Publications by authors named "Zhichao Zhang"

226 Publications

Specific interaction of an RNA-binding protein with the 3'-UTR of its target mRNA is critical to oomycete sexual reproduction.

PLoS Pathog 2021 Oct 14;17(10):e1010001. Epub 2021 Oct 14.

Department of Plant Pathology, Nanjing Agricultural University, Nanjing, Jiangsu, China.

Sexual reproduction is an essential stage of the oomycete life cycle. However, the functions of critical regulators in this biological process remain unclear due to a lack of genome editing technologies and functional genomic studies in oomycetes. The notorious oomycete pathogen Pythium ultimum is responsible for a variety of diseases in a broad range of plant species. In this study, we revealed the mechanism through which PuM90, a stage-specific Puf family RNA-binding protein, regulates oospore formation in P. ultimum. We developed the first CRISPR/Cas9 system-mediated gene knockout and in situ complementation methods for Pythium. PuM90-knockout mutants were significantly defective in oospore formation, with empty oogonia or oospores larger in size with thinner oospore walls compared with the wild type. A tripartite recognition motif (TRM) in the Puf domain of PuM90 could specifically bind to a UGUACAUA motif in the mRNA 3' untranslated region (UTR) of PuFLP, which encodes a flavodoxin-like protein, and thereby repress PuFLP mRNA level to facilitate oospore formation. Phenotypes similar to PuM90-knockout mutants were observed with overexpression of PuFLP, mutation of key amino acids in the TRM of PuM90, or mutation of the 3'-UTR binding site in PuFLP. The results demonstrated that a specific interaction of the RNA-binding protein PuM90 with the 3'-UTR of PuFLP mRNA at the post-transcriptional regulation level is critical for the sexual reproduction of P. ultimum.
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http://dx.doi.org/10.1371/journal.ppat.1010001DOI Listing
October 2021

Identification of the Specific Spoilage Organism in Farmed Sturgeon () Fillets and Its Associated Quality and Flavour Change during Ice Storage.

Foods 2021 Aug 28;10(9). Epub 2021 Aug 28.

Beijing Laboratory for Food Quality and Safety, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China.

Hybrid sturgeon, a popular commercial fish, plays important role in the aquaculture in China, while its spoilage during storage significantly limits the commercial value. In this study, the specific spoilage organisms (SSOs) from ice stored-sturgeon fillet were isolated and identified by analyzing their spoilage related on sensory change, microbial growth, and biochemical properties, including total volatile base nitrogen (TVBN), thiobarbituric acid reactive substances (TBARS), and proteolytic degradation. In addition, the effect of the SSOs on the change of volatile flavor compounds was evaluated by solid phase microextraction (SPME) and gas chromatography-mass spectrometry (GC-MS). The results showed that the , , and were the main SSOs in the ice stored-sturgeon fillet, and significantly affect the odors by changing the volatile compounds in the sturgeon. Compared with the fresh sturgeon, the appreciable increase of polycyclic aromatic hydrocarbons and tetramethyl-pyrazine might be the spoilage indicators of the sturgeon contaminated by ; the appreciable increase of 1-octen-3-ol and (z)-2-penten-1-o might be the potential marker of the sturgeon contaminated by ; and the appreciable increase of 1-(3,3-dimethylbicyclo [2.2.1] hept-2-yl)-ethanon and butylated hydroxytoluene were associated with . This study reveals the relationship between the SSOs and flavor changes in sturgeon fillets, which will contribute to the sturgeon preservation and shelf-life extension.
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http://dx.doi.org/10.3390/foods10092021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8469357PMC
August 2021

Glypican 4 Regulates Aβ Internalization in Neural Stem Cells Partly Low-Density Lipoprotein Receptor-Related Protein 1.

Front Cell Neurosci 2021 6;15:732429. Epub 2021 Sep 6.

Institute of Neurobiology, Department of Neurobiology, Xi'an Jiaotong University Health Science Center, Xi'an, China.

Neural stem cell (NSC) damage has been reported in patients with Alzheimer's disease. Intracellular Aβ plays a vital role in NSC damage. Heparan sulfate proteoglycans are potent mediators of Aβ enrichment in the brain. We hypothesized the heparan sulfate proteoglycan glypican 4 (Gpc4) regulates Aβ internalization by NSCs. We evaluated Gpc4 expression in NSCs from P0-P2 generations using immunofluorescence. Adenovirus and lentivirus were used to regulate Gpc4 expression in NSCs and APP/PS1 mice, respectively. Co-immunoprecipitation was used to determine the relationship between Gpc4, Aβ, and low-density lipoprotein receptor-related protein 1 (LRP1). Intracellular Aβ concentrations were detected using enzyme-linked immunosorbent assay and immunofluorescence. The role of Gpc4/LRP1 on toxic/physical Aβ-induced effects was evaluated using the JC-1 kit, terminal deoxynucleotidyl transferase dUPT nick end labeling, and western blotting. Gpc4 was stably expressed in NSCs, neurons, and astrocytes. Gpc4 was upregulated by Aβ in NSCs and regulated Aβ internalization. Gpc4 attenuation reduced Aβ uptake; Gpc4 overexpression increased Aβ uptake. Gpc4 regulated Aβ internalization through LRP1 and contributed to Aβ internalization and toxic/physical concentrations of Aβ-induced mitochondrial membrane potential and cell apoptosis, partly LRP1. Therefore, Gpc4 is a key regulator of Aβ enrichment in NSCs. Inhibiting Gpc4 rescued the Aβ-induced toxic effect and attenuated the nontoxic Aβ enrichment into intracellular toxic concentrations. Gpc4 contributed to Aβ internalization and toxic/physical concentrations of Aβ-induced mitochondrial membrane potential damage and cell apoptosis, partly LRP1. These findings suggest a potential role of Gpc4 in treating Alzheimer's disease at an early stage, by targeting NSCs.
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http://dx.doi.org/10.3389/fncel.2021.732429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8450433PMC
September 2021

Wet-Milling Synthesis of Superionic Lithium Argyrodite Electrolytes with Different Concentrations of Lithium Vacancy.

