CELL RESEARCH
·
2021
·Vol. 31
·期 10
·1047-1060
·
IF 25.617
Hu Wei,Zhang Yong,Fei Panyu,Zhang Tongtong,Yao Danmei,Gao Yufei,Liu Jia,Chen Hui,Lu Qiao,Mudianto Tenny,Zhang Xinrui,Xiao Chuxuan,Ye Yang,Sun Qiming,Zhang Jing,Xie Qi,Wang Pei-Hui,Wang Jun,Li Zhenhai,Lou Jizhong,Chen Wei
The outbreak of SARS-CoV-2 (SARS2) has caused a global COVID-19 pandemic. The spike protein of SARS2 (SARS2-S) recognizes host receptors, including ACE2, to initiate viral entry in a complex biomechanical environment. Here, we reveal that tensile force, generated by bending of the host cell membrane, strengthens spike recognition of ACE2 and accelerates the detachment of spike’s S1 subunit from the S2 subunit to rapidly prime the viral fusion machinery. Mechanistically, such mechano-activation is fulfilled by force-induced opening and rotation of spike’s receptor-binding domain to prolong the bond lifetime of spike/ACE2 binding, up to 4 times longer than that of SARS-S binding with ACE2 under 10 pN force application, and subsequently by force-accelerated S1/S2 detachment which is up to ~10 3 times faster than that in the no-force condition. Interestingly, the SARS2-S D614G mutant, a more infectious variant, shows 3-time stronger force-dependent ACE2 binding and 35-time faster force-induced S1/S2 detachment. We also reveal that an anti-S1/S2 non-RBD-blocking antibody that was derived from convalescent COVID-19 patients with potent neutralizing capability can reduce S1/S2 detachment by 3 × 10 6 times under force. Our study sheds light on the mechano-chemistry of spike activation and on developing a non-RBD-blocking but S1/S2-locking therapeutic strategy to prevent SARS2 invasion.
研究领域:
病毒学
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分子生物学
·
生物物理学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2019
·
IF 4.784
Kun Wang,Mengmeng Niu,Di Yao,Jing Zhao,Yue Wu,Baoxin Lu,Xiqun Zheng
A cell-bound exopolysaccharide (c-EPS) from Lactobacillus fermentum S1 was isolated and purified to near homogeneity by anion exchange and gel filtration chromatography. The c-EPS is a homogeneous heteropolysaccharide with an average molecular weight of 7.19 × 10 5 Da and comprises mainly mannose, rhamnose, glucose, and galactose. Fourier transform infrared spectroscopy spectrum of the c-EPS exhibited typical characteristic absorption peaks of polysaccharides. Methylation and NMR analyses showed that the c-EPS had a backbone of α-D-Gal p -(1 → 3), α-L-Rha p -(1 → 2), α-D-Glc p -(1 → 3), β-D-Gal p -(1 → 3), β-D-Glcl p -(1 → 2), and β-L-Rha p -(1 → 3,4) residues, terminated with α-D-Man p -(1 → residue. The advanced structure study indicated the c-EPS not to have a triple-helical conformation, while the microstructural study revealed a hollow porous structure for c-EPS. Further, the thermal analysis showed that the degradation temperature for the c-EPS was 288.0 °C; its peak temperature was 89.4 °C with an enthalpy value of 273.1 J/g. Moreover, the c-EPS exhibited potent DPPH, hydroxyl, and ABTS + radicals scavenging activities, as well as FRAP in a dose-dependent manner, which could significantly enhance the T-AOC and SOD activity and reduce MDA level in Caenorhabditis elegans. Therefore, this c-EPS could be utilized as a promising natural antioxidant for application in functional foods.
研究领域:
食品科学
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生物化学
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微生物学
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DOI
PubMed
高影响因子
NANO LETTERS
·
2021
·
IF 11.189
Hua Kang,Xuejun Wang,Mingquan Guo,Changhao Dai,Renzhong Chen,Lei Yang,Yanling Wu,Tianlei Ying,Zhaoqin Zhu,Dapeng Wei,Yunqi Liu,Dacheng Wei
The fast spread of SARS-CoV-2 has severely threatened the public health. Establishing a sensitive method for SARS-CoV-2 detection is of great significance to contain the worldwide pandemic. Here, we develop a graphene field-effect transistor (g-FET) biosensor and realize ultrasensitive SARS-CoV-2 antibody detection with a limit of detection (LoD) down to 10–18 M (equivalent to 10–16 g mL–1) level. The g-FETs are modified with spike S1 proteins, and the SARS-CoV-2 antibody biorecognition events occur in the vicinity of the graphene surface, yielding an LoD of ∼150 antibodies in 100 μL full serum, which is the lowest LoD value of antibody detection. The diagnoses time is down to 2 min for detecting clinical serum samples. As such, the g-FETs leverage rapid and precise SARS-CoV-2 screening and also hold great promise in prevention and control of other epidemic outbreaks in the future.
