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Article ; Online: Microfluidic Chip-Assisted Upconversion Luminescence Biosensing Platform for Point-of-Care Virus Diagnostics.

Liu, Yuan / Lao, Xinyue / Wong, Man-Chung / Song, Menglin / Lai, Huang / Wang, Pui / Ma, Yingjin / Li, Lihua / Yang, Mo / Chen, Honglin / Hao, Jianhua

Advanced healthcare materials

2024 , Page(s) e2303897

Abstract: Epidemics caused by multiple viruses continue to emerge, which have brought a terrible impact on human society. Identification of viral infections with high sensitivity and portability is of significant importance for the screening and management of ... ...

Abstract	Epidemics caused by multiple viruses continue to emerge, which have brought a terrible impact on human society. Identification of viral infections with high sensitivity and portability is of significant importance for the screening and management of diseases caused by viruses. Herein, a microfluidic chip (MFC)-assisted upconversion luminescence biosensing platform is designed and fabricated for point-of-care virus detection. Upconversion nanoparticles with excellent stability are successfully synthesized as luminescent agents for optical signal generation in the portable virus diagnostic platform. The relevant investigation results illustrate that the MFC-assisted virus diagnostic platform possesses outstanding performance such as good integration, high sensitivity (1.12 pg mL
Language	English
Publishing date	2024-03-07
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2649576-4
ISSN	2192-2659 ; 2192-2640
ISSN (online)	2192-2659
ISSN	2192-2640
DOI	10.1002/adhm.202303897
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Article: Multiplexed detection of SARS-CoV-2 based on upconversion luminescence nanoprobe/MXene biosensing platform for COVID-19 point-of-care diagnostics.

Song, Menglin / Ma, Yingjing / Li, Lihua / Wong, Man-Chung / Wang, Pui / Chen, Jiangkun / Chen, Honglin / Wang, Feng / Hao, Jianhua

Materials & design

2022 Volume 223, Page(s) 111249

Abstract: Multiplexed detection is essential in biomedical sciences since it is more efficient and accurate than single-analyte detection. For an accurate early diagnosis of COVID-19, a multiplexed detection strategy is required to avoid false negatives with the ... ...

Abstract	Multiplexed detection is essential in biomedical sciences since it is more efficient and accurate than single-analyte detection. For an accurate early diagnosis of COVID-19, a multiplexed detection strategy is required to avoid false negatives with the existing gold standard assay. Nb
Language	English
Publishing date	2022-10-10
Publishing country	England
Document type	Journal Article
ISSN	0264-1275
ISSN	0264-1275
DOI	10.1016/j.matdes.2022.111249
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Article ; Online: Cellular 5'-3' mRNA Exoribonuclease XRN1 Inhibits Interferon Beta Activation and Facilitates Influenza A Virus Replication.

Liu, Yen-Chin / Mok, Bobo Wing-Yee / Wang, Pui / Kuo, Rei-Lin / Chen, Honglin / Shih, Shin-Ru

mBio

2021 Volume 12, Issue 4, Page(s) e0094521

Abstract: Cellular 5'-3' exoribonuclease 1 (XRN1) is best known for its role as a decay factor, which by degrading 5' monophosphate RNA after the decapping of DCP2 in P-bodies (PBs) ... ...