ACS Appl Mater Interfaces 2021 Oct 22;13(39):46644-46649. Epub 2021 Sep 22.

Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo 315201, P. R. China.

The ionic conductivities of argyrodite electrolytes are significantly affected by the concentrations of lithium vacancy. Herein, a facile and rapid synthesis route is proposed to systematically investigate LiPSCl (0 ≤ ≤ 0.8) with different lithium vacancies by adjusting ratios of S/Cl. The highest ionic conductivity of the wet-milling synthesized LiPSCl is 6.18 mS cm, which is attributed to higher lithium vacancy concentration and lower electrostatic interaction for ion migration. The Li/LiPSCl/Li symmetric cell cycles stably for 2000 h at 0.1 mA cm, showing excellent dendrite suppression capability. Moreover, the initial discharge capacity of LiCoO/LiPSCl/Li all-solid-state battery is 126.0 mAh g at 0.1C and the capacity retention is 83% after 50 cycles. The wet-milling method provides the possibility for rapid exploration and preparation of other argyrodite electrolytes in the future.
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http://dx.doi.org/10.1021/acsami.1c13031DOI Listing
October 2021

Improved Whole-Genome Sequence of Fusarium meridionale, the Fungal Pathogen Causing Fusarium Head Blight in Rice.

Mol Plant Microbe Interact 2021 Sep 17. Epub 2021 Sep 17.

Institute of Food Safey and Nutrition, Jiangsu Academy of Agricultural Sciences, Nanjing, China;

Members of the Fusarium graminearum species complex (FGSC) cause extensive yield losses in cereal production worldwide and food safety concerns due to the accumulation of Fusarium toxins in infected grains. Among these pathogens, F. meridionale is responsible for Fusarium head blight of wheat and rice, ear and stalk rot of maize, and pod blight of soybean. Here, we present an improved genome assembly of F. meridionale strain SR5 isolated from rice in China based on PacBio long-read sequencing and Illumina short-read sequencing technology. The assembled genome of SR5 has a total size of 36.82 Mb, an N50 scaffold length of 7.82 Mb, 9 scaffolds and encodes 12,409 predicted genes. These high-quality data expand FGSC genomic resources and provide a valuable resource for better understanding their genetic diversity and the molecular basis of pathogenesis, which will facilitate the development of an effective control strategy.
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http://dx.doi.org/10.1094/MPMI-07-21-0182-ADOI Listing
September 2021

Comprehensive analysis of pivotal biomarkers, immune cell infiltration and therapeutic drugs for steroid-induced osteonecrosis of the femoral head.

Bioengineered 2021 12;12(1):5971-5984

Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan China.

Steroid-induced osteonecrosis of the femoral head (SONFH) is a progressive disease that leads to an increased disability rate. This study aimed to ascertain biomarkers, infiltrating immune cells, and therapeutic drugs for SONFH. The gene expression profile of the GSE123568 dataset was downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified using the NetworkAnalyst platform. Functional enrichment, protein-protein interaction network (PPI), and module analyses were performed using Metascape tools. An immune cell abundance identifier was used to explore immune cell infiltration. Furthermore, hub genes were identified based on maximal clique centrality (MCC) evaluation using cytoHubba application and confirmed by qRT-PCR using clinical samples. Finally, the L1000 platform was used to determine potential drugs for SONFH treatment. The SONFH mouse model was used to determine the therapeutic effects of aspirin. In total, 429 DEGs were identified in SONFH samples. Functional enrichment analysis showed that these DEGs were enriched in myeloid leukocyte activation and osteoclast differentiation processes. A set of nine immune cell types was confirmed to be markedly different between the SONFH and control samples. All 10 hub genes were significantly highly expressed in the serum of SONFH patients, as shown by qRT-PCR. Finally, the therapeutic effect of aspirin on SONFH was examined in animal experiments. Taken together, our data revealed the hub genes and infiltrating immune cells in SONFH, and we also screened potential drugs for use in SONFH treatment.
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http://dx.doi.org/10.1080/21655979.2021.1972081DOI Listing
December 2021

The Impact of Host Genotype, Intestinal Sites and Probiotics Supplementation on the Gut Microbiota Composition and Diversity in Sheep.

Biology (Basel) 2021 Aug 12;10(8). Epub 2021 Aug 12.

Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.

Three sampling strategies with a 16s rRNA high-throughput sequencing and gene expression assay (by RT-PCR) were designed, to better understand the host and probiotics effect on gut microbiota in sheep. Sampling: (1) colon contents and back-fat tissues from small-tailed Han sheep (SHS), big-tailed Hulun Buir sheep (BHBS), and short-tailed Steppe sheep (SHBS) ( = 12, 14, 12); (2) jejunum, cecum and colon contents, and feces from Tan sheep (TS, = 6); (3) feces from TS at 4 time points (nonfeeding, 30 and 60 feeding days, and stop feeding 30 days) with probiotics supplementation ( = 7). The results indicated SHS had the highest abundance, the thinnest back-fat, and the lowest expression of , , , , and . Some bacteria orders and families could be potential biomarkers for sheep breeds with a distinct distribution of bacterial abundance, implying the host genotype is predominant in shaping unique microbiota under a shared environment. The microbiota diversity and populations significantly changed after 60 days of feeding but restored to its initial state, with mostly colonies, after 30 days ceased. The microbiota composition was greatly different between the small and large intestines, but somewhat different between the large intestine and feces; feces may be reliable for studying large intestinal microbiota in ruminants.
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http://dx.doi.org/10.3390/biology10080769DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8389637PMC
August 2021

Feeding mice a diet high in oxidized linoleic acid metabolites does not alter liver oxylipin concentrations.

