Publications by authors named "Fei Guo"

648 Publications

MARCH8 inhibits influenza A virus infection by targeting viral M2 protein for ubiquitination-dependent degradation in lysosomes.

Nat Commun 2021 07 20;12(1):4427. Epub 2021 Jul 20.

NHC Key Laboratory of Systems Biology of Pathogens and Center for AIDS Research, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

The membrane-associated RING-CH (MARCH) proteins are E3 ligases that regulate the stability of various cellular membrane proteins. MARCH8 has been reported to inhibit the infection of HIV-1 and a few other viruses, thus plays an important role in host antiviral defense. However, the antiviral spectrum and the underlying mechanisms of MARCH8 are incompletely defined. Here, we demonstrate that MARCH8 profoundly inhibits influenza A virus (IAV) replication both in vitro and in mice. Mechanistically, MARCH8 suppresses IAV release through redirecting viral M2 protein from the plasma membrane to lysosomes for degradation. Specifically, MARCH8 catalyzes the K63-linked polyubiquitination of M2 at lysine residue 78 (K78). A recombinant A/Puerto Rico/8/34 virus carrying the K78R M2 protein shows greater replication and more severe pathogenicity in cells and mice. More importantly, we found that the M2 protein of the H1N1 IAV has evolved to acquire non-lysine amino acids at positions 78/79 to resist MARCH8-mediated ubiquitination and degradation. Together, our data support the important role of MARCH8 in host anti-IAV intrinsic immune defense by targeting M2, and suggest the inhibitory pressure of MARCH8 on H1N1 IAV transmission in the human population.
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http://dx.doi.org/10.1038/s41467-021-24724-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292393PMC
July 2021

Protocol for nuclear export signal characterization of cGAS in mammalian cells.

STAR Protoc 2021 Sep 3;2(3):100649. Epub 2021 Jul 3.

NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, and Center for AIDS Research, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, P. R. China.

The cyclic GMP-AMP synthase (cGAS) is the principal DNA sensor, which binds DNA and triggers the type I interferon production. We used ISD45 or inactivated Vaccinia Virus (VACV) to stimulate cGAS and monitored cellular localization by immunofluorescence microscopy, Operetta high-content screening, and cytoplasmic/nuclear fractionation. LocNES server was used to predict cGAS nuclear export signal (NES) sequence and characterized the function by mutagenesis. This protocol provides a prototype of cGAS subcellular distribution or the identification of NES in other proteins. For complete details on the use and execution of this protocol, please refer to Sun et al. Sun et al. (2021).
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http://dx.doi.org/10.1016/j.xpro.2021.100649DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261000PMC
September 2021

Application of Combined Prediction Model Based on Core and Coritivity Theory in Continuous Blood Pressure Prediction.

Comb Chem High Throughput Screen 2021 Jul 4. Epub 2021 Jul 4.

School of Mathematics Physics and Statistics, Shanghai University of Engineering Science, Shanghai 201620, China.

Background And Objective: Blood pressure is vital evidence for clinicians to predict diseases and check the curative effect of diagnosis and treatment. To further improve the prediction accuracy of blood pressure, this paper proposes a combined prediction model of blood pressure based on coritivity theory and photoplethysmography.

Method: First of all, we extract eight features of photoplethysmogram, followed by using eight machine learning prediction algorithms such as K-nearest neighbor, classification and regression trees and random forest to predict systolic blood pressure. Secondly, aiming at the problem of sub-model selection of combination forecasting model, from the point of graph theory, we construct an undirected network graph G, the results of each single prediction model constitute a vertex set. If the maximum mutual information coefficient between vertices is greater than or equal to 0.69, the vertices are connected by edges. The maximum core of graph G is a submodel of the combinatorial model.

Results: According to the definition of core and coritivity, the maximum core of G is random forest regression and Gaussian kernel support vector regression model. The results show that the SDP estimation error of the combined prediction model based on random forest regression and Gaussian kernel support vector regression is 3.56 ±5.28mmhg, which is better than other single models and meets the AAMI standards.

Conclusion: The combined model determined by core and coritivity has higher prediction performance for blood pressure.
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http://dx.doi.org/10.2174/1386207324666210705113121DOI Listing
July 2021

A study based on four immunoassays: Hepatitis C virus antibody against different antigens may have unequal contributions to detection.

Virol J 2021 Jul 3;18(1):137. Epub 2021 Jul 3.

National Center for Clinical Laboratories, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, No.1 Dahua Road, Beijing, 100730, People's Republic of China.

Background: All commercial Hepatitis C virus antibody (anti-HCV) assays use a combination of recombinant antigens to detect antibody response. Antibody responses to individual antigenic regions (core, NS3/4 and NS5) used in assays have not been investigated.

Methods: In this study, we quantified HCV viral load, tested anti-HCV with four commercial assays (Ortho-ELISA, Murex-ELISA, Architect-CMIA and Elecsys-ECLIA) in 682 plasma specimens. In antigenic region ELISA platform, microwells were coated with three antigens: core (c22-3), NS3/4 (c200) and NS5 individually. The signal-to-cutoff (S/Co) values of different assays, and antibody responses to individual antigens were compared. The specimens were divided into HCV RNA positive group, anti-HCV consistent group, and anti-HCV discrepant group.

Results: Anti-core and anti-NS3/4 were simultaneously detected in 99.2% of HCV RNA positive specimens and showed great consistency with total anti-HCV signals. Responses to the core region were more robust than those to the NS3/4 region in anti-HCV consistent group (p < 0.001). Anti-NS5 only occurred in companying with responses to the core and NS3/4 antigens, and failed to affect the final anti-HCV positive signals. In anti-HCV discrepant group, 39.0% of positive signals could not be traced back to any single antigenic region.

