Cell Reports Medicine
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2025
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IF 10.6
Zhi Yang,Yizheng Yao,Xi Chen,Victoria Madigan,Shanrui Pu,Xianqun Fan,Jun Pu,Fengfeng Bei
Efficient gene delivery vectors are crucial for respiratory and lung disease therapies. We report that AAV.CPP.16, an engineered adeno-associated virus (AAV) variant derived from AAV9, efficiently transduces airway and lung cells in mice and non-human primates via intranasal administration. AAV.CPP.16 outperforms AAV6 and AAV9, two wild-type AAVs with demonstrated tropism for respiratory tissues, and efficiently targets key respiratory cell types. It supports gene supplementation and editing therapies in two clinically relevant mouse models of respiratory and lung diseases. A single intranasal dose of AAV.CPP.16 expressing a dual-target, vascular endothelial growth factor (VEGF)/transforming growth factor (TGF)-β1-neutralizing protein protected lungs from idiopathic pulmonary fibrosis, while a similar application of AAV.CPP.16 carrying an “all-in-one” CRISPR-Cas13d system inhibited transcription of the SARS-CoV-2-derived RNA-dependent RNA polymerase (Rdrp) gene. Our findings highlight AAV.CPP.16 as a promising vector for respiratory and lung gene therapy.
研究领域:
医学
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基因治疗
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病毒学
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DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
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2017
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IF 5.099
Mengjie Guo,Yan Lyu,Tingting Xu,Bo Yao,Weihua Song,Mei Li,Xin Yang,Tiantao Cheng,Xiang Li
This study presents the particle size distribution and respiratory deposition estimates of airborne perfluoroalkyl acids (PFAAs) during the haze period. Size-segregated haze aerosols were collected from an urban location in Shanghai using an eight-stage air sampler. The samples were analyzed for eight PFAAs using ultra-high-performance liquid chromatography tandem triple quadrupole mass spectrometry. The quantification results showed that the concentrations of particle-bound Σ 8PFAAs ranged from 0.26 to 1.90 ng m −3 (mean: 1.44 ng m −3 ). All of the measured PFAAs particle size distributions had a bimodal mode that peaked respectively in accumulation size range (0.4 < Dp < 2.1 μm) and coarse size ranges ( Dp > 2.1 μm), but the width of each distribution somewhat varied by compound. The emission source, molecular weight , and volatility of the PFAAs were important factors influencing the size distribution of particle-bound PFAAs. Of these compounds, PFUnDA presented a strong accumulation in the fine size range (average 75% associated with particles <2.1 μm), followed by PFOA (69%) and PFDA (64%). The human risk assessment of PFOS via inhalation was addressed and followed the same pattern as the size distribution, with a 2-fold higher risk for the fine particle fraction compared to the coarse particle fraction at urban sites. Approximately 30.3–82.0% of PFAA deposition (∑PFAA: 72.5%) in the alveolar region was associated with particles <2.1 μm, although the contribution of fine particles to the total PFAAs concentration in urban air was only 28–57% (∑8PFAAs: 48%). These results suggested that fine particles are significant contributors to the deposition of PFAAs in the alveolar region of the lung.
