Publications by authors named "Qiwei Zhang"

126 Publications

Yoshimura-origami Based Earthworm-like Robot With 3-dimensional Locomotion Capability.

Front Robot AI 2021 20;8:738214. Epub 2021 Aug 20.

School of Aerospace Engineering and Applied Mechanics, Tongji University, Shanghai, China.

Earthworm-like robots have received great attention due to their prominent locomotion abilities in various environments. In this research, by exploiting the extraordinary three-dimensional (3D) deformability of the Yoshimura-origami structure, the state of the art of earthworm-like robots is significantly advanced by enhancing the locomotion capability from 2D to 3D. Specifically, by introducing into the virtual creases, kinematics of the non-rigid-foldable Yoshimura-ori structure is systematically analyzed. In addition to exhibiting large axial deformation, the Yoshimura-ori structure could also bend toward different directions, which, therefore, significantly expands the reachable workspace and makes it possible for the robot to perform turning and rising motions. Based on prototypes made of PETE film, mechanical properties of the Yoshimura-ori structure are also evaluated experimentally, which provides useful guidelines for robot design. With the Yoshimura-ori structure as the skeleton of the robot, a hybrid actuation mechanism consisting of SMA springs, pneumatic balloons, and electromagnets is then proposed and embedded into the robot: the SMA springs are used to bend the origami segments for turning and rising motion, the pneumatic balloons are employed for extending and contracting the origami segments, and the electromagnets serve as anchoring devices. Learning from the earthworm's locomotion mechanism--retrograde peristalsis wave, locomotion gaits are designed for controlling the robot. Experimental tests indicate that the robot could achieve effective rectilinear, turning, and rising locomotion, thus demonstrating the unique 3D locomotion capability.
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http://dx.doi.org/10.3389/frobt.2021.738214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417593PMC
August 2021

HIF-1α promotes SARS-CoV-2 infection and aggravates inflammatory responses to COVID-19.

Signal Transduct Target Ther 2021 08 18;6(1):308. Epub 2021 Aug 18.

The First Affiliated Hospital, Jinan University, Guangzhou, China.

Cytokine storm induced by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a major pathological feature of Coronavirus Disease 2019 (COVID-19) and a crucial determinant in COVID-19 prognosis. Understanding the mechanism underlying the SARS-CoV-2-induced cytokine storm is critical for COVID-19 control. Here, we identify that SARS-CoV-2 ORF3a and host hypoxia-inducible factor-1α (HIF-1α) play key roles in the virus infection and pro-inflammatory responses. RNA sequencing shows that HIF-1α signaling, immune response, and metabolism pathways are dysregulated in COVID-19 patients. Clinical analyses indicate that HIF-1α production, inflammatory responses, and high mortalities occurr in elderly patients. HIF-1α and pro-inflammatory cytokines are elicited in patients and infected cells. Interestingly, SARS-CoV-2 ORF3a induces mitochondrial damage and Mito-ROS production to promote HIF-1α expression, which subsequently facilitates SARS-CoV-2 infection and cytokines production. Notably, HIF-1α also broadly promotes the infection of other viruses. Collectively, during SARS-CoV-2 infection, ORF3a induces HIF-1α, which in turn aggravates viral infection and inflammatory responses. Therefore, HIF-1α plays an important role in promoting SARS-CoV-2 infection and inducing pro-inflammatory responses to COVID-19.
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http://dx.doi.org/10.1038/s41392-021-00726-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371950PMC
August 2021

Mechanism of Cross-Resistance to Fusion Inhibitors Conferred by the K394R Mutation in Respiratory Syncytial Virus Fusion Protein.

J Virol 2021 Aug 11:JVI0120521. Epub 2021 Aug 11.

Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM & New Drugs Research, Jinan University, Guangzhou 510632, China.

The fusion glycoprotein (F) is essential for respiratory syncytial virus (RSV) entry and has become an attractive target for anti-RSV drug development. Despite the promising prospect of RSV F inhibitors, issues of drug resistance remain challenging. In this study, we established a dual-luciferase protocol for RSV fusion inhibitor discovery. A small-molecule inhibitor, salvianolic acid R (LF-6), was identified to inhibit virus-cell and cell-cell fusion mediated by RSV F protein. Sequence analysis of the resultant resistant viruses identified a K394R mutation in the viral F protein. The K394R mutant virus also conferred cross-resistance to multiple RSV fusion inhibitors, including several inhibitors undergoing clinical trials. Our study further showed that K394R mutation not only increased the triggering rate of F protein in prefusion conformation but also enhanced fusion activity of F protein, both of which were positively correlated with the resistance to fusion inhibitors. Moreover, the K394R mutation also showed cooperative effects with other escape mutations to increase the fusion activity of F protein. By substitution of K394 into different amino acids, we found that K394R or K394H substitution resulted in hyperfusiogenic F proteins, whereas F variants with other substitutions exhibited lower fusion activity. Both K394R and K394H in F protein exhibited cross-resistance to RSV fusion inhibitors. Collectively, these findings reveal a positive correlation existed between membrane fusion activity of F protein and the resistance of corresponding inhibitors. All the results demonstrate that K394R in F protein confers cross-resistance to fusion inhibitors through destabilizing F protein and increasing its membrane fusion activity. Respiratory syncytial virus (RSV) causes serious respiratory tract disease in children and the elderly. Therapeutics against RSV infection are urgently needed. This study reports the discovery of a small-molecule inhibitor of RSV fusion glycoprotein by using a dual-luciferase protocol. The escape mutation (K394R) of this compound also confers cross-resistance to multiple RSV fusion inhibitors that have been reported previously, including two candidates currently in clinical development. The combination of K394R with other escape mutations can increase the resistance of F protein to these inhibitors through destabilizing F protein and enhancing the membrane fusion activity of F protein. By amino acid deletion or substitution, we found that positively charged residue at the 394 site is crucial for the fusion ability of F protein as well as for the cross-resistance against RSV fusion inhibitors. These results reveal the mechanism of cross-resistance conferred by K394R mutation and the possible cross-resistance risk of RSV fusion inhibitors.
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http://dx.doi.org/10.1128/JVI.01205-21DOI Listing
August 2021

SARS-CoV-2 N protein promotes NLRP3 inflammasome activation to induce hyperinflammation.