Conclusion: Antibody responses to the core and NS3/4 antigens were stronger, whereas responses to the NS5 antigen were the weakest, indicating that individual antigenic regions played different roles in total anti-HCV signals. This study provides an impetus for optimizing commercial anti-HCV assays.
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http://dx.doi.org/10.1186/s12985-021-01608-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255013PMC
July 2021

Multiphysics modelling of electroporation under uni- or bipolar nanosecond pulse sequences.

Bioelectrochemistry 2021 Jun 22;141:107878. Epub 2021 Jun 22.

Institute of Ecological Safety, Chongqing University of Posts and Telecommunications, Chongqing 400065, China.

A nonlinear dispersive multiphysics model of single-cell electroporation was proposed in this paper. The time-domain Debye model was utilised to describe the membrane dispersion while the dynamic pore radius function was deployed to modify the plasma membrane conductivity. The dynamic spatial distributions of the ion concentration were dominated by the Nernst-Planck function. First, a single nanosecond pulsed electric field was applied to verify our model and to explore the effects of dispersion and dynamic pore radius on the redistribution of the electric field. The dispersive membrane was found to increase the transmembrane potential, expedite the electroporation process, and weaken the membrane permeability; however, adding the dynamic pore radius function had the opposite effect on transmembrane potential and membrane permeability. The responses of the cells exposed to unipolar and bipolar nanosecond pulse sequences were subsequently simulated. During the application of unipolar pulse sequences, the pore radius and perforation area showed a step-like accumulation, and significant increases in the perforation area and intracellular ion concentration were observed with higher frequency pulse sequences and wider subpulse intervals. The bipolar cancellation effect was also observed in terms of membrane permeability and pore radius.
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http://dx.doi.org/10.1016/j.bioelechem.2021.107878DOI Listing
June 2021

Novel Insights into the Molecular-Level Mechanism Linking the Chemical Diversity and Copper Binding Heterogeneity of Biochar-Derived Dissolved Black Carbon and Dissolved Organic Matter.

Environ Sci Technol 2021 Jul 1. Epub 2021 Jul 1.

Stockbridge School of Agriculture, University of Massachusetts, Amherst, Massachusetts 01003, United States.

Biochar-derived dissolved black carbon (DBC) varies in chemical composition and significantly affects the environmental fate of metal ions. However, the intrinsic molecular composition of DBC fractions and their molecular interaction mechanisms with metal ions remain unclear. We propose a novel, molecular-level covariant binding mechanism to comparatively interpret the heterogeneities, active sites, and sequential responses of copper binding with molecular compounds in DBC and natural dissolved organic matter (DOM). Relatively large proportions of lipid/aliphatic/peptide-like compounds with low mass distributions and lignin-like compounds with oxidized/unsaturated groups existed in acidic- and alkaline-extracted DBC, respectively. A larger percentage of tannin-like/condensed aromatic compounds and higher average conditional stability constants (log) of visible fluorescent components were found for DOM than for DBC. Overall, 200-320 Da and 320-480 Da molecular components contributed significantly to the log values of UVA and visible fluorescent components, respectively, in DBC/DOM. Nitrogenous groups likely exhibited stronger binding affinities than phenolic/carboxylic groups. The sequential copper-binding responses of molecular compounds in DBC/DOM generally followed the order lipid/aliphatic/peptide-like compounds → tannin-like compounds → condensed aromatic compounds. These insights will improve the prediction of the potential effects of DBC on various contaminants and the risks of biochar application to ecosystems.
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http://dx.doi.org/10.1021/acs.est.1c00083DOI Listing
July 2021

Predicting MHC class I binder: existing approaches and a novel recurrent neural network solution.

Brief Bioinform 2021 Jun 15. Epub 2021 Jun 15.

School of Computer Science and Engineering, Central South University, Changsha, China.

Major histocompatibility complex (MHC) possesses important research value in the treatment of complex human diseases. A plethora of computational tools has been developed to predict MHC class I binders. Here, we comprehensively reviewed 27 up-to-date MHC I binding prediction tools developed over the last decade, thoroughly evaluating feature representation methods, prediction algorithms and model training strategies on a benchmark dataset from Immune Epitope Database. A common limitation was identified during the review that all existing tools can only handle a fixed peptide sequence length. To overcome this limitation, we developed a bilateral and variable long short-term memory (BVLSTM)-based approach, named BVLSTM-MHC. It is the first variable-length MHC class I binding predictor. In comparison to the 10 mainstream prediction tools on an independent validation dataset, BVLSTM-MHC achieved the best performance in six out of eight evaluated metrics. A web server based on the BVLSTM-MHC model was developed to enable accurate and efficient MHC class I binder prediction in human, mouse, macaque and chimpanzee.
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http://dx.doi.org/10.1093/bib/bbab216DOI Listing
June 2021

Photochemical Reactivity of Humic Substances in an Aquatic System Revealed by Excitation-Emission Matrix Fluorescence.

Front Chem 2021 28;9:679286. Epub 2021 May 28.

School of Environmental and Municipal Engineering, Qingdao University of Technology, Qingdao, China.