研究领域:
环境科学
·
公共卫生
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DOI
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2023
·
IF 12.6
Jienan Shen,Zhi Chen,Ruibin Xie,Jingfeng Li,Chunyan Liu,Yaqing He,Xiaopeng Ma,Hui Yang,Zhongjian Xie
Respiratory viruses have long been a major cause of a global pandemic, emphasizing the urgent need for high-sensitivity diagnostic tools. Typical PCR technology can only determine the type of virus in the sample, which is unable to detect different variants of the same virus without costly and time-consuming gene sequencing. Here, we introduce a simple, fully enclosed, and highly integrated microfluidic system based on CRISPR/Cas12a and isothermal amplification techniques (LOC-CRISPR) that can specifically identify multiple common respiratory viruses and their variants. The LOC-CRISPR chip integrates viral nucleic acid extraction, recombinant polymerase amplification, and CRISPR/Cas12a cleavage reaction-based detection, contamination-free detection. In addition, the LOC-CRISPR chip was designed for multiplexed detection (two-sample input and ten-result outputs), which can not only detect the presence of SARS-CoV-2, H 1 N 1 , H 3 N 2 , IVB and HRSV but also differentiate the BA.1, BA.2, and BA.5 variants of SARS-COV-2. For clinical validation, the LOC-CRISPR chip was used to analyze 50 nasopharyngeal swab samples (44 positive and 6 negative) and achieved excellent sensitivity (97.8%) and specificity (100%). This innovative LOC-CRISPR system has the ability to quickly, sensitively, and accurately detect multiple target nucleic acid sequences with single-base mutations, which will further improve the rapid identification and traceability of respiratory viruses infectious diseases.
研究领域:
分子生物学
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医学诊断
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病毒学
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DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2025
·
IF 3.1
Shaodong Wang,Lili Lin,Yueyue Lei,Qiuyuan Li,Linxiu Peng
Respiratory syncytial virus (RSV) is a highly pathogenic respiratory virus that severely impacts infants under 2 years, adults over 60, and immunocompromised individuals. Currently, no safe, low-toxicity, or cost-effective therapy is available for RSV. Research indicates that RSV infection disrupts pulmonary surfactant lipid metabolism. Through lipidomic analysis of bronchoalveolar lavage (BAL) fluid and lung tissue, we observed an increase in most phosphatidylcholines (PCs) and phosphatidylethanolamines (PEs), while all phosphatidylglycerols (PGs) decreased. Additionally, all lysophospholipids in lung tissue increased. Among the altered lipids, 27 showed significant changes in both BAL fluid and lung tissue, including 15 phospholipids (7 PCs, 5 PEs, 3 PGs, and 1 phosphatidylinositol (PI)). From the decreased PGs, we identified an active lipid, PG 16:0–18:2, which correlated strongly between BAL fluid and lung tissue. Further studies confirmed that PG 16:0–18:2 significantly reduces viral load, mitigates RSV-induced lung damage, and reduces pulmonary inflammation. In vitro experiments demonstrated that PG 16:0–18:2 directly inhibits RSV replication and proliferation in epithelial cells. These findings suggest that PG 16:0–18:2 could serve as an effective and non-toxic antiviral agent, offering a promising complementary approach to RSV treatment.
研究领域:
医学
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生物学
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病毒学
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脂质代谢
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2024
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IF 13.3
Jingye Zhao,Ping Li,Qi Zhang,Zhilu Ye,Yijing Wang,Jingyu Tian,Zhe Xu,Niancai Peng,Hui Ren,Xiaohui Zhang
The concentration of nitric oxide (NO) in exhaled breath is linked to respiratory diseases, requiring precise detection. Traditional two-dimensional (2D) carbon-based materials used in chemiresistive gas sensors suffer from high detection limits due to a lack of functional sites, while metal oxide sensors are limited by poor selectivity and high operating temperatures, restricting their development. Recently, metal–organic frameworks (MOFs) have emerged as an effective material for NO monitoring due to their superior selectivity; however, their inherent insulating properties hinder practical use. In this study, we synthesized Ni, Co-MOF-74-Carbon Nanotube (CNT) heterostructured nanoflowers, leveraging their bimetallic active sites and large specific surface area to enhance NO adsorption. This composite material, integrated with breathable nanofibrous membranes through physical deposition, exhibits high selection to NO, achieving a linear response range of 30 to 1000 ppb at room temperature and a limit of detection (LOD) of 18.6 ppb. This sensor can accurately detect NO levels in the exhaled breath of both healthy and diseased individuals, confirming its potential for respiratory disease diagnosis. Additionally, we developed a portable device integrating the Ni, Co-MOF-74-CNT-polyacrylonitrile (PAN) membrane, a microcontroller unit (MCU), and a Bluetooth module for real-time NO detection. The systematic design and successful validation of this portable gas sensor pave the way for future home-based real-time monitoring of airway inflammation.
