Publications by authors named "Xue Gao"

454 Publications

Transcription factor 3 (TCF3) combined with histone deacetylase 3 (HDAC3) down-regulates microRNA-101 to promote Burkitt lymphoma cell proliferation and inhibit apoptosis.

Bioengineered 2021 Dec;12(1):7995-8005

Department of Hematology, Henan Institute of Hematology, the Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.

To explore the function of transcription factor 3 (TCF3) on the proliferation and apoptosis of Burkitt lymphoma cells and its mechanism. qRT-PCR was performed to determine the expression of TCF3, histone deacetylase 3 (HDAC3), and microRNA-101 (miR-101) in the Burkitt lymphoma (BL) tumor tissues and lymph node tissues with reactive lymph node hyperplasia (RLNH). We found that the expression of TCF3 and HDAC3 was up-regulated in BL tumor tissues and lymphoma cells, and the miR-101 expression was down-regulated. And TCF3 and HDAC3 were negatively correlated with the expression of miR-101, respectively. In addition, knockdown of TCF3 can inhibit BL cell proliferation, reduce cell viability and promote cell apoptosis, retain the cell cycle in the G0/G1 phase, and inhibit the expression of Akt/mTOR pathway-related proteins (p-Akt and p-mTOR). When miR-101 was overexpressed, the results were the same as when TCF3 was knocked down. Moreover, we used Co-immunoprecipitation (Co-IP) to detect the interaction between TCF3 and HDAC3, and performed the Chromatin immunoprecipitation (ChIP) experiment to detect the enrichment of TCF3 and HDAC3 in the promoter region of miR-101. We found that TCF3 can interact with HDAC3 and is enriched in the miR-101 promoter region. In conclusion, TCF3 combined with HDAC3 down-regulates the expression of miR-101, thereby promoting the proliferation of BL cells and inhibiting their apoptosis.
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http://dx.doi.org/10.1080/21655979.2021.1977557DOI Listing
December 2021

A fluorescent and colorimetric dual-recognition probe based on copper(II)-decorated carbon dots for detection of phosphate.

Anal Methods 2021 Oct 12. Epub 2021 Oct 12.

College of Food Science and Technology, Bohai University, National & Local Joint Engineering Research Center of Storage, Processing and Safety Control Technology for Fresh Agricultural and Aquatic Products, Food Safety Key Lab of Liaoning Province, The Fresh Food Storage and Processing Technology Research Institute of Liaoning Provincial Universities, China.

In the present article, we report a novel fluorescent and colorimetric dual-signal sensing probe based on a CD-Cu complex for the detection of the phosphate ion (Pi). The yellow fluorescent carbon quantum dots (CDs) were simply synthesized one-step hydrothermal treatment of -phenylenediamine (OPD) and 4-aminobutyric acid (GABA). The method was based on the combination of the CDs and Cu to form a coordination complex. Pi can capture Cu on the surface of CDs, which brings about two kinds of signal change through competitive complexation, including fluorescence and UV-vis absorption. The probe could detect the Pi with a linear range of 0.01-1 mM with a detection limit of 3.75 μM for the fluorescence signal and a linear range of 0.01-1 mM with a detection limit of 4.38 μM for the colorimetric signal. And the change in absorption signal can be used to visually detect Pi. Furthermore, the proposed sensing system was successfully applied to determine Pi in practical water samples.
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http://dx.doi.org/10.1039/d1ay01394gDOI Listing
October 2021

Characteristics of and risk factors for biliary pathogen infection in patients with acute pancreatitis.

BMC Microbiol 2021 Oct 5;21(1):269. Epub 2021 Oct 5.

Binzhou Medical University, Yantai City, 264003, Shandong, China.

Background: Infection in patients with acute pancreatitis, especially severe acute pancreatitis patients, is a common and important phenomenon, and the distributions and drug resistance profiles of bacteria causing biliary infection and related risk factors are dynamic. We conducted this study to explore the characteristics of and risk factors for bacterial infection in the biliary tract to understand antimicrobial susceptibility, promote the rational use of antibiotics, control multidrug-resistant bacterial infections and provide guidance for the treatment of acute pancreatitis caused by drug-resistant bacteria.

Methods: The distribution of 132 strains of biliary pathogenic bacteria in patients with acute pancreatitis from January 2016 to December 2020 were analyzed. We assessed drug resistance in the dominant Gram-negative bacteria and studied the drug resistance profiles of multidrug-resistant bacteria by classifying Enterobacteriaceae and nonfermentative bacteria. We then retrospectively analyzed the clinical data and risk factors associated with 72 strains of Gram-negative bacilli, which were divided into multidrug-resistant bacteria (50 cases) and non-multidrug-resistant bacteria (22 cases).

Results: The main bacteria were Escherichia coli, Acinetobacter baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa. Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli had a 66.67% detection rate. Acinetobacter baumannii had more than 50.00% drug resistance to carbapenems, ESBL-producing Klebsiella pneumoniae had 100.00% drug resistance, and Pseudomonas aeruginosa had 66.67% resistance to carbapenems. Multivariate logistic regression analysis suggested that the administration of third- or fourth-generation cephalosporins was an independent risk factor for Gram-negative multidrug-resistant biliary bacterial infection in acute pancreatitis patients.

Conclusion: Drug resistance among biliary pathogens in acute pancreatitis patients remains high; therefore, rational antimicrobial drug use and control measures should be carried out considering associated risk factors to improve diagnosis and treatment quality in acute pancreatitis patients.
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http://dx.doi.org/10.1186/s12866-021-02332-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8493750PMC
October 2021

The Novel Antioxidant Compound JSH-23 Prevents Osteolysis by Scavenging ROS During Both Osteoclastogenesis and Osteoblastogenesis.

Front Pharmacol 2021 9;12:734774. Epub 2021 Sep 9.

Department of Orthopaedics, Xijing Hospital, the Fourth Military Medical University, Xi'an, China.