Nat Commun 2021 08 2;12(1):4664. Epub 2021 Aug 2.

The First Affiliated Hospital of Jinan University, Guangzhou, China.

Excessive inflammatory responses induced upon SARS-CoV-2 infection are associated with severe symptoms of COVID-19. Inflammasomes activated in response to SARS-CoV-2 infection are also associated with COVID-19 severity. Here, we show a distinct mechanism by which SARS-CoV-2 N protein promotes NLRP3 inflammasome activation to induce hyperinflammation. N protein facilitates maturation of proinflammatory cytokines and induces proinflammatory responses in cultured cells and mice. Mechanistically, N protein interacts directly with NLRP3 protein, promotes the binding of NLRP3 with ASC, and facilitates NLRP3 inflammasome assembly. More importantly, N protein aggravates lung injury, accelerates death in sepsis and acute inflammation mouse models, and promotes IL-1β and IL-6 activation in mice. Notably, N-induced lung injury and cytokine production are blocked by MCC950 (a specific inhibitor of NLRP3) and Ac-YVAD-cmk (an inhibitor of caspase-1). Therefore, this study reveals a distinct mechanism by which SARS-CoV-2 N protein promotes NLRP3 inflammasome activation and induces excessive inflammatory responses.
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http://dx.doi.org/10.1038/s41467-021-25015-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8329225PMC
August 2021

Biliopancreatic Limb Length of Small Intestinal Bypass in Non-obese Goto-Kakizaki (GK) Rats Correlates with Gastrointestinal Hormones, Adipokines, and Improvement in Type 2 Diabetes.

Obes Surg 2021 Jul 26. Epub 2021 Jul 26.

Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wannan Medical College, Wuhu, China.

Background: The purpose of this study was to explore the effects on type 2 diabetes, gastrointestinal hormones, and adipokines after the small intestinal bypass of different biliopancreatic limb (BPL) lengths in non-obese type 2 diabetic rats.

Method: Small intestinal bypass with the BPL length at 10cm, 20cm, 30cm, and 40cm, respectively, and sham surgery were performed in non-obese GK rats. Fasting serum was collected at 2 days preoperatively and 1, 3, 6, and 9 weeks postoperatively. Body weight and fasting blood glucose (FBG) were measured during the experiment. Glycated hemoglobin (GHb), fasting insulin (FINS), C-peptide, ghrelin, leptin, adiponectin, and somatostatin were measured postoperatively.

Result: Rats with a bypassed length of 40cm died within 5-9 weeks. No statistically significant was observed in body weight between the sham group and the bypass groups at the 9th week postoperatively. FBG, GHb, FINS, C-peptide, and HOMA-IR in the bypass groups were lower than those in the sham group postoperatively and were negatively correlated with BPL length. Ghrelin and leptin declined compared with preoperative but were not associated with BPL length. Adiponectin of the bypass groups increased after operation and was positively correlated with BPL length. Somatostatin remained stable among groups during the experiment.

Conclusion: Ghrelin and leptin of non-obese GK rats decreased postoperatively without a linear relationship with the BPL length, while adiponectin increased with positively correlation with the BPL length. In addition, somatostatin remained steady after small intestinal bypass. Further studies are expected to confirm the effect of the BPL length of small intestinal bypass on gastrointestinal hormones and adipokines.
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http://dx.doi.org/10.1007/s11695-021-05604-6DOI Listing
July 2021

DENV NS1 and MMP-9 cooperate to induce vascular leakage by altering endothelial cell adhesion and tight junction.

PLoS Pathog 2021 Jul 26;17(7):e1008603. Epub 2021 Jul 26.

Guangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou, China.

Dengue virus (DENV) is a mosquito-borne pathogen that causes a spectrum of diseases including life-threatening dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Vascular leakage is a common clinical crisis in DHF/DSS patients and highly associated with increased endothelial permeability. The presence of vascular leakage causes hypotension, circulatory failure, and disseminated intravascular coagulation as the disease progresses of DHF/DSS patients, which can lead to the death of patients. However, the mechanisms by which DENV infection caused the vascular leakage are not fully understood. This study reveals a distinct mechanism by which DENV induces endothelial permeability and vascular leakage in human endothelial cells and mice tissues. We initially show that DENV2 promotes the matrix metalloproteinase-9 (MMP-9) expression and secretion in DHF patients' sera, peripheral blood mononuclear cells (PBMCs), and macrophages. This study further reveals that DENV non-structural protein 1 (NS1) induces MMP-9 expression through activating the nuclear factor κB (NF-κB) signaling pathway. Additionally, NS1 facilitates the MMP-9 enzymatic activity, which alters the adhesion and tight junction and vascular leakage in human endothelial cells and mouse tissues. Moreover, NS1 recruits MMP-9 to interact with β-catenin and Zona occludens protein-1/2 (ZO-1 and ZO-2) and to degrade the important adhesion and tight junction proteins, thereby inducing endothelial hyperpermeability and vascular leakage in human endothelial cells and mouse tissues. Thus, we reveal that DENV NS1 and MMP-9 cooperatively induce vascular leakage by impairing endothelial cell adhesion and tight junction, and suggest that MMP-9 may serve as a potential target for the treatment of hypovolemia in DSS/DHF patients.
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http://dx.doi.org/10.1371/journal.ppat.1008603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8341711PMC
July 2021

Desmoglein 2 (DSG2) Is A Receptor of Human Adenovirus Type 55 Causing Adult Severe Community-Acquired Pneumonia.

Virol Sin 2021 Jul 5. Epub 2021 Jul 5.

Guangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou, 510632, China.