研究领域:
材料科学
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医学诊断
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传感器技术
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DOI
高影响因子
Science Advances
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2023
·Vol. 9
·期 23
·
IF 13.6
Zheng Dong,Juan Ma,Jiahuang Qiu,Quanzhong Ren,Qing’e Shan,Xuefeng Duan,Guangle Li,Yi Y. Zuo,Yu Qi,Yajun Liu,Guoliang Liu,Iseult Lynch,Min Fang,Sijin Liu
Mounting data suggest that environmental pollution due to airborne fine particles (AFPs) increases the occurrence and severity of respiratory virus infection in humans. However, it is unclear whether and how interactions with AFPs alter viral infection and distribution. We report synergetic effects between various AFPs and the H1N1 virus, regulated by physicochemical properties of the AFPs. Unlike infection caused by virus alone, AFPs facilitated the internalization of virus through a receptor-independent pathway. Moreover, AFPs promoted the budding and dispersal of progeny virions, likely mediated by lipid rafts in the host plasma membrane. Infected animal models demonstrated that AFPs favored penetration of the H1N1 virus into the distal lung, and its translocation into extrapulmonary organs including the liver, spleen, and kidney, thus causing severe local and systemic disorders. Our findings revealed a key role of AFPs in driving viral infection throughout the respiratory tract and beyond. These insights entail stronger air quality management and air pollution reduction policies.
研究领域:
环境科学
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病毒学
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公共卫生
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呼吸医学
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产品关联
DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2024
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IF 10.7
Shixiang Yang,Wenjin Hu,Shengyang Wang,Xi Li,Liusheng Lei,Xiaxia Wei,Huai Lin
Accurately differentiating respiratory diseases caused by viruses is challenging because of the similarity in their early or clinical symptoms. Moreover, different infection sources require different treatments. However, the current diagnostic methods have limited differentiating efficiency and sensitivity. We developed a dual-system immunosensor with a bilayer fluorescent label as a signal amplifier for the on-site, sensitive, and accurate identification of multiple respiratory viruses (RVs). The nanomaterial, comprising a polystyrene (PS) nanosphere core encapsulated by two layers of CdSe@ZnS-COOH quantum dots (QDs), outperforms the conventional color and fluorescent labels in RV detection. The dual-system detection platform, comprising a PS@DQD-based lateral flow immunoassay (LFIA) and a PS@DQD-based homogeneous sensor, enables qualitative and quantitative screening of multiple respiratory viruses within 10 and 30 min, respectively, depending on the specific detection requirements for different application scenarios. This remarkable method provides 51.2 to 1000 times sensitivity improvement over commercial antigen detection kits and greater than 12.5 to 100 times improvement over QD-based immunosensors. Furthermore, we comprehensively evaluated the specificity, reproducibility, and stability of the integrated dual-system detection platform, demonstrating its reliability. Remarkably, the respiratory viral testing was validated using biological samples, thus illustrating its promise and convenience in the detection of respiratory viruses.