The photochemical reactivity of humic substances plays a critical role in the global carbon cycle, and influences the toxicity, mobility, and bioavailability of contaminants by altering their molecular structure and the mineralization of organic carbon to CO. Here, we examined the simulated irradiation process of Chinese standard fulvic acid (FA) and humic acid (HA) by using excitation-emission matrix fluorescence combined with fluorescence regional integration (FRI), parallel factor (PARAFAC) analysis, and kinetic models. Humic-like and fulvic-like materials were the main materials (constituting more than 90%) of both FA and HA, according to the FRI analysis. Four components were identified by the PARAFAC analysis: fulvic-like components composed of both carboxylic-like and phenolic-like chromophores (C1), terrestrial humic-like components primarily composed of carboxylic-like chromophores (C2), microbial humic-like overwhelming composed of phenolic-like fluorophores (C3), and protein-like components (C4). After irradiation for 72 h, the maximum fluorescence intensity ( ) of C1 and C2 of FA was reduced to 36.01-58.34%, while the of C3 of both FA and HA also decreased to 0-9.63%. By contrast, for HA, the of its C1 and C2 increased to 236.18-294.77% when irradiated for 72 h due to greater aromaticity and photorefractive tendencies. The first-order kinetic model ( = 0.908-0.990) fitted better than zero-order kinetic model ( = 0-0.754) for the C1, C2, and C3, of both FA and HA, during their photochemical reactivity. The photodegradation rate constant ( ) of C1 had values (0.105 for FA; 0.154 for HA) that surpassed those of C2 (0.059 for FA, 0.079 for HA) and C3 (0.079 for both FA and HA) based on the first-order kinetic model. The half-life times of C1, C2, and C3 ranged from 6.61-11.77 h to 4.50-8.81 h for FA and HA, respectively. Combining an excitation-emission matrix with FRI and PARAFAC analyses is a powerful approach for elucidating changes to humic substances during their irradiation, which is helpful for predicting the environmental toxicity of contaminants in natural ecosystems.
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http://dx.doi.org/10.3389/fchem.2021.679286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193985PMC
May 2021

Weighted RSA: An Improved Framework on the Perception of Audio-visual Affective Speech in Left Insula and Superior Temporal Gyrus.

Neuroscience 2021 08 11;469:46-58. Epub 2021 Jun 11.

College of Intelligence and Computing, Tianjin Key Lab of Cognitive Computing and Application, Tianjin University, Tianjin, China; School of Information Science, Japan Advanced Institute of Science and Technology, Japan.

Being able to accurately perceive the emotion expressed by the facial or verbal expression from others is critical to successful social interaction. However, only few studies examined the multimodal interactions on speech emotion, and there is no consistence in studies on the speech emotion perception. It remains unclear, how the speech emotion of different valence is perceived on the multimodal stimuli by our human brain. In this paper, we conducted a functional magnetic resonance imaging (fMRI) study with an event-related design, using dynamic facial expressions and emotional speech stimuli to express different emotions, in order to explore the perception mechanism of speech emotion in audio-visual modality. The representational similarity analysis (RSA), whole-brain searchlight analysis, and conjunction analysis of emotion were used to interpret the representation of speech emotion in different aspects. Significantly, a weighted RSA approach was creatively proposed to evaluate the contribution of each candidate model to the best fitted model and provided a supplement to RSA. The results of weighted RSA indicated that the fitted models were superior to all candidate models and the weights could be used to explain the representation of ROIs. The bilateral amygdala has been shown to be associated with the processing of both positive and negative emotions except neutral emotion. It is indicated that the left posterior insula and the left anterior superior temporal gyrus (STG) play important roles in the perception of multimodal speech emotion.
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http://dx.doi.org/10.1016/j.neuroscience.2021.06.002DOI Listing
August 2021

Bibliometric Analysis of Global Circular RNA Research Trends from 2007 to 2018.

Cell J 2021 Jul 26;23(2):238-246. Epub 2021 May 26.

Department of Orthopaedics, Changhai Hospital, Second Military Medical University, Shanghai, China. Email:

Objective: Circular RNA (circRNA) is of significant interest in genetic research. The aim of this study was to assess global trends in circRNA research production in order to shed new light on future research frontiers.

Materials And Methods: In this retrospective study, we conducted a literature search using the Web of Science Core Collection (WoSCC) database on March 21, 2019 to retrieve publications from 2007 to 2018. Excel 2013, CiteSpace V, and VOSviewer were used to evaluate bibliometric features that included publication output, countries/regions, institutions, journals, citation frequency, H-index, and research hotspots.

Results: Global cumulative publication output on circRNA consisted of 998 papers with a total citation of 28 595 during 2007-2018. China, the US, and Germany were the most prolific countries. China ranked first in H-index (60 times) and citations (13 333 times). The most productive institution was Nanjing Medical University with 73 papers. Biochemical and Biophysical Research Communications (impact factor [IF]2017:2.559) ranked first among journals in the number of publications (64 papers). The keywords shifted from "sequence", "intron", and "splice-site" to "transcriptome", "microRNA sponge", "exon circularization", and "circRNA biogenesis" overtime. The burst keywords "transcriptome", "microRNA sponge", "exon circularization", and "circRNA biogenesis" were the latest frontiers by 2018.

Conclusion: This is a relatively novel bibliometric analysis to inspect research related to circRNA. The results show that publications have continuously increased in the past decade. China, the US, and Germany were the leading countries/regions in terms of quantity. Recent studies on topics related to circRNA biogenesis and function should be closely followed in this field.
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http://dx.doi.org/10.22074/cellj.2021.7143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8181316PMC
July 2021

Roles of Gut Microbial Metabolites in Diabetic Kidney Disease.

Front Endocrinol (Lausanne) 2021 20;12:636175. Epub 2021 May 20.

Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China.

Diabetes is a highly prevalent metabolic disease that has emerged as a global challenge due to its increasing prevalence and lack of sustainable treatment. Diabetic kidney disease (DKD), which is one of the most frequent and severe microvascular complications of diabetes, is difficult to treat with contemporary glucose-lowering medications. The gut microbiota plays an important role in human health and disease, and its metabolites have both beneficial and harmful effects on vital physiological processes. In this review, we summarize the current findings regarding the role of gut microbial metabolites in the development and progression of DKD, which will help us better understand the possible mechanisms of DKD and explore potential therapeutic approaches for DKD.
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http://dx.doi.org/10.3389/fendo.2021.636175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173181PMC
May 2021

Intra- and intercellular signaling pathways associated with drug-induced cardiac pathophysiology.