Abstract	Cellular 5'-3' exoribonuclease 1 (XRN1) is best known for its role as a decay factor, which by degrading 5' monophosphate RNA after the decapping of DCP2 in P-bodies (PBs) in
MeSH term(s)	A549 Cells ; Down-Regulation ; Exoribonucleases/genetics ; Exoribonucleases/immunology ; Host-Pathogen Interactions ; Humans ; Immunity, Innate ; Influenza A virus/immunology ; Influenza A virus/physiology ; Interferon Regulatory Factor-3/immunology ; Interferon Regulatory Factor-3/metabolism ; Interferon-beta/antagonists & inhibitors ; Interferon-beta/immunology ; Microtubule-Associated Proteins/genetics ; Microtubule-Associated Proteins/immunology ; Virus Replication
Chemical Substances	IRF3 protein, human ; Interferon Regulatory Factor-3 ; Microtubule-Associated Proteins ; Interferon-beta (77238-31-4) ; Exoribonucleases (EC 3.1.-) ; XRN1 protein, human (EC 3.1.13.1)
Language	English
Publishing date	2021-07-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	2557172-2
ISSN	2150-7511 ; 2161-2129
ISSN (online)	2150-7511
ISSN	2161-2129
DOI	10.1128/mBio.00945-21
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Article ; Online: Attenuating innate immunity and facilitating β-coronavirus infection by NSP1 of SARS-CoV-2 through specific redistributing hnRNP A2/B1 cellular localization.

Zhou, Fanghang / Wan, Qianya / Chen, Sheng / Chen, Ying / Wang, Pui-Hui / Yao, Xi / He, Ming-Liang

Signal transduction and targeted therapy

2021 Volume 6, Issue 1, Page(s) 371

MeSH term(s)	COVID-19 ; Heterogeneous-Nuclear Ribonucleoprotein Group A-B ; Humans ; Immunity, Innate ; SARS-CoV-2
Chemical Substances	Heterogeneous-Nuclear Ribonucleoprotein Group A-B ; hnRNP A2
Language	English
Publishing date	2021-10-26
Publishing country	England
Document type	Letter ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	2886872-9
ISSN	2059-3635 ; 2095-9907
ISSN (online)	2059-3635
ISSN	2095-9907
DOI	10.1038/s41392-021-00786-y
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Article ; Online: An intranasal influenza virus-vectored vaccine prevents SARS-CoV-2 replication in respiratory tissues of mice and hamsters.

Deng, Shaofeng / Liu, Ying / Tam, Rachel Chun-Yee / Chen, Pin / Zhang, Anna Jinxia / Mok, Bobo Wing-Yee / Long, Teng / Kukic, Anja / Zhou, Runhong / Xu, Haoran / Song, Wenjun / Chan, Jasper Fuk-Woo / To, Kelvin Kai-Wang / Chen, Zhiwei / Yuen, Kwok-Yung / Wang, Pui / Chen, Honglin

Nature communications

2023 Volume 14, Issue 1, Page(s) 2081

Abstract: Current available vaccines for COVID-19 are effective in reducing severe diseases and deaths caused by SARS-CoV-2 infection but less optimal in preventing infection. Next-generation vaccines which are able to induce mucosal immunity in the upper ... ...

Abstract	Current available vaccines for COVID-19 are effective in reducing severe diseases and deaths caused by SARS-CoV-2 infection but less optimal in preventing infection. Next-generation vaccines which are able to induce mucosal immunity in the upper respiratory to prevent or reduce infections caused by highly transmissible variants of SARS-CoV-2 are urgently needed. We have developed an intranasal vaccine candidate based on a live attenuated influenza virus (LAIV) with a deleted NS1 gene that encodes cell surface expression of the receptor-binding-domain (RBD) of the SARS-CoV-2 spike protein, designated DelNS1-RBD4N-DAF. Immune responses and protection against virus challenge following intranasal administration of DelNS1-RBD4N-DAF vaccines were analyzed in mice and compared with intramuscular injection of the BioNTech BNT162b2 mRNA vaccine in hamsters. DelNS1-RBD4N-DAF LAIVs induced high levels of neutralizing antibodies against various SARS-CoV-2 variants in mice and hamsters and stimulated robust T cell responses in mice. Notably, vaccination with DelNS1-RBD4N-DAF LAIVs, but not BNT162b2 mRNA, prevented replication of SARS-CoV-2 variants, including Delta and Omicron BA.2, in the respiratory tissues of animals. The DelNS1-RBD4N-DAF LAIV system warrants further evaluation in humans for the control of SARS-CoV-2 transmission and, more significantly, for creating dual function vaccines against both influenza and COVID-19 for use in annual vaccination strategies.
MeSH term(s)	Animals ; Cricetinae ; Humans ; Influenza Vaccines ; SARS-CoV-2/genetics ; Administration, Intranasal ; COVID-19 Vaccines ; COVID-19/prevention & control ; Spike Glycoprotein, Coronavirus/genetics ; Antibodies, Neutralizing ; BNT162 Vaccine ; Orthomyxoviridae ; Antibodies, Viral
Chemical Substances	Influenza Vaccines ; spike protein, SARS-CoV-2 ; COVID-19 Vaccines ; Spike Glycoprotein, Coronavirus ; Antibodies, Neutralizing ; BNT162 Vaccine ; Antibodies, Viral
Language	English
Publishing date	2023-04-12
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-37697-1
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Article ; Online: Multi-omics analysis of attenuated variant reveals potential evaluation marker of host damaging for SARS-CoV-2 variants.