Inflammatory osteolysis is a pathological skeletal disease associated with not only the production of inflammatory cytokines but also local oxidative status. Excessive reactive oxygen species (ROS) promote bone resorption by osteoclasts and induce the apoptosis of osteoblasts. In consideration of the lack of effective preventive or treatments options against osteolysis, the exploitation of novel pharmacological compounds/agents is critically required. In our study, we found that a novel antioxidant compound, JSH-23, plays a role in restoring bone homeostasis by scavenging intracellular ROS during both osteoclastogenesis and osteoblastogenesis. Mechanically, JSH-23 suppressed RANKL-induced osteoclastogenesis, bone resorption and the expression of specific genes (including NFATc1, c-Fos, TRAP, CTSK and DC-STAMP) via inhibition of the NF-κB signaling pathway. Meanwhile, JSH-23 suppressed RANKL-induced ROS generation via the TRAF6/Rac1/NOX1 pathway and the enhanced expression of Nrf2/HO-1. In addition, JSH-23 attenuated HO-induced apoptosis and mineralization reduction in osteoblasts by reducing ROS production and enhancing Nrf2/HO-1 expression. Our results further revealed that JSH-23 exerts its protective effects on bone mass through its antioxidant activity. In conclusion, our results show that the application of JSH-23 might be a novel and plausible strategy for the treatment of osteolysis-related disease.
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http://dx.doi.org/10.3389/fphar.2021.734774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8458573PMC
September 2021

Runs of homozygosity analysis reveals consensus homozygous regions affecting production traits in Chinese Simmental beef cattle.

BMC Genomics 2021 Sep 21;22(1):678. Epub 2021 Sep 21.

Key Laboratory of Animal Genetics Breeding and Reproduction, Ministry of Agriculture and Rural Affairs, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Yuanmingyuan West Road 2#, Haidian District, 100193, Beijing, China.

Background: Genomic regions with a high frequency of runs of homozygosity (ROH) are related to important traits in farm animals. We carried out a comprehensive analysis of ROH and evaluated their association with production traits using the BovineHD (770 K) SNP array in Chinese Simmental beef cattle.

Results: We detected a total of 116,953 homozygous segments with 2.47Gb across the genome in the studied population. The average number of ROH per individual was 99.03 and the average length was 117.29 Mb. Notably, we detected 42 regions with a frequency of more than 0.2. We obtained 17 candidate genes related to body size, meat quality, and reproductive traits. Furthermore, using Fisher's exact test, we found 101 regions were associated with production traits by comparing high groups with low groups in terms of production traits. Of those, we identified several significant regions for production traits (P < 0.05) by association analysis, within which candidate genes including ECT2, GABRA4, and GABRB1 have been previously reported for those traits in beef cattle.

Conclusions: Our study explored ROH patterns and their potential associations with production traits in beef cattle. These results may help to better understand the association between production traits and genome homozygosity and offer valuable insights into managing inbreeding by designing reasonable breeding programs in farm animals.
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http://dx.doi.org/10.1186/s12864-021-07992-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8454143PMC
September 2021

HCV Core Protein Induces Chemokine CCL2 and CXCL10 Expression Through NF-κB Signaling Pathway in Macrophages.

Front Immunol 2021 31;12:654998. Epub 2021 Aug 31.

Department of Immunology, Hebei Medical University, Shijiazhuang, China.

HCV core protein is the first structural protein synthesized during hepatitis C virus (HCV) infection and replication. It is released from virus infected liver cells and mediates multiple functions to affect host cell response. The innate immune response is the first line of defense against viral infection. After HCV infection, Kupffer cells (KCs) which are liver macrophages play an important role in host innate immune response. Kupffer cells act as phagocytes and release different cytokines and chemokines to counter viral infection and regulate inflammation and fibrosis in liver. Earlier, we have demonstrated that HCV core protein interacts with gC1qR and activates MAPK, NF-κB and PI3K/AKT pathways in macrophages. In this study, we explored the effect of HCV core protein on CCL2 and CXCL10 expression in macrophages and the signaling pathways involved. Upon silencing of gC1qR, we observed a significant decrease expression of CCL2 and CXCL10 in macrophages in the presence of HCV core protein. Inhibiting NF-κB pathway, but not P38, JNK, ERK and AKT pathways greatly reduced the expression of CCL2 and CXCL10. Therefore, our results indicate that interaction of HCV core protein with gC1qR could induce CCL2 and CXCL10 secretion in macrophages NF-κB signaling pathway. These findings may shed light on the understanding of how leukocytes migrate into the liver and exaggerate host-derived immune responses and may provide novel therapeutic targets in HCV chronic inflammation.
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http://dx.doi.org/10.3389/fimmu.2021.654998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438213PMC
October 2021

PacBio Single-Molecule Long-Read Sequencing Provides New Light on the Complexity of Full-Length Transcripts in Cattle.

Front Genet 2021 30;12:664974. Epub 2021 Aug 30.

Laboratory of Molecular Biology and Bovine Breeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China.

Cattle () is one of the most widely distributed livestock species in the world, and provides us with high-quality milk and meat which have a huge impact on the quality of human life. Therefore, accurate and complete transcriptome and genome annotation are of great value to the research of cattle breeding. In this study, we used error-corrected PacBio single-molecule real-time (SMRT) data to perform whole-transcriptome profiling in cattle. Then, 22.5 Gb of subreads was generated, including 381,423 circular consensus sequences (CCSs), among which 276,295 full-length non-chimeric (FLNC) sequences were identified. After correction by Illumina short reads, we obtained 22,353 error-corrected isoforms. A total of 305 alternative splicing (AS) events and 3,795 alternative polyadenylation (APA) sites were detected by transcriptome structural analysis. Furthermore, we identified 457 novel genes, 120 putative transcription factors (TFs), and 569 novel long non-coding RNAs (lncRNAs). Taken together, this research improves our understanding and provides new insights into the complexity of full-length transcripts in cattle.
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http://dx.doi.org/10.3389/fgene.2021.664974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8437344PMC
August 2021

A highly sensitive ratiometric fluorescent sensor for copper ions and cadmium ions in scallops based on nitrogen doped graphene quantum dots cooperating with gold nanoclusters.