研究领域:
生物传感器
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纳米技术
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医学诊断
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材料科学
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DOI
PubMed
高影响因子
Food & Function
·
2017
·Vol. 8
·期 7
·2437-2443
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IF 3.247
Guangpu Xue,Lihu Gong,Cai Yuan,Mingming Xu,Xu Wang,Longguang Jiang,Mingdong Huang
Quercetin is a member of the flavonoids and was previously demonstrated to inhibit trypsin-like serine proteases at micromolar potencies. Different molecular models were proposed to explain such inhibition. However, controversies remain on the molecular details of inhibition. Here, we report the X-ray crystal structure of quercetin in a complex with the urokinase-type plasminogen activator (uPA), an archetypical serine protease. The structure showed that quercetin binds to the specific substrate binding pocket (S1 pocket) of uPA mainly through its two neighboring phenolic hydroxyl groups. Our study thus provides unambiguous evidence to support quercetin binding to serine proteases and defines the molecular basis of the interaction. Our results further establish that natural products with two adjacent phenolic hydroxyl groups (or catechol) are likely to inhibit other trypsin-like serine proteases, a new mechanism formerly under-recognized.
研究领域:
生物化学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
ACS Applied Bio Materials
·
2024
·
IF 4.6
Hao Chen,Xilin Xiong,Yuan Huang,Bo Huang,Xinxin Luo,Qi Ke,Pengyu Wu,Suxiao Wang
The global outbreak of the COVID-19 pandemic has indisputably wreaked havoc on societies worldwide, compelling the scientific community to seek urgently needed therapeutic agents with low-cost and low-side effect profiles. Numerous approaches have been investigated in the quest to prevent or treat COVID-19, but many of them exhibit unwelcome side effects, such as dysfunctional viral immune responses and inflammation. Herein, we present the preparation of solid natural human pulmonary alveolar epithelial cell (ATII) membrane-coated PLGA NPs (PLGA NPs@ATII-M), which demonstrate remarkable affinity and competitiveness to neutralize the SARS-CoV-2 S1 protein-coated NPs (SCMMA NPs–S1), which are employed as a surrogate for coronavirus particles. In addition, we first considered the antifouling properties of these types of NPs, and we found that this membrane-coated NP formulation boasts excellent antifouling capabilities, which serve to protect their neutralization properties out of shielding by protein coronas in blood circulation. Moreover, this formulation is easily prepared and stored with a low-cost profile and exhibits good specificity, high targeting efficiency, and potentially side effect avoiding, thus making it a highly promising candidate for COVID-19 treatment.
研究领域:
药学
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纳米技术
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病毒学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Nanotechnology Reviews
·
2022
·Vol. 11
·期 1
·2526-2534
·
IF 6.739
Ling Tan,Qiandan Fan,Fei Huang,Xin Tian,Wei Wei,Tongxin Bian,Yifan Guo,Xiaoling Xu,Zuowan Zhou
Capturing and detecting Fe 3+ ions in aqueous solution is of great significance in biological systems as well as the water treatment industry. Herein, pyrene-modified cellulose nanocrystal (CNC-1-Pyr) acting as a fluorescent probe was prepared by a one-step esterification reaction, which shows geometry relaxation under UV-light excitation. Experiments and density functional theory-based simulations revealed that the structural geometry relaxation is controlled by the electron excitation and fluorescence emission. The S1 state of CNC-1-Pyr provides a conformation match for coordination with Fe 3+ under the excitation of UV light, facilitating the detecting and capturing of Fe 3+ efficiently.
