Publications by authors named "Zhong Jin"

330 Publications

Development of a New Reverse Genetics System for Ebola Virus.

mSphere 2021 May 5;6(3). Epub 2021 May 5.

Unit of Viral Hepatitis, CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Shanghai, China

Ebola virus (EBOV) is a highly pathogenic negative-stranded RNA virus that has caused several deadly endemics in the past decades. EBOV reverse genetics systems are available for studying live viruses under biosafety level 4 (BSL-4) or subviral particles under BSL-2 conditions. However, these systems all require cotransfection of multiple plasmids expressing viral genome and viral proteins essential for EBOV replication, which is technically challenging and unable to naturally mimic virus propagation using the subviral particle. Here, we established a new EBOV reverse genetics system only requiring transfection of a single viral RNA genome into an engineered cell line that stably expresses viral nucleoprotein (NP), viral protein 35 (VP35), VP30, and large (L) proteins and has been fine-tuned for its superior permissiveness for EBOV replication. Using this system, subviral particles expressing viral VP40, glycoprotein (GP), and VP24 could be produced and continuously propagated and eventually infect the entire cell population. We demonstrated the authentic response of the subviral system to antivirals and uncovered that the VP35 amount is critical for optimal virus replication. Furthermore, we showed that fully infectious virions can be efficiently rescued by delivering the full-length EBOV genome into the same supporting cell, and the efficiency is not affected by genome polarity or virus variant specificity. In summary, our work provides a new tool for studying EBOV under different biosafety levels. Ebola virus is among the most dangerous viral pathogens, with a case fatality rate of up to 90%. Since 2013, the two largest and most complex Ebola outbreaks in Africa have revealed the lack of investigation on this notorious virus. A reverse genetics system is an important tool for studying viruses by producing mutant viruses or generating safer and convenient model systems. Here, we developed an EBOV life cycle modeling system in which subviral particles can spontaneously propagate in cell culture. In addition, this system can be employed to rescue infectious virions of homologous or heterologous EBOV isolates using either sense or antisense viral RNA genomes. In summary, we developed a new tool for EBOV research.
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http://dx.doi.org/10.1128/mSphere.00235-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103987PMC
May 2021

Bacteriocins: Potential for Human Health.

Oxid Med Cell Longev 2021 10;2021:5518825. Epub 2021 Apr 10.

State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.

Due to the challenges of antibiotic resistance to global health, bacteriocins as antimicrobial compounds have received more and more attention. Bacteriocins are biosynthesized by various microbes and are predominantly used as food preservatives to control foodborne pathogens. Now, increasing researches have focused on bacteriocins as potential clinical antimicrobials or immune-modulating agents to fight against the global threat to human health. Given the broad- or narrow-spectrum antimicrobial activity, bacteriocins have been reported to inhibit a wide range of clinically pathogenic and multidrug-resistant bacteria, thus preventing the infections caused by these bacteria in the human body. Otherwise, some bacteriocins also show anticancer, anti-inflammatory, and immune-modulatory activities. Because of the safety and being not easy to cause drug resistance, some bacteriocins appear to have better efficacy and application prospects than existing therapeutic agents do. In this review, we highlight the potential therapeutic activities of bacteriocins and suggest opportunities for their application.
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http://dx.doi.org/10.1155/2021/5518825DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055394PMC
May 2021

UNC93B1 curbs cytosolic DNA signaling by promoting STING degradation.

Eur J Immunol 2021 Apr 10. Epub 2021 Apr 10.

Unit of Viral Hepatitis, Institut Pasteur of Shanghai, CAS Key Laboratory of Molecular Virology and Immunology, Chinese Academy of Sciences, Shanghai, China.

UNC93B1 is a trafficking chaperone of endosomal Toll-like receptors (TLRs) and plays an essential role in the TLR-mediated innate signaling. However, whether it is also involved in other innate immune sensing or cellular pathways remains largely unexplored. Here we investigated the role of UNC93B1 in cytosolic DNA-triggered cGAS-STING signaling in mouse and human cell lines. We showed that while UNC93B1 deficiency blunts the signal transduction by TLR3, it augments innate immune responses to cytosolic DNA stimulation and DNA virus infection. Mechanistic study reveals a distinct action of UNC93B1 upon STING, but not other parts along the cGAS-STING-TBK1 axis, through regulating the protein level of STING at both resting and cytosolic DNA-stimulated conditions. UNC93B1 can directly interact and traffic along with STING, and the disruption of this interaction causes accumulation of STING that subsequently leads to augmented signaling responses upon its activation. These findings reveal a new function of UNC93B1 in negatively regulating STING-mediated signaling responses.
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http://dx.doi.org/10.1002/eji.202048901DOI Listing
April 2021

Inhibitor Development against p7 Channel in Hepatitis C Virus.

Molecules 2021 Mar 3;26(5). Epub 2021 Mar 3.

State Key Laboratory of Molecular Biology, Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 333 Haike Road, Shanghai 201203, China.