Xie, Guangshan / Zhu, Lin / Liu, Siwen / Li, Cun / Diao, Xin / Zhang, Yanhao / Su, Xiuli / Song, Yuanyuan / Cao, Guodong / Zhong, Li / Wang, Pui / Liu, Xiaojuan / Mok, Bobo Wing-Yee / Zhang, Shusheng / Jin, Dong-Yan / Zhou, Jie / Chen, Honglin / Cai, Zongwei

Science China. Life sciences

2023 Volume 67, Issue 1, Page(s) 83–95

Abstract: SARS-CoV-2 continues to threaten human society by generating novel variants via mutation and recombination. The high number of mutations that appeared in emerging variants not only enhanced their immune-escaping ability but also made it difficult to ... ...

Abstract	SARS-CoV-2 continues to threaten human society by generating novel variants via mutation and recombination. The high number of mutations that appeared in emerging variants not only enhanced their immune-escaping ability but also made it difficult to predict the pathogenicity and virulence based on viral nucleotide sequences. Molecular markers for evaluating the pathogenicity of new variants are therefore needed. By comparing host responses to wild-type and variants with attenuated pathogenicity at proteome and metabolome levels, six key molecules on the polyamine biosynthesis pathway including putrescine, SAM, dc-SAM, ODC1, SAMS, and SAMDC were found to be differentially upregulated and associated with pathogenicity of variants. To validate our discovery, human airway organoids were subsequently used which recapitulates SARS-CoV-2 replication in the airway epithelial cells of COVID-19 patients. Using ODC1 as a proof-of-concept, differential activation of polyamine biosynthesis was found to be modulated by the renin-angiotensin system (RAS) and positively associated with ACE2 activity. Further experiments demonstrated that ODC1 expression could be differentially activated upon a panel of SARS-CoV-2 variants of concern (VOCs) and was found to be correlated with each VOCs' pathogenic properties. Particularly, the presented study revealed the discriminative ability of key molecules on polyamine biosynthesis as a predictive marker for virulence evaluation and assessment of SARS-CoV-2 variants in cell or organoid models. Our work, therefore, presented a practical strategy that could be potentially applied as an evaluation tool for the pathogenicity of current and emerging SARS-CoV-2 variants.
MeSH term(s)	Humans ; SARS-CoV-2/genetics ; COVID-19 ; Multiomics ; Putrescine
Chemical Substances	Putrescine (V10TVZ52E4)
Language	English
Publishing date	2023-09-15
Publishing country	China
Document type	Journal Article
ZDB-ID	2546732-3
ISSN	1869-1889 ; 1674-7305
ISSN (online)	1869-1889
ISSN	1674-7305
DOI	10.1007/s11427-022-2379-x
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Article ; Online: A CRISPR-Cas12a integrated SERS nanoplatform with chimeric DNA/RNA hairpin guide for ultrasensitive nucleic acid detection.