Food Chem 2022 Feb 26;369:130964. Epub 2021 Aug 26.

College of Food Science and Technology, Bohai University, National & Local Joint Engineering Research Center of Storage, Processing and Safety Control Technology for Fresh Agricultural and Aquatic Products, Food Safety Key Lab of Liaoning Province, The Fresh Food Storage and Processing Technology Research Institute of Liaoning Provincial Universities, China. Electronic address:

Based on the electrostatic interaction, we constructed a ratiometric fluorescence nanomixture of graphene quantum dots-gold nanoclusters (GQDs-AuNCs) for the quantitative detection of Cu and Cd. When Cu or Cd was added into the reaction system, the fluorescence of GSH-AuNCs at 565 nm can be quenched by Cu and enhanced by Cd while the intensity of N-GQDs at 403 nm stayed constant. Under the optimized conditions, the fluorescence intensity ratio (I/I) of the GQDs-AuNCs system was proportional to the concentration of Cu and Cd in the range of 8×10 mol/L-6×10 mol/L and 1×10 mol/L-4×10 mol/L, respectively, with detection limits of 4.12×10 mol/L and 9.43×10 mol/L, respectively. In the presence of Cu and Cd, the paper-based vision sensor would produce visible fluorescent color changes, which can be used for rapid detection on site. The method has been successfully applied to the determination of Cu and Cd in scallops with satisfactory results.
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http://dx.doi.org/10.1016/j.foodchem.2021.130964DOI Listing
February 2022

Sequential Bilateral Cochlear Implantation in a Child with Severe External, Middle, and Inner Ear Malformations: Surgical Considerations and Practical Aspects.

ORL J Otorhinolaryngol Relat Spec 2021 Aug 25:1-7. Epub 2021 Aug 25.

Department of Otolaryngology, PLA Rocket Force Characteristic Medical Center, Beijing, China.

Cochlear implantation (CI) is a safe and beneficial surgery for children with congenital inner ear malformations, with the exception of cochlear nerve aplasia. The combination of microtia with middle and inner ear abnormalities is extremely uncommon and sufficiently severe to make a surgical approach to the cochlea difficult. We report herein the case of a 2-year-old girl who presented with profound bilateral sensorineural hearing loss, congenital aural atresia, microtia, and inner ear malformations. High-resolution computed tomography revealed poor development of the bilateral middle ear spaces, absence of the incus and stapes, aberrant courses of facial nerves, aplastic lateral semicircular canals, and covered round windows. With intraoperative imaging assistance, sequential bilateral CI was performed using a transmastoid approach with no complication. We propose that CI is feasible in patients with severe external and middle ear malformations. However, major malformations increase the risk of complications. As the facial nerve and cochlea are difficult to locate due to the lack of important anatomical landmarks, detailed planning and adequate preparation, including review of the preoperative imaging data, and the use of facial nerve monitoring and intraoperative imaging are very important. In addition, experienced surgeons should perform CI to ensure the success of the operation.
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http://dx.doi.org/10.1159/000515179DOI Listing
August 2021

Ulinastatin protects against sepsis‑induced myocardial injury by inhibiting NLRP3 inflammasome activation.

Mol Med Rep 2021 10 20;24(4). Epub 2021 Aug 20.

Department of Critical Care Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.

Myocardial injury is the primary manifestation of multiple organ dysfunction during sepsis, however, the mechanisms underlying sepsis‑induced myocardial injury remain unclear. Similarly, no effective therapeutics have yet been developed for myocardial injury. In the present study, the role of the NOD‑like receptor 3 (NLRP3) inflammasome on cardiac function were characterized and the effects of different ulinastatin (UTI) doses in protecting a septic rat model from myocardial injury were elucidated. To evaluate UTI efficacy on cardiac function, its effects on anti‑inflammatory mediators were analyzed and its cardioprotective effects were investigated. It was demonstrated that circulatory levels of tumor necrosis factor‑α and interleukin‑1β were elevated during sepsis. It was also observed that NLRP3 and caspase‑1 expression enhanced post‑cecal ligation and puncture (CLP), and that high UTI levels protected against myocardial injury induced by sepsis. To the best of our knowledge, this is the first study to demonstrate that the mechanisms underpinning UTI‑mediated myocardial protection were due to the downregulation of the NLRP3/caspase‑1/IL‑1β signaling pathway. Based on these findings, it is proposed that UTI exerts beneficial effects during sepsis‑induced myocardial injury.
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http://dx.doi.org/10.3892/mmr.2021.12369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8404092PMC
October 2021

Stomata and ROS changes during Botrytis elliptica infection in diploid and tetraploid Lilium rosthornii Diels.

Plant Physiol Biochem 2021 Oct 6;167:366-375. Epub 2021 Aug 6.

