SEPARATION AND PURIFICATION TECHNOLOGY
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2024
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IF 8.1
Yamin Chai,Yanchun Li,Wenyan Han,Yanjia Zhang,Yunzheng Du,Biao Wang,Mengya Chen,Nan Li,Xiaoyu Zha,Zhidong Hu,Lichun Wang,Lailiang Ou
Due to variations in virus structures and their high variability, treating viral infections remains challenging. Moreover, developing vaccines and medications for newly emerged viruses demands a significant time investment. Efficient methods are required to prevent dangerous infections caused by unknown pathogens. Hemoperfusion, with its low cost, can effectively remove toxins from the blood quickly, thus achieving therapeutic effects. The core of the hemoperfusion technology lies in the adsorbent. Therefore, the development of a viral adsorbent aiming to combat viruses through hemoperfusion was envisioned, following general principles to effectively save lives and buy time for the research and development of vaccines and medications. Towards this goal, a facile, green, and low-priced magnetic biochar/quaternary ammonium salt (Fe 3 O 4 /C-2) was constructed using the hydrothermal carbonization (HTC) method. HIV lentiviruses were used as a model pathogen to quantify the adsorption capacity and elucidate the adsorption mechanism. Benefiting from a macroporous structure and electrostatic interactions, fabricated Fe 3 O 4 /C-2 has a high adsorption capacity (965 ng g −1 ) and strong suppression of infectious activity (99.99%). Moreover, a low hemolysis ratio (<2%), high cell viability (>100%), high activated partial thromboplastin time (APTT) (67.29 s), and low protein adsorption (<5%) indicate outstanding biocompatibility and good anticoagulant activity. Therefore, Fe 3 O 4 /C-2 is expected to serve as a simple and efficient pathogen sorbent for viral diseases treatment.
研究领域:
医学
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材料科学
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高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2023
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IF 5.8
Yujia Li,Yike Huang,Kehui Zhu,Xiaoqiong Duan,Shilin Li,Min Xu,Chunhui Yang,Jiaxin Liu,Hans Bäumler,Pin Yu,He Xie,Bin Li,Ye Cao,Limin Chen
The coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), resulting in a serious burden on public health and social economy worldwide. SARS-CoV-2 infection is mainly initialized in the nasopharyngeal cavity through the binding of viral spike (S) protein to human angiotensin-converting enzyme 2 (hACE2) receptors which are widely expressed in many human cells. Thus, blockade of the interaction between viral S protein and hACE2 receptor in the primary entry site is a promising prevention strategy for the management of COVID-19. Here we showed protein microparticles (PMPs) decorated with hACE2 could bind and neutralize SARS-CoV-2 S protein-expressing pseudovirus (PSV) and protect host cells from infection in vitro. In the hACE2 transgenic mouse model, administration of intranasal spray with hACE2-decorated PMPs markedly decreased the viral load of SARS-CoV-2 in the lungs though the inflammation was not attenuated significantly. Our results provided evidence for developing functionalized PMPs as a potential strategy for preventing emerging air-borne infectious pathogens, such as SARS-CoV-2 infection.
研究领域:
病毒学
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药学
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传染病学
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生物技术
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DOI
PubMed
高影响因子
Environmental Science-Nano
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2022
·Vol. 9
·期 8
·2653-2664
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IF 9.473
Guofang Zhang,Guoli Cao,Rong-Hua Luo,Qingle Song,Yanqiao Zeng,Ke Liu,Jing Qu,Xian Lin,Feng-Liang Liu,Guocheng Wang,Hongchang Li,Liang Li,Yong-Tang Zheng,Diana Boraschi,Lidong Wu,Yan-Zhong Chang,Yang Li
Microplastics (MP) pollution is a global issue that raises concerns about potential toxicity for environmental and human health. The notion that SARS-CoV-2 is more stable when adsorbed on plastic surfaces urged us to examine whether the virus can attach to MP, which may facilitate infection upon inhalation or ingestion. Here, we describe that MP can bind SARS-CoV-2 pseudovirus on their surface and enhance infection of human cells in vitro. This enhanced in vitro infectivity was confirmed with authentic SARS-CoV-2, in parallel with increased expression of inflammation-related caspase-3, IL-8 and TNF-α genes. These results suggest that the presence of MP in the environment or in our respiratory or gastrointestinal tracts has the potential to interact with SARS-CoV-2, and potentially increase viral infectivity and spreading.