Human adenovirus type 55 (HAdV-B55) is a re-emergent acute respiratory disease pathogen that causes adult community-acquired pneumonia (CAP). Previous studies have shown that the receptor of HAdV-B14, which genome is highly similar with HAdV-B55, is human Desmoglein 2 (DSG2). However, whether the receptor of HAdV-B55 is DSG2 is undetermined because there are three amino acid mutations in the fiber gene between HAdV-B14 and HAdV-B55. Here, firstly we found the 3T3 cells, a mouse embryo fibroblast rodent cell line which does not express human DSG2, were able to be infected by HAdV-B55 after transfected with pcDNA3.1-DSG2, while normal 3T3 cells were still unsusceptible to HAdV-B55 infection. Next, A549 cells with hDSG2 knock-down by siRNA were hard to be infected by HAdV-B3/-B14/-B55, while the control siRNA group was still able to be infected by all these types of HAdVs. Finally, immunofluorescence confocal microscopy indicated visually that Cy3-conjugated HAdV-B55 viruses entered A549 cells by binding to DSG2 protein. Therefore, DSG2 is a major receptor of HAdV-B55 causing adult CAP. Our finding is important for better understanding of interactions between adenoviruses and host cells and may shed light on the development of new drugs that can interfere with these processes as well as for the development of potent prophylactic vaccines.
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http://dx.doi.org/10.1007/s12250-021-00414-7DOI Listing
July 2021

Construction and Analysis of a circRNA-Mediated ceRNA Network in Lung Adenocarcinoma.

Onco Targets Ther 2021 8;14:3659-3669. Epub 2021 Jun 8.

Department of Thoracic Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, People's Republic of China.

Background: Circular RNAs (circRNAs), a new class of regulatory noncoding RNAs, are involved in gene regulation and may play a role in cancer development. The aim of this study was to identify circRNAs involved in lung adenocarcinoma (LUAD) using bioinformatics analysis.

Methods: CircRNA (GSE101684, GSE101586), miRNA (GSE135918), and mRNA (GSE130779) microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database to identify differentially expressed circRNAs (DECs), miRNAs (DEMs), and mRNAs (DEGs) in LUAD. Circinteractome and StarBase were used to predict miRNAs and mRNAs, respectively. A circRNA-miRNA-mRNA-ceRNA network was constructed. Patient survival was analyzed using UALCAN, and a sub-network was established. Real-time quantitative PCR (qRT-PCR) was used to verify the expressed of DECs between LUAD tissues and paired adjacent normal tissues.

Results: Hsa_circ_0072088 was identified as a differentially expressed (upregulated) circRNA in the two datasets. Intersection analysis identified hsa-miR-532-3p and hsa-miR-942 as the two miRNAs with the highest potential for binding to hsa_circ_0072088. Differential expression analysis and target gene prediction were performed to build a ceRNA network of hsa_circ_0072088 using Circinteractome/StarBase 3.0. Intersection analysis showed that TMEM52, IL24, POF1B, KIF1A, NHS, LBH, HIST2H2BE, ABCC3, PYCR1, CD79A, IGF2BP3, ANKRD17, GTSE1, MKI67, CLSPN, PLAU, LUC7L, MAGIX, GPATCH4, and ABAT were potential downstream mRNAs. The association between the expression level of 20 DEGs and LUAD patient survival was analyzed using UALCAN and GEPIA, which showed that IGF2BP3, MKI67, CD79A, and ABAT were related to patient survival. Hsa_circ_0072088 was verified upregulated by qRT-PCR.

Conclusion: The circRNA hsa_circ_0072088, the DEMs (hsa-miR-532-3p and hsa-miR-942-5p), and the DEGs (IGF2BP3, MKI67, CD79A, and ABAT) may serve as prognostic markers in LUAD.
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http://dx.doi.org/10.2147/OTT.S305030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8197624PMC
June 2021

V367F Mutation in SARS-CoV-2 Spike RBD Emerging during the Early Transmission Phase Enhances Viral Infectivity through Increased Human ACE2 Receptor Binding Affinity.

J Virol 2021 07 26;95(16):e0061721. Epub 2021 Jul 26.

Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China.

The current pandemic of COVID-19 is caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The SARS-CoV-2 spike protein receptor-binding domain (RBD) is the critical determinant of viral tropism and infectivity. To investigate whether naturally occurring RBD mutations during the early transmission phase have altered the receptor binding affinity and infectivity, we first analyzed the binding dynamics between SARS-CoV-2 RBD mutants and the human angiotensin-converting enzyme 2 (ACE2) receptor. Among 32,123 genomes of SARS-CoV-2 isolates (December 2019 through March 2020), 302 nonsynonymous RBD mutants were identified and clustered into 96 mutant types. The six dominant mutations were analyzed applying molecular dynamics simulations (MDS). The mutant type V367F continuously circulating worldwide displayed higher binding affinity to human ACE2 due to the enhanced structural stabilization of the RBD beta-sheet scaffold. The MDS also indicated that it would be difficult for bat SARS-like CoV to infect humans. However, the pangolin CoV is potentially infectious to humans. The increased infectivity of V367 mutants was further validated by performing receptor-ligand binding enzyme-linked immunosorbent assay (ELISA), surface plasmon resonance, and pseudotyped virus assays. Phylogenetic analysis of the genomes of V367F mutants showed that during the early transmission phase, most V367F mutants clustered more closely with the SARS-CoV-2 prototype strain than the dual-mutation variants (V367F+D614G), which may derivate from recombination. The analysis of critical RBD mutations provides further insights into the evolutionary trajectory of early SARS-CoV-2 variants of zoonotic origin under negative selection pressure and supports the continuing surveillance of spike mutations to aid in the development of new COVID-19 drugs and vaccines. A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused the pandemic of COVID-19. The origin of SARS-CoV-2 was associated with zoonotic infections. The spike protein receptor-binding domain (RBD) is identified as the critical determinant of viral tropism and infectivity. Thus, whether mutations in the RBD of the circulating SARS-CoV-2 isolates have altered the receptor binding affinity and made them more infectious has been the research hot spot. Given that SARS-CoV-2 is a novel coronavirus, the significance of our research is in identifying and validating the RBD mutant types emerging during the early transmission phase and increasing human angiotensin-converting enzyme 2 (ACE2) receptor binding affinity and infectivity. Our study provides insights into the evolutionary trajectory of early SARS-CoV-2 variants of zoonotic origin. The continuing surveillance of RBD mutations with increased human ACE2 affinity in human or other animals is critical to the development of new COVID-19 drugs and vaccines against these variants during the sustained COVID-19 pandemic.
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http://dx.doi.org/10.1128/JVI.00617-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373230PMC
July 2021

Development and Application of a Fast Method to Acquire the Accurate Whole-Genome Sequences of Human Adenoviruses.