Trends Pharmacol Sci 2021 Aug 4;42(8):675-687. Epub 2021 Jun 4.

Functional and Mechanistic Safety, Clinical Pharmacology and Safety Sciences, Research and Development, AstraZeneca, Cambridge, UK. Electronic address:

Cardiac physiology and homeostasis are maintained by the interaction of multiple cell types, via both intra- and intercellular signaling pathways. Perturbations in these signaling pathways induced by oncology therapies can reduce cardiac function, ultimately leading to heart failure. As cancer survival increases, related cardiovascular complications are becoming increasingly prevalent, thus identifying the perturbations and cell signaling drivers of cardiotoxicity is increasingly important. Here, we discuss the homotypic and heterotypic cellular interactions that form the basis of intra- and intercellular cardiac signaling pathways, and how oncological agents disrupt these pathways, leading to heart failure. We also highlight the emerging systems biology techniques that can be applied, enabling a deeper understanding of the intra- and intercellular signaling pathways across multiple cell types associated with cardiovascular toxicity.
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http://dx.doi.org/10.1016/j.tips.2021.05.004DOI Listing
August 2021

Ectopic Overexpression of Histone H3K4 Methyltransferase CsSDG36 from Tea Plant Decreases Hyperosmotic Stress Tolerance in .

Int J Mol Sci 2021 May 11;22(10). Epub 2021 May 11.

Key Laboratory of Horticultural Plant Biology, Ministry of Education, College of Horticulture and Forestry Sciences, Huazhong Agricultural University, Wuhan 430070, China.

Histone methylation plays an important regulatory role in the drought response of many plants, but its regulatory mechanism in the drought response of the tea plant remains poorly understood. Here, drought stress was shown to induce lower relative water content and significantly downregulate the methylations of histone H3K4 in the tea plant. Based on our previous analysis of the SET Domain Group () gene family, the full-length coding sequence (CDS) of was cloned from the tea cultivar ''. Bioinformatics analysis showed that the open reading frame (ORF) of the gene was 3138 bp, encoding 1045 amino acids and containing the conserved structural domains of PWWP, PHD, SET and PostSET. The CsSDG36 protein showed a close relationship to AtATX4 of the TRX subfamily, with a molecular weight of 118,249.89 Da, and a theoretical isoelectric point of 8.87, belonging to a hydrophilic protein without a transmembrane domain, probably located on the nucleus. The expression of was not detected in the wild type, while it was clearly detected in the over-expression lines of Arabidopsis. Compared with the wild type, the over-expression lines exhibited lower hyperosmotic resistance by accelerating plant water loss, increasing reactive oxygen species (ROS) pressure, and increasing leaf stomatal density. RNA-seq analysis suggested that the overexpression caused the differential expression of genes related to chromatin assembly, microtubule assembly, and leaf stomatal development pathways. qRT-PCR analysis revealed the significant down-regulation of stomatal development-related genes (, , , , , , , , and ) in the overexpression lines. This study provides a novel sight on the function of histone methyltransferase CsSDG36 under drought stress.
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http://dx.doi.org/10.3390/ijms22105064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150943PMC
May 2021

A sequence-based multiple kernel model for identifying DNA-binding proteins.

BMC Bioinformatics 2021 May 31;22(Suppl 3):291. Epub 2021 May 31.

School of Computer Science and Engineering, Central South University, Changsha, People's Republic of China.

Background: DNA-Binding Proteins (DBP) plays a pivotal role in biological system. A mounting number of researchers are studying the mechanism and detection methods. To detect DBP, the tradition experimental method is time-consuming and resource-consuming. In recent years, Machine Learning methods have been used to detect DBP. However, it is difficult to adequately describe the information of proteins in predicting DNA-binding proteins. In this study, we extract six features from protein sequence and use Multiple Kernel Learning-based on Centered Kernel Alignment to integrate these features. The integrated feature is fed into Support Vector Machine to build predictive model and detect new DBP.

Results: In our work, date sets of PDB1075 and PDB186 are employed to test our method. From the results, our model obtains better results (accuracy) than other existing methods on PDB1075 ([Formula: see text]) and PDB186 ([Formula: see text]), respectively.

Conclusion: Multiple kernel learning could fuse the complementary information between different features. Compared with existing methods, our method achieves comparable and best results on benchmark data sets.
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http://dx.doi.org/10.1186/s12859-020-03875-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167993PMC
May 2021

Quinoline and Quinazoline Derivatives Inhibit Viral RNA Synthesis by SARS-CoV-2 RdRp.

ACS Infect Dis 2021 06 26;7(6):1535-1544. Epub 2021 May 26.

Institute of Medicinal Biotechnology, Chinese Academy of Medical Science, Beijing 100050, China.

Coronavirus disease 2019 (COVID-19) is a fatal respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The identification of potential drugs is urgently needed to control the pandemic. RNA dependent RNA polymerase (RdRp) is a conserved protein within RNA viruses and plays a crucial role in the viral life cycle, thus making it an attractive target for development of antiviral drugs. In this study, 101 quinoline and quinazoline derivatives were screened against SARS-CoV-2 RdRp using a cell-based assay. Three compounds , , and exhibit remarkable potency in inhibiting RNA synthesis driven by SARS-CoV-2 RdRp and relatively low cytotoxicity. Among these three compounds, showed the strongest inhibition upon RNA synthesis driven by SARS-CoV-2 RdRp, the resistance to viral exoribonuclease activity and the inhibitory effect on the replication of CoV, thus holding potential of being drug candidate for treatment of SARS-CoV-2.
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http://dx.doi.org/10.1021/acsinfecdis.1c00083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188755PMC
June 2021

Identification of nucleic acid aptamers against lactate dehydrogenase via SELEX and high-throughput sequencing.

Anal Bioanal Chem 2021 Jul 24;413(17):4427-4439. Epub 2021 May 24.