研究领域:
环境科学
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病毒学
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毒理学
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细胞生物学
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DOI
高影响因子
Infectious Diseases and Therapy
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2021
·Vol. 10
·期 1
·483-494
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IF 5.322
Xu Huan,Liu Bing,Xiao Zhen,Zhou Meiling,Ge Lin,Jia Fan,Liu Yanling,Jin Hongshan,Zhu Xiuliang,Gao Jian,Akhtar Javed,Xiang Bai,Tan Ke,Wang Guanyu
Introduction Since December 2019, severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) has caused the coronavirus disease 2019 (COVID-19) pandemic in China and worldwide. New drugs for the treatment of COVID-19 are in urgent need. Considering the long development time for new drugs, the identification of promising inhibitors from FDA-approved drugs is an imperative and valuable strategy. Recent studies have shown that the S1 and S2 subunits of the spike protein of SARS-CoV-2 utilize human angiotensin-converting enzyme 2 (hACE2) as the receptor to infect human cells. Methods We combined molecular docking and surface plasmon resonance (SPR) to identify potential inhibitors for ACE2 from available commercial medicines. We also designed coronavirus pseudoparticles that contain the spike protein assembled onto green fluorescent protein or luciferase reporter gene-carrying vesicular stomatitis virus core particles. Results We found that thymoquinone, a phytochemical compound obtained from the plant Nigella sativa , is a potential drug candidate. SPR analysis confirmed the binding of thymoquinone to ACE2. We found that thymoquinone can inhibit SARS-CoV-2, SARS-CoV, and NL63 pseudoparticles infecting HEK293-ACE2 cells, with half-maximal inhibitory concentrations of 4.999, 7.598, and 6.019 μM, respectively. The SARS-CoV-2 pseudoparticle inhibition had half-maximal cytotoxic concentration of 35.100 μM and selection index = 7.020. Conclusion Thymoquinone is a potential broad-spectrum inhibitor for the treatment of coronavirus infections.
研究领域:
药理学
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病毒学
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分子生物学
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药物发现
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DOI
PubMed
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PLoS Neglected Tropical Diseases
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2021
·Vol. 15
·期 3
·e0008403
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IF 4.411
Yuan Zhang,Yanqiu Wei,Yunlong Li,Xuan Wang,Yang Liu,Deyu Tian,Xiaojuan Jia,Rui Gong,Wenjun Liu,Limin Yang
Ebola virus (EBOV) is one of the most virulent pathogens that causes hemorrhagic fever and displays high mortality rates and low prognosis rates in both humans and nonhuman primates. The post-exposure antibody therapies to prevent EBOV infection are considered effective as of yet. However, owing to the poor thermal stability of mammalian antibodies, their application in the tropics has remained limited. Therefore, a thermostable therapeutic antibody against EBOV was developed modelled on the poultry(chicken) immunoglobulin Y (IgY). The IgY antibodies retaining their neutralising activity at 25°C for one year, displayed excellent thermal stability, opposed to conventional polyclonal antibodies (pAbs) or monoclonal antibodies (mAbs). Laying hens were immunised with a variety of EBOV vaccine candidates and it was confirmed that VSVΔG/EBOVGP encoding the EBOV glycoprotein could induce high titer neutralising antibodies against EBOV. The therapeutic efficacy of immune IgY antibodies in vivo was evaluated in the newborn Balb/c mice who have been challenged with the VSVΔG/EBOVGP model. Mice that have been challenged with a lethal dose of the pseudovirus were treated 2 or 24 h post-infection with different doses of anti-EBOV IgY. The group receiving a high dose of 10 6 NAU/kg (neutralising antibody units/kilogram) showed complete protection with no symptoms of a disease, while the low-dose group was only partially protected. Conversely, all mice receiving naive IgY died within 10 days. In conclusion, the anti-EBOV IgY exhibits excellent thermostability and protective efficacy. Anti-EBOV IgY shows a lot of promise in entering the realm of efficient Ebola virus treatment regimens.
Despite the amount of efficient Ebola virus therapeutic antibodies reported in recent years, their application in tropical endemic areas has remained limited due to the low thermal stability of mammalian antibodies. A highly thermostable therapeutic polyclonal antibody against EBOV was developed based on chicken immunoglobulin Y (IgY). The EBOV specific IgY antibodies displayed excellent thermal stability, retaining their neutralising activity at 25°C for one year. The newborn mice receiving the passive transfer of IgY achieved complete protection against a lethal dose of virus challenge proving that the anti-EBOV IgY provides a promising recourse to solve some of the current clinical application hindrances of Ebola antibody-based treatments in Africa due to thermal stability.