Yin, Bohan / Zhang, Qin / Xia, Xinyue / Li, Chuanqi / Ho, Willis Kwun Hei / Yan, Jiaxiang / Huang, Yingying / Wu, Honglian / Wang, Pui / Yi, Changqing / Hao, Jianhua / Wang, Jianfang / Chen, Honglin / Wong, Siu Hong Dexter / Yang, Mo

Theranostics

2022 Volume 12, Issue 13, Page(s) 5914–5930

Abstract: Background: ...

Abstract	Background:
MeSH term(s)	CRISPR-Cas Systems/genetics ; DNA/chemistry ; Gold/chemistry ; Metal Nanoparticles/chemistry ; Nucleic Acids ; RNA
Chemical Substances	Nucleic Acids ; RNA (63231-63-0) ; Gold (7440-57-5) ; DNA (9007-49-2)
Language	English
Publishing date	2022-08-08
Publishing country	Australia
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2592097-2
ISSN	1838-7640 ; 1838-7640
ISSN (online)	1838-7640
ISSN	1838-7640
DOI	10.7150/thno.75816
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Article ; Online: Rapid point-of-care detection of SARS-CoV-2 RNA with smartphone-based upconversion luminescence diagnostics.

Song, Menglin / Wong, Man-Chung / Li, Lihua / Guo, Feng / Liu, Yuan / Ma, Yingjing / Lao, Xinyue / Wang, Pui / Chen, Honglin / Yang, Mo / Hao, Jianhua

Biosensors & bioelectronics

2022 Volume 222, Page(s) 114987

Abstract: Accurate COVID-19 screening via molecular technologies is still hampered by bulky instrumentation, complicated procedure, high cost, lengthy testing time, and the need for specialized personnel. Herein, we develop point-of-care upconversion luminescence ... ...

Abstract	Accurate COVID-19 screening via molecular technologies is still hampered by bulky instrumentation, complicated procedure, high cost, lengthy testing time, and the need for specialized personnel. Herein, we develop point-of-care upconversion luminescence diagnostics (PULD), and a streamlined smartphone-based portable platform facilitated by a ready-to-use assay for rapid SARS-CoV-2 nucleocapsid (N) gene testing. With the complementary oligo-modified upconversion nanoprobes and gold nanoprobes specifically hybridized with the target N gene, the luminescence resonance energy transfer effect leads to a quenching of fluorescence intensity that can be detected by the easy-to-use diagnostic system. A remarkable detection limit of 11.46 fM is achieved in this diagnostic platform without the need of target amplification, demonstrating high sensitivity and signal-to-noise ratio of the assay. The capability of the developed PULD is further assessed by probing 9 RT-qPCR-validated SARS-CoV-2 variant clinical samples (B.1.1.529/Omicron) within 20 min, producing reliable diagnostic results consistent with those obtained from a standard fluorescence spectrometer. Importantly, PULD is capable of identifying the positive COVID-19 samples with superior sensitivity and specificity, making it a promising front-line tool for rapid, high-throughput screening and infection control of COVID-19 or other infectious diseases.
Language	English
Publishing date	2022-12-05
Publishing country	England
Document type	Journal Article
ZDB-ID	1011023-9
ISSN	1873-4235 ; 0956-5663
ISSN (online)	1873-4235
ISSN	0956-5663
DOI	10.1016/j.bios.2022.114987
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Article: Multiple basic amino acids in the cleavage site of H7N9 hemagglutinin contribute to high virulence in mice.

Song, Wenjun / Huang, Xiaofeng / Guan, Wenda / Chen, Pin / Wang, Pui / Zheng, Min / Li, Zhengtu / Wang, Yutao / Yang, Zifeng / Chen, Honglin / Wang, Xinhua

Journal of thoracic disease

2021 Volume 13, Issue 8, Page(s) 4650–4660

Abstract: Background: Avian influenza A (H7N9) virus has caused more than 1,500 cases of human infection since its emergence in early 2013. Displaying little or no pathogenicity in poultry, but a 40% case-fatality rate in humans, five waves of H7N9 human ... ...