Prostaglandins Leukot Essent Fatty Acids 2021 Sep 24;172:102316. Epub 2021 Jun 24.

Department of Food Science and Technology, College of Agriculture and Environmental Sciences, University of California Davis, Davis, CA, Unites States. Electronic address:

The oxidation of dietary linoleic acid (LA) produces oxidized LA metabolites (OXLAMs) known to regulate multiple signaling pathways in vivo. Recently, we reported that feeding OXLAMs to mice resulted in liver inflammation and apoptosis. However, it is not known whether this is due to a direct effect of OXLAMs accumulating in the liver, or to their degradation into bioactive shorter chain molecules (e.g. aldehydes) that can provoke inflammation and related cascades. To address this question, mice were fed a low or high LA diet low in OXLAMs, or a low LA diet supplemented with OXLAMs from heated corn oil (high OXLAM diet). Unesterified oxidized fatty acids (i.e. oxylipins), including OXLAMs, were measured in liver after 8 weeks of dietary intervention using ultra-high pressure liquid chromatography coupled to tandem mass-spectrometry. The high OXLAM diet did not alter liver oxylipin concentrations compared to the low LA diet low in OXLAMs. Significant increases in several omega-6 derived oxylipins and reductions in omega-3 derived oxylipins were observed in the high LA dietary group compared to the low LA group. Our findings suggest that dietary OXLAMs do not accumulate in liver, and likely exert pro-inflammatory and pro-apoptotic effects via downstream secondary metabolites.
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http://dx.doi.org/10.1016/j.plefa.2021.102316DOI Listing
September 2021

Cyclic Tensile Stress to Rat Thoracolumbar Ligamentum Flavum Inducing the Ossification of Ligamentum Flavum: An In Vivo Experimental Study.

Spine (Phila Pa 1976) 2021 Sep;46(17):1129-1138

Department of Orthopedics, Shanghai Changzheng Hospital, Naval Medical University (Second Military Medical University), Shanghai, People's Republic of China.

Study Design: Western blot, reverse transcription-polymerase chain reaction (RT-PCR), radiological, and histological analyses of the rat ossification of ligamentum flavum (OLF) induced by cyclic tensile stress.

Objective: The aim of this study was to induce the OLF using cyclic tensile stress to rat thoracolumbar ligamentum flavum, and to investigate the possible molecular mechanism of tension-induced OLF.

Summary Of Background Data: Tensile stress has been considered as an important factor leading to the OLF. So far, however, no OLF induced by tension has been reported.

Methods: Forty rats were randomly divided into five equal groups. For control groups, the blank and anesthesia groups were not subjected to tension. For experimental groups, the 4-, 8-, and 12-week groups were subjected to cyclic tensile stress of ligamentum flavum after abdominal anesthesia for 4 weeks, 8 weeks, and 12 weeks, respectively, using an original stress apparatus for rats. The radiological and morphological changes of rat spine, as well as the protein and mRNA expressions of CD44, bone morphogenetic protein-2 (BMP-2), integrin β3, collagen protein type I (COL1), osteopontin (OPN), runt-related transcription factor 2 (RUNX-2), and vascular endothelial growth factor (VEGF), were concerned.

Results: The micro-CT showed OLF in the 4-, 8-, and 12-week group. The axial maximum occupied area of ossifications was 1.42 mm2, 3.35 mm2, and 7.28 mm2, respectively. In histopathology, chondrocytes proliferated in the experimental model; woven bone arose in the 8- and 12-week groups, and was more noticeable in the 12-week group. According to western blot and RT-PCR, the expressions of seven osteogenesis-related molecules were all increased in three experimental groups.

Conclusion: Cyclic tensile stress to the ligamentum flavum in rats can induce the OLF, and the longer the duration, the more visible the osteogenesis. The upregulation and synergism of osteogenesis-related molecules may contribute to the OLF induced by tensile stress.Level of Evidence: N/A.
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http://dx.doi.org/10.1097/BRS.0000000000004087DOI Listing
September 2021

Diketopiperazine Formation from FPGK ( = 1-9) Peptides: Rates of Structural Rearrangements and Mechanisms.

J Phys Chem B 2021 07 16;125(29):8107-8116. Epub 2021 Jul 16.

Department of Chemistry, Indiana University, Bloomington, Indiana, United States.

Peptides with penultimate proline residues undergo isomerization of the Phe-Pro peptide bond followed by spontaneous bond cleavage at the Pro-Xxx bond (where Xxx is another amino acid residue), leading to cleavage of the Pro-Xxx bond and formation of a diketopiperazine (DKP). In this paper, ion mobility spectrometry and mass spectrometry techniques were used to study the dissociation kinetics of nine peptides [Phe-Pro-Gly-Lys ( = 1-9)] in ethanol. Shorter ( = 1-3) peptides are found to be more stable than longer ( = 4-9) peptides. Alanine substitution studies indicate that, when experiments are initiated, the Phe-Pro bond of the = 9 peptide exists exclusively in the configuration, while the = 1-8 peptides appear to exist initially with both - and Phe-Pro configured bonds. Molecular dynamics simulations indicate that intramolecular hydrogen bonding interactions stabilize conformations of shorter peptides, thus inhibiting DKP formation. Similar stabilizing interactions appear less frequently in longer peptides. In addition, in smaller peptides, the N-terminal amino group is more likely to be charged compared to the same group in longer peptides, which would inhibit the dissociation through the DKP formation mechanism. Analysis of temperature-dependent kinetics measurements provides insight about the mechanism of bond cleavage. The analysis gives the following transition state thermochemistry: Δ values range from 94.6 ± 0.9 to 101.5 ± 1.9 kJ·mol, values of Δ range from 89.1 ± 0.9 to 116.7 ± 1.5 kJ·mol, and Δ values range from -25.4 ± 2.6 to 50.8 ± 4.2 J·mol·K. Proposed mechanisms and thermochemistry are discussed.
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http://dx.doi.org/10.1021/acs.jpcb.1c03515DOI Listing
July 2021

Structure-Based Optimization of 3-Phenyl--(2-(3-phenylureido)ethyl)thiophene-2-sulfonamide Derivatives as Selective Mcl-1 Inhibitors.