研究领域:
病毒学
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免疫学
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治疗学
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传染病
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DOI
PubMed
高影响因子
CHEMOSPHERE
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2021
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IF 7.086
Shuqing Zhou,Min Jin,Rong Tan,Zhiqiang Shen,Jing Yin,Zhigang Qiu,Zhengshan Chen,Danyang Shi,Haibei Li,Zhongwei Yang,Huaran Wang,Zhixian Gao,Junwen Li,Dong Yang
The latent dangers of waterborne viral transmission have become a major public health concern. In this study, reduced graphene oxide (rGO)-Fe 3 O 4 nanoparticles were decorated with cetyltrimethylammonium bromide (CTAB) to adsorb severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike pseudovirus and three human enteric viruses (HuNoV, HRV, and HAdV). The successful combination of CTAB with rGO-Fe 3 O 4 was confirmed by transmission electron microscopy, X-ray diffraction, Fourier-transform infrared spectroscopy, zeta potential, Brunner-Emmet-Teller, and vibrating sample magnetometer measurements. The adsorption of HuNoV and HAdV followed pseudo-first-order kinetics, while that of HRV conformed to the pseudo-second-order model. CTAB-functionalized rGO-Fe 3 O 4 exhibited exceptionally high adsorption of HuNoV, HRV, HAdV and SARS-CoV-2 spike pseudovirus, with maximum adsorption capacities of 3.55 × 10 7 , 7.01 × 10 7 , 2.21 × 10 7 and 6.92 × 10 6 genome copies mg −1 , respectively. Moreover, the composite could effectively adsorb the four types of virus particles from coastal, tap, and river water. In addition, concentrating the virions using CTAB functionalized rGO-Fe 3 O 4 composites before qPCR analysis significantly improved the detection limit. The results indicate that viruses are captured on the surface of CTAB functionalized rGO-Fe 3 O 4 composites through electrostatic interactions and the intrinsic adsorption ability of rGO. Overall, CTAB-functionalized rGO-Fe 3 O 4 composites are promising materials for the adsorption and detection of human enteric viruses as well as SARS-CoV-2 from complex aqueous environments.
研究领域:
环境科学
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生物学
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材料科学
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PubMed
高影响因子
CARBOHYDRATE POLYMERS
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2022
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IF 10.723
Lihua Geng,Quanbin Zhang,Qishan Suo,Jing Wang,Yingxia Wang,Cong Wang,Ning Wu
COVID-19 caused by SARS-CoV-2 has spread around the world at an unprecedented rate. A more homogeneous oligo-porphyran with mean molecular weight of 2.1 kD, named OP145, was separated from Pyropia yezoensis . NMR analysis showed OP145 was mainly composed of →3)-β- d -Gal-(1 → 4)-α- l -Gal (6S) repeating units with few replacement of 3,6-anhydride, and the molar ratio was 1:0.85:0.11. MALDI-TOF MS revealed OP145 contained mainly tetrasulfate-oligogalactan with Dp range from 4 to 10 and with no more than two 3,6-anhydro-α- l -Gal replacement. The inhibitory activity of OP145 against SARS-CoV-2 was investigated in vitro and in silico. OP145 could bind to Spike glycoprotein (S-protein) through SPR result, and pseudovirus tests confirmed that OP145 could inhibite the infection with an EC50 of 37.52 μg/mL. Molecular docking simulated the interaction between the main component of OP145 and S-protein. All the results indicated that OP145 had the potency to treat and prevent COVID-19.