Front Microbiol 2021 14;12:661382. Epub 2021 May 14.

Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China.

The whole-genome sequencing (WGS) of human adenoviruses (HAdVs) plays an important role in identifying, typing, and mutation analysis of HAdVs. Nowadays, three generations of sequencing have been developed. The accuracy of first-generation sequencing is up to 99.99%, whereas this technology relies on PCR and is time consuming; the next-generation sequencing (NGS) is expensive and not cost effective for determining a few special samples; and the third-generation sequencing technology has a higher error rate. In this study, first, we developed an efficient HAdV genomic DNA extraction method. Using the complete genomic DNA instead of the PCR amplicons as the direct sequencing template and a set of walking primers, we developed the HAdV WGS method based on first-generation sequencing. The HAdV whole genomes were effectively sequenced by a set of one-way sequencing primers designed, which reduced the sequencing time and cost. More importantly, high sequence accuracy is guaranteed. Four HAdV strains (GZ01, GZ02, HK35, and HK91) were isolated from children with acute respiratory diseases (ARDs), and the complete genomes were sequenced using this method. The accurate sequences of the whole inverted terminal repeats (ITRs) at both ends of the HAdV genomes were also acquired. The genome sequence of human adenovirus type 14 (HAdV-B14) strain GZ01 acquired by this method is identical to the sequence released in GenBank, which indicates that this novel sequencing method has high accuracy. The comparative genomic analysis identified that strain GZ02 isolated in September 2010 had the identical genomic sequence with the HAdV-B14 strain GZ01 (October 2010). Therefore, strain GZ02 is the first HAdV-B14 isolate emergent in China (September 2010; GenBank acc no. MW692349). The WGS of HAdV-C2 strain HK91 and HAdV-E4 strain HK35 isolated from children with acute respiratory disease in Hong Kong were also determined by this sequencing method. In conclusion, this WGS method is fast, accurate, and universal for common human adenovirus species B, C, and E. The sequencing strategy may also be applied to the WGS of the other DNA viruses.
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http://dx.doi.org/10.3389/fmicb.2021.661382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160523PMC
May 2021

Sox4 represses host innate immunity to facilitate pathogen infection by hijacking the TLR signaling networks.

Virulence 2021 12;12(1):704-722

Guangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University , Guangzhou, China.

Toll-like receptors (TLRs) are essential for the protection of the host from pathogen infections by initiating the integration of contextual cues to regulate inflammation and immunity. However, without tightly controlled immune responses, the host will be subjected to detrimental outcomes. Therefore, it is important to balance the positive and negative regulations of TLRs to eliminate pathogen infection, yet avert harmful immunological consequences. This study revealed a distinct mechanism underlying the regulation of the TLR network. The expression of sex-determining region Y-box 4 (Sox4) is induced by virus infection in viral infected patients and cultured cells, which subsequently represses the TLR signaling network to facilitate viral replication at multiple levels by a distinct mechanism. Briefly, Sox4 inhibits the production of myeloid differentiation primary response gene 88 (MyD88) and most of the TLRs by binding to their promoters to attenuate gene transcription. In addition, Sox4 blocks the activities of the TLR/MyD88/IRAK4/TAK1 and TLR/TRIF/TRAF3/TBK1 pathways by repressing their key components. Moreover, Sox4 represses the activation of the nuclear factor kappa-B (NF-κB) through interacting with IKKα/α, and attenuates NF-kB and IFN regulatory factors 3/7 (IRF3/7) abundances by promoting protein degradation. All these contributed to the down-regulation of interferons (IFNs) and IFN-stimulated gene (ISG) expression, leading to facilitate the viral replications. Therefore, we reveal a distinct mechanism by which viral pathogens evade host innate immunity and discover a key regulator in host defense.
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http://dx.doi.org/10.1080/21505594.2021.1882775DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894441PMC
December 2021

COVID-19: Coronavirus Vaccine Development Updates.

Front Immunol 2020 23;11:602256. Epub 2020 Dec 23.

Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China.

Coronavirus Disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a newly emerged coronavirus, and has been pandemic since March 2020 and led to many fatalities. Vaccines represent the most efficient means to control and stop the pandemic of COVID-19. However, currently there is no effective COVID-19 vaccine approved to use worldwide except for two human adenovirus vector vaccines, three inactivated vaccines, and one peptide vaccine for early or limited use in China and Russia. Safe and effective vaccines against COVID-19 are in urgent need. Researchers around the world are developing 213 COVID-19 candidate vaccines, among which 44 are in human trials. In this review, we summarize and analyze vaccine progress against SARS-CoV, Middle-East respiratory syndrome Coronavirus (MERS-CoV), and SARS-CoV-2, including inactivated vaccines, live attenuated vaccines, subunit vaccines, virus like particles, nucleic acid vaccines, and viral vector vaccines. As SARS-CoV-2, SARS-CoV, and MERS-CoV share the common genus, , this review of the major research progress will provide a reference and new insights into the COVID-19 vaccine design and development.
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http://dx.doi.org/10.3389/fimmu.2020.602256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785583PMC
January 2021

Temperature dependence of the SARS-CoV-2 affinity to human ACE2 determines COVID-19 progression and clinical outcome.

Comput Struct Biotechnol J 2021 16;19:161-167. Epub 2020 Dec 16.

MOE Key Laboratory of Tumor Molecular Biology and Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou 510632, China.

