查找使用阿拉丁产品的科研文献

Electrochemical biosensor based on topological insulator Bi2Se3 tape electrode for HIV-1 DNA detection

Xiong Xiaolu,Zhu Peng,Li Shanshan,Jiang Yujiu,Ma Yurong,Shi Qingfan,Zhang Xu,Shu Xiaoming,Wang Zhiwei,Sun Linfeng,Han Junfeng

A large-size Bi 2 Se 3 tape electrode (BTE) was prepared by peeling off a 2 × 1 × 0.5 cm high-quality single crystal. The feasibility of using the flexible BTE as an efficient bioplatform to load Au nanoparticles and probe DNA for HIV-1 DNA electrochemical sensing was explored. Differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS) show that the resultant biosensor has a wide linear range from 0.1 fM to 1 pM, a low detection limit of 50 aM, excellent selectivity, reproducibility and stability, and is superior to the pM DNA detection level of Pt-Au, graphene-AuNPs hybrid biosensors. This outstanding performance is attributed to the intrinsic surface state of Bi 2 Se 3 topological insulator in facilitating electron transfer. Therefore, BTE electrochemical biosensor platform has great potential in the application for sensitive detection of DNA biomarkers. Graphical abstract

DABCO-Catalyzed Michael/Alkylation Cascade Reactions Involving α-Substituted Ammonium Ylides for the Construction of Spirocyclopropyl Oxindoles: Access to the Powerful Chemical Leads against HIV-1

Lin Chen,Jin He

A novel Michael/alkylation cascade reaction of N-unprotected 3-bromooxindoles with α,β-unsaturated acyl phosphonates using DABCO as a robust catalyst followed by the derivatization of the acyl phosphonate intermediates in situ has been developed. This scenario enables rapid access to a diverse set of highly functionalized spirocyclopropyl oxindoles in moderate yields with good to excellent diastereoselectivities, which are analogues of a high active non-nucleoside reverse transcriptase inhibitor against HIV-1. The synthetic potential of this tactic has been highlighted by a gram-scale reaction and Suzuki cross-coupling reactions of the product. Moreover, the reaction mechanism has been tentatively elucidated by control experiments and dynamic high-resolution mass spectrometry studies, which indicates that the Michael/alkylation cascade reaction involves DABCO-derived α-substituted ammonium ylides.

Curcumin Protects Microglia and Primary Rat Cortical Neurons against HIV-1 gp120-Mediated Inflammation and Apoptosis

Luyan Guo,Yanyan Xing,Rui Pan,Mingliang Jiang,Zheng Gong,Liqing Lin,Junbing Wang,Guoyin Xiong,Jun Dong

Curcumin is a molecule found in turmeric root that has anti-inflammatory, antioxidant, and anti-tumor properties and has been widely used as both an herbal drug and a food additive to treat or prevent neurodegenerative diseases. To explore whether curcumin is able to ameliorate HIV-1-associated neurotoxicity, we treated a murine microglial cell line (N9) and primary rat cortical neurons with curcumin in the presence or absence of neurotoxic HIV-1 gp120 (V3 loop) protein. We found that HIV-1 gp120 profoundly induced N9 cells to produce reactive oxygen species (ROS), tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1). HIV-1 gp120 also induced apoptosis of primary rat cortical neurons. Curcumin exerted a powerful inhibitory effect against HIV-1 gp120-induced neuronal damage, reducing the production of ROS, TNF-α and MCP-1 by N9 cells and inhibiting apoptosis of primary rat cortical neurons. Curcumin may exert its biological activities through inhibition of the delayed rectification and transient outward potassium (K + ) current, as curcumin effectively reduced HIV-1 gp120-mediated elevation of the delayed rectification and transient outward K + channel current in neurons. We conclude that HIV-1 gp120 increases ROS, TNF-α and MCP-1 production in microglia, and induces cortical neuron apoptosis by affecting the delayed rectification and transient outward K + channel current. Curcumin reduces production of ROS and inflammatory mediators in HIV-1-gp120-stimulated microglia, and protects cortical neurons against HIV-1-mediated apoptosis, most likely through inhibition of HIV-1 gp120-induced elevation of the delayed rectification and transient outward K + current.

Imidazole metal-organic frameworks embedded in layered Ti3C2Tx Mxene as a high-performance electrochemiluminescence biosensor for sensitive detection of HIV-1 protein

Yunfei Wang,Wenjie Sun,Yixiao Li,Xuming Zhuang,Chunyuan Tian,Feng Luan,Xiuli Fu

Human immunodeficiency virus (HIV) is still a significant global health concern. Hence, developing a rapid and sensitive method for the detection of HIV is important in early detection. In this paper, we focus on the preparation of a sensitive electrochemical luminescence (ECL) biosensor that uses Ti 3 C 2 T x modified ZIF-8 as an ECL emitter to detect HIV-1 protein. This ECL biosensor used 0.05 M K 2 S 2 O 8 as the co-reactant and conductive carbon black combined with magnetic nanoparticles as the quenching agent. Under the optimized experimental conditions, the relationship was linear in the range from 1 fM to 1 nM (R 2  = 0.993) and the detection limit was 0.3 fM (S/N = 3). Finally, we used the constructed Ti 3 C 2 T x /ZIF-8 nanocomposites to detect HIV-1 in real serum samples and obtained great recoveries. The results demonstrated that this biosensor, which not only exhibited improved electrical conductivity but also demonstrated an excellent ECL response, could be a promising candidate for HIV-1 detection.