研究领域:
病毒学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
ANALYST
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2023
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IF 4.2
Xinxin Ke,Yi Hu,Chuanxia Chen,Tao Hu
Clustered regularly interspaced short palindromic repeats (CRISPR)-based diagnostics have been considered as the next generation molecular diagnosis tool. Single-readout mode has been extensively employed in massive CRISPR/Cas12a-based biosensors. In this work, we propose a one-tube dual-readout biosensor for ultrasensitive nucleic acids and non-nucleic acids detection by harnessing CRISPR-ALP tandem assay for the first time (termed CRISAT). In the presence of target, the Cas12a is activated to randomly cut the single-stranded hyDNA sequence of MB@hyDNA-cALP, thus releasing abundant alkaline phosphatase (ALP) in the supernatant solution. By using 4-aminophenol phosphate as the substrate of ALP, p-aminophenol is produced and then reacts with N-[3-(trimethoxysilyl)propyl]ethylenediamine or diethylenetriamine to generate silicon-containing polymer carbon dots (Si PCDs) or polymer carbon dots (PCDs) in situ, which can be observed by naked eye or detected by a fluorescent device in the same solution. Using this strategy, a fluoroscence and colorimetry dual-readout nanoplatform for CRISPR-based biosensor can be rationally developed. We ascertain the applicability of CRISAT through detecting SARS-CoV-2 pseudovirus, achieving superior sensitivity and specificity. With simple modification of crRNAs, the CRISAT platform can be also employed to detect monkeypox virus (MPXV) and non-nucleic acids of adenosine triphosphate (ATP). This work provides a great potential for nucleic acids and non-nucleic acids detection.
研究领域:
分子诊断
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生物传感器
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纳米技术
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病毒学
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分析化学
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PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY A
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2024
·
IF 3.8
Jiaming Yuan,Jincai Wang,Zhixu Chen,Yuexiang Chang,Litong Chen,Zhizeng Gao,Jacques Crommen,Tingting Zhang,Zhengjin Jiang
In this study, a novel at-line nanofractionation platform was established for screening SARS-CoV-2 fusion inhibitors from natural products for the first time by combining HPLC-MS/MS with high-throughput fluorescence polarization (FP) bioassay. A time-course FP bioassay in 384 well-plates was conducted in parallel with MS/MS to simultaneously obtain chemical and biological information of potential fusion inhibitors in Lonicerae Japonicae Flos (LJF) and Lianhua Qingwen capsules (LHQW). Semi-preparative liquid chromatography and orthogonal HPLC separation were employed to enrich and better identify the co-eluted components. After comprehensive evaluation and validation, 28 potential SARS-CoV-2 fusion inhibitors were screened out and identified. Several compounds at low micromolar activity were validated by in vitro inhibitory assay, molecular docking, cytotoxicity test, and pseudovirus assay. Moreover, four potential dual-target inhibitors against influenza and COVID-19 were discovered from LJF using this method, offering novel insights for the development of future pharmaceuticals targeting epidemic respiratory diseases.
研究领域:
药学
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分析化学
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病毒学
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药物发现
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产品关联
DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
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2024
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IF 5.4
Jingyuan Ji,Chenjia Zhao,Chen Hua,Lu Lu,Yuan Pang,Wei Sun
As attempting personalized medicine, 3D-printed tissue engineering scaffolds are employed to combine with therapeutic proteins/peptides especially in the clinical treatment of infectious diseases, genetic diseases, and cancers. However, current drug-loading methods, such as immersion and encapsulation, usually lead to the burst release of the drugs. To address these issues, we proposed an integrated strategy toward the long-term controlled release of protein. In this study, patient-customized 3D scaffolds incorporated with drug-loaded microspheres were printed to realize the effective delivery of the anti-human papillomavirus (anti-HPV) protein after cervical conization in the treatment of cervical cancer. The 3D-printed scaffold could provide mechanical support to the defect site and ensure local release of the drug to avoid systemic administration. Meanwhile, microspheres serve as functional components to prevent the inactivation of proteins, as well as regulate their release period to meet the time requirement of different treatment courses. The research also utilized bovine serum albumin as a model protein to validate the feasibility of these scaffolds as a generic technology platform. The bioactivity of the released anti-HPV protein was validated using a pseudovirus model, which demonstrated that the microsphere encapsulation would not cause protein denaturation during the scaffold fabrication process. Besides, 3D-printed scaffolds incorporated with carboxylated chitosan microspheres were biocompatible and beneficial for cell attachment, which have been demonstrated by favorable cell viability and better coverage results for HeLa and HFF-1. This study highlights the great potential of scaffolds incorporated with microspheres to serve as tissue engineering candidate products with the function of effective protein delivery in a long-term controlled manner and personalized shapes for clinical trials.
研究领域:
生物医学工程
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药学
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组织工程
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癌症研究
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药物递送系统
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个性化医疗
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DOI
PubMed
高影响因子