Hepatitis C Virus (HCV) is the key cause of chronic and severe liver diseases. The recent direct-acting antiviral agents have shown the clinical success on HCV-related diseases, but the rapid HCV mutations of the virus highlight the sustaining necessity to develop new drugs. p7, the viroporin protein from HCV, has been sought after as a potential anti-HCV drug target. Several classes of compounds, such as amantadine and rimantadine have been testified for p7 inhibition. However, the efficacies of these compounds are not high. Here, we screened some novel p7 inhibitors with amantadine scaffold for the inhibitor development. The dissociation constant (d) of 42 ARD-series compounds were determined by nuclear magnetic resonance (NMR) titrations. The efficacies of the two best inhibitors, ARD87 and ARD112, were further confirmed using viral production assay. The binding mode analysis and binding stability for the strongest inhibitor were deciphered by molecular dynamics (MD) simulation. These ARD-series compounds together with 49 previously published compounds were further analyzed by molecular docking. Key pharmacophores were identified among the structure-similar compounds. Our studies suggest that different functional groups are highly correlated with the efficacy for inhibiting p7 of HCV, in which hydrophobic interactions are the dominant forces for the inhibition potency. Our findings provide guiding principles for designing higher affinity inhibitors of p7 as potential anti-HCV drug candidates.
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http://dx.doi.org/10.3390/molecules26051350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961618PMC
March 2021

Comparative analysis reveals the species-specific genetic determinants of ACE2 required for SARS-CoV-2 entry.

PLoS Pathog 2021 03 24;17(3):e1009392. Epub 2021 Mar 24.

Center for Infectious Disease Research, School of Medicine, Tsinghua University, Beijing, China.

Coronavirus interaction with its viral receptor is a primary genetic determinant of host range and tissue tropism. SARS-CoV-2 utilizes ACE2 as the receptor to enter host cell in a species-specific manner. We and others have previously shown that ACE2 orthologs from New World monkey, koala and mouse cannot interact with SARS-CoV-2 to mediate viral entry, and this defect can be restored by humanization of the restrictive residues in New World monkey ACE2. To better understand the genetic determinants behind the ability of ACE2 orthologs to support viral entry, we compared koala and mouse ACE2 sequences with that of human and identified the key residues in koala and mouse ACE2 that restrict viral receptor activity. Humanization of these critical residues rendered both koala and mouse ACE2 capable of binding the spike protein and facilitating viral entry. Our study shed more lights into the genetic determinants of ACE2 as the functional receptor of SARS-CoV-2, which facilitates our understanding of viral entry.
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http://dx.doi.org/10.1371/journal.ppat.1009392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990223PMC
March 2021

A novel cell culture system modeling the SARS-CoV-2 life cycle.

PLoS Pathog 2021 03 12;17(3):e1009439. Epub 2021 Mar 12.

School of Medicine, Tsinghua University, Beijing, China.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the global pandemic of COVID-19. SARS-CoV-2 is classified as a biosafety level-3 (BSL-3) agent, impeding the basic research into its biology and the development of effective antivirals. Here, we developed a biosafety level-2 (BSL-2) cell culture system for production of transcription and replication-competent SARS-CoV-2 virus-like-particles (trVLP). This trVLP expresses a reporter gene (GFP) replacing viral nucleocapsid gene (N), which is required for viral genome packaging and virion assembly (SARS-CoV-2 GFP/ΔN trVLP). The complete viral life cycle can be achieved and exclusively confined in the cells ectopically expressing SARS-CoV or SARS-CoV-2 N proteins, but not MERS-CoV N. Genetic recombination of N supplied in trans into viral genome was not detected, as evidenced by sequence analysis after one-month serial passages in the N-expressing cells. Moreover, intein-mediated protein trans-splicing approach was utilized to split the viral N gene into two independent vectors, and the ligated viral N protein could function in trans to recapitulate entire viral life cycle, further securing the biosafety of this cell culture model. Based on this BSL-2 SARS-CoV-2 cell culture model, we developed a 96-well format high throughput screening for antivirals discovery. We identified salinomycin, tubeimoside I, monensin sodium, lycorine chloride and nigericin sodium as potent antivirals against SARS-CoV-2 infection. Collectively, we developed a convenient and efficient SARS-CoV-2 reverse genetics tool to dissect the virus life cycle under a BSL-2 condition. This powerful tool should accelerate our understanding of SARS-CoV-2 biology and its antiviral development.
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http://dx.doi.org/10.1371/journal.ppat.1009439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990224PMC
March 2021

Nanocapillarity and Nanoconfinement Effects of Pipet-like [email protected] Nanotubes for Highly Efficient Electrocatalytic CO Reduction.

Nano Lett 2021 Mar 12;21(6):2650-2657. Epub 2021 Mar 12.

MOE Key Laboratory of Mesoscopic Chemistry, MOE Key Laboratory of High Performance Polymer Materials and Technology, Jiangsu Key Laboratory of Advanced Organic Materials, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China.

Electrocatalytic CO reduction reaction is regarded as an intriguing route for producing renewable chemicals and fuels, but its development is limited by the lack of highly efficient and stable electrocatalysts. Herein, we propose the pipet-like bismuth (Bi) nanorods semifilled in nitrogen-doped carbon nanotubes ([email protected]) for highly selective electrocatalytic CO reduction. Benefited from the prominent capillary and confinement effects, the [email protected] act as nanoscale conveyors that can significantly facilitate the mass transport, adsorption,and concentration of reactants onto the active sites, realizing rapid reaction kinetics and low cathodic polarization. The spatial encapsulation and separation by the NCNT shells prevents the self-aggregation and surface oxidation of Bi-NRs, increasing the dispersity and stability of the electrocatalyst. As a result, the [email protected] exhibit high activity and durable catalytic stability for CO-to-formate conversion over a wide potential range. The Faradaic efficiency for formate production reaches 90.9% at a moderate applied potential of -0.9 V vs reversible hydrogen electrode (RHE).
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http://dx.doi.org/10.1021/acs.nanolett.1c00390DOI Listing
March 2021

Full-color micro-LED displays with cadmium-free quantum dots patterned by photolithography technology: retraction.