J Med Chem 2021 07 6;64(14):10260-10285. Epub 2021 Jul 6.

Department of Medicinal Chemistry, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, People's Republic of China.

Selective Mcl-1 inhibitors may overcome the drug resistance caused by current anti-apoptotic Bcl-2 protein inhibitors in tumors with Mcl-1 overexpression. Based on previously discovered compounds with a 3-phenylthiophene-2-sulfonamide core moiety, in this work, we have obtained new compounds with improved binding affinity and/or selectivity under the guidance of structure-based design. The most potent compounds achieved sub-micromolar binding affinities to Mcl-1 ( ∼ 0.4 μM) and good cytotoxicity (IC < 10 μM) on several tumor cells. N-heteronuclear single-quantum coherence NMR spectra suggested that these compounds bound to the BH3-binding groove on Mcl-1. Several cellular assays revealed that as well as its precursor effectively induced caspase-dependent apoptosis, and their target engagement at Mcl-1 was confirmed by co-immunoprecipitation experiments. Treatment with at 50 mg/kg every 2 days on an RS4;11 xenograft mouse model for 22 days led to 75% reduction in tumor volume without body weight loss.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00690DOI Listing
July 2021

Discovery of a Fluorogenic Probe for In Situ Pyruvate Kinase M2 Isoform (PKM2) Labeling through Chemoselective SAr with a Binding Site Lysine Residue.

Anal Chem 2021 07 5;93(28):9669-9676. Epub 2021 Jul 5.

State Key Laboratory of Fine Chemicals, Zhang Dayu School of Chemistry, Dalian University of Technology, Dalian, Liaoning 116024, China.

The key challenge of developing reaction-based turn-on probes is to establish latent electrophilic fluorophores exhibiting high reactivity only upon binding to a specific protein(s). Herein, we identified such a fluorophore, 6-arylthioether-substituted 3-cyano-1-oxo-1-phenalene-2-carboxylate, which chemoselectively labels binding site Cys or Lys residues. Based on this fluorophore, we developed the first reaction-based turn-on pyruvate kinase M2 isoform (PKM2) fluorescent probe , which selectively labels PKM2 with the binding site Lys305. The latent electrophilic reactivity of the fluorophore endows the probe with precise detection of the expression of PKM2 in situ by means of both in-gel fluorescence imaging at the proteome level and real-time no-wash cell imaging approaches, which has the potential to be applied in cancer diagnoses.
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http://dx.doi.org/10.1021/acs.analchem.1c00208DOI Listing
July 2021

Combination of Quercetin and Vitamin E Supplementation Promotes Yolk Precursor Synthesis and Follicle Development in Aging Breeder Hens via Liver-Blood-Ovary Signal Axis.

Animals (Basel) 2021 Jun 28;11(7). Epub 2021 Jun 28.

Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China.

The fertility of female animals is negatively correlated with increasing chronological age. In aging broiler breeder hens, there is a decline in the functionality of the ovary and liver accompanied by hormonal or endocrine changes, a reduction in antioxidant capacity, and a decrease in folliculogenesis. Therefore, improving the reproductive function in aging breeder hens using dietary strategies is of great concern to the poultry breeder. This study evaluated the capacity of dietary quercetin (Q), vitamin E (VE), and their combination (Q + VE) to promote follicle development and attenuate organ inflammation by improving the antioxidant capacity of aging breeder hens. In this study, 400 broiler breeder hens (Tianfu broilers breeder hens, 435 days old) were allotted into four groups (100 birds each) with four replicates each (25 birds each). They were fed diets containing Q (0.4 g/kg), VE (0.2 g/kg), Q + VE (0.4 g/kg + 0.2 g/kg), and a basal diet for 10 weeks. The results showed that Q + VE improved the organ characteristics ( < 0.05), and also that Q + VE showed protective effects on the liver against injury, as well as increasing the antioxidant capacity of the liver, serum, and ovary ( < 0.05). Furthermore, liver lipid synthesis was increased remarkably, as indicated by the changes in triglyceride levels in hens fed Q + VE ( < 0.05). Levels of E2, FSH, and LH, their receptors, and mRNAs related to yolk precursor synthesis were increased by the Q + VE ( < 0.05). Therefore, the combination of quercetin and vitamin E synergistically promotes and regulates the transportation and exchange of synthetic substances among the liver-blood-ovary alliances to ensure the synchronous development and functional coordination between the liver and ovary in aging breeder hens.
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http://dx.doi.org/10.3390/ani11071915DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8300405PMC
June 2021

PAH residue and consumption risk assessment in four commonly consumed wild marine fishes from Zhoushan Archipelago, East China Sea.

Mar Pollut Bull 2021 Sep 26;170:112670. Epub 2021 Jun 26.