研究领域:
材料科学
·
分析化学
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环境科学
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纳米技术
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产品关联
DOI
高影响因子
Oncotarget
·
2017
·
IF 5.168
Na Huang,Shuai Lu,Xiao-Ge Liu,Jie Zhu,Yu-Jiong Wang,Rui-Tian Liu
Alzheimer's disease (AD) is the most common form of dementia, characterized by the formation of extracellular senile plaques and neuronal loss caused by amyloid β (Aβ) aggregates in the brains of AD patients. Conventional strategies failed to treat AD in clinical trials, partly due to the poor solubility, low bioavailability and ineffectiveness of the tested drugs to cross the blood-brain barrier (BBB). Moreover, AD is a complex, multifactorial neurodegenerative disease; one-target strategies may be insufficient to prevent the processes of AD. Here, we designed novel kind of poly(lactide-co-glycolic acid) (PLGA) nanoparticles by loading with Aβ generation inhibitor S1 (PQVGHL peptide) and curcumin to target the detrimental factors in AD development and by conjugating with brain targeting peptide CRT (cyclic CRTIGPSVC peptide), an iron-mimic peptide that targets transferrin receptor (TfR), to improve BBB penetration. The average particle size of drug-loaded PLGA nanoparticles and CRT-conjugated PLGA nanoparticles were 128.6 nm and 139.8 nm, respectively. The results of Y-maze and new object recognition test demonstrated that our PLGA nanoparticles significantly improved the spatial memory and recognition in transgenic AD mice. Moreover, PLGA nanoparticles remarkably decreased the level of Aβ, reactive oxygen species (ROS), TNF-α and IL-6, and enhanced the activities of super oxide dismutase (SOD) and synapse numbers in the AD mouse brains. Compared with other PLGA nanoparticles, CRT peptide modified-PLGA nanoparticles co-delivering S1 and curcumin exhibited most beneficial effect on the treatment of AD mice, suggesting that conjugated CRT peptide, and encapsulated S1 and curcumin exerted their corresponding functions for the treatment.
研究领域:
神经科学
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药理学
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纳米技术
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF VIROLOGY
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2023
·Vol. 97
·期 5
·
IF 5.4
Renrong You,Kangchengyin Liu,Min Huang,Lihua Tang,Xuehui Zhang,Yahui Huang,Jing Zhao,Ye Zhao,Lilin Ye,Guozhong Zhang
Infectious bronchitis virus (IBV) infections are initiated by the transmembrane spike (S) glycoprotein, which binds to host factors and fuses the viral and cell membranes. The N-terminal domain of the S1 subunit of IBV S protein binds to sialic acids, but the precise location of the sialic acid binding domain (SABD) and the role of the SABD in IBV-infected chickens remain unclear. Here, we identify the S1 N-terminal amino acid (aa) residues 19 to 227 (209 aa total) of IBV strains SD (GI-19) and GD (GI-7), and the corresponding region of M41 (GI-1), as the minimal SABD using truncated protein histochemistry and neuraminidase assays. Both α-2,3- and α-2,6-linked sialic acids on the surfaces of CEK cells can be used as attachment receptors by IBV, leading to increased infection efficiency. However, 9-O acetylation of the sialic acid glycerol side chain inhibits IBV S1 and SABD protein binding. We further constructed recombinant strains in which the S1 gene or the SABD in the GD and SD genomes were replaced with the corresponding region from M41 by reverse genetics. Infecting chickens with these viruses revealed that the virulence and nephrotropism of rSDM41-S1, rSDM41-206, rGDM41-S1, and rGDM41-206 strains were decreased to various degrees compared to their parental strains. A positive sera cross-neutralization test showed that the serotypes were changed for the recombinant viruses. Our results provide insight into IBV infection of host cells that may aid vaccine design.IMPORTANCE To date, only α-2,3-linked sialic acid has been identified as a potential host binding receptor for IBV. Here, we show the minimum region constituting the sialic acid binding domain (SABD) and the binding characteristics of the S1 subunit of spike (S) protein of IBV strains SD (GI-19), GD (GI-7), and M41 (GI-1) to various sialic acids. The 9-O acetylation modification partially inhibits IBV from binding to sialic acid, while the virus can also bind to sialic acid molecules linked to host cells through an α-2,6 linkage, serving as another receptor determinant. Substitution of the putative SABD from strain M41 into strains SD and GD resulted in reduced virulence, nephrotropism, and a serotype switch. These findings suggest that sialic acid binding has diversified during the evolution of γ-coronaviruses, impacting the biological properties of IBV strains. Our results offer insight into the mechanisms by which IBV invades host cells.
研究领域:
病毒学
·
分子生物学
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免疫学
·
动物健康
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DOI
PubMed
高影响因子
Food & Function
·
2020
·Vol. 11
·期 12
·10568-10579
·
IF 4.171
Jing Xu,Shan Jin,Fei Gan,Hui Xiong,Zhinan Mei,Yu Chen,Guangzhong Yang
The fruits of Garcinia xanthochymus can be eaten raw or processed into jams, preserves and vinegar. They provide not only vitamin and protein nutrients, but also pharmacologically active compounds, among which polycyclic polyprenylated acylphloroglucinols (PPAPs) are a major class. According to the literature, PPAPs exhibited good anti-cancer effects. This study investigated the antitumor effects and the underlying mechanism of S1 (the regioisomeric mixture of xanthochymol and guttiferone E) and S2 (the regioisomeric mixture of isoxanthochymol and cycloxanthochymol) isolated from the fruits of G. xanthochymus. In an H22 allograft mouse model, S1 and S2 could suppress the liver tumor growth and phosphorylation of STAT3. Computational modeling showed that S1 and S2 could form hydrogen bonds with the SH2 domain of STAT3. In HepG2 and MCF-7 cell lines, S1 and S2 downregulated the expression of p-STAT3Tyr705. Moreover, S1 and S2 inhibited the phosphorylation of JAK2 and Src, which are the upstream kinases of STAT3, and the expression of various STAT3-regulated genes, including anti-apoptotic (Bcl-XL, Mcl-1 and survivin), proliferative (cyclin D1) and angiogenic (VEGF) genes. As a result, S1 and S2 arrested the cell cycle and induced cell apoptosis, which were proved by the activation of cleaved caspase-3 and caspase-8. These results demonstrated that S1 and S2 from G. xanthochymus exhibited antitumor effects through the inactivation of STAT3, and could be promising candidates for cancer treatment.