Key Laboratory of Horticultural Plant Biology, Ministry of Education, College of Horticulture and Forestry Sciences, Huazhong Agricultural University, Wuhan, 430070, Hubei, China.

Nucleic acid aptamers are small fragments of DNA or RNA molecules binding specifically to targets, which can be obtained through in vitro screening via systematic evolution of ligands by exponential enrichment (SELEX). Lactate dehydrogenase (LDH) is an important tumor marker, whose level in patients is of great significance for diagnosis of many diseases. Here, we report the identification of LDH aptamers by 9 rounds of screening from a length-mixed single-stranded DNA library using the SELEX technology. After the 3rd and 7th rounds of aptamer screening, affinity was significantly improved, and fluorescence quantitative analysis showed stronger affinity for the aptamers selected from the 7th to 9th rounds of screening. After high-throughput sequencing, motif analysis, and secondary structure prediction, we finally chose and further investigated 15 candidate LDH aptamer sequences with obvious differences in secondary structure in the 7th to 9th rounds of screening. Among them, LDH7-1, LDH7-9, LDH8-2, and LDH9-1 were shown to bind to LDH protein with high affinity and specificity with K < 25 nM. This study provides new ideas for rapid detection of LDH protein content and enzyme activity, thus contributing to the development of rapid medical detection.
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http://dx.doi.org/10.1007/s00216-021-03397-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141549PMC
July 2021

The application of virtual reality training for anastomosis during robot-assisted radical prostatectomy.

Asian J Urol 2021 Apr 4;8(2):204-208. Epub 2019 Dec 4.

Department of Urology, Changhai Hospital, Second Military Medical University, Shanghai, China.

Objective: To investigate the application of virtual reality training in vesicourethral anastomosis during robot-assisted radical prostatectomy (RARP).

Methods: Three certified robotic urologists who underwent virtual reality training were enrolled in the study group. The other three without training were enrolled in the control group. Parameters were recorded before and after the training. Then a total of 18 patients undergoing RARP were enrolled and randomized assigned to receive anastomosis procedures with certified urologists who either obtained or did not obtain training. The quality of the anastomosis was evaluated.

Results: For the virtual training evaluation, the overall score was significantly improved from 65.0±10.8 to 92.7±3.5 (=0.014); the time of anastomosis was shortened; the economy of motion improved; instrument collisions decreased after training (<0.05). Besides, the effectiveness of the virtual training was evaluated in the 18 real anastomosis procedures which were completed either by three urologists with training or three urologists without training. Most intriguingly, the average time of anastomosis was shortened from 40.0±12.4 min to 25.1±7.1 min (=0.015). The parameters including time of operation, creatinine level of drainage, postoperative hospital stay and duration of catheter drainage were comparable before and after training. Two leakages, which were observed in procedures by doctors without training, needed salvage sutures by a senior doctor.

Conclusions: Virtual reality training enabled surgeons to become quickly familiar with robotic system manipulation, improved their skills for vesicourethral anastomosis and shortened the learning curve, thus helping them operate with high efficacy and quality.
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http://dx.doi.org/10.1016/j.ajur.2019.11.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099643PMC
April 2021

Exploring effectiveness of ab-initio protein-protein docking methods on a novel antibacterial protein complex dataset.

Brief Bioinform 2021 May 6. Epub 2021 May 6.

School of Computer Science and Technology, College of Intelligence and Computing, Tianjin University, Tianjin, China.

Diseases caused by bacterial infections become a critical problem in public heath. Antibiotic, the traditional treatment, gradually loses their effectiveness due to the resistance. Meanwhile, antibacterial proteins attract more attention because of broad spectrum and little harm to host cells. Therefore, exploring new effective antibacterial proteins is urgent and necessary. In this paper, we are committed to evaluating the effectiveness of ab-initio docking methods in antibacterial protein-protein docking. For this purpose, we constructed a three-dimensional (3D) structure dataset of antibacterial protein complex, called APCset, which contained $19$ protein complexes whose receptors or ligands are homologous to antibacterial peptides from Antimicrobial Peptide Database. Then we selected five representative ab-initio protein-protein docking tools including ZDOCK3.0.2, FRODOCK3.0, ATTRACT, PatchDock and Rosetta to identify these complexes' structure, whose performance differences were obtained by analyzing from five aspects, including top/best pose, first hit, success rate, average hit count and running time. Finally, according to different requirements, we assessed and recommended relatively efficient protein-protein docking tools. In terms of computational efficiency and performance, ZDOCK was more suitable as preferred computational tool, with average running time of $6.144$ minutes, average Fnat of best pose of $0.953$ and average rank of best pose of $4.158$. Meanwhile, ZDOCK still yielded better performance on Benchmark 5.0, which proved ZDOCK was effective in performing docking on large-scale dataset. Our survey can offer insights into the research on the treatment of bacterial infections by utilizing the appropriate docking methods.
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http://dx.doi.org/10.1093/bib/bbab150DOI Listing
May 2021

MMFGRN: a multi-source multi-model fusion method for gene regulatory network reconstruction.

Brief Bioinform 2021 May 3. Epub 2021 May 3.

College of Intelligence and Computing, Tianjin University, Tianjin, China.