Key Laboratory of Health Risk Factors for Seafood of Zhejiang Province, Zhoushan Center for Disease Control and Prevention, Zhoushan 316022, PR China. Electronic address:

The concentration, constitution, distribution, possible sources, and associated consumption risks of polycyclic aromatic hydrocarbons (PAHs) in four marine fishes in the Zhoushan Archipelago were investigated. The concentrations of PAHs in the edible muscle of these four fishes ranged from 34.7 to 108 ng/g wet weight. Four-ring and six-ring PAH congeners constitute the most and least percentages of the total PAHs, respectively. The highest PAH concentrations were found in Mugil cephalus, followed by Sebastiscus marmoratus, Lateolabrax maculatus, and Collichthys lucidus. The highest PAH concentrations were found at the sampling island Liuheng, followed by Gouqi, Qushan, Dongji, and Zhujiajian. PAH concentrations in wet weight were remarkably different among these four fish species but not among different locations. High-molecular-weight congeners predominated the PAH composition pattern in most of the samples. Results showed that the consumption of M. cephalus might have potential carcinogenic risk. This study provided baseline data on PAH concentrations in seafood and consequent human consumption risk.
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http://dx.doi.org/10.1016/j.marpolbul.2021.112670DOI Listing
September 2021

Ectopic BH3-only protein Bim acts as a co-chaperone to positively regulate Hsp70 in yeast.

J Biochem 2021 Jun 29. Epub 2021 Jun 29.

State Key Laboratory of Fine Chemicals, School of Chemistry, Dalian University of Technology, Dalian, China.

The chaperone heat shock protein 70 (Hsp70) is conserved from bacteria to humans and is crucial for avoiding protein misfolding under stress. Bim functions mainly as one of the Bcl-2 family pro-apoptotic members, was identified to be a co-chaperone of Hsp70. Herein, we reported that ectopic Bim could constitute the interactions with intrinsic Hsp70 and translate its positive co-chaperone activity in vitro to the yeast growth promotion and help Hsp70 to fold its client Ras-like protein. With the help of a specific Hsp70/Bim disruptor, we illustrated that Hsp70/Bim dimers rescue yeast from heat shock. In an organism lacks apoptotic Bcl-2 factors, the pro-apoptotic Bim in mammalian cells exhibits pro-survival functions.
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http://dx.doi.org/10.1093/jb/mvab073DOI Listing
June 2021

Bim transfer between Bcl-2-like protein and Hsp70 underlines Bcl-2/Hsp70 crosstalk to regulate apoptosis.

Biochem Pharmacol 2021 Aug 18;190:114660. Epub 2021 Jun 18.

State Key Laboratory of Fine Chemicals, Zhang Dayu School of Chemistry, Dalian University of Technology, Dalian, Liaoning, China. Electronic address:

The chaperone heat shock protein 70 (Hsp70) is crucial for avoiding protein misfolding under stress, but it is also upregulated in many kinds of cancers, where its ability to buffer cellular stress prevents apoptosis. Previous research has suggested that Bim, a BH3-only member of the Bcl-2 family proteins, also serves as a cochaperone for Hsp70, which modulates the folding and stabilization of many Hsp70 oncogenic substrates in tumor cells. However, a definitive demonstration of crosstalk between Bcl-2 and Hsp70 family proteins and molecular mechanism remain unclear. Herein, we examined the effects of pan-Bcl-2 inhibitor S1, Hsp70 inhibitor S1g-6 on the K562, U937, H23, HL-60 cell lines and these inhibitors synergistically induce mitochondrial apoptosis in cancer cell lines. Moreover, we identified that Bim transfer between Bcl-2-like protein and Hsp70 underlines Bcl-2/Hsp70 crosstalk in mitochondrial apoptosis pathway. Thus, the synergy of S1 and S1g-6 to induce a panel of cancer cell lines apoptosis by inhibiting free Bim and facilitating oncogenic client AKT folding and activation. Together, our results demonstrated the combination of Bcl-2 inhibitor and Hsp70 inhibitor showed synergistic effect in cancer cells and the potential to decrease tumor regression.
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http://dx.doi.org/10.1016/j.bcp.2021.114660DOI Listing
August 2021

Identification of crucial genes and pathways associated with prostate cancer in multiple databases.

J Int Med Res 2021 Jun;49(6):3000605211016624

Department of Urology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China.

Objective: Prostate cancer (PCa) is a malignant neoplasm of the urinary system. This study aimed to use bioinformatics to screen for core genes and biological pathways related to PCa.

Methods: The GSE5957 gene expression profiles were obtained from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the DEGs were constructed by R language. Furthermore, protein-protein interaction (PPI) networks were generated to predict core genes. The expression levels of core genes were examined in the Tumor Immune Estimation Resource (TIMER) and Oncomine databases. The cBioPortal tool was used to study the co-expression and prognostic factors of the core genes. Finally, the core genes of signaling pathways were determined using gene set enrichment analysis (GSEA).

Results: Overall, 874 DEGs were identified. Hierarchical clustering analysis revealed that these 24 core genes have significant association with carcinogenesis and development (), , and directly related to the recurrence and prognosis of PCa.

Conclusions: This study identified the core genes and pathways in PCa and provides candidate targets for diagnosis, prognosis, and treatment.
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http://dx.doi.org/10.1177/03000605211016624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182368PMC
June 2021

Potential protective mechanisms of green tea polyphenol EGCG against COVID-19.

Trends Food Sci Technol 2021 Aug 25;114:11-24. Epub 2021 May 25.

State Key Laboratory of Tea Plant Biology and Utilization, School of Tea & Food Science, Anhui Agricultural University, Hefei, 230036, China.

Background: The world is in the midst of the COVID-19 pandemic. In this comprehensive review, we discuss the potential protective effects of (-)-epigallocatechin-3-gallate (EGCG), a major constituent of green tea, against COVID-19.

Scope And Approach: Information from literature of clinical symptoms and molecular pathology of COVID-19 as well as relevant publications in which EGCG shows potential protective activities against COVID-19 is integrated and evaluated.