Abstract	Background: Avian influenza A (H7N9) virus has caused more than 1,500 cases of human infection since its emergence in early 2013. Displaying little or no pathogenicity in poultry, but a 40% case-fatality rate in humans, five waves of H7N9 human infections occurred in China during 2013-2017, caused solely by a low pathogenicity strain. However, avian isolates possessing a polybasic connecting peptide in the hemagglutinin (HA) protein were detected in mid-2016, indicating that a highly pathogenic virus had emerged and was co-circulating with the low pathogenicity strains. Methods: Here we characterize the pathogenicity of a newly emerged human H7N9 variant with a PEVPKRKRTAR/GLF insertion motif at the cleavage site of the HA protein Results: This variant replicates in MDCK cells independently of TPCK-trypsin, which is indicative of high pathogenicity in chickens. The 50% mouse lethal dose (MLD Conclusions: Our results demonstrate that the multiple basic amino acid insertion in the HA protein of the H7N9 variant confers high virulence in mammals, highlighting a potential risk to humans. Continuous viral surveillance is therefore necessary in the China region to improve pandemic preparedness.
Language	English
Publishing date	2021-07-26
Publishing country	China
Document type	Journal Article
ZDB-ID	2573571-8
ISSN	2077-6624 ; 2072-1439
ISSN (online)	2077-6624
ISSN	2072-1439
DOI	10.21037/jtd-21-226
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Article ; Online: Intradermal vaccination of live attenuated influenza vaccine protects mice against homologous and heterologous influenza challenges.

Lee, Andrew Chak-Yiu / Zhang, Anna Jinxia / Li, Can / Chen, Yanxia / Liu, Feifei / Zhao, Yan / Chu, Hin / Fong, Carol Ho-Yan / Wang, Pui / Lau, Siu-Ying / To, Kelvin Kai-Wang / Chen, Honglin / Yuen, Kwok-Yung

NPJ vaccines

2021 Volume 6, Issue 1, Page(s) 95

Abstract: We previously developed a temperature-sensitive, and NS1 gene deleted live attenuated influenza vaccine (DelNS1-LAIV) and demonstrated its potent protective efficacy in intranasally vaccinated mice. Here we investigated whether intradermal (i.d.) ... ...

Abstract	We previously developed a temperature-sensitive, and NS1 gene deleted live attenuated influenza vaccine (DelNS1-LAIV) and demonstrated its potent protective efficacy in intranasally vaccinated mice. Here we investigated whether intradermal (i.d.) vaccination induces protective immunity. Our results showed that DelNS1-LAIV intradermal vaccination conferred effective and long-lasting protection against lethal virus challenge in mice. A single intradermal injection of DelNS1-LAIV conferred 100% survival with no weight loss in mice after A(H1N1)09 influenza virus (H1N1/415742Md) challenge. DelNS1-LAIV injection resulted in a significant reduction of lung viral load and reduced airway epithelial cell death and lung inflammatory cytokine responses at day 2 and 4 post challenge. Full protections of mice lasted for 6 months after immunization. In vitro infection of DelNS1-LAIV in monocyte-derived dendritic cells (MoDCs) demonstrated activation of antigen-presenting cells at 33 °C, together with the results of abortive replication of DelNS1-LAIV in skin tissue and strong upregulation of inflammatory cytokines/chemokines expression, our results suggested the strong immunogenicity of this vaccine. Further, we demonstrate that the underlying protection mechanism induced by intradermal DelNS1-LAIV is mainly attributed to antibody responses. Together, this study opens up an alternative route for the administration of LAIV, which may benefit individuals not suitable for intranasal LAIV immunization.
Language	English
Publishing date	2021-08-04
Publishing country	England
Document type	Journal Article
ISSN	2059-0105
ISSN (online)	2059-0105
DOI	10.1038/s41541-021-00359-8
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