The SARS-CoV-2 virus and its homolog SARS-CoV penetrate human cells by binding of viral spike protein and human angiotensin converting enzyme II (ACE2). SARS-CoV causes high fever in almost all patients, while SARS-CoV-2 does not. Moreover, analysis of the clinical data revealed that the higher body temperature is a protective factor in COVID-19 patients, making us to hypothesize a temperature-dependent binding affinity of SARS-CoV-2 to human ACE2 receptor. In this study, our molecular dynamics simulation and protein surface plasmon resonance cohesively proved the SARS-CoV-2-ACE2 binding was less affinitive and stable under 40 °C (~18 nM) than the optimum temperature 37 °C (6.2 nM), while SARS-CoV-ACE2 binding was not (6.4 nM vs. 8.5 nM), which evidenced the temperature-dependent affinity and explained that higher temperature is related to better clinical outcome. The decreased infection at higher temperature was also validated by pseudovirus entry assay using Vero and Caco-2 cells. We also demonstrated the structural basis of the distinct temperature-dependence of the two coronaviruses. Furthermore, the meta-analysis revealed a milder inflammatory response happened in the early stage of COVID-19, which explained the low fever tendency of COVID-19 and indicated the co-evolution of the viral protein structure and the inflammatory response. The temperature dependence of the binding affinity also indicated that higher body temperature at early stages might be beneficial to the COVID-19 patients.
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http://dx.doi.org/10.1016/j.csbj.2020.12.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738279PMC
December 2020

COVID-19: Antiviral Agents, Antibody Development and Traditional Chinese Medicine.

Virol Sin 2020 Dec 30;35(6):685-698. Epub 2020 Sep 30.

Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, 510515, China.

The World Health Organization (WHO) has declared coronavirus disease 2019 (COVID-19) is the first pandemic caused by coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, there is no effective anti-SARS-CoV-2 drug approved worldwide for treatment of patients with COVID-19. Therapeutic options in response to the COVID-19 outbreak are urgently needed. To facilitate the better and faster development of therapeutic COVID-19 drugs, we present an overview of the global promising therapeutic drugs, including repurposing existing antiviral agents, network-based pharmacology research, antibody development and traditional Chinese medicine. Among all these drugs, we focus on the most promising drugs (such as favipiravir, tocilizumab, SARS-CoV-2 convalescent plasma, hydroxychloroquine, Lianhua Qingwen, interferon beta-1a, remdesivir, etc.) that have or will enter the final stage of human testing-phase III-IV clinical trials.
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http://dx.doi.org/10.1007/s12250-020-00297-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524871PMC
December 2020

[Progress in engineering application of human adenovirus].

Sheng Wu Gong Cheng Xue Bao 2020 Jul;36(7):1269-1276

Yunnan Provincial Center for Molecular Diagnosis, Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, Yunnan, China.

Human adenoviruses are widespread causative agent that induces respiratory diseases, epidemic keratoconjunctivitis and other related diseases. Adenoviruses are commonly used in experimental and clinical areas. It is one of the most commonly used virus vectors in gene therapy, and it has attracted a lot of attention and has a high research potential in tumor gene therapy and virus oncolytic. Here, we summarize the biological characteristics, epidemiology and current application of adenovirus, in order to provide reference for engineering application of adenovirus.
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http://dx.doi.org/10.13345/j.cjb.190496DOI Listing
July 2020

Characterization of Influenza A and B Viruses Circulating in Southern China During the 2017-2018 Season.

Front Microbiol 2020 29;11:1079. Epub 2020 May 29.

Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China.

The trivalent seasonal influenza vaccine was the only approved and available vaccine during the 2016-2018 influenza seasons. It did not include the B/Yamagata strain. In this study, we report an acute respiratory disease outbreak associated with influenza B/Yamagata infections in Guangzhou, Southern China (January through March, 2018). Among the 9914 patients, 2241 (22.6%) were positive for the influenza B virus, with only 312 (3.1%) positive for the influenza A virus. The influenza B/Yamagata lineage dominated during this period in Southern China. The highest incidence of influenza A virus infection occurred in the children aged 5-14 years. In contrast, populations across all age groups were susceptible to the influenza B virus. Phylogenetic, mutations, and 3D structure analyses of hemagglutinin (HA) genes were performed to assess the vaccine-virus relatedness. The recommended A/H1N1 vaccine strain (A/Michigan/45/2015) during both 2017-2018 and 2018-2019 was antigen-specific for these circulating isolates (clade 6B.1) in Spring 2018. An outbreak of influenza B/Yamagata (clade 3) infections in 2018 occurred during the absence of the corresponding vaccine during 2016-2018. The recommended influenza B/Yamagata vaccine strain (B/Phuket/3073/2013) for the following season (2018-2019) was antigen-specific. Although there were only a few influenza B/Victoria infections in Spring 2018, five amino acid mutations were identified in the HA antigenic sites of the 19 B/Victoria isolates (clade 1A), when compared with the 2016-2018 B/Victoria vaccine strain. The number was larger than expected and suggested that the influenza B HA gene may be more variable than previously thought. One of the mutations (K180N) was noted to likely alter the epitope and to potentially affect the viral antigenicity. Seven mutations were also identified in the HA antigenic sites of 2018-2020 B/Victoria vaccine strain, of which some or all may reduce immunogenicity and the protective efficacy of the vaccine, perhaps leading to more outbreaks in subsequent seasons. The combined epidemiological, phylogenetic, mutations, and 3D structural analyses of the HA genes of influenza strains reported here contribute to the understanding and evaluation of how HA mutations affect vaccine efficacy, as well as to providing important data for screening and selecting more specific, appropriate, and effective influenza vaccine candidate strains.
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http://dx.doi.org/10.3389/fmicb.2020.01079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7272714PMC
May 2020

Construction and Characterization of a Novel Recombinant Attenuated and Replication-Deficient Candidate Human Adenovirus Type 3 Vaccine: "Adenovirus Vaccine Within an Adenovirus Vector".

Virol Sin 2021 Jun 26;36(3):354-364. Epub 2020 May 26.

Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, 510515, China.