研究领域:
医学诊断
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纳米生物技术
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病毒学
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产品关联
DOI
PubMed
高影响因子
Micromachines
·
2024
·Vol. 15
·期 6
·685
·
IF 3
Xiaohui Yang,Yixian Li,Josh Zixi Lee,Yuanmin Sun,Xin Tan,Yijie Liu,Yang Yu,Huiqiang Li,Xue Li
Conventional microfluidic systems that rely on capillary force have a fixed structure and limited sensitivity, which cannot meet the demands of clinical applications. Herein, we propose a dual-drive microfluidic device for sensitive and flexible detection of multiple pathogenic microorganisms antigens/antibodies. The device comprises a portable microfluidic analyzer and a dual-drive microfluidic chip. Along with capillary force, a second active driving force is provided by a removable self-driving valve in the waste chamber. The interval between these two driving forces can be adjusted to control the reaction time in the microchannel, optimizing the formation of antigen-antibody complexes and enhancing sensitivity. Moreover, the material used in the self-driving valve can be changed to adjust the active force strength needed for different tests. The device offers quantitative analysis for respiratory syncytial virus antigen and SARS-CoV-2 antigen using a 35 μL sample, delivering results within 5 min. The detection limits of the system were 1.121 ng/mL and 0.447 ng/mL for respiratory syncytial virus recombinant fusion protein and SARS-CoV-2 recombinant nucleoprotein, respectively. Although the dual-drive microfluidic device has been used for immunoassay for respiratory syncytial virus and SARS-CoV-2 in this study, it can be easily adapted to other immunoassay applications by changing the critical reagents.
研究领域:
生物医学工程
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病毒学
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诊断学
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DOI
PubMed
高影响因子
Nature Communications
·
2022
·Vol. 13
·期 1
·1-14
·
IF 17.694
Xu Zhichen,Chen Dongjuan,Li Tao,Yan Jiayu,Zhu Jiang,He Ting,Hu Rui,Li Ying,Yang Yunhuang,Liu Maili
Fast, inexpensive, and multiplexed detection of multiple nucleic acids is of great importance to human health, yet it still represents a significant challenge. Herein, we propose a nucleic acid testing platform, named MiCaR, which couples a mi crofluidic device with CRISPR- C as12a a nd multiplex r ecombinase polymerase amplification. With only one fluorescence probe, MiCaR can simultaneously test up to 30 nucleic acid targets through microfluidic space coding. The detection limit achieves 0.26 attomole, and the multiplexed assay takes only 40 min. We demonstrate the utility of MiCaR by efficiently detecting the nine HPV subtypes targeted by the 9-valent HPV vaccine, showing a sensitivity of 97.8% and specificity of 98.1% in the testing of 100 patient samples at risk for HPV infection. Additionally, we also show the generalizability of our approach by successfully testing eight of the most clinically relevant respiratory viruses. We anticipate this effective, undecorated and versatile platform to be widely used in multiplexed nucleic acid detection.
研究领域:
生物技术
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分子生物学
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医学诊断
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DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Li An,Qianwen Zhai,Keyu Tao,Yingcai Xiong,Weiying Ou,Ziwei Yu,Xingyu Yang,Jianjian Ji,Mengjiang Lu
Background Quercetin has received extensive attention for its therapeutic potential treating respiratory syncytial virus (RSV) infection diseases. Recent studies have highlighted quercetin's ability of suppressing alveolar macrophages (AMs)-derived lung inflammation. However, the anti-inflammatory mechanism of quercetin against RSV infection still remains elusive. Purpose This study aims to elucidate the mechanism about quercetin anti-inflammatory effect on RSV infection. Methods BALB/c mice were intranasally infected with RSV and received quercetin (30, 60, 120 mg/kg/d) orally for 3 days. Additionally, an in vitro infection model utilizing mouse alveolar macrophages (MH-S cells) was employed to validate the proposed mechanism. Results Quercetin exhibited a downregulatory effect on glycolysis and tricarboxylic acid (TCA) cycle metabolism in RSV-infected AMs. However, it increased itaconic acid production, a metabolite derived from citrate through activating immune responsive gene 1 (IRG1), and further inhibiting succinate dehydrogenase (SDH) activity. While the suppression of SDH activity orchestrated a cascading downregulation of Hif-1α/NLRP3 signaling, ultimately causing AMs polarization from M1 to M2 phenotypes. Conclusion Our study demonstrated quercetin stimulated IRG1-mediated itaconic acid anabolism and further inhibited SDH/Hif-1α/NLRP3 signaling pathway, which led to M1 to M2 polarization of AMs so as to ameliorate RSV-induced lung inflammation.