Beijing Key Laboratory of Ornamental Plants Germplasm Innovation & Molecular Breeding, National Engineering Research Center for Floriculture, Beijing Laboratory of Urban and Rural Ecological Environment, Key Laboratory of Genetics and Breeding in Forest Trees and Ornamental Plant of Ministry of Education, School of Landscape Architecture, Beijing Forestry University, Beijing, 100083, China. Electronic address:

Polyploid plants often show improved resistance against many diseases, but whether they show increased resistance to grey mould, a devastating disease caused by Botrytis spp. fungi, is seldom reported. Stomata and reactive oxygen species (ROS) play dual roles in defence against grey mould, and it is unclear how their roles change after polyploidization. We addressed these questions in diploid and colchicine-induced Lilium rosthornii after B. elliptica infection. Tetraploids were less susceptible to grey mould, with lower morality rates in naturally infected plants. Before the stomata closed in artificially infected leaves, tetraploids, with larger stomatal apertures, were more easily invaded by the pathogen than diploids. However, the lesion area increased more slowly in tetraploids than in diploids, which may be explained by three causes based on histological and physiological characteristics. First, the pathogen required more time to penetrate the epidermis and closed stomata in tetraploids than in diploids. Second, the pathogen penetrated the reopened stomata more easily than the epidermis, and stomatal density was lower in tetraploids than in diploids. Third, tetraploids showed faster ROS accumulation, a more effective ROS-scavenging system and less malondialdehyde (MDA) accumulation than diploids. Stomatal starch and abnormal guard cell nuclei were present in the infected leaves. This phenomenon may be caused by oxalic acid, a pathogenic factor for many pathogens that promotes stomatal starch degradation and stomatal reopening in Sclerotinia spp., a pathogen closely related to Botrytis spp. This suggestion was primarily confirmed by immersing healthy leaves in oxalic acid solution.
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http://dx.doi.org/10.1016/j.plaphy.2021.08.008DOI Listing
October 2021

Genomic Prediction Using LD-Based Haplotypes Inferred From High-Density Chip and Imputed Sequence Variants in Chinese Simmental Beef Cattle.

Front Genet 2021 29;12:665382. Epub 2021 Jul 29.

Laboratory of Molecular Biology and Bovine Breeding, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China.

A haplotype is defined as a combination of alleles at adjacent loci belonging to the same chromosome that can be transmitted as a unit. In this study, we used both the Illumina BovineHD chip (HD chip) and imputed whole-genome sequence (WGS) data to explore haploblocks and assess haplotype effects, and the haploblocks were defined based on the different LD thresholds. The accuracies of genomic prediction (GP) for dressing percentage (DP), meat percentage (MP), and rib eye roll weight (RERW) based on haplotype were investigated and compared for both data sets in Chinese Simmental beef cattle. The accuracies of GP using the entire imputed WGS data were lower than those using the HD chip data in all cases. For DP and MP, the accuracy of GP using haploblock approaches outperformed the individual single nucleotide polymorphism (SNP) approach (GBLUP_In_Block) at specific LD levels. Hotelling's test confirmed that GP using LD-based haplotypes from WGS data can significantly increase the accuracies of GP for RERW, compared with the individual SNP approach (∼1.4 and 1.9% for GBLUP and GBLUP+GBLUP, respectively). We found that the accuracies using haploblock approach varied with different LD thresholds. The LD thresholds ( ≥ 0.5) were optimal for most scenarios. Our results suggested that LD-based haploblock approach can improve accuracy of genomic prediction for carcass traits using both HD chip and imputed WGS data under the optimal LD thresholds in Chinese Simmental beef cattle.
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http://dx.doi.org/10.3389/fgene.2021.665382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8358323PMC
July 2021

Rates and trends in stage-specific prostate cancer incidence by age and race/ethnicity, 2000-2017.

Prostate 2021 Oct 28;81(14):1071-1077. Epub 2021 Jul 28.

Department of Medical Oncology, The Fourth Affiliated Hospital of China Medical University, Shenyang, China.

Background: The 2008 and 2012 United States Preventive Services Task Force (USPSTF) recommendations against prostate-specific antigen (PSA) screening have led to changes in the incidence pattern of prostate cancer. We sought to examine rates and trends in stage-specific prostate cancer incidence by age and race/ethnicity using the most recent data obtained from Surveillance, Epidemiology, and End Results (SEER) program.

Methods: SEER*Stat version 8.3.6 was used to analyze annual prostate cancer incidence rates between 2000 and 2017 according to the SEER summary stage, age group, and race/ethnicity group. Incidence rates per 100,000 men were calculated and age-adjusted to 2000 US standard population. Annual percentage change (APC) was performed to identify the trend in prostate cancer incidence.

Results: Between 2008 and 2012, trends in incidence of overall and localized prostate cancer significantly declined in comparison with between 2000 and 2007 (APC, -5.4 and -6.0, respectively). However, there was an increase in the incidence rate of both overall and localized prostate cancer from 2014 to 2017 (43.3-46 and 34-34.9 per 100,000 men, respectively). The incidence of regional prostate cancer significantly increased between 2013 and 2017 (5.9-6.8 per 100,000 men; APC, 4.3). Distant disease incidence increased continually between 2008 and 2012 (2.9-3.3 per 100,000 men; APC, 2.3) and between 2013 and 2017 (3.4-4.3 per 100,000 men; APC, 6.0). In addition, these increases in incidence occurred in men of all stratified age and race/ethnicity groups, except for men aged <50 years and American Indian/Alaska Native men.

Conclusion: This study demonstrates that the longer-term effects of USPSTF recommendations against PSA screening may have resulted in a reversal of downtrend in prostate cancer incidence, as incidence rates of overall and localized prostate cancer gradually increased from 2014 to 2017. Meanwhile, the trend in stage migration toward advanced disease increased incrementally.
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http://dx.doi.org/10.1002/pros.24204DOI Listing
October 2021

miR-29a-3p inhibits endometrial cancer cell proliferation, migration and invasion by targeting VEGFA/CD C42/PAK1.

BMC Cancer 2021 Jul 21;21(1):843. Epub 2021 Jul 21.

Department of Obstetrics and Gynecology, Zibo Hospital of Traditional Chinese Medicine, No. 75 Xinajian Middle Road, Zhoucun District, Zibo City, 255300, Shandong, China.

Background: This study aimed to investigate the mechanism of miR-29a-3p in regulating endometrial cancer (EC) progression.

Methods: A total of 72 EC patients were enrolled. EC cells were transfected. Cells proliferation, cloning ability, migration and invasion were researched by MTT assay, colony formation experiment, cell scratch test and Transwell experiment respectively. Dual-luciferase reporter assay was performed. Xenograft experiment was conducted using nude mice. miR-29a-3p, VEGFA, CDC42, PAK1 and p-PAK1 expression in cells/tissues was investigated by qRT-PCR and Western blot.