Human adenoviruses (HAdVs) are highly contagious and result in large number of acute respiratory disease (ARD) cases with severe morbidity and mortality. Human adenovirus type 3 (HAdV-3) is the most common type that causes ARD outbreaks in Asia, Europe, and the Americas. However, there is currently no vaccine approved for its general use. The hexon protein contains the main neutralizing epitopes, provoking strong and lasting immunogenicity. In this study, a novel recombinant and attenuated adenovirus vaccine candidate against HAdV-3 was constructed based on a commercially-available replication-defective HAdV-5 gene therapy and vaccine vector. The entire HAdV-3 hexon gene was integrated into the E1 region of the vector by homologous recombination using a bacterial system. The resultant recombinants expressing the HAdV-3 hexon protein were rescued in AD293 cells, identified and characterized by RT-PCR, Western blots, indirect immunofluorescence, and electron microscopy. This potential vaccine candidate had a similar replicative efficacy as the wild-type HAdV-3 strain. However, and importantly, the vaccine strain had been rendered replication-defective and was incapable of replication in A549 cells after more than twenty-generation passages in AD293 cells. This represents a significant safety feature. The mice immunized both intranasally and intramuscularly by this vaccine candidate raised significant neutralizing antibodies against HAdV-3. Therefore, this recombinant, attenuated, and safe adenovirus vaccine is a promising HAdV-3 vaccine candidate. The strategy of using a clinically approved and replication-defective HAdV-5 vector provides a novel approach to develop universal adenovirus vaccine candidates against all the other types of adenoviruses causing ARDs and perhaps other adenovirus-associated diseases.
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http://dx.doi.org/10.1007/s12250-020-00234-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7248191PMC
June 2021

Programmable stopbands and supratransmission effects in a stacked Miura-origami metastructure.

Phys Rev E 2020 Apr;101(4-1):042206

Institute of AI and Robotics, Fudan University, Shanghai 200433, China.

Origami-based mechanical metamaterials and metastructure have been demonstrated to exhibit unique properties originating from their intricate geometries of folding. This research aims to extend the current investigation level from quasistatics to dynamics. In detail, this research focuses on the wave dynamics of a metastructure composed of stacked Miura-origami (SMO) units. The SMO unit could possess two stable configurations, endowing the metastructure with rich possibilities in the layout of its periodic repeating cell. Through linear dispersion analyses and numerical studies, we show that the long-desired stopband tunability and programmability of the metastructure along the three principal directions can be acquired by strategically programming the layout of the periodic cell. Based upon that, we further discover that energy supratransmission through the metastructure is possible within the stopband by increasing the driving amplitude. Through numerical means, the amplitude threshold of supratransmission is obtained. We demonstrate that the fundamental mechanism that triggers the supratransmission phenomenon is the transition of the responses from the low-energy intrawell oscillations to the high-energy interwell oscillations. Numerical studies also indicate that the supratransmission threshold can be effectively tailored by adjusting the periodic cell layout. The results of this research provide a wealth of fundamental insights into the origami wave dynamics and offer useful guidelines for developing origami metastructures with tunable and programmable dynamic characteristics.
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http://dx.doi.org/10.1103/PhysRevE.101.042206DOI Listing
April 2020

Simultaneous Enhancement and Modulation of Upconversion by Thermal Stimulation in ScMoO Crystals.

J Phys Chem Lett 2020 Apr 3;11(8):3020-3024. Epub 2020 Apr 3.

Department of Materials Science and Engineering, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong SAR, China.

Rational control of photoluminescence against a change in temperature is important for fundamental research and technological applications. Herein, we report an anomalous temperature dependence of upconversion luminescence in Yb/Ho co-doped ScMoO crystals. By leveraging negative thermal expansion of the crystal lattice, energy transfer between the lanthanide dopants is promoted as the temperature is increased from 303 to 573 K, resulting in an ∼5-fold enhancement of the emission. Meanwhile, the emission profile is also substantially altered due to the concurrent thermal quenching of selective energy states, corresponding to a clear shift in color from green to red. Via correlation of the red-to-green emission intensity ratio of Ho dopant ions with temperature, a ratiometric luminescence thermometer is constructed with a maximum sensitivity of 2.75% K at 543 K. As the ScMoO crystals are thermally stable and nonhygroscopic, our findings highlight a general approach for highly reversible control of upconversion by temperature in ambient air.
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http://dx.doi.org/10.1021/acs.jpclett.0c00628DOI Listing
April 2020

miR-4999-5p Predicts Colorectal Cancer Survival Outcome and Reprograms Glucose Metabolism by Targeting PRKAA2.

Onco Targets Ther 2020 11;13:1199-1210. Epub 2020 Feb 11.

Department of Gastrointestinal Surgery, The First Affiliated Hospital, Yijishan Hospital of Wannan Medical College, Wuhu 241000, Anhui, People's Republic of China.

Purpose: Colorectal cancer (CRC) is the third most common cancer, and the second leading cause of cancer death worldwide. Dysregulation of microRNAs has been shown to modulate glucose metabolic reprogramming in CRC. However, the functional role of miR-4999-5p in the CRC glucose metabolic shift has not been characterized.

Patients And Methods: The levels of miR-4999-5p and PRKAA2 were evaluated by RT-qPCR. Univariate and multivariate survival analyses were conducted to evaluate the prognostic value of miR-4999-5p. Cell proliferation was assessed using the CCK-8 and colony formation assays. Extracellular acidification rate, glucose uptake, cellular glucose-6-phosphate level, and lactate production were evaluated to assess the effects of miR-4999-5p on CRC glycolysis. Dual-luciferase reporter assay was conducted to investigate the direct interaction between miR-4999-5p and PRKAA2. Mouse xenograft models were established to assess the functions of miR-4999-5p in vivo.

Results: miR-4999-5p was highly expressed in CRC tissues and cell lines. In addition, miR-4999-5p was associated with tumor differentiation and TNM stage, and elevated expression of miR-4999-5p was an independent predictor of poorer overall survival. Furthermore, miR-4999-5p promoted cell proliferation and glycolysis in CRC. miR-4999-5p targeted PRKAA2 to exert its tumor-promoting functions, and PRKAA2 knockdown rescued decreased cell proliferation and glycolysis in miR-4999-5p-silenced CRC cells. In vivo experiments showed that miR-4999-5p promoted CRC growth.

Conclusion: miR-4999-5p facilitated cell growth and glucose metabolic reprogramming through direct targeting of PRKAA2. Our results showed that miR-4999-5p may be a novel prognostic marker and therapeutic target for CRC.
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http://dx.doi.org/10.2147/OTT.S234666DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7024870PMC
February 2020

Composition and divergence of coronavirus spike proteins and host ACE2 receptors predict potential intermediate hosts of SARS-CoV-2.

J Med Virol 2020 06 11;92(6):595-601. Epub 2020 Mar 11.