Appl Opt 2021 Mar;60(8):2281

The referenced article [Appl. Opt.59, 11112 (2020)APOPAI0003-693510.1364/AO.412267] has been retracted by the author.
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http://dx.doi.org/10.1364/AO.423154DOI Listing
March 2021

Corrigendum to "DDB1 is a cellular substrate of NS3/4A protease and required for hepatitis C virus replication" [Virology 435 (2013) 385-394].

Virology 2021 May 8;557:101-102. Epub 2021 Feb 8.

College of Life Sciences, State Key Laboratory of Virology, Wuhan University, Wuhan, Hubei, 430072, China. Electronic address:

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http://dx.doi.org/10.1016/j.virol.2021.01.013DOI Listing
May 2021

Photo-catalyzed TiO inactivates pathogenic viruses by attacking viral genome.

Chem Eng J 2021 Jun 3;414:128788. Epub 2021 Feb 3.

CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China.

Previous observations have been reported that viruses were inactivated using strong irradiation. Here, new evidence was disclosed by studying the effects of nanosized TiO on viral pathogens under a low irradiation condition (0.4 mW/cm at UVA band) that mimics the field setting. We showed that photo-activated TiO efficiently inhibits hepatitis C virus infection, and weak indoor light with intensity of 0.6 mW/cm at broad-spectrum wavelength and around 0.15 mW/cm of UVA band also lead to partial inhibition. Mechanistic studies demonstrated that hydroxyl radicals produced by photo-activated TiO do not destroy virion structure and contents, but attack viral RNA genome, thus inactivating the virus. Furthermore, we showed that photo-activated TiO inactivates a broad range of human viral pathogens, including SARS-CoV-2, a novel coronavirus responsible for the ongoing COVID-19 pandemic. In conclusion, we showed that photo-catalyzed nanosized TiO inactivates pathogenic viruses, paving a way to its field application in control of viral infectious diseases.
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http://dx.doi.org/10.1016/j.cej.2021.128788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857067PMC
June 2021

TRIM26 is a critical host factor for HCV replication and contributes to host tropism.

Sci Adv 2021 Jan 8;7(2). Epub 2021 Jan 8.

Unit of Viral Hepatitis, CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China.

Hepatitis C virus (HCV) remains a major human pathogen that requires better understanding of virus-host interactions. In this study, we performed a genome-wide CRISPR-Cas9 screening and identified TRIM26, an E3 ligase, as a critical HCV host factor. Deficiency of TRIM26 specifically impairs HCV genome replication. Mechanistic studies showed that TRIM26 interacts with HCV-encoded NS5B protein and mediates its K27-linked ubiquitination at residue K51, and thus promotes the NS5B-NS5A interaction. Moreover, mouse TRIM26 does not support HCV replication because of its unique six-amino acid insert that prevents its interaction with NS5B. Ectopic expression of human TRIM26 in a mouse hepatoma cell line that has been reconstituted with other essential HCV host factors promotes HCV infection. In conclusion, we identified TRIM26 as a host factor for HCV replication and a new determinant of host tropism. These results shed light on HCV-host interactions and may facilitate the development of an HCV animal model.
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http://dx.doi.org/10.1126/sciadv.abd9732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793585PMC
January 2021

Forecasting System of Computational Time of DFT/TDDFT Calculations under the Multiverse Ansatz via Machine Learning and Cheminformatics.

ACS Omega 2021 Jan 14;6(3):2001-2024. Epub 2021 Jan 14.

Computer Network Information Center, Chinese Academy of Sciences, Beijing 100190, China.

With the view of achieving a better performance in task assignment and load-balancing, a top-level designed forecasting system for predicting computational times of density-functional theory (DFT)/time-dependent DFT (TDDFT) calculations is presented. The computational time is assumed as the intrinsic property for the molecule. Based on this assumption, the forecasting system is established using the "reinforced concrete", which combines the cheminformatics, several machine-learning (ML) models, and the framework of many-world interpretation (MWI) in multiverse ansatz. Herein, the cheminformatics is used to recognize the topological structure of molecules, the ML models are used to build the relationships between topology and computational cost, and the MWI framework is used to hold various combinations of DFT functionals and basis sets in DFT/TDDFT calculations. Calculated results of molecules from the DrugBank dataset show that (1) it can give quantitative predictions of computational costs, typical mean relative errors can be less than 0.2 for DFT/TDDFT calculations with derivations of ±25% using the exactly pretrained ML models and (2) it can also be employed to various combinations of DFT functional and basis set cases without exactly pretrained ML models, while only slightly enlarge predicting errors.
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http://dx.doi.org/10.1021/acsomega.0c04981DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841786PMC
January 2021

Near-Infrared-Responsive Photo-Driven Nitrogen Fixation Enabled by Oxygen Vacancies and Sulfur Doping in Black TiOS Nanoplatelets.

ACS Appl Mater Interfaces 2021 Feb 19;13(4):4975-4983. Epub 2021 Jan 19.

MOE Key Laboratory of Mesoscopic Chemistry, MOE Key Laboratory of High Performance Polymer Materials and Technology, Jiangsu Key Laboratory of Advanced Organic Materials, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China.