Results: miR-29a-3p expression was aberrantly reduced in EC patients, which was associated with poor outcome. miR-29a-3p inhibited EC cells proliferation, cloning formation, migration and invasion (P <  0.05 or P <  0.01 or P <  0.001). miR-29a-3p inhibited CDC42/PAK1 signaling pathway activity in EC cells (P <  0.01). VEGFA expression was directly inhibited by miR-29a-3p. miR-29a-3p suppressed EC cells malignant phenotype in vitro and growth in vivo by targeting VEGFA/CDC42/PAK1 signaling pathway (P < 0.05 or P < 0.01).

Conclusion: miR-29a-3p inhibits EC cells proliferation, migration and invasion by targeting VEGFA/CDC42/PAK1 signaling pathway.
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http://dx.doi.org/10.1186/s12885-021-08506-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8293590PMC
July 2021

Lysine acetylation restricts mutant IDH2 activity to optimize transformation in AML cells.

Mol Cell 2021 09 20;81(18):3833-3847.e11. Epub 2021 Jul 20.

Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA; Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USA; Section of Hematology and Oncology, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA. Electronic address:

Mutant isocitrate dehydrogenase (IDH) 1 and 2 play a pathogenic role in cancers, including acute myeloid leukemia (AML), by producing oncometabolite 2-hydroxyglutarate (2-HG). We recently reported that tyrosine phosphorylation activates IDH1 R132H mutant in AML cells. Here, we show that mutant IDH2 (mIDH2) R140Q commonly has K413 acetylation, which negatively regulates mIDH2 activity in human AML cells by attenuating dimerization and blocking binding of substrate (α-ketoglutarate) and cofactor (NADPH). Mechanistically, K413 acetylation of mitochondrial mIDH2 is achieved through a series of hierarchical phosphorylation events mediated by tyrosine kinase FLT3, which phosphorylates mIDH2 to recruit upstream mitochondrial acetyltransferase ACAT1 and simultaneously activates ACAT1 and inhibits upstream mitochondrial deacetylase SIRT3 through tyrosine phosphorylation. Moreover, we found that the intrinsic enzyme activity of mIDH2 is much higher than mIDH1, thus the inhibitory K413 acetylation optimizes leukemogenic ability of mIDH2 in AML cells by both producing sufficient 2-HG for transformation and avoiding cytotoxic accumulation of intracellular 2-HG.
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http://dx.doi.org/10.1016/j.molcel.2021.06.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8455438PMC
September 2021

Advances in the role of autophagy in the development of retinoblastoma.

Oncol Lett 2021 Aug 1;22(2):632. Epub 2021 Jul 1.

Guangxi Key Laboratory of Brain and Cognitive Neuroscience, Guilin Medical University, Guilin, Guangxi 541199, P.R. China.

Autophagy is a feedback regulatory mechanism of cells to external stress, which helps cells to adapt to changes in physiological conditions and environmental stress. Autophagy possesses a variety of target genes that control a wide range of signaling pathways. Maintenance of an appropriate level of autophagy is essential for the growth, metastasis and characteristics of tumors. Retinoblastoma (RB) is the most common primary intraocular malignant tumor found in the eyes of children following exposure to extreme environmental factors, such as mitochondrial defects, oxidative stress and excessive autophagy; this leads to the development of DNA damage and progressive loss of the function of the eye, which results in the occurrence of RB. Recent studies have documented the involvement of autophagy in the transformation, occurrence and metastasis of RB. High or low levels of autophagy exert notably promotive or repressive effects on the development, invasion, drug resistance and survival of RB, respectively. The present review reports the research progress on the association between autophagy and RB.
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http://dx.doi.org/10.3892/ol.2021.12893DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258627PMC
August 2021

The characteristics and functions of GAPDH S-nitrosylation during controlled aging of elm and Arabidopsis seeds.

J Exp Bot 2021 Jul 9. Epub 2021 Jul 9.

Beijing Advanced Innovation Center for Tree Breeding by Molecular Design, Institute of Tree Development and Genome Editing, College of Biological Sciences and Biotechnology, Beijing Forestry University, 35 Tsinghua East Road, Beijing, 100083, China.

Seed aging is the gradual decline in seed vigor, during which programmed cell death (PCD) occurs. The functions of nitric oxide (NO) are exerted through protein S-nitrosylation, a reversible post-translational modification. During seed aging, more than 80 proteins are S-nitrosylated, but the particular role of individual proteins is unknown. Here, we showed that the S-nitrosylation level of elm GAPDH (UpGAPDH) increased after controlled deterioration treatment (CDT). UpGAPDH was S-nitrosylated at Cys154 during the GSNO treatment, and its oligomerization was triggered both in vitro and in elm seeds. Interestingly, UpGAPDH interacted with the mitochondrial protein UpVDAC in an S-nitrosylation-dependent way. Some UpGAPDH-GFP proteins in Arabidopsis protoplasts co-localized with mitochondria during the GSNO treatment, while the S-nitrosylation-defected UpGAPDH C154S-GFP proteins did not. Seeds of the oxUpGAPDH lines showed cell death and lost seed vigor rapidly during CDT-triggered seed aging, while overexpression of S-nitrosylation-defected UpGAPDH-Cys154 did not. Our results suggest that S-nitrosylation of UpGAPDH may accelerate cell death and seed deterioration during CDT. These results provide insight into the effects of UpGAPDH S-nitrosylation on protein interactions and seed aging.
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http://dx.doi.org/10.1093/jxb/erab322DOI Listing
July 2021

Genetic architecture and phenotypic landscape of deafness and onychodystrophy syndromes.

Hum Genet 2021 Jul 7. Epub 2021 Jul 7.