Lots of biological processes are controlled by gene regulatory networks (GRNs), such as growth and differentiation of cells, occurrence and development of the diseases. Therefore, it is important to persistently concentrate on the research of GRN. The determination of the gene-gene relationships from gene expression data is a complex issue. Since it is difficult to efficiently obtain the regularity behind the gene-gene relationship by only relying on biochemical experimental methods, thus various computational methods have been used to construct GRNs, and some achievements have been made. In this paper, we propose a novel method MMFGRN (for "Multi-source Multi-model Fusion for Gene Regulatory Network reconstruction") to reconstruct the GRN. In order to make full use of the limited datasets and explore the potential regulatory relationships contained in different data types, we construct the MMFGRN model from three perspectives: single time series data model, single steady-data model and time series and steady-data joint model. And, we utilize the weighted fusion strategy to get the final global regulatory link ranking. Finally, MMFGRN model yields the best performance on the DREAM4 InSilico_Size10 data, outperforming other popular inference algorithms, with an overall area under receiver operating characteristic score of 0.909 and area under precision-recall (AUPR) curves score of 0.770 on the 10-gene network. Additionally, as the network scale increases, our method also has certain advantages with an overall AUPR score of 0.335 on the DREAM4 InSilico_Size100 data. These results demonstrate the good robustness of MMFGRN on different scales of networks. At the same time, the integration strategy proposed in this paper provides a new idea for the reconstruction of the biological network model without prior knowledge, which can help researchers to decipher the elusive mechanism of life.
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http://dx.doi.org/10.1093/bib/bbab166DOI Listing
May 2021

Mass Transfer Analysis of Air-Cooled Membrane Distillation Configuration for Desalination.

Membranes (Basel) 2021 Apr 10;11(4). Epub 2021 Apr 10.

Key Laboratory of Ocean Energy Utilization and Energy Conservation of Ministry of Education, School of Energy and Power Engineering, Dalian University of Technology, No. 2 Linggong Road, Dalian 116024, China.

It has been proposed that the air-cooled configuration for air gap membrane distillation is an effective way to simplify the system design and energy source requirement. This offers potential for the practical applications of membrane distillation on an industrial scale. In this work, membrane distillation tests were performed using a typical water-cooled membrane distillation (WCMD) configuration and an air-cooled membrane distillation (ACMD) configuration with various condensing plates and operating conditions. To increase the permeate flux of an ACMD system, the condensing plate in the permeate side should transfer heat to the atmosphere more effectively, such as using a more thermally conductive plate, adding fins, or introducing forced convection air flow. Importantly, a practical mass transfer model was proposed to describe the ACMD performance in terms of permeate flux. This model can be simplified by introducing specific correction values to the mass transfer coefficient of a WCMD process under the same conditions. The two factors relate to the capacity () and the efficiency (σ), which can be considered as the characteristic factors of a membrane distillation (MD) system. The experimental results are consistent with the theoretical estimations based on this model, which can be used to describe the performance of an MD process.
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http://dx.doi.org/10.3390/membranes11040281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069192PMC
April 2021

Experimental Investigation on Floating Solar-Driven Membrane Distillation Desalination Modules.

Membranes (Basel) 2021 Apr 21;11(5). Epub 2021 Apr 21.

School of Energy and Power Engineering, Dalian University of Technology, Dalian 116024, China.

Membrane distillation (MD) processes need a relatively mild temperature gradient as the driving force for desalination. In the field, it is reasonable to utilize solar energy as the heat source for the feed, and seawater as the infinite cold source for condensation. Solar-driven MD provides a route for the practical application of seawater desalination at a small scale. In this work, we focus on floating MD modules with a solar heating bag as the power source, and perform proof-of-principle experiments on the MD performance under various conditioning parameters, including feed flow rate, feed temperature, salinity, air gap, and sea waves. The results indicate that floating solar-driven MD modules are feasible in terms of permeate flux and salt rejection ratio, and the upward evaporation MD configuration leads to a better performance in terms of permeate flux. The simulation and experiments also show that the natural sea waves disturb the heating bag and the MD module floating on the surface of seawater, and effectively enhance the feed circulation and transport in the system.
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http://dx.doi.org/10.3390/membranes11050304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143288PMC
April 2021

Multidimensional healthy life expectancy of the older population in China.

Popul Stud (Camb) 2021 Apr 27:1-22. Epub 2021 Apr 27.

Peking University.

Research on healthy life expectancy (HLE) that considers cognitive impairment has been inadequate, particularly in the context of less developed countries. Using data from the China Health and Retirement Longitudinal Study, our study fills this research gap by computing active life expectancy (ALE), cognitive-impairment-free life expectancy (CIFLE), and active cognitive-impairment-free life expectancy (ACIFLE) for China's older population, using multistate life tables. Results show that at age 60, the three life expectancies were 19.4 years (ALE), 9.5 years (CIFLE), and 8.8 years (ACIFLE) during the period 2011-13. HLE exhibits significant differentials by sex, urban/rural residence, educational level, marital status, and health status at age 60. Among China's older people, males and those living in urban areas experience higher CIFLE, and those who live with a spouse, are more educated, and are healthy at age 60 expect more years in good health according to all three HLE measures..
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http://dx.doi.org/10.1080/00324728.2021.1914854DOI Listing
April 2021

A cell-based assay to discover inhibitors of SARS-CoV-2 RNA dependent RNA polymerase.

Antiviral Res 2021 06 21;190:105078. Epub 2021 Apr 21.

Institute of Medicinal Biotechnology, Chinese Academy of Medical Science, Beijing, China. Electronic address:

Antiviral therapeutics is one effective avenue to control and end this devastating COVID-19 pandemic. The viral RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 has been recognized as a valuable target of antivirals. However, the cell-free SARS-CoV-2 RdRp biochemical assay requires the conversion of nucleotide prodrugs into the active triphosphate forms, which regularly occurs in cells yet is a complicated multiple-step chemical process in vitro, and thus hinders the utility of this cell-free assay in the rapid discovery of RdRp inhibitors. In addition, SARS-CoV-2 exoribonuclease provides the proof-reading capacity to viral RdRp, thus creates relatively high resistance threshold of viral RdRp to nucleotide analog inhibitors, which must be examined and evaluated in the development of this class of antivirals. Here, we report a cell-based assay to evaluate the efficacy of nucleotide analog compounds against SARS-CoV-2 RdRp and assess their tolerance to viral exoribonuclease-mediated proof-reading. By testing seven commonly used nucleotide analog viral polymerase inhibitors, Remdesivir, Molnupiravir, Ribavirin, Favipiravir, Penciclovir, Entecavir and Tenofovir, we found that both Molnupiravir and Remdesivir showed the strong inhibition of SARS-CoV-2 RdRp, with EC50 value of 0.22 μM and 0.67 μM, respectively. Moreover, our results suggested that exoribonuclease nsp14 increases resistance of SARS-CoV-2 RdRp to nucleotide analog inhibitors. We also determined that Remdesivir presented the highest resistance to viral exoribonuclease activity in cells. Therefore, we have developed a cell-based SARS-CoV-2 RdRp assay which can be deployed to discover SARS-CoV-2 RdRp inhibitors that are urgently needed to treat COVID-19 patients.
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http://dx.doi.org/10.1016/j.antiviral.2021.105078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059291PMC
June 2021

The clinical and prognostic significance of LGR5 in GC: A meta-analysis of IHC assay and bioinformatics analysis.

Neoplasma 2021 Apr 23. Epub 2021 Apr 23.

Department of Emergency, Tianjin First Central Hospital, Tianjin, China.

Recently, leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) is a newly identified cancer stem cell marker and Wnt target gene. However, the role of LGR5 in gastric cancer (GC) remains uncertain. This study was performed to investigate the effect of LGR5 expression in GC. The eligible studies were searched via electronic databases. The odds ratios (ORs) with 95% confidence intervals (CIs) or hazard ratios (HRs) with 95% CIs were applied to estimate the effect of LGR5. Further bioinformatics validation data were used to confirm our results. Eleven studies consisting of 2,646 GC patients were identified. LGR5 expression was not associated with age, gender, tumor stage, T stage, tumor size, lymphatic invasion, lymph node metastasis, and distal metastasis. LGR5 expression was related to tumor type (intestinal vs. diffuse: OR = 2.25, P = 0.032). LGR5 expression was negatively correlated with tumor grade (grade 3-4 vs. grade 1-2: OR = 0.40, P = 0.033). Further TCGA validation data also showed similar findings, and LGR5 expression was also found to have a negative association with tumor grade. LGR5 expression was associated with worse overall survival (OS) using multivariate Cox analysis (HR = 2.54, P = 0.009). Further bioinformatics data showed that LGR5 expression was still correlated with shorter OS in 876 GCs. LGR5 expression was negatively correlated with tumor grade and its expression was higher in intestinal-type than in diffuse-type. Moreover, LGR5 may be a potential prognostic factor for survival prediction in GC.
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http://dx.doi.org/10.4149/neo_2021_200714N726DOI Listing
April 2021

[Factors Affecting the Translocation and Accumulation of Cadmium in a Soil-Crop System in a Typical Karst Area of Guangxi Province, China].

Huan Jing Ke Xue 2021 Mar;42(3):1514-1522

Institute of Geophysical & Geochemical Exploration, Chinese Academy of Geological Sciences, Langfang 065000, China.

To understand the main factors influencing the translocation and accumulation of cadmium (Cd) in soil-crop systems in typical karst areas, 68 sets of paddy soil and rice grain samples were collected in Guangxi Province. These were used to analyze Cd concentrations and soil properties (pH, organic matter (OM) content, oxide content, and texture). Spearman's correlation coefficients and principal component analysis (PCA) were used to examine the effects of soil properties on Cd concentrations and identify the main influencing factors. The studied soils were highly enriched in iron oxide (TFeO), aluminum oxide (AlO), and manganese oxide (MnO) compared to background levels, with average concentrations of 20.2%, 19.0%, and 0.2%, respectively. However, the soils are relatively depleted in silica (SiO), with an average concentration of 41.0%. The soils are strongly weathered and leached in study area, giving rise to rich occurrences of Fe-Mn nodules. The concentrations of TFeO and MnO in the study soils were significantly correlated with soil Cd, rice seed Cd, and the Cd bioconcentration factor (BCF). The PCA analysis further showed that TFeO and MnO in soils were the main factors affecting the migration and enrichment of Cd while soil pH, OM, and AlO had less of an influence. Furthermore, SiO and soil texture indirectly affected the migration and enrichment of Cd. It is suggested that the Fe-Mn nodules effectively adsorb and immobilize Cd in the study area soils, acting as a heavy metal scavenger that reduced the biological accessibility of Cd.
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http://dx.doi.org/10.13227/j.hjkx.202007138DOI Listing
March 2021

The CREB Regulated Transcription Coactivator 2 Suppresses HIV-1 Transcription by Preventing RNA Pol II from Binding to HIV-1 LTR.

Virol Sin 2021 Mar 15. Epub 2021 Mar 15.

Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical School, Beijing, 100050, China.

The CREB-regulated transcriptional co-activators (CRTCs), including CRTC1, CRTC2 and CRTC3, enhance transcription of CREB-targeted genes. In addition to regulating host gene expression in response to cAMP, CRTCs also increase the infection of several viruses. While human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) promoter harbors a cAMP response element and activation of the cAMP pathway promotes HIV-1 transcription, it remains unknown whether CRTCs have any effect on HIV-1 transcription and HIV-1 infection. Here, we reported that CRTC2 expression was induced by HIV-1 infection, but CRTC2 suppressed HIV-1 infection and diminished viral RNA expression. Mechanistic studies revealed that CRTC2 inhibited transcription from HIV-1 LTR and diminished RNA Pol II occupancy at the LTR independent of its association with CREB. Importantly, CRTC2 inhibits the activation of latent HIV-1. Together, these data suggest that in response to HIV-1 infection, cells increase the expression of CRTC2 which inhibits HIV-1 gene expression and may play a role in driving HIV-1 into latency.
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http://dx.doi.org/10.1007/s12250-021-00363-1DOI Listing
March 2021

The Interactive Effect of Prepregnancy Overweight/Obesity and Isolated Maternal Hypothyroxinemia on Macrosomia.