Department of Respiratory, Department of Infectious Diseases, School of Basic Medical Sciences, Renmin Hospital, Hubei University of Medicine, Shiyan, China.

From the beginning of 2002 and 2012, severe respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) crossed the species barriers to infect humans, causing thousands of infections and hundreds of deaths, respectively. Currently, a novel coronavirus (SARS-CoV-2), which has become the cause of the outbreak of Coronavirus Disease 2019 (COVID-19), was discovered. Until 18 February 2020, there were 72 533 confirmed COVID-19 cases (including 10 644 severe cases) and 1872 deaths in China. SARS-CoV-2 is spreading among the public and causing substantial burden due to its human-to-human transmission. However, the intermediate host of SARS-CoV-2 is still unclear. Finding the possible intermediate host of SARS-CoV-2 is imperative to prevent further spread of the epidemic. In this study, we used systematic comparison and analysis to predict the interaction between the receptor-binding domain (RBD) of coronavirus spike protein and the host receptor, angiotensin-converting enzyme 2 (ACE2). The interaction between the key amino acids of S protein RBD and ACE2 indicated that, other than pangolins and snakes, as previously suggested, turtles (Chrysemys picta bellii, Chelonia mydas, and Pelodiscus sinensis) may act as the potential intermediate hosts transmitting SARS-CoV-2 to humans.
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http://dx.doi.org/10.1002/jmv.25726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7228221PMC
June 2020

MicroRNA expression profiling of peripheral blood mononuclear cells associated with syphilis.

BMC Infect Dis 2020 Feb 22;20(1):165. Epub 2020 Feb 22.

Dermatology Hospital, Southern Medical University, Guangzhou, China.

Background: Treponema pallidum (T. pallidum) infection evokes significant immune responses, resulting in tissue damage. The immune mechanism underlying T. pallidum infection is still unclear, although microRNAs (miRNAs) have been shown to influence immune cell function and, consequently, the generation of antibody responses during other microbe infections. However, these mechanisms are unknown for T. pallidum.

Methods: In this study, we performed a comprehensive analysis of differentially expressed miRNAs in healthy individuals, untreated patients with syphilis, patients in the serofast state, and serologically cured patients. miRNAs were profiled from the peripheral blood of patients obtained at the time of serological diagnosis. Then, both the target sequence analysis of these different miRNAs and pathway analysis were performed to identify important immune and cell signaling pathways. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was performed for microRNA analysis.

Results: A total of 74 differentially regulated miRNAs were identified. Following RT-qPCR confirmation, three miRNAs (hsa-miR-195-5p, hsa-miR-223-3p, hsa-miR-589-3p) showed significant differences in the serofast and serologically cured states (P < 0.05). One miRNA (hsa-miR-195-5p) showed significant differences between untreated patients and healthy individuals.

Conclusions: This is the first study of miRNA expression differences in peripheral blood mononuclear cells (PBMCs) in different stages of T. pallium infection. Our study suggests that the combination of three miRNAs has great potential to serve as a non-invasive biomarker of T. pallium infections, which will facilitate better diagnosis and treatment of T. pallium infections.
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http://dx.doi.org/10.1186/s12879-020-4846-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7036247PMC
February 2020

Electrochemically C-H/S-H Oxidative Cross-Coupling between Quinoxalin-2(1)-ones and Thiols for the Synthesis of 3-Thioquinoxalinones.

J Org Chem 2020 03 2;85(6):4365-4372. Epub 2020 Mar 2.

Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou 310014, P. R. China.

An electrochemical method for the C(sp)-H thioetherification of quinoxalin-2(1)-ones with primary, secondary, and tertiary thiols has been reported. Various quinoxalin-2(1)-ones underwent this thioetherification smoothly under metal- and chemical oxidant-free conditions, affording 3-alkylthiol-substituted quinoxalin-2(1)-ones in moderate to good yields.
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http://dx.doi.org/10.1021/acs.joc.0c00050DOI Listing
March 2020

Coronavirus infections and immune responses.

J Med Virol 2020 04 7;92(4):424-432. Epub 2020 Feb 7.

Guangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou, China.

Coronaviruses (CoVs) are by far the largest group of known positive-sense RNA viruses having an extensive range of natural hosts. In the past few decades, newly evolved Coronaviruses have posed a global threat to public health. The immune response is essential to control and eliminate CoV infections, however, maladjusted immune responses may result in immunopathology and impaired pulmonary gas exchange. Gaining a deeper understanding of the interaction between Coronaviruses and the innate immune systems of the hosts may shed light on the development and persistence of inflammation in the lungs and hopefully can reduce the risk of lung inflammation caused by CoVs. In this review, we provide an update on CoV infections and relevant diseases, particularly the host defense against CoV-induced inflammation of lung tissue, as well as the role of the innate immune system in the pathogenesis and clinical treatment.
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http://dx.doi.org/10.1002/jmv.25685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7166547PMC
April 2020

MicroRNA-101-3p Downregulates TLR2 Expression, Leading to Reduction in Cytokine Production by Treponema pallidum-Stimulated Macrophages.

J Invest Dermatol 2020 08 11;140(8):1566-1575.e1. Epub 2020 Jan 11.

Research Center, Dermatology Hospital, Southern Medical University, Guangzhou, China. Electronic address:

Treponema pallidum (Tp) infection-induced immune responses can cause tissue damage. However, the underlying mechanism by which Tp infection induces immune response is unclear. Recent studies suggest a regulatory role of microRNAs in host immunity. We assessed whether microRNAs also have a regulatory role in immune response to Tp infection in vitro. Our results showed that microRNA-101-3p (miR-101-3p) levels were significantly higher in peripheral blood mononuclear cells of patients with primary syphilis and those in the serofast state, whereas toll-like receptor (TLR) 2 levels were higher in patients with syphilis than in healthy controls. In vitro, stimulation of THP-1 cells with Tp increased miR-101-3p expression. Moreover, miR-101-3p reduced expression levels of TLR2 mRNA and protein in THP-1 cells via binding to the 3' untranslated region of TLR2. Likewise, miR-101-3p inhibited production of inflammatory cytokines, including IL-1β, IL-6, tumor necrosis factor-α, and IL-12, in Tp-stimulated macrophages. IL-1β and IL-6 mRNA expression levels were reduced by transfection of macrophages with a TLR2-specific small interfering RNA. Conversely, overexpression of TLR2 upregulated cytokine expression. Patients with secondary syphilis exhibited the highest levels of plasma IL-6, which were negatively correlated with miR-101-3p. In conclusion, Tp infection upregulates miR-101-3p expression, which in turn inhibits the TLR2 signaling pathway, leading to reduced cytokine production.
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http://dx.doi.org/10.1016/j.jid.2019.12.012DOI Listing
August 2020

Profiling of isomer-specific IgG N-glycosylation in cohort of Chinese colorectal cancer patients.