College of Otolaryngology Head and Neck Surgery, Chinese PLA General Hospital, Chinese PLA Medical School, 28 Fuxing Road, Beijing, 100853, People's Republic of China.

Deafness and onychodystrophy syndromes are a group of phenotypically overlapping syndromes, which include DDOD syndrome (dominant deafness-onychodystrophy), DOORS syndrome (deafness, onychodystrophy, osteodystrophy, mental retardation and seizures) and Zimmermann-Laband syndrome (gingival hypertrophy, coarse facial features, hypoplasia or aplasia of nails and terminal phalanges, intellectual disability, and hypertrichosis). Pathogenic variants in four genes, ATP6V1B2, TBC1D24, KCNH1 and KCNN3, have been shown to be associated with deafness and onychodystrophy syndromes. ATP6V1B2 encodes a component of the vacuolar H-ATPase (V-ATPase) and TBC1D24 belongs to GTPase-activating protein, which are all involved in the regulation of membrane trafficking. The overlapping clinical phenotype of TBC1D24- and ATP6V1B2- related diseases and their function with GTPases or ATPases activity indicate that they may have some physiological link. Variants in genes encoding potassium channels KCNH1 or KCNN3, underlying human Zimmermann-Laband syndrome, have only recently been recognized. Although further analysis will be needed, these findings will help to elucidate an understanding of the pathogenesis of these disorders better and will aid in the development of potential therapeutic approaches. In this review, we summarize the latest developments of clinical features and molecular basis that have been reported to be associated with deafness and onychodystrophy disorders and highlight the challenges that may arise in the differential diagnosis.
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http://dx.doi.org/10.1007/s00439-021-02310-2DOI Listing
July 2021

Structural basis of the stereoselective formation of the spirooxindole ring in the biosynthesis of citrinadins.

Nat Commun 2021 07 6;12(1):4158. Epub 2021 Jul 6.

Department of Chemical and Biomolecular Engineering, Rice University, Houston, TX, USA.

Prenylated indole alkaloids featuring spirooxindole rings possess a 3R or 3S carbon stereocenter, which determines the bioactivities of these compounds. Despite the stereoselective advantages of spirooxindole biosynthesis compared with those of organic synthesis, the biocatalytic mechanism for controlling the 3R or 3S-spirooxindole formation has been elusive. Here, we report an oxygenase/semipinacolase CtdE that specifies the 3S-spirooxindole construction in the biosynthesis of 21R-citrinadin A. High-resolution X-ray crystal structures of CtdE with the substrate and cofactor, together with site-directed mutagenesis and computational studies, illustrate the catalytic mechanisms for the possible β-face epoxidation followed by a regioselective collapse of the epoxide intermediate, which triggers semipinacol rearrangement to form the 3S-spirooxindole. Comparing CtdE with PhqK, which catalyzes the formation of the 3R-spirooxindole, we reveal an evolutionary branch of CtdE in specific 3S spirocyclization. Our study provides deeper insights into the stereoselective catalytic machinery, which is important for the biocatalysis design to synthesize spirooxindole pharmaceuticals.
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http://dx.doi.org/10.1038/s41467-021-24421-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260726PMC
July 2021

Human pluripotent stem cell-derived eosinophils reveal potent cytotoxicity against solid tumors.

Stem Cell Reports 2021 Jul 1;16(7):1697-1704. Epub 2021 Jul 1.

School of Basic Medical Sciences, State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, and the MOE Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100191, China. Electronic address:

Eosinophils are attractive innate immune cells to use to potentiate T cell antitumor efficacy because they are capable of infiltrating tumors at early stages and modulating the tumor microenvironment. However, the limited number of functional eosinophils caused by the scarcity and short life of primary eosinophils in peripheral blood has greatly impeded the development of eosinophil-based immunotherapy. In this study, we established an efficient chemically defined protocol to generate a large quantity of functional eosinophils from human pluripotent stem cells (hPSCs) with nearly 100% purity expressing eosinophil peroxidase. These hPSC-derived eosinophils transcriptionally resembled their primary counterpart. Moreover, hPSC-derived eosinophils showed competent tumor killing capacity in established solid tumors. Furthermore, the combination of hPSC-derived eosinophils with CAR-T cells exhibited potential synergistic effects, inhibiting tumor growth and enhancing mouse survival. Our study opens up new avenues for the development of eosinophil-based immunotherapies to treat cancer.
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http://dx.doi.org/10.1016/j.stemcr.2021.06.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282466PMC
July 2021

Validation of the Prediction Accuracy for 13 Traits in Chinese Simmental Beef Cattle Using a Preselected Low-Density SNP Panel.

Animals (Basel) 2021 Jun 25;11(7). Epub 2021 Jun 25.

Laboratory of Molecular Biology and Bovine Breeding, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China.

Chinese Simmental beef cattle play a key role in the Chinese beef industry due to their great adaptability and marketability. To achieve efficient genetic gain at a low breeding cost, it is crucial to develop a customized cost-effective low-density SNP panel for this cattle population. Thirteen growth, carcass, and meat quality traits and a BovineHD Beadchip genotyping of 1346 individuals were used to select trait-associated variants and variants contributing to great genetic variance. In addition, highly informative SNPs with high MAF in each 500 kb sliding window and in each genic region were also included separately. A low-density SNP panel consisting of 30,684 SNPs was developed, with an imputation accuracy of 97.4% when imputed to the 770 K level. Among 13 traits, the average prediction accuracy levels evaluated by genomic best linear unbiased prediction (GBLUP) and BayesA/B/Cπ were 0.22-0.47 and 0.18-0.60 for the ~30 K array and BovineHD Beadchip, respectively. Generally, the predictive performance of the ~30 K array was trait-dependent, with reduced prediction accuracies for seven traits. While differences in terms of prediction accuracy were observed among the 13 traits, the low-density SNP panel achieved moderate to high accuracies for most of the traits and even improved the accuracies for some traits.
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http://dx.doi.org/10.3390/ani11071890DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8300368PMC
June 2021

Full-length transcriptome analysis provides new insights into the early bolting occurrence in medicinal Angelica sinensis.

