coding RNAs among 9,804 pan-cancer samples. We used clustering analysis to identify m6A subtypes and constructed the m6A signature based on an unsupervised approach. We used the signatures to identify potential m6A modification targets across the genome. The prognostic value of one target was further validated in 3,444 samples from six external datasets. We developed three distinct m6A modification subtypes with different tumor microenvironment cell infiltration degrees: immunological, intermediate, and tumor proliferative. They were significantly associated with overall survival in 24 of 27 cancer types. Our constructed individual-level m6A signature was associated with survival, tumor mutation burden, and classical pathways. With the signature, we identified 114 novel genes as potential m6A targets. The gene shared most commonly between cancer types, BCL9L, is an oncogene and interacts with m6A patterns in the Wnt signaling pathway. In conclusion, m6A regulators and their interactive genes impact the outcome of various cancers. Evaluating the m6A subtype and the signature of individual tumors may inform the design of adjuvant treatments.
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http://dx.doi.org/10.1186/s12943-021-01362-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045265PMC
April 2021

An Omnibus Test for Detecting Multiple Phenotype Associations Based on GWAS Summary Level Data.

Front Genet 2021 17;12:644419. Epub 2021 Mar 17.

Department of Statistics and Actuarial Science, The University of Hong Kong, Hong Kong, China.

Abundant Genome-wide association study (GWAS) findings have reflected the sharing of genetic variants among multiple phenotypes. Exploring the association between genetic variants and multiple traits can provide novel insights into the biological mechanism of complex human traits. In this article, we proposed to apply the generalized Berk-Jones (GBJ) test and the generalized higher criticism (GHC) test to identify the genetic variants that affect multiple traits based on GWAS summary statistics. To be more robust to different gene-multiple traits association patterns across the whole genome, we proposed an omnibus test (OMNI) by using the aggregated Cauchy association test. We conducted extensive simulation studies to investigate the type one error rates and compare the powers of the proposed tests (i.e., the GBJ, GHC and OMNI tests) and the existing tests (i.e., the minimum of the -values (MinP) and the cross-phenotype association test (CPASSOC) in a wide range of simulation settings. We found that all of these methods could control the type one error rates well and the proposed OMNI test has robust power. We applied those methods to the summary statistics dataset from Global Lipids Genetics Consortium and identified 19 new genetic variants that were missed by the original single trait association analysis.
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http://dx.doi.org/10.3389/fgene.2021.644419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009968PMC
March 2021

MRCIP: a robust Mendelian randomization method accounting for correlated and idiosyncratic pleiotropy.

Brief Bioinform 2021 Mar 11. Epub 2021 Mar 11.

Department of Statistics and Actuarial Science, The University of Hong Kong, Pokfulam Road, Hong Kong, China.

Mendelian randomization (MR) is a powerful instrumental variable (IV) method for estimating the causal effect of an exposure on an outcome of interest even in the presence of unmeasured confounding by using genetic variants as IVs. However, the correlated and idiosyncratic pleiotropy phenomena in the human genome will lead to biased estimation of causal effects if they are not properly accounted for. In this article, we develop a novel MR approach named MRCIP to account for correlated and idiosyncratic pleiotropy simultaneously. We first propose a random-effect model to explicitly model the correlated pleiotropy and then propose a novel weighting scheme to handle the presence of idiosyncratic pleiotropy. The model parameters are estimated by maximizing a weighted likelihood function with our proposed PRW-EM algorithm. Moreover, we can also estimate the degree of the correlated pleiotropy and perform a likelihood ratio test for its presence. Extensive simulation studies show that the proposed MRCIP has improved performance over competing methods. We also illustrate the usefulness of MRCIP on two real datasets. The R package for MRCIP is publicly available at https://github.com/siqixu/MRCIP.
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http://dx.doi.org/10.1093/bib/bbab019DOI Listing
March 2021

Accumulation and cross-linkage of β-1,3/1,6-glucan lead to loss of basal stipe cell wall extensibility in mushroom Coprinopsis cinerea.

Carbohydr Polym 2021 May 2;259:117743. Epub 2021 Feb 2.