Solar-driven nitrogen fixation is a promising clean and mild approach for ammonia synthesis beyond the conventional energy-intensive Haber-Bosch process. However, it is still challenging to design highly active, stable, and low-cost photocatalysts for activating inert N molecules. Herein, we report the synthesis of anatase-phase black TiOS nanoplatelets enriched with abundant oxygen vacancies and sulfur anion dopants (-S-rich TiOS) by ion exchange method at gentle conditions. The -S-rich TiOS nanoplatelets display a narrowed bandgap of 1.18 eV and much stronger light absorption that extends to the near-infrared (NIR) region. The co-presence of oxygen vacancies and sulfur dopants facilitates the adsorption of N molecules, promoting the reaction rate of N photofixation. Theoretical calculations reveal the synergistic effect of oxygen vacancies and sulfur dopants on visible-NIR light adsorption and photoexcited carrier transfer/separation. The -S-rich TiOS exhibits improved ammonia yield rates of 114.1 μmol g h under full-spectrum irradiation and 86.2 μmol g h under visible-NIR irradiation, respectively. Notably, even under only NIR irradiation (800-1100 nm), the -S-rich TiOS can still deliver an ammonia yield rate of 14.1 μmol g h. This study presents the great potential to regulate the activity of photocatalysts by rationally engineering the defect sites and dopant species for room-temperature N reduction.
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http://dx.doi.org/10.1021/acsami.0c17947DOI Listing
February 2021

EGCG Enhanced the Anti-tumor Effect of Doxorubicine in Bladder Cancer via NF-κB/MDM2/p53 Pathway.

Front Cell Dev Biol 2020 23;8:606123. Epub 2020 Dec 23.

Key Laboratory of Medical Programming Technology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, China.

Doxorubicin (DOX), the first-line chemotherapy for bladder cancer, usually induces side effects. We previously demonstrated that green tea polyphenol EGCG had potent anti-tumor effect in bladder cancer via down regulation of NF-κB. This study aimed to investigate the additive/synergistic effect EGCG and DOX against bladder cancer. Our results demonstrated that the combined use of DOX and EGCG inhibited T24 and SW780 cell proliferation. EGCG enhanced the apoptosis induction effect of DOX in both SW780 and T24 cells and resulted in significant differences. Besides, EGCG promoted the inhibitory effect of DOX against bladder cancer cell migration. In addition, the results demonstrated that DOX in combination with EGCG showed the most potent anti-tumor effects among DOX, EGCG and DOX+EGCG treatment groups. Further mechanistic studies determined that the combination of DOX and EGCG inhibited phosphorylated NF-κB and MDM2 expression, and up-regulated p53 expression in tumor, as assessed by western blot and immunohistochemistry. Western blot in SW780 cells also confirmed that the combined use of EGCG and DOX caused significant increase in p53, p21, and cleaved-PARP expression, and induced significant inhibition in phosphorylated NF-κB and MDM2. When NF-κB was inhibited, the expression of p53 and p-MDM2 were changed, and the combination of DOX and EGCG showed no obvious effect in transwell migration and cell viability. In conclusion, the novel application of chemotherapy DOX and EGCG demonstrated potent anti-tumor, anti-migration and anti-proliferation effects against bladder cancer. EGCG enhanced the anti-tumor effect of DOX in bladder cancer via NF-κB/MDM2/p53 pathway, suggesting the potential clinical application against bladder cancer patients.
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http://dx.doi.org/10.3389/fcell.2020.606123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793730PMC
December 2020

Full-color micro-LED displays with cadmium-free quantum dots patterned by photolithography technology.

Appl Opt 2020 Dec;59(35):11112-11122

A full-color display consisting of red and green photoluminescence cadmium-free quantum dots (QDs) as the color conversion material and excited by a 68×68 blue micro-LED flip chip array mounted on an active-matrix driving board was completed in this study. The QD photoresist (QDPR) lithography technology was reported in detail, and it has been proven to be a stable process route. The suitable thickness of 12±1µ of the QDPR and black matrix was proposed to reduce the light cross talk between different sub-pixels. The thickness of the common color filter of 1-2 µm was made successfully between the quantum dot film and the cover glass, which can greatly reduce the leakage of blue backlight and decrease the quantum dots excitation by the ambient light, as well as improve the color gamut and color purity of the display panel. In addition, the high red and green light conversion efficiency reaches up to 78.1% and 296.5%, respectively, and the screen display can reach 98.8% NTSC on the CIE 1931 chromaticity. Representative RGB monochromatic pictures were displayed successfully and ≤0.04 viewing angle deviation of the display was measured precisely.
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http://dx.doi.org/10.1364/AO.412267DOI Listing
December 2020

Proteomic and microRNA-omic profiles and potential mechanisms of dysfunction in pancreatic islet cells primed by inflammation.

Exp Ther Med 2021 Feb 3;21(2):122. Epub 2020 Dec 3.

Shenzhen Key Lab of Health Science and Technology, Institute of Biopharmaceutical and Health Engineering, Shenzhen International Graduate School, Tsinghua University, Shenzhen, Guangdong 518055, P.R. China.