Biochim Biophys Acta Gen Subj 2020 03 27;1864(3):129510. Epub 2019 Dec 27.

The Key Laboratory for Biomedical Photonics of MOE at Wuhan National Laboratory for Optoelectronics-Hubei Bioinformatics & Molecular Imaging Key Laboratory, Systems Biology Theme, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China. Electronic address:

Backgroud: Given the increasing morbidity and mortality of colorectal cancer (CRC), it is urgent to develop a noninvasive screening strategy for early diagnosis of CRC. Altered IgG glycosylation is associated with CRC progression, whereas the association of IgG isomeric glycosylation with CRC were not investigated.

Methods: Methylamidation of IgG N-glycans was conducted prior to PGC-based nanoLC-ESI-MS/MS analysis. Data processing was operated by a self-developed application based on MATLAB solution. Statistical analysis including K-S test, t-test, ROC curve and OPLS-DA were successively performed. Additionally, an independent set was utilized to validate the results.

Results: Total 28 IgG glycans and 79 compositional isomers were identified, over half of which are firstly identified so far. Statistical analysis showed that CRC associates with increase in IgG agalactosylation, decrease in IgG sialylation and fucosylation of sialylated glycans. Additionally, it was found that three compositional isomers (H3N4F1-a, H3N4F1-b and H4N3S1F1-e) could distinguish CRC and early stages from controls with an accurate area under the receiver operating characteristic curve. Significantly, these results were validated in an independent set by multivariate statistical analysis.

Conclusions: This is the first comprehensively profiling of isomer-specific IgG N-glycosylation, which could differentiate normal controls from colorectal disease patients. The candidate IgG glyco-biomarkers provide important screening indicators for early diagnosis of CRC.

General Significance: Colorectal cancer progression is strongly associated with isomer-specific IgG N-glycosylation.
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http://dx.doi.org/10.1016/j.bbagen.2019.129510DOI Listing
March 2020

Visible-Light-Induced -Selective C(sp)-H Difluoroalkylation of Diverse (Hetero)aromatic Carbonyls.

Org Lett 2020 Jan 19;22(1):68-72. Epub 2019 Dec 19.

Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals , Zhejiang University of Technology , Hangzhou 310014 , P.R. China.

An efficient visible-light-induced -selective C(sp)-H difluoroalkylation of diverse electron-deficient (hetero)aromatic carbonyls (aldehydes and ketones) at ambient temperature has been developed by employing Ir(ppy) as the catalyst and 1,10-phenanthroline as the additive. This protocol was highlighted by its wide substrate scope, high regioselectivity, low catalyst usage, and operational simplicity.
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http://dx.doi.org/10.1021/acs.orglett.9b03923DOI Listing
January 2020

Antibiotic resistance genes removal and membrane fouling in secondary effluents by combined processes of PAC/BPAC-UF.

J Water Health 2019 Dec;17(6):910-920

Beijing Waterworks Group Co., Ltd., Beijing 100000, China.

Antibiotic resistance genes (ARGs), as emerging environmental contaminants, are becoming a threat to human health. In this study, the combined processes of powdered activated carbon (PAC)/biological PAC (BPAC)-ultrafiltration (UF) were adopted to reduce the levels of ARGs in secondary effluents from a wastewater treatment plant. The removal of dissolved organic carbon (DOC) and the change of normalized flux in the UF process were investigated. In addition, the structural characteristics of the microorganisms of the BPAC were analyzed. The results showed that the appropriate dosage of PAC and BPAC was 40 mg/L. At this dosage, PAC/BPAC-UF combined processes could effectively remove the ARGs in secondary effluents by 1.26-2.69-log and 1.55-2.97-log, respectively; and the removal rates of DOC would be 60.7% and 54.1%, respectively. Relative to the direct UF, the membrane fluxes of the two combined processes were increased by 15.6% and 25.1%, respectively. Significant removal correlations were found between ARGs, intI1, DOC and 16SrDNA. These results revealed that the PAC/BPAC-UF combined process might play a promising role in ARG reduction in secondary effluents from wastewater treatment plants.
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http://dx.doi.org/10.2166/wh.2019.160DOI Listing
December 2019

[Advances in derivatization for the analysis of sialic acids by chromatography and/or mass spectrometry].

Se Pu 2019 Dec;37(12):1261-1267

Key Laboratory of Optoelectronic Chemical Materials and Devices of Ministry of Education, Institute for Interdisciplinary Research, School of Chemistry and Environmental Engineering, Jianghan University, Wuhan 430056, China.

Sialic acids are a family of 9-carbon carboxylated monosaccharides. They are widely found in vertebrates, as well as some invertebrates, fungi and bacteria. Sialic acids in the organisms exist in free form or as important components at the terminal positions of glycoconjugates. They are involved in a variety of physiological activities, and are closely related to disease, such as inflammation and cancer. Analytical methods based on chromatography and/or mass spectrometry are the most widely used for characterizing sialic acids from biological samples. In order to improve the detection sensitivity and/or efficiency of chromatographic separation, it is necessary to derivatize the sialic acids prior to analysis. A variety of derivatization methods have been developed in the past few decades. The present review focuses on the derivatization methods for the analysis of sialic acids by chromatography and/or mass spectrometry at the monosaccharide, free sialic acid, /-glycan and glycosphingolipid levels. The applications and development trends in this field are also prospected.
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http://dx.doi.org/10.3724/SP.J.1123.2019.05025DOI Listing
December 2019
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