J Clin Endocrinol Metab 2021 Jun;106(7):e2639-e2646

The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Context: Prepregnancy overweight/obesity (OWO) and isolated maternal hypothyroxinemia (IMH) may increase the risk of macrosomia, but little is known about their potential combined effect on macrosomia.

Objective: The aim of this study was to assess whether prepregnancy OWO and first-trimester IMH have a synergistic effect on the risk of macrosomia.

Methods: A large prospective cohort study in a Chinese population from January 2016 to December 2018 in a tertiary care center. In total, 34 930 pregnant women were included. The main outcome measure was macrosomia.

Results: A total of 34 930 participants comprising IMH and euthyroid cases was included in this study. Prepregnancy OWO and first-trimester IMH were independently associated with an increased risk of macrosomia (adjusted odds ratio [OR] 2.48, 95% CI 2.22, 2.78, and adjusted OR 1.65, 95% CI 1.34, 2.01, respectively). The coexistence of prepregnancy OWO and IMH was associated with macrosomia, with an adjusted OR of 5.26 (95% CI 3.9, 7.0) compared with pregnant women without either condition. The additive interaction between prepregnancy OWO and IMH was found to be significant with regard to macrosomia.

Conclusion: Prepregnancy OWO and IMH in the first trimester may synergistically increase the risk of macrosomia.
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http://dx.doi.org/10.1210/clinem/dgab171DOI Listing
June 2021

Structural Basis for Selective Oxidation of Phosphorylated Ethylphenols by Cytochrome P450 Monooxygenase CreJ.

Appl Environ Microbiol 2021 05 11;87(11). Epub 2021 May 11.

Shandong Provincial Key Laboratory of Synthetic Biology, CAS Key Laboratory of Biofuels, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao, Shandong, China

Selective oxidation of C-H bonds in alkylphenols holds great significance for not only structural derivatization in pharma- and biomanufacturing but also biological degradation of these toxic chemicals in environmental protection. A unique chemomimetic biocatalytic system using enzymes from a -cresol biodegradation pathway has recently been developed. As the central biocatalyst, the cytochrome P450 monooxygenase CreJ oxidizes diverse - and -alkylphenol phosphates with perfect stereoselectivity at different efficiencies. However, the mechanism of regio- and stereoselectivity of this chemomimetic biocatalytic system remained unclear. Here, using - and -ethylphenol substrates, we elucidate the CreJ-catalyzed key steps for selective oxidations. The crystal structure of CreJ in complex with -ethylphenol phosphate was solved and compared with its complex structure with -ethylphenol phosphate isomer. The results indicate that the conformational changes of substrate-binding residues are slight, while the substrate promiscuity is achieved mainly by the available space in the catalytic cavity. Moreover, the catalytic preferences of regio- and stereoselective hydroxylation for the two ethylphenol substrates is explored by molecular dynamics simulations. The ethyl groups in the complexes display different flexibilities, and the distances of the active oxygen to H and H of methylene agree with the experimental stereoselectivity. The regioselectivity can be explained by the distances and bond dissociation energy. These results provide not only the mechanistic insights into CreJ regio- and stereoselectivity but also the structural basis for further P450 enzyme design and engineering. The key cytochrome P450 monooxygenase CreJ showed excellent regio- and stereoselectivity in the oxidation of various alkylphenol substrates. C-H bond functionalization of these toxic alkylphenols holds great significance for both biological degradation of these environmental chemicals and production of value-added structural derivatives in pharmaceutical and biochemical industries. Our results, combined with enzymatic assays, crystal structure determination of enzyme-substrate complex, and molecular dynamics simulations, provide not only significant mechanism elucidation of the regio- and stereoselective catalyzation mediated by CreJ but also the promising directions for future engineering efforts of this enzyme toward more useful products. It also has great extendable potential to couple this multifunctional P450 enzyme with other biocatalysts (e.g., hydroxyl-based glycosylase) to access more alkylphenol-derived high-value chemicals through environment-friendly biocatalysis and biotransformation.
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http://dx.doi.org/10.1128/AEM.00018-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208161PMC
May 2021

Biological mechanisms of growth performance and meat quality in porcine muscle tissue.

Anim Biotechnol 2021 Mar 11:1-9. Epub 2021 Mar 11.

Yunnan Key Laboratory of Animal Nutrition and Feed Science, Yunnan Agricultural University, Kunming, China.

Growth performance and meat quality are important traits for pig production. The aim of the present study was to investigate the molecular mechanisms underlying growth performance and meat quality, and to identify novel target molecules for predicting the growth performance and meat quality. The differentially expressed genes (DEGs) in Diannan small ears pigs (DSP) and Landrace pigs (LP) were assessed by RNA-sequencing analyzing technology. A total of 339 DEGs were obtained between DSP and LP. 146 DEGs were upregulated in LP compared with DSP and 193 DEGs were upregulated in DSP compared with LP. The DEGs were significantly enriched in 26 GO and 3 KEGG pathways. The protein-protein interaction (PPI) network with 201 nodes and 382 edges was constructed and 5 modules were extracted from the entire network. The identified upregulated expression of genes involved in glycolysis and myogenesis as well as extracellular matrix may be associated with fast body and muscle deposition rates in LP. Increased expression of genes involved in PPAR signaling pathway and fatty acid metabolism as well as oxidative phosphate processes could be related to the intramuscular fat deposition and meat quality in DSP. The present study may provide an improved understanding of the growth performance and meat quality.
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http://dx.doi.org/10.1080/10495398.2021.1886939DOI Listing
March 2021
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