Diabetes is an inflammatory disease that induces pancreatic islet dysfunction. However, to the best of our knowledge, the potential underlying molecular mechanisms of this inflammatory process remains unknown. The present study investigated microRNA (miRNA/miR) and protein expression profiles through proteomics and miRNA-omics. Lipopolysaccharide-induced macrophage cell medium (LRM) was used to stimulate inflammation in mouse Beta-TC-6 islet cells. Protein analysis revealed that 87 proteins were upregulated and 42 proteins were downregulated in LRM-treated Beta-TC-6 cells compared with control cells. Additionally, miRNA analysis revealed that 11 miRNAs were upregulated, while 28 miRNAs were downregulated in LRM-treated Beta-TC-6 cells compared with control cells. Islet cells exposed to inflammation exhibited markedly downregulated protein levels of transcription factor MafA, pancreatic and duodenal homeobox 1, paired box 6, homeobox protein Nkx-2.2, synaptosomal-associated protein 25, glucagon and insulin-2, while the expression of miR-146a-5p and miR-21a-5p were upregulated. It was also determined that upregulated miR-146a-5p and miR-21a-5p levels may be mediated by NF-κB activation. The downregulation of islet functional factor mRNA was partially reversed by treating islet cells with an inhibitor of miR-21a-5p. However, treatment with an miR-146a-5p inhibitor did not exert the same effect. Overall, the present study determined the molecular profiles of islet cell inflammation based on proteomics and miRNA-omics, and indicated that the proteins and miRNAs with altered expressions may form a large network that serves a role in islet dysfunction. Particularly, miR-21a-5p upregulation in response to inflammation may contribute to islet cell dysfunction. However, how these miRNAs regulated the expression of certain mRNAs and proteins in islet cell inflammation requires further investigation.
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http://dx.doi.org/10.3892/etm.2020.9554DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7739849PMC
February 2021

Circular RNA circ_ASAP2 promotes cell viability, migration, and invasion of gastric cancer cells by regulating the miR-770-5p/CDK6 axis.

Int J Clin Exp Pathol 2020 1;13(11):2806-2819. Epub 2020 Nov 1.

Department of Cadre/VIP Surgery, The First Affiliated Hospital of Xinjiang Medical University Urumchi 830054, Xinjiang Uygur Autonomous Region, China.

Background: Gastric cancer (GC) is one of the most common causes of cancer death. GSE83521 microarray analysis suggested that circular RNA circ_ASAP2 (hsa_circ_0008768) expression was increased in GC tissues. However, the molecular mechanism of circ_ASAP2 remains unknown.

Methods: Expression levels of circ_ASAP2, microRNA-770-5p (miR-770-5p), and the cyclin-dependent kinase 6 (CDK6) were detected by using real time PCR (RT-PCR). 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and transwell assays were applied to explore cell viability, migration, and invasion, respectively. The interactions between miR-770-5p and circ_ASAP2 or CDK6 was predicted by using Starbase software, and then confirmed by luciferase reporter assay. Xenograft tumor model was also used to estimate the effect of circ_ASAP2 on tumor growth .

Results: The expression levels of circ_ASAP2 and CDK6 were increased, and miR-770-5p level was decreased in GC tissues and cells. Furthermore, circ_ASAP2 knockdown inhibited cell viability, migration, and invasion of GC cells. Mechanically, circ_ASAP2 functioned as a sponge of miR-770-5p to regulate CDK6 expression, thereby boosting the progression of GC cells. Circ_ASAP2 silencing hindered the tumor growth of GC .

Conclusion: Circ_ASAP2 knockdown can repress the development of GC cells partly through regulating the miR-770-5p/CDK6 axis, suggesting an underlying circRNA-targeted therapy for GC treatment.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716128PMC
November 2020

High-Performance Lithium-Ion Capacitors Based on Porosity-Regulated Zirconium Metal-Organic Frameworks.

Small 2021 Jun 3;17(22):e2005209. Epub 2020 Dec 3.

State Key Laboratory of Coordination Chemistry, Collaborative Innovation Center of Advanced Microstructures, Key Laboratory of Mesoscopic Chemistry of MOE, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, Jiangsu, 210023, China.

Comprised of a battery anode and a supercapacitor cathode, hybrid lithium-ion capacitors (HLICs) are found to be an effective solution to realize both high power density and high energy density at the same time. Organic-inorganic hybrid materials with well-organized framework guided by the reticular chemistry are one of the promising anode materials for HLICs because of rich active sites and ordered porosity. Herein, metal-organic framework consisting of Zr metal ions and tetrathiafulvalene-based ligands (Zr-MOF) is proposed as the pseudocapacitive anode of HLICs. The Zr-MOF possesses high stability, high crystallinity, and multiple meso-microporous channels favorable for ion transport. The as-prepared Zr-MOF||activated carbon HLICs present high energy density (122.5 Wh kg ), high power density (12.5 kW kg ), and stable cycling performance (86% capacity retention after 1000 cycles at 2000 mA g ) within the operating voltage range of 1.0-4.0 V. The results expand the direct application of MOF for bridging the performance gap between batteries and supercapacitors.
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http://dx.doi.org/10.1002/smll.202005209DOI Listing
June 2021

Controllable synthesis of nitrogen-doped carbon nanobubbles to realize high-performance lithium and sodium storage.

Dalton Trans 2020 Nov;49(44):15712-15717

School of Petrochemical Engineering, Changzhou University, Changzhou, 213164, China.