Sci Rep 2021 06 21;11(1):13000. Epub 2021 Jun 21.

College of Agronomy, Gansu Provincial Key Lab of Good Agricultural Production for Traditional Chinese Medicines, Gansu Provincial Engineering Research Centre for Medical Plant Cultivation and Breeding, Gansu Agricultural University, Lanzhou, 730070, China.

Angelica sinensis (Oliv.) Diels root part is an integral component of traditional Chinese medicine, widely prescribed to improve blood circulation and blood stasis. However, early bolting of A. sinensis compromises the quality of the roots and hence is a major limitation for yield of medicinal materials. To date, little information about the molecular mechanisms underlying bolting is available for this important medicinal plant. To identify genes putatively involved in early bolting, we have conducted the transcriptome analysis of the shoot tips of the early-bolting plants and non-bolting (normal) plants of A. sinensis, respectively, using a combination of third-generation sequencing and next-generation sequencing. A total of 43,438 non-redundant transcripts were collected and 475 unique differentially expressed genes (DEGs) were identified. Gene annotation and functional analyses revealed that DEGs were highly involved in plant hormone signaling and biosynthesis pathways, three main flowering pathways, pollen formation, and very-long-chain fatty acids biosynthesis pathways. The levels of endogenous hormones were also changed significantly in the early bolting stage of A. sinensis. This study provided new insights into the transcriptomic control of early bolting in A. sinensis, which could be further applied to enhance the yield of medicinally important raw materials.
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http://dx.doi.org/10.1038/s41598-021-92494-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217430PMC
June 2021

Analysis of genotype-phenotype relationships in 90 Chinese probands with Waardenburg syndrome.

Hum Genet 2021 Jun 17. Epub 2021 Jun 17.

Key Lab of Hearing Impairment Science of Ministry of Education, Key Lab of Hearing Impairment Prevention and Treatment of Beijing, National Clinical Research Center for Otolaryngologic Diseases, College of Otolaryngology Head and Neck Surgery, Chinese PLA General Hospital, Chinese PLA Medical School, #28 Fuxing Road, Beijing, 100853, China.

Waardenburg syndrome (WS) is a phenotypically and genetically heterogeneous disorder characterised by hearing loss and pigmentary abnormalities. We clarified the clinical and genetic features in 90 Chinese WS probands. Disease-causing variants were detected in 55 probands, for a molecular diagnosis rate of 61%, including cases related to PAX3 (14.4%), MITF (24.4%), and SOX10 (22.2%). Altogether, 48 variants were identified, including 44 single-nucleotide variants and 4 copy number variants. By parental genotyping, de novo variants were observed in 60% of probands and 15.4% of the de novo variation was associated with mosaicism. Statistical analyses revealed that brown freckles on the skin were more frequently seen in probands with MITF variants; patchy depigmented skin, asymmetric hearing loss, and white forelocks occurred more often in cases with PAX3 variants; and congenital inner ear malformations were more common and cochlear hypoplasia III was exclusively observed in those with SOX10 variants. In addition, we found that ranges of W-index values overlapped between WS probands with different genetic variants, and the use of the W-index as a tool for assessing dystopia canthorum may be problematic in Chinese. Herein, we report the spectrum of a cohort of WS probands and elucidate the relationship between genotype and phenotype.
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http://dx.doi.org/10.1007/s00439-021-02301-3DOI Listing
June 2021

Transcriptome profiling analysis of muscle tissue reveals potential candidate genes affecting water holding capacity in Chinese Simmental beef cattle.

Sci Rep 2021 06 7;11(1):11897. Epub 2021 Jun 7.

Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, 100193, China.

Water holding capacity (WHC) is an important sensory attribute that greatly influences meat quality. However, the molecular mechanism that regulates the beef WHC remains to be elucidated. In this study, the longissimus dorsi (LD) muscles of 49 Chinese Simmental beef cattle were measured for meat quality traits and subjected to RNA sequencing. WHC had significant correlation with 35 kg water loss (r = - 0.99, p < 0.01) and IMF content (r = 0.31, p < 0.05), but not with SF (r = - 0.20, p = 0.18) and pH (r = 0.11, p = 0.44). Eight individuals with the highest WHC (H-WHC) and the lowest WHC (L-WHC) were selected for transcriptome analysis. A total of 865 genes were identified as differentially expressed genes (DEGs) between two groups, of which 633 genes were up-regulated and 232 genes were down-regulated. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment revealed that DEGs were significantly enriched in 15 GO terms and 96 pathways. Additionally, based on protein-protein interaction (PPI) network, animal QTL database (QTLdb), and relevant literature, the study not only confirmed seven genes (HSPA12A, HSPA13, PPARγ, MYL2, MYPN, TPI, and ATP2A1) influenced WHC in accordance with previous studies, but also identified ATP2B4, ACTN1, ITGAV, TGFBR1, THBS1, and TEK as the most promising novel candidate genes affecting the WHC. These findings could offer important insight for exploring the molecular mechanism underlying the WHC trait and facilitate the improvement of beef quality.
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http://dx.doi.org/10.1038/s41598-021-91373-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184995PMC
June 2021

Research Advances of Soil Corrosion of Grounding Grids.

Micromachines (Basel) 2021 May 2;12(5). Epub 2021 May 2.

The State Key Laboratory of Power Transmission Equipment & System Security and New Technology, Chongqing University, Chongqing 400044, China.

A grounding grid plays the role of discharging current and balancing voltage to ensure the safety of the power system. However, soil corrosion can damage the grounding grid, which then can endanger the safe operation of power system. This paper reviewed recent research advances of soil corrosion of grounding grid. The cause, mechanism, types, and influencing factors of soil corrosion of grounding grids were summarized, and the corresponding detection technology and protective measures were also introduced. The paper pointed out that soil corrosion is a serious threat to the grounding grid system. Moreover, the impact mechanism of AC stray current, new corrosion detection technology, and better protective measures still need in-depth research.
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http://dx.doi.org/10.3390/mi12050513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147463PMC
May 2021

[Posterior tibialis tendon dysfunction induced by gouty tophus:a case report].