研究领域:
免疫学
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药理学
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病毒学
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代谢组学
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产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2017
·Vol. 9
·期 41
·16086-16092
·
IF 7.367
Xiao Xi Yang,Chun Mei Li,Yuan Fang Li,Jian Wang,Cheng Zhi Huang
The diseases attributable to viruses remain a global burden. The respiratory syncytial virus (RSV), which is considered as the major viral pathogen of the lower respiratory tract of infants, has been implicated in severe lung disease. In this contribution, we developed a β-cyclodextrin (CD) functionalized graphene oxide (GO) composite, which displayed excellent antiviral activity and could load curcumin efficiently. RSV, a negative-sense single-stranded enveloped RNA virus, was employed as a model virus to investigate the antiviral activity of multifunctional GO. Proved by the tissue culture infectious dose assay and immunofluorescence assay, the curcumin loaded functional GO was confirmed with highly efficient inhibition for RSV infection and great biocompatibility to the host cells. The results showed that the composite could prevent RSV from infecting the host cells by directly inactivating the virus and inhibiting the viral attachment, and possessed prophylactic and therapeutic effects towards the virus. Our data indicate that the composite may provide new insights into antiviral therapy for RSV infection.
研究领域:
医学
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病毒学
·
纳米材料科学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2025
·
IF 5.4
Xiaolong Feng,Xinru Tao,Penghui Li,Jun Chen,Kaiyi Chen,Jinsheng Jiang,Yuan Cai,Yanmei Peng
Ethnopharmacological relevance Yuye Jiedu Granule (YYJD), a traditional herb preparation developed by Hunan Changde Sanjin Pharmaceutical Co., Ltd., has been used in clinical settings for many years to manage upper respiratory tract infections (URTI) attributed to exogenous wind-heat. Although its effectiveness is well recognized, the active constituents responsible for its effects and the molecular pathways involved are not clear yet. Aim of the study To identify the bioactive constituents of YYJD and elucidate its molecular mechanisms in treating URTI. Materials and methods Initially, the chemical composition of YYJD was analyzed using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) in combination with a molecular networking approach. Anti-inflammatory components within the formula were then identified using a UPLC-based separation system and a dual-luciferase reporter gene screening assay, followed by in vitro validation. Subsequently, an acute pneumonia model was developed using Pseudomonas aeruginosa infection to comprehensively assess the therapeutic efficacy of YYJD through integrated transcriptomic, metabolomic, and network pharmacology analyses. Finally, the underlying molecular mechanisms were experimentally confirmed. Results A total of 145 chemical constituents were identified in YYJD, among which 15 were found to inhibit NF-κB. In vivo studies demonstrated that YYJD notably decreased mortality, lung indices, and serum pro-inflammatory cytokines in P. aeruginosa -infected mice. Integrated multi-omics analysis highlighted adenosine monophosphate (AMP) as a central metabolite, with major bioactive compounds classified as organic acids, flavonoids, iridoid glycosides, and triterpenoid saponins . Nine pivotal targets and the AMPK-mTORC1/2-PI3K/Akt/NF-κB axis were identified as central to YYJD’s anti-URTI effects. Mechanistically, YYJD modulated the phosphorylation of GSK3β, Akt, IκBα, mTOR, and AMPK, along with the p65 expression. Conclusion This study presents the first in-depth analysis of YYJD’s chemical profile and elucidates its multi-target therapeutic mechanisms against URTI through AMPK-centered metabolic-inflammatory interplay. These results offer a stronger scientific foundation for the clinical use of YYJD and introduce a potential new approach for treating respiratory infections.
研究领域:
免疫学
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呼吸病学
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药理学
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分子生物学
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药物代谢
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转化医学
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感染性疾病
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）