Carbon nanobubbles are regarded as one of the most promising carbon-based anode materials for lithium-ion batteries (LIBs) and sodium-ion batteries (SIBs), with significantly improved capacity and superior cycling stability. The wet-chemistry method is a cost-effective and readily scalable method of preparing carbon nanobubbles when compared to common pyrolysis, but balancing the relationship between high capacity and low initial coulombic efficiency still remains challenging. Herein, we present a solution-polymerization method associated with a removable template to realize the controllable synthesis of N-doped carbon nanobubbles (NCN). The obtained NCN material delivers impressive high specific capacity as an anode for both LIBs and SIBs (799 mA h g-1 at 0.8 A g-1 for 385 cycles in LIBs; 248 mA h g-1 at 0.3 A g-1 for 200 cycles in SIBs). Meanwhile, the NCN anode exhibits an initial coulombic efficiency of nearly 80% for both LIBs and SIBs, which is ascribed to the moderate specific surface area and rational structure design.
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http://dx.doi.org/10.1039/d0dt03258aDOI Listing
November 2020

New developments in RiPP discovery, enzymology and engineering.

Nat Prod Rep 2021 01 16;38(1):130-239. Epub 2020 Sep 16.

Department of Microbiology, University of Granada, Spain.

Covering: up to June 2020Ribosomally-synthesized and post-translationally modified peptides (RiPPs) are a large group of natural products. A community-driven review in 2013 described the emerging commonalities in the biosynthesis of RiPPs and the opportunities they offered for bioengineering and genome mining. Since then, the field has seen tremendous advances in understanding of the mechanisms by which nature assembles these compounds, in engineering their biosynthetic machinery for a wide range of applications, and in the discovery of entirely new RiPP families using bioinformatic tools developed specifically for this compound class. The First International Conference on RiPPs was held in 2019, and the meeting participants assembled the current review describing new developments since 2013. The review discusses the new classes of RiPPs that have been discovered, the advances in our understanding of the installation of both primary and secondary post-translational modifications, and the mechanisms by which the enzymes recognize the leader peptides in their substrates. In addition, genome mining tools used for RiPP discovery are discussed as well as various strategies for RiPP engineering. An outlook section presents directions for future research.
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http://dx.doi.org/10.1039/d0np00027bDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864896PMC
January 2021

Strigolactone Analogues Derived from Dihydroflavonoids as Potent Seed Germinators for the Broomrapes.

J Agric Food Chem 2020 Oct 23;68(40):11077-11087. Epub 2020 Sep 23.

State Key Laboratory of Elemento-organic Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China.

The broomrapes ( and spp.) and witchweeds ( spp.) are a class of parasitic weeds, which are distributed widely in the tropical, subtropical, and temperate areas of the globe. Since they have completely consistent lifecycles with the host plants, it is difficult to control them selectively through using the conventional herbicides. Inducing suicidal germination of these weed seeds by small molecular signaling agents proved to be a promising strategy for the management of parasitic weeds. As a class of naturally occurring terpenoid metabolites, strigolactones (SLs) show significant biological activities including stimulation germination of weed seeds, inhibition of shoot-branching, and so on. However, the widespread application of these natural SLs is greatly limited by their extremely low natural abundance and complex molecular structures. Design and synthesis of the simplified analogues as natural SLs alternatives provide a viable avenue for the efficient control of these parasitic weeds. We herein disclose the development of a novel class of SLs analogues derived from dihydroflavonoids as potent seed germinators of parasitic weeds. It was shown that one of them displayed a higher potential toward the seed germination of the broomrapes than the positive control GR24. The structure-activity relationship of these SLs analogues was further validated on the basis of the binding affinity experiment to strigolactone receptor protein by using a YLG fluorescent probe method.
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http://dx.doi.org/10.1021/acs.jafc.9b08044DOI Listing
October 2020

MAVS Is a Dual Target during Hepatitis C Virus Infection for Innate Immune Evasion and Viral Replication via NF-κB.

J Immunol 2020 10 9;205(8):2091-2099. Epub 2020 Sep 9.

Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China;

Hepatitis C virus (HCV) infection is the cause of severe liver disease in many people. The restricted species tropism of HCV hinders the research and development of drugs and vaccines. The Chinese tree shrew () is a close relative of primates and can be infected by HCV, but the underlying mechanisms are unknown. In this study, we have characterized the functions of tree shrew MAVS (tMAVS) in response to HCV infection and defined the capacity of HCV replication. HCV was shown to be colocalized with tMAVS in primary tree shrew hepatocytes and cleaved tMAVS at site Cys508 via its NS3/4A protease, with a modulating effect by site Glu of tMAVS. The tMAVS cleavage by HCV NS3/4A impaired the IRF3-mediated induction of IFN-β but maintained the activated NF-κB signaling in the tree shrew primary cells. Activation of the tMAVS-dependent NF-κB signaling inversely inhibited HCV replication and might limit the establishment of persistent infection. Overall, our study has revealed an elegant example of the balance between the host defenses and HCV infection via the MAVS-mediated antiviral signaling and has provided an insight into the mechanisms underpinning HCV infection in the Chinese tree shrew.
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http://dx.doi.org/10.4049/jimmunol.2000376DOI Listing
October 2020

Inhibition of Phase Segregation in Cesium Lead Mixed-Halide Perovskites by B-Site Doping.

iScience 2020 Aug 29;23(8):101415. Epub 2020 Jul 29.