Key Findings And Conclusions: EGCG, via activating Nrf2, can suppress ACE2 (a cellular receptor for SARS-CoV-2) and TMPRSS2, which mediate cell entry of the virus. Through inhibition of SARS-CoV-2 main protease, EGCG may inhibit viral reproduction. EGCG via its broad antioxidant activity may protect against SARS-CoV-2 evoked mitochondrial ROS (which promote SARS-CoV-2 replication) and against ROS burst inflicted by neutrophil extracellular traps. By suppressing ER-resident GRP78 activity and expression, EGCG can potentially inhibit SARS-CoV-2 life cycle. EGCG also shows protective effects against 1) cytokine storm-associated acute lung injury/acute respiratory distress syndrome, 2) thrombosis via suppressing tissue factors and activating platelets, 3) sepsis by inactivating redox-sensitive HMGB1, and 4) lung fibrosis through augmenting Nrf2 and suppressing NF-κB. These activities remain to be further substantiated in animals and humans. The possible concerted actions of EGCG suggest the importance of further studies on the prevention and treatment of COVID-19 in humans. These results also call for epidemiological studies on potential preventive effects of green tea drinking on COVID-19.
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http://dx.doi.org/10.1016/j.tifs.2021.05.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146271PMC
August 2021

Screening and identification of key genes in imatinib-resistant chronic myelogenous leukemia cells: a bioinformatics study.

Hematology 2021 Dec;26(1):408-414

State Key Laboratory of Fine Chemicals, School of Life Science and Technology, Dalian University of Technology, Dalian, People's Republic of China.

Background: Chronic myelogenous leukemia (CML) is one of the most common cancers in the world. Imatinib is one of the most effective therapeutic strategies to inhibit the BCR-ABL tyrosine Kinase in patients with CML, but resistance is increasingly encountered.

Material And Methods: Microarray data GSE7114, GSE92624 and GSE97562 were downloaded and analyzed from Gene Expression Omnibus (GEO) to identify the candidate genes in the imatinib-resistant CML cells. The differentially expressed genes (DEGs) were appraised, and the protein-protein interaction (PPI) network was created by using STRING and Cytoscape.

Results: We screened a total of 217 DEGs, including 151 upregulated genes and 66 downregulated genes. The enriched functions and pathways of genes include insulin-like growth factor I binding, cysteine-type endopeptidase inhibitor activity involved in apoptotic process, cell adhesion, positive regulation of nitric oxide biosynthetic process and hematopoietic cell lineage. Nine hub genes were appraised and Gene Ontology enrichment analysis revealed that these genes are mainly enriched in cell cycle, peptidase inhibitor activity and cell division. Several genes such as BIRC5, CCNE2 and MCM4 were identified in survival analysis and these genes alteration are significantly associated with worse overall survival and disease-free survival.

Conclusions: These genes have the potential to become surrogate markers for a clinical evaluation of imatinib-resistant CML patients. Our results provide potential target genes for diagnosis and treatment of imatinib-resistant CML patients.
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http://dx.doi.org/10.1080/16078454.2021.1931740DOI Listing
December 2021

Resource-constrained FPGA/DNN co-design.

Neural Comput Appl 2021 May 15:1-11. Epub 2021 May 15.

School of Engineering, Deakin University, Geelong, VIC 3216 Australia.

Deep neural networks (DNNs) have demonstrated super performance in most learning tasks. However, a DNN typically contains a large number of parameters and operations, requiring a high-end processing platform for high-speed execution. To address this challenge, hardware-and-software co-design strategies, which involve joint DNN optimization and hardware implementation, can be applied. These strategies reduce the parameters and operations of the DNN, and fit it into a low-resource processing platform. In this paper, a DNN model is used for the analysis of the data captured using an electrochemical method to determine the concentration of a neurotransmitter and the recoding electrode. Next, a DNN miniaturization algorithm is introduced, involving combined pruning and compression, to reduce the DNN resource utilization. Here, the DNN is transformed to have sparse parameters by pruning a percentage of its weights. The Lempel-Ziv-Welch algorithm is then applied to compress the sparse DNN. Next, a DNN overlay is developed, combining the decompression of the DNN parameters and DNN inference, to allow the execution of the DNN on a FPGA on the PYNQ-Z2 board. This approach helps avoid the need for inclusion of a complex quantization algorithm. It compresses the DNN by a factor of 6.18, leading to about 50% reduction in the resource utilization on the FPGA.
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http://dx.doi.org/10.1007/s00521-021-06113-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8122185PMC
May 2021

Small-molecule inhibitor targeting the Hsp70-Bim protein-protein interaction in CML cells overcomes BCR-ABL-independent TKI resistance.

Leukemia 2021 Oct 18;35(10):2862-2874. Epub 2021 May 18.

State Key Laboratory of Fine Chemicals, Zhang Dayu School of Chemistry, Dalian University of Technology, Dalian, Liaoning, China.

Herein, we screened a novel inhibitor of the Hsp70-Bim protein-protein interaction (PPI), S1g-2, from a Bcl-2 inhibitor library; this compound specifically disrupted the Hsp70-Bim PPI by direct binding to an unknown site adjacent to that of an allosteric Hsp70 inhibitor MKT-077, showing binding affinity in sub-μM concentration range. S1g-2 exhibited overall 5-10-fold higher apoptosis-inducing activity in CML cells, primary CML blasts, and BCR-ABL-transformed BaF3 cells than other cancer cells, normal lymphocytes, and BaF3 cells, illustrating Hsp70-Bim PPI driven by BCR-ABL protects CML through oncoclient proteins that enriched in three pathways: eIF2 signaling, the regulation of eIF4E and p70S6K signaling, and the mTOR signaling pathways. Moreover, S1g-2 progressively enhanced lethality along with the increase in BCR-ABL-independent TKI resistance in the K562 cell lines and is more effective in primary samples from BCR-ABL-independent TKI-resistant patients than those from TKI-sensitive patients. By comparing the underlying mechanisms of S1g-2, MKT-077, and an ATP-competitive Hsp70 inhibitor VER-155008, the Hsp70-Bim PPI was identified to be a CML-specific target to protect from TKIs through the above three oncogenic signaling pathways. The in vivo activity against CML and low toxicity endows S1g-2 a first-in-class promising drug candidate for both TKI-sensitive and resistant CML.
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http://dx.doi.org/10.1038/s41375-021-01283-5DOI Listing
October 2021

Blink-sensing glasses: A flexible iontronic sensing wearable for continuous blink monitoring.

iScience 2021 May 3;24(5):102399. Epub 2021 Apr 3.

Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.

Blink reflex has long been considered closely related to physiological states, from which abundant information on ocular health and activities can be revealed. In this study, a smart glasses wearable has been developed, incorporating a flexible and sensitive pressure sensor, to monitor blink patterns by continuously detecting ocular muscular movements, referred to as blink-sensing glasses. By applying the emerging flexible iontronic sensing (FITS) sensor with the sensitivity of 340 pF/mmHg, the skin pressure variations induced by movements of the orbicularis oculi muscles can be monitored in real time. The blink-sensing glasses can successfully capture blink patterns with a high accuracy of 96.3% and have been used to differentiate the blink features from both dry-eye subjects and healthy controls. This device can be potentially used as a new clinical and research monitoring tool for continuous eye blink analysis, while providing patients with high comfortableness in long-term ambulatory and home settings.
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http://dx.doi.org/10.1016/j.isci.2021.102399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102906PMC
May 2021

Analysis of mutagenic components of oxidative hair dyes with the Ames test.

Hum Exp Toxicol 2021 May 4:9603271211013433. Epub 2021 May 4.

Pharmacology and Toxicology Department, Shanghai Institute for Food and Drug Control, Shanghai, China.

Oxidative hair dyes consist of two components (I and II) that are mixed before use. Aromatic amines in component I and their reaction with hydrogen peroxide after mixing them with component II have been of primary concern. In addition, two genotoxicity assays are still required for the approval of the final products of oxidative hair dyes in China, and the substance in the oxidative hair dye that causes the high rate of positive results in genotoxicity tests, especially the Ames test, has not been fully elucidated. In this study, we analyzed the formulation of 55 different oxidative hair dyes from 7 color series and performed Ames tests in the strain TA98 with the S9 mix (oxidative hair dyes No. 1-30) and in strain TA97a without the S9 mix (oxidative hair dyes No. 31-55). We found that toluene-2,5-diamine sulfate (2,5-diaminotoluene sulfate, DATS) in component I may be the cause of mutagenicity in TA98, and hydrogen peroxide in component II may be the cause of mutagenicity in TA97a, and their positive concentrations were consistent with those that we calculated from Ames tests. The results suggest that the positive results for the oxidative hair dye in the Ames test were inevitable because of the existence of DATS in component I and of hydrogen peroxide in component II. Therefore, we should carry out safety assessments on each raw material and carry out risk assessments on the final products of oxidative hair dyes instead of genotoxicity tests in China.
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http://dx.doi.org/10.1177/09603271211013433DOI Listing
May 2021

Publisher Correction: Triacylglycerols are preferentially oxidized over free fatty acids in heated soybean oil.

NPJ Sci Food 2021 Apr 28;5(1):13. Epub 2021 Apr 28.

Department of Food Science and Technology, College of Agriculture and Environmental Sciences, University of California Davis, Davis, CA, USA.

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http://dx.doi.org/10.1038/s41538-021-00095-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080563PMC
April 2021

A novel Hsp70 inhibitor specifically targeting the cancer-related Hsp70-Bim protein-protein interaction.

Eur J Med Chem 2021 Aug 14;220:113452. Epub 2021 Apr 14.

State Key Laboratory of Fine Chemicals, Zhang Dayu School of Chemistry, Dalian University of Technology, Dalian, Liaoning, 116024, China. Electronic address:

Targeting cancer-related Hsp70-Bim protein-protein interactions (PPIs) offers a new strategy for the design of Hsp70 inhibitors. Herein, we discovered a novel Hsp70 inhibitor, S1g-6, based on the established BH3 mimetics. S1g-6 exhibited sub-μM binding affinity toward Hsp70 and selectively disrupted Hsp70-Bim PPI. The target specificity of S1g-6in situ was validated by affinity-based protein profiling, co-immunoprecipitation, and cell-based shRNA assays. S1g-6 specifically antagonized the ATPase activity of Hsp70 upon recruiting Bim and showed selective apoptosis induction in some cancer cell lines over normal ones through suppression of some oncogenic clients of Hsp70, representing a new class of antitumor candidates. Hsp70-Bim PPI exhibited cancer-dependent role as a potential anti-cancer target.
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http://dx.doi.org/10.1016/j.ejmech.2021.113452DOI Listing
August 2021

Triacylglycerols are preferentially oxidized over free fatty acids in heated soybean oil.

NPJ Sci Food 2021 Apr 1;5(1). Epub 2021 Apr 1.

Department of Food Science and Technology, College of Agriculture and Environmental Sciences, University of California Davis, Davis, CA, USA.