Jiangsu Key Laboratory for Microbes and Microbial Functional Genomics, Jiangsu Engineering and Technology Research Center for Industrialization of Microbial Resources, College of Life Science, Nanjing Normal University, 1 Wenyuan Rd, Xianlin University Park, Nanjing 210046, PR China. Electronic address:

The mature basal stipe of mushroom Coprinopsis cinerea loses wall extensibility. We found that an endo-β-1,3-glucanase ENG from C. cinerea could restore mature basal stipe wall extensibility via pretreatment such that the ENG-pretreated basal stipe walls could be induced to extend by chitinase ChiIII. ENG pretreatment released glucose, laminaribiose, and 3-O-D-gentiobiose-D-glucose from the basal stipe walls, consistent with ENG-digested products of β-1,6-branched β-1,3-glucan. Different effects of endo-β-1,3-glucanase ENG and exo-β-1,3-glucanase EXG pretreatment on the structure, amount and ratio (β-1,3-glucoside bonds to β-1,6-glucoside bonds) of products from the basal stipe and the apical stipe cell walls, respectively, and on the cell wall extensibility and the cell wall ultra-architecture of the basal stipes were analyzed. All results demonstrate that the more accumulation and cross-linkage of β-1,6-branched β-1,3-glucan with wall maturation lead to loss of wall extensibility of the basal stipe regions compared to the apical stipe cell walls.
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http://dx.doi.org/10.1016/j.carbpol.2021.117743DOI Listing
May 2021

An Improved Genome-Wide Polygenic Score Model for Predicting the Risk of Type 2 Diabetes.

Front Genet 2021 11;12:632385. Epub 2021 Feb 11.

Department of Statistics and Actuarial Science, The University of Hong Kong, Hong Kong, China.

Polygenic risk score (PRS) has been shown to be predictive of disease risk such as type 2 diabetes (T2D). However, the existing studies on genetic prediction for T2D only had limited predictive power. To further improve the predictive capability of the PRS model in identifying individuals at high T2D risk, we proposed a new three-step filtering procedure, which aimed to include truly predictive single-nucleotide polymorphisms (SNPs) and avoid unpredictive ones into PRS model. First, we filtered SNPs according to the marginal association -values (≤ 5× 10) from large-scale genome-wide association studies. Second, we set linkage disequilibrium (LD) pruning thresholds ( ) as 0.2, 0.4, 0.6, and 0.8. Third, we set -value thresholds as 5× 10, 5× 10, 5× 10, and 5× 10. Then, we constructed and tested multiple candidate PRS models obtained by the PRSice-2 software among 182,422 individuals in the UK Biobank (UKB) testing dataset. We validated the predictive capability of the optimal PRS model that was chosen from the testing process in identifying individuals at high T2D risk based on the UKB validation dataset ( = 274,029). The prediction accuracy of the PRS model evaluated by the adjusted area under the receiver operating characteristics curve (AUC) showed that our PRS model had good prediction performance [AUC = 0.795, 95% confidence interval (CI): (0.790, 0.800)]. Specifically, our PRS model identified 30, 12, and 7% of the population at greater than five-, six-, and seven-fold risk for T2D, respectively. After adjusting for sex, age, physical measurements, and clinical factors, the AUC increased to 0.901 [95% CI: (0.897, 0.904)]. Therefore, our PRS model could be useful for population-level preventive T2D screening.
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http://dx.doi.org/10.3389/fgene.2021.632385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905203PMC
February 2021

Achieving the Super Gas-Wetting Alteration by Functionalized Nano-Silica for Improving Fluid Flowing Capacity in Gas Condensate Reservoirs.

ACS Appl Mater Interfaces 2021 Mar 26;13(9):10996-11006. Epub 2021 Feb 26.

College of Petroleum Engineering, China University of Petroleum (East China), Qingdao 266580, China.

It is well-known that the production of gas-condensate reservoirs is significantly affected by the liquid condensation near the wellbore region. Gas-wetting alteration can be one of the most effective approaches to alleviate condensate accumulation and improve liquid distribution. However, gas well deliverability is still limited because the wettability of cores is altered only from liquid-wetting to intermediate gas-wetting by using traditional chemical stimulation. To solve this bottleneck problem, herein, we developed a fluorine-functionalized nanosilica to achieve super gas-wetting alteration, increasing the contact angles of water and n-hexadecane on the treated core surface from 23 and 0° to 157 and 145°, respectively. The surface free energy reduces rapidly from 67.97 to 0.23 mN/m. The super gas-wetting adsorption layer on the core surface formed by functionalized nanosilica not only increases the surface roughness but also reduces the surface free energy. The core flooding confirms that the required pressure for displacement is apparently reduced. Meanwhile, the core permeability can be dramatically restored after the super gas-wetting alteration. The microscopic visualization is employed to further understand the impact of fluorine-functionalized nanosilica on the fluid flow behavior and mechanism in porous media. The oil saturation in the micromodel decreases sharply from 48.75 to 7.84%, eliminating the "water locking effect" and "Jiamin effect", which indicates that the added functional nanosilica effectively improves fluid flow capacity and may contribute to production in the gas condensate reservoirs. In addition, this work reveals the fluid flow behavior and mechanism in the reservoir in detail, which will expand the better application of this material to many oilfields and other mining engineering systems.
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http://dx.doi.org/10.1021/acsami.0c22831DOI Listing
March 2021