Key Laboratory of Mesoscopic Chemistry of MOE, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, Jiangsu 210023, China. Electronic address:

The emergence of all-inorganic halide perovskites has shown great potential in photovoltaic and optoelectronic devices. However, the photo-induced phase segregation in lead mixed-halide perovskites has severely limited their application. Herein, by real-time monitoring the photoluminescence (PL) spectra of metal mixed-halide perovskites under light irradiation, we found that the photo-induced phase transition can be significantly inhibited by B-site doping. For pristine mixed-halide perovskites, an intermediate phase of CsPbBrI can only be stabilized under low excitation power. After introducing Sn ions, such intermediate phase can be stabilized in nitrogen atmosphere under high excitation power and phase segregation can be started after the exposure in oxygen due to oxidization of Sn. Replacing Sn by Mn can further improve the intermediate phase's tolerance to oxygen proving that B-site doping in perovskites structure by Sn or Mn could effectively minimize the light-induced phase segregation and promote them to serve as promising candidates in photovoltaic and light-emitting devices.
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http://dx.doi.org/10.1016/j.isci.2020.101415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7424214PMC
August 2020

Ellagic Acid and Its Microbial Metabolite Urolithin A Alleviate Diet-Induced Insulin Resistance in Mice.

Mol Nutr Food Res 2020 10 23;64(19):e2000091. Epub 2020 Aug 23.

Center for Human Nutrition, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA.

Scope: This work aims at evaluating the effect of dietary ellagic acid (EA) and its microbial metabolite urolithin A (UA) on glucose metabolism and insulin resistance (IR) in mice with diet-induced IR.

Methods And Results: DBA2J mice are fed a high fat/high sucrose diet (HF/HS) for 8 weeks to induce IR and then 0.1% EA, UA, or EA and UA (EA+UA) are added to the HF/HS-diet for another 8 weeks. UA significantly decreases fasting glucose and increases adiponectin compared with HF/HS-controls. During intraperitoneal insulin tolerance test, EA+UA significantly improve insulin-mediated glucose lowering effects at 15 and 120 min and reduce blood triglycerides compared with HF/HS-controls. Serum free fatty acids are significantly decreased by EA, UA, and EA+UA. Differential expression of genes related to mitochondrial function by EA, UA, and EA+UA in liver and skeletal muscle is observed. Primary hepatocytes from IR-mice have higher proton leak, basal and ATP-linked oxygen consumption rates compared with healthy controls. EA and EA+UA but not UA reduce the proton leak in hepatocytes from IR-mice.

Conclusion: EA and UA induce different metabolic benefits in IR mice. The effects of EA and UA on mitochondrial function suggest a potentially novel mechanism modulating metabolism.
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http://dx.doi.org/10.1002/mnfr.202000091DOI Listing
October 2020

Cooperative Low-Rank Models for Removing Stripe Noise From OCTA Images.

IEEE J Biomed Health Inform 2020 12 4;24(12):3480-3490. Epub 2020 Dec 4.

Optical coherence tomography angiography (OCTA) is an emerging non-invasive imaging technique for imaging the microvasculature of the eye based on phase variance or amplitude decorrelation derived from repeated OCT images of the same tissue area. Stripe noise occurs during the OCTA acquisition process due to the involuntary movement of the eye. To remove the stripe noise (or 'destriping') effectively, we propose two novel image decomposition models to simultaneously destripe all the OCTA images of the same eye cooperatively: cooperative uniformity destriping (CUD) model and cooperative similarity destriping (CSD) model. Both the models consider stripe noise by low-rank constraint but in different ways: the CUD model assumes that stripe noise is identical across all the layers while the CSD model assumes that the stripe noise at different layers are different and have to be considered in the model. Compared to the CUD model, CSD is a more general solution for real OCTA images. An efficient solution (CSD+) is developed for model CSD to reduce the computational complexity. The models were extensively evaluated against state-of-the-art methods on both synthesized and real OCTA datasets. The experiments demonstrated not only the effectiveness of the CSD and CSD+ models in terms of peak signal-to-noise ratio (PSNR) and structural similarity index (SSIM) and CSD+ is twice faster than CSD, but also their beneficiary effect on the vessel segmentation of OCTA images. We expect our models will become a powerful tool for clinical applications.
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http://dx.doi.org/10.1109/JBHI.2020.2997381DOI Listing
December 2020

Reflective temperature sensor based on a fiber Bragg grating combined with a fiber loop ringdown technique.

Appl Opt 2020 Jul;59(19):5693-5696

In this paper, a reflective fiber sensing system combined with a fiber loop ringdown technique for temperature detection is proposed. A fiber Bragg grating (FBG) with an initial center wavelength of 1543.33 nm was set as the sensor head. The experimental results showed that the average sensitivity of temperature was 1.003 µs/°C in the temperature range of 30-38°C, and the resolution was 0.007°C, which is 14 times better than the current FBG sensing demodulator. In addition, the system has the advantages of simple structure, low cost, and insensitivity to optical power fluctuation.
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http://dx.doi.org/10.1364/AO.392423DOI Listing
July 2020

Protein acetylation in mitochondria plays critical functions in the pathogenesis of fatty liver disease.

BMC Genomics 2020 Jun 26;21(1):435. Epub 2020 Jun 26.

Shandong Key Laboratory of Animal Bioengineering and Disease Prevention, College of Animal Science and Technology, Shandong Agricultural University, No. 61 Daizong Street, Taian, Shandong, 271018, P. R. China.

Background: Fatty liver is a high incidence of perinatal disease in dairy cows caused by negative energy balance, which seriously threatens the postpartum health and milk production. It has been reported that lysine acetylation plays an important role in substance and energy metabolism. Predictably, most metabolic processes in the liver, as a vital metabolic organ, are subjected to acetylation. Comparative acetylome study were used to quantify the hepatic tissues from the severe fatty liver group and normal group. Combined with bioinformatics analysis, this study provides new insights for the role of acetylation modification in fatty liver disease of dairy cows.