Zhongguo Gu Shang 2021 05;34(5):476-8

Orthopaedics Center, the 2nd Hospital of Jilin University, Changchun 130041, Jilin, China.

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http://dx.doi.org/10.12200/j.issn.1003-0034.2021.05.016DOI Listing
May 2021

Flexible zirconium doped strontium titanate nanofibrous membranes with enhanced visible-light photocatalytic performance and antibacterial activities.

J Colloid Interface Sci 2021 Oct 5;600:127-137. Epub 2021 May 5.

Innovation Center for Textile Science and Technology, Donghua University, Shanghai 200051, China.

Constructing flexible perovskite structured ceramic fibrous materials would potentially facilitate applications of photocatalysis, wearable devices, and energy storage. However, current perovskite structured ceramic fibrous materials were fragile with small deformation resistance, which have limited their wide applications. Herein, flexible zirconium doped strontium titanate (ZSTO) nanofibrous membranes were fabricated via combining sol-gel and electrospinning methods. The microstructures (pore and crystal) of ZSTO nanofibers were affected by zirconium doping contents and closely relevant to flexibility of resultant membranes. The probable mechanism for flexibility of ZSTO nanofibrous membranes was presented. Furthermore, the silver phosphate modified ZSTO (AZSTO) exhibited superior photocatalytic performance towards tetracycline hydrochloride (TCHC) and antibacterial performance towards Gram-negative and Gram-positive bacteria with visible-light irradiation, including 85% degradation towards TCHC within 60 min, >99.99% inhibition rate and > 3 mm inhibition zone against Gram bacteria. Furthermore, the·superoxide free radical (O) and holes played significant roles in the degradation of TCHC that verified by radical scavenger experiment. Additionally, the membranes exhibited good reusability over five cycles without tedious recycling operations needed for micro/nanoparticle-based catalysts. The successful fabrication of ZSTO nanofibrous membranes would provide a new insight into photocatalysts, antibacterial materials, and wearable device.
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http://dx.doi.org/10.1016/j.jcis.2021.05.005DOI Listing
October 2021

Macrophages Inhibit Ciliary Protein Levels by Secreting BMP-2 Leading to Airway Epithelial Remodeling Under Cigarette Smoke Exposure.

Front Mol Biosci 2021 26;8:663987. Epub 2021 Apr 26.

Department of Immunology, Key Laboratory of Immune Mechanism and Intervention on Serious Disease in Hebei Province, Hebei Medical University, Shijiazhuang, China.

Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease with high morbidity and mortality worldwide. So far, smoking is still its leading cause. The characteristics of COPD are emphysema and airway remodeling, as well as chronic inflammation, which were predominated by macrophages. Some studies have reported that macrophages were involved in emphysema and chronic inflammation, but whether there is a link between airway remodeling and macrophages remains unclear. In this study, we found that both acute and chronic cigarette smoke exposure led to an increase of macrophages in the lung and a decrease of ciliated cells in the airway epithelium of a mouse model. The results of experiments showed that the ciliary protein (β-tubulin-IV) levels of BEAS-2B cells could be inhibited when co-cultured with human macrophage line THP-1, and the inhibitory effect was augmented with the stimulation of cigarette smoke extract (CSE). Based on the results of transcriptome sequencing, we focused on the protein, bone morphogenetic protein-2 (BMP-2), secreted by the macrophage, which might mediate this inhibitory effect. Further studies confirmed that BMP-2 protein inhibited β-tubulin-IV protein levels of BEAS-2B cells under the stimulation of CSE. Coincidentally, this inhibitory effect could be nearly blocked by the BMP receptor inhibitor, LDN, or could be interfered with BMP-2 siRNA. This study suggests that activation and infiltration of macrophages in the lung induced by smoke exposure lead to a high expression of BMP-2, which in turn inhibits the ciliary protein levels of the bronchial epithelial cells, contributing to the remodeling of airway epithelium, and aggravates the development of COPD.
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http://dx.doi.org/10.3389/fmolb.2021.663987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107431PMC
April 2021

KCRR: a nonlinear machine learning with a modified genomic similarity matrix improved the genomic prediction efficiency.

Brief Bioinform 2021 May 8. Epub 2021 May 8.

Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, P. R. China.

Nowadays, advances in high-throughput sequencing benefit the increasing application of genomic prediction (GP) in breeding programs. In this research, we designed a Cosine kernel-based KRR named KCRR to perform GP. This paper assessed the prediction accuracies of 12 traits with various heritability and genetic architectures from four populations using the genomic best linear unbiased prediction (GBLUP), BayesB, support vector regression (SVR), and KCRR. On the whole, KCRR performed stably for all traits of multiple species, indicating that the hypothesis of KCRR had the potential to be adapted to a wide range of genetic architectures. Moreover, we defined a modified genomic similarity matrix named Cosine similarity matrix (CS matrix). The results indicated that the accuracies between GBLUP_kinship and GBLUP_CS almost unanimously for all traits, but the computing efficiency has increased by an average of 20 times. Our research will be a significant promising strategy in future GP.
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http://dx.doi.org/10.1093/bib/bbab132DOI Listing
May 2021

Correspondence on "DOORS syndrome and a recurrent truncating ATP6V1B2 variant" by Beauregard-Lacroix et al.

Genet Med 2021 08 3;23(8):1578-1579. Epub 2021 May 3.

College of Otolaryngology Head and Neck Surgery, Chinese PLA General Hospital, Chinese PLA Medical School, Beijing, China.

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http://dx.doi.org/10.1038/s41436-021-01167-0DOI Listing
August 2021
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