研究领域:
药理学
·
肿瘤学
·
分子生物学
·
生物化学
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2022
·
IF 5.518
Yanan Jia,Lin Hao,Jun Zhang,Xing Zhang,Siying An,Ming Su,Huan Wang,Yufan Zhang
We describe a PCR-free, enzyme-free, and simple biosensing platform for the electrochemical monitoring of telomerase activity based on Au nanorods (AuNRs) as an electrocatalytic redox mediator, which enhances the electrochemical signal by catalyzing acetaminophen (AP). In this process, acid-functionalized ordered mesoporous carbon (OMC) was modified on a glassy carbon electrode (GCE) surface to offer -COOH sites. Moreover, the amino-modified S1 was fixed on the modified electrode by conducting an amide reaction. TS is extended to (TTAGGG) n repeat units in the presence of telomerase extract and dNTPs. One end (5′) is hybridized with S1 on the electrode, and the remaining end (3′) is combined with AuNRs-S2 probe. Clearly, the telomerase activity is relevant to the amount of connected AuNRs, resulting in different response signals. Therefore, with the telomerase extension triggered hybridization reaction, a large amount of AuNRs catalyst was introduced onto the surface of GCE as the sensing platform, thus achieving a sensitive electrochemical telomerase activity assay in the range of 20–2.15 × 10 6 HeLa cells mL −1 . This sensing platform shows that the limit of detection is 1.74 HeLa cells mL −1 , thus providing a promising method for the determination of telomerase activity and a powerful biosensor for accurate cancer monitoring and diagnosis.
研究领域:
生物传感器
·
电化学
·
癌症诊断
·
纳米技术
✓ 已验证
产品关联
DOI
高影响因子
ANALYTICAL CHEMISTRY
·
2022
·
IF 8.008
Chaowei Han,Tianbao Dong,Pengcheng Wang,Feimeng Zhou
Unlike conventional surface plasmon resonance (SPR) using an antifouling film to anchor biomolecules and a reference channel for background subtraction, SPR microscopy for single-cell analysis uses a protein- or polypeptide-modified gold substrate to immobilize cells and a cell-free area as the reference. In this work, we show that such a substrate is prone to nonspecific adsorption (NSA) of species from the cell culture media, resulting in false background signals that cannot be correctly subtracted. To obtain accurate kinetic results, we patterned a dual-channel substrate using a microfluidic device, with one channel having poly-l-lysine deposited in situ onto a preformed polyethylene glycol (PEG) self-assembled monolayer for cell immobilization and the other channel remaining as PEG-covered for reference. The two 2.0 mm-wide channels are separated by a 75 μm barrier, and parts of the channels can be readily positioned into the field of view of an SPR microscope. The use of this dual-channel substrate for background subtraction is contrasted with the conventional approach through the following binding studies: (1) wheat germ agglutinin (WGA) attachment to the N-acetyl glucosamine and N-acetyl-neuraminic acid sites of glycans on HFF cells, and (2) the S1 protein of the COVID-19 virus conjugation with angiotensin-converting enzyme 2 (ACE2) on the HEK293 cells. Both studies revealed that interferences by NSA and the surface plasmon polariton wave diffracted by cells can be excluded with the dual-channel substrate, and the much smaller refractive index changes caused by the injected solutions can be correctly subtracted. Consequently, sensorgrams with higher signal-to-noise ratios and shapes predicted by the correct binding model can be obtained with accurate kinetic and affinity parameters that are more biologically relevant. The affinity between S1 protein and ACE2 is comparable to that measured with recombinant ACE2, yet the binding kinetics is different, suggesting that the cell membrane does impose a kinetic barrier to their interaction.
研究领域:
生物物理学
·
生物化学
·
微流控技术
·
细胞生物学
·
分析化学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）