Results: We identified 1841 differential acetylation sites on 665 proteins. Among of them, 1072 sites on 393 proteins were quantified. Functional enrichment analysis shows that higher acetylated proteins are significantly enriched in energy metabolic pathways, while lower acetylated proteins are significantly enriched in pathways related to immune response, such as drug metabolism and cancer. Among significantly acetylated proteins, many mitochondrial proteins were identified to be interacting with multiple proteins and involving in lipid metabolism. Furthermore, this study identified potential important proteins, such as HADHA, ACAT1, and EHHADH, which may be important regulatory factors through modification of acetylation in the development of fatty liver disease in dairy cows and possible therapeutic targets for NAFLD in human beings.

Conclusion: This study provided a comprehensive acetylome profile of fatty liver of dairy cows, and revealed important biological pathways associated with protein acetylation occurred in mitochondria, which were involved in the regulation of the pathogenesis of fatty liver disease. Furthermore, potential important proteins, such as HADHA, ACAT1, EHHADH, were predicted to be essential regulators during the pathogenesis of fatty liver disease. The work would contribute to the understanding the pathogenesis of NAFLD, and inspire in the development of new therapeutic strategies for NAFLD.
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http://dx.doi.org/10.1186/s12864-020-06837-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7318365PMC
June 2020

A Novel Approach To Display Structural Proteins of Hepatitis C Virus Quasispecies in Patients Reveals a Key Role of E2 HVR1 in Viral Evolution.

J Virol 2020 08 17;94(17). Epub 2020 Aug 17.

CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China

Hepatitis C virus (HCV) infection remains a major worldwide health problem despite development of highly effective direct-acting antivirals. HCV rapidly evolves upon acute infection and generates multiple viral variants (quasispecies), leading to immune evasion and persistent viral infection. Identification of epitopes of broadly neutralizing anti-HCV antibodies (nAbs) is critical to guide HCV vaccine development. In this study, we developed a new reverse genetics system for HCV infection based on -complementation of viral structural proteins. The HCV genome (JFH1 strain) lacking the structural protein-coding sequence can be efficiently rescued by ectopic expression of core-E1-E2-p7-NS2 (core-NS2) or core-E1-E2-p7 (core-p7) in , leading to production of single-round infectious virions designated HCVΔS. JFH1-based HCVΔS can be also rescued by expressing core-NS2 of other HCV genotypes, rendering it an efficient tool to display the structural proteins of HCV strains of interests. Furthermore, we successfully rescued HCVΔS with structural proteins from clinical isolates. Multiple viral structural proteins with different sensitivities to nAbs were identified from a same patient serum, demonstrating the genetic diversity of HCV quasispecies Interestingly, the structural protein-coding sequences of highly divergent viral quasispecies from the same patient can be clustered based on their hypervariable region 1 (HVR1) in viral envelope protein E2, which critically dictates the sensitivity to neutralizing antibodies. In summary, we developed a novel reverse genetics system that efficiently displays viral structural proteins from HCV clinical isolates, and analysis of quasispecies from the same patient using this system demonstrated that E2 HVR1 is the major determinant of viral evolution A cell culture model that can recapitulate the diversity of HCV quasispecies in patients is important for analysis of neutralizing epitopes and HCV vaccine development. In this study, we developed a new reverse genetics system for HCV infection based on -complementation of viral structural proteins (HCVΔS). This system can be used to display structural proteins of HCV strains of multiple genotypes as well as clinical isolates. By using this system, we showed that multiple different HCV structural proteins from a same patient were displayed on HCVΔS. Interestingly, these variant structural proteins within the same patient can be classified according to the sequence of HVR1in E2, which dictates viral sensitivity to nAbs and viral evolution Our work provided a new tool to study highly divergent HCV quasispecies and shed light on underlying mechanisms driving HCV evolution.
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http://dx.doi.org/10.1128/JVI.00622-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431814PMC
August 2020

Effects of Lactobacillus hilgardii 60TS-2, with or without homofermentative Lactobacillus plantarum B90, on the aerobic stability, fermentation quality and microbial community dynamics in sugarcane top silage.

Bioresour Technol 2020 Sep 30;312:123600. Epub 2020 May 30.

State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; School of Life Science, University of Chinese Academy of Sciences, Beijing 100039, China. Electronic address:

This study investigated the effects of Lactobacillus hilgardii (LH), alone or in combination with Lactobacillus plantarum (LP), on the aerobic stability, fermentation quality and dynamics of the bacterial and fungal communities of sugarcane top silage. Results demonstrated that LH and LHLP (LH combined with LP) improved the aerobic stability of sugarcane top silages. As the exposure time increased, the pH values and the contents of lactic acid, acetic acid, as well as propionic acid remained stable in silage treated with LH and LHLP. The abundance of L. hilgardii was enriched and the undesirable microorganisms, such as Acetobacter pasteurianus, Paenibacillus amylolyticus and yeasts like Kazachstania humilis, were suppressed in silages treated with LH and LHLP. In conclusion, LH-treated silage, whether with LP or not, positively impacted the fungal and bacterial microbes. This improved the quality of fermentation, the aerobic stability, and reduced aerobic spoilage in sugarcane top silage.
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http://dx.doi.org/10.1016/j.biortech.2020.123600DOI Listing
September 2020