In oil, free fatty acids (FFAs) are thought compared the efficiency of hydrolysis wto be the preferred substrate for lipid oxidation although triacylglycerols (TAGs) are the predominant lipid class. We determined the preferential oxidation substrate (TAGs versus FFAs) in soybean oil heated at 100 °C for 24 h, after validating a method for quantifying esterified and free lipid oxidation products (i.e., oxylipins) with mass-spectrometry. Reaction velocities and turnover (velocity per unit substrate) of FFA, and free and TAG-bound (esterified) oxylipins were determined. FFA hydrolysis rate and turnover were orders of magnitude greater (16-4217 fold) than that of esterified and free oxylipin formation. The velocity and turnover of TAG-bound oxylipins was significantly greater than free oxylipins by 282- and 3-fold, respectively. The results suggest that during heating, TAGs are preferentially oxidized over FFAs, despite the rapid hydrolysis and availability of individual FFAs as substrates for oxidation. TAG-bound oxylipins may serve as better markers of lipid oxidation.
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http://dx.doi.org/10.1038/s41538-021-00086-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016982PMC
April 2021

Improved Whole-Genome Sequence of Generated by Long-Read Sequencing.

Mol Plant Microbe Interact 2021 Jul 24;34(7):866-869. Epub 2021 Aug 24.

Shanghai Key Laboratory of Plant Molecular Sciences, College of Life Sciences, Shanghai Normal University, Shanghai 200234, China.

The soilborne oomycete is the most destructive pathogen of vegetable crops and is responsible for substantial economic losses worldwide. Here, we present an improved genome assembly of generated by Oxford Nanopore long-read sequencing (for de novo assembly) and Illumina short-read sequencing (for polishing). The genome of is 100.5 Mb in length (GC content = 50.8%) and contains 26,069 predicted protein-coding genes. The whole genome of is assembled into 194 scaffolds, 90% of which are larger than 300 kb. The N scaffold length and maximum scaffold length are 1.0 and 4.1 Mb, respectively. The whole-genome sequence of will broaden our knowledge of this pathogen and enhance our understanding of the molecular basis of its pathogenicity, which will facilitate the development of effective management strategies.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.
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http://dx.doi.org/10.1094/MPMI-12-20-0356-ADOI Listing
July 2021

Genome Sequence Resource of YC2-1, a Fungal Pathogen Causing Phomopsis Stem Blight in Soybean.

Mol Plant Microbe Interact 2021 Jul 15;34(7):842-844. Epub 2021 Aug 15.

Department of Plant Pathology, Nanjing Agricultural University, Nanjing, Jiangsu 210095, China.

- disease complex causes considerable yield losses in soybean production worldwide. As one of the major pathogens, T. W. Hobbs (syn. ) is not only the primary agent of Phomopsis seed decay but is also one of the agents of Phomopsis pod and stem blight and Phomopsis stem canker. We performed both PacBio long-read sequencing and Illumina short-read sequencing and obtained a genome assembly for the strain YC2-1, which was isolated from soybean stem with Phomopsis stem blight disease. The 63.1 Mb genome assembly contains 87 scaffolds, with a minimum, maximum, and N scaffold length of 20 kb, 4.6 Mb, and 1.5 Mb respectively, and a total of 17,407 protein-coding genes. The high-quality data expand the genomic resource of species and will provide a solid foundation for a better understanding of their genetic diversity and pathogenic mechanisms.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.
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http://dx.doi.org/10.1094/MPMI-12-20-0340-ADOI Listing
July 2021

Multiple chiroptical switches and logic circuit based on salicyl‒ imine‒chitosan hydrogel.

Carbohydr Polym 2021 Apr 30;257:117534. Epub 2020 Dec 30.

College of Chemistry and Chemical Engineering, Cangzhou Normal University, Cangzhou, 061001, PR China.

A chitosan-based chiral hydrogel was fabricated by grafting achiral salicylaldehyde (SA) on chitosan chains, followed by supramolecular assembly (CS-SA hydrogel hereafter). The structures and properties of the CS-SA hydrogel were characterized and investigated. The results indicated that the swelling ability of the CS-SA hydrogel depended on the medium pH and crosslinking degree. Circular dichroism measurements revealed that the chiral information of the chitosan was successfully transcribed to the achiral salicylic chromophores through imine bonds. Chiroptical switches based on acid-base responses of the imine bond and the OH fragment of SA and the swelling properties of the CS-SA hydrogel were fabricated, which is first reported for a chitosan-based hydrogel. In addition, a gel film showed good fatigue resistance under external stimuli. IMPLICATION, INHIBIT, and PASS logic gates and a logic circuit based on the chiroptical switches were successfully designed. This study suggests a new method of constructing biobased chiral functional materials.
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http://dx.doi.org/10.1016/j.carbpol.2020.117534DOI Listing
April 2021

Plant Disease Detection using Generated Leaves Based on DoubleGAN.

IEEE/ACM Trans Comput Biol Bioinform 2021 Feb 3;PP. Epub 2021 Feb 3.

Plant leaves can be used to effectively detect plant diseases. However, the number of images of unhealthy leaves collected from various plants is usually unbalanced. It is difficult to detect diseases using such an unbalanced dataset. We used DoubleGAN (a double generative adversarial network) to generate images of unhealthy plant leaves to balance such datasets. We proposed using DoubleGAN to generate high-resolution images of unhealthy leaves using fewer samples. DoubleGAN is divided into two stages. In stage 1, we used healthy leaves and unhealthy leaves as inputs. First, the healthy leaf images were used as inputs for the WGAN (Wasserstein generative adversarial network) to obtain the pretrained model. Then, unhealthy leaves were used for the pretrained model to generate 64*64 pixel images of unhealthy leaves. In stage 2, a superresolution generative adversarial network (SRGAN) was used to obtain corresponding 256*256 pixel images to expand the unbalanced dataset. Finally, compared with images generated by DCGAN (Deep convolution generative adversarial network). The dataset expanded with DoubleGAN, the generated images are clearer than DCGAN, and the accuracy of plant species and disease recognition reached 99.80% and 99.53%, respectively. The recognition results are better than those from the original dataset.
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http://dx.doi.org/10.1109/TCBB.2021.3056683DOI Listing
February 2021
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