Cascade toehold-mediated strand displacement along with non-enzymatic target recycling amplification for the electrochemical determination of the HIV-1 related gene

Yin Dan,Tao Yiyi,Tang Lan,Li Wei,Zhang Zhang,Li Junlong,Xie Guoming

The authors describe a dual-signal electrochemical biosensor for highly sensitive determination of the HIV-1 related gene. This method is based on the application of cascaded toehold-mediated strand displacement reactions (TMSDRs) in combination with non-enzymatic target recycling amplification (TRA). A DNA machine with two TMSDRs was designed, and this resulted in reusable target and an output of two oligonucleotides, referred to as strand A (AS) labeled with the redox tag methylene blue (MB) and as untagged strand B (BS). A ferrocene (Fc)-modified signal probe (Fc-P 1 ) is immobilized on the gold electrode surface by hybridizing with a thiolated probe (P 2 ). The labeled AS causes the dissociation of Fc molecules and the gathering of MB molecules via strand displacement reaction. The target gene triggers TMSDRs and TRA. This leads to an increase in the distance changes between the redox tags and the gold electrode. The assay works in the 1 pM to 10 nM concentration range. On account of target recycling and dual recognition, the limit of detection is as low as 0.88 pM (at an S/N ratio of 3). The assay also has a remarkable selectivity which is ascribed to the use of both cascaded TMSDRs and dual recognition. In our perception, this assay represents a robust means of wide scope in that it may be applied to the detection of various kinds of nucleic acid even in complex samples. Schematic of a dual-signal electrochemical biosensor based on cascaded toehold-mediated strand displacement and non-enzymatic target recycling amplification strategy for the HIV-1 related gene detection. Two electroactive molecules are used to produce electrochemical signals in this “signal-on/off” sensing system.

Fluorescence and visual immunoassay of HIV-1 p24 antigen in clinical samples via multiple selective recognitions of CdTe QDs

Tang Zhuoyun,Wei Zeliang,Huang Ke,Wei Yinhao,Li Dongdong,Yan Shixin,Huang Jin,Geng Jia,Tao Chuanmin,Chen Piaopiao,Ying Binwu

Human immunodeficiency virus (HIV) infection inflicts significant economic and social burdens on many countries worldwide. Given the substantial morbidity and mortality from HIV infection, there is an urgent need for accurate and early detection of the virus. In this study, immunofluorescence and visual techniques are described that detect the HIV-1 p24 antigen, which relied on selective recognition of Ag + /Ag nanoparticles (Ag NPs) and Cu 2+ /Cu + using cadmium telluride quantum dots (CdTe QDs). After the sandwich immunoreactions were accomplished, the alkaline phosphatase (ALP) hydrolyzed L-ascorbic acid 2-phosphate (AAP) to form ascorbic acid (AA) that further reduces Ag + and Cu 2+ to Ag NPs and Cu + , respectively. This method was highly sensitive and selective and could detect as low as 1 pg/mL of p24 antigen by naked eyes and had a good linearity in the concentration range 1–100 pg/mL. When using Ag + and Cu 2+ as media, the limit of detection (LOD) of the new method was 0.3 pg/mL and 0.2 pg/mL, respectively. Compared with clinical electrochemiluminescence immunoassay (ECLIA) results and clinical data, this method demonstrated good consistency for the quantification of HIV-1 p24 antigen in 34 clinical serum samples. In addition, this method could accurately distinguish HIV from other viruses and infections such as hepatitis B virus , systemic lupus erythematosus , hepatitis C virus , Epstein-Barr virus , cytomegalovirus , lipemia , and hemolysis . Therefore, our dual-mode analysis method may provide additional solutions to identify clinical HIV infection. Graphical abstract An immunofluorescence and visualization dual-mode strategy for the detection of p24 antigen was constructed based on immune recognition reaction and a phenomenon that cadmium telluride quantum dots (CdTe QDs) can selectively recognize Ag + /Ag nanoparticles (Ag NPs) and Cu 2+ /Cu + .

A General Biosensing Strategy Based on Cascade Amplification for Enhanced HIV Detection Sensitivity

Yirui Zhang,Jieyu Yan,Wangheng Hou,Qian Gao,Tao Zhang,Yan Gao,Jingwen Li,Kun Han

Objective: Accurate and rapid detection of disease biomarkers is critical for early diagnosis, timely intervention, and effective disease management. Impact Statement: This strategy is exemplified through the development of 2 biosensors for detecting HIV-1 DNA and HIV-1 p24, biomarkers associated with acquired immunodeficiency syndrome (AIDS). Introduction: We propose a general biosensing strategy that leverages a treble signal amplification cascade, demonstrating its versatility and applicability across diverse biomolecular targets. Methods: The method integrates multiple amplification mechanisms to achieve unparalleled sensitivity. Initially, the hybridization of 2 aided probes with the target triggers isothermal amplification facilitated by polymerase and nicking enzyme, providing a robust preliminary signal enhancement. Repeated cycles of primer extension, nicking, and signal primer dissociation then generate multiple signal primers. These primers are further amplified via rolling circle amplification (RCA), resulting in an important secondary signal boost. Finally, the amplified products activate CRISPR-Cas12a-mediated trans-cleavage, achieving a tertiary level of signal enhancement. Results: This cascade amplification approach achieves remarkable sensitivity, with detection limits of 62 aM for nucleic acids and 8.48 pg/ml for proteins, positioning it as a broadly applicable framework. Clinical samples were assayed, which indicates its capability in clinical diagnosis. Conclusion: Beyond HIV detection, the modular design of this strategy allows adaptation for various biomarkers, showcasing its potential as a universal platform for molecular diagnostics in healthcare and research.

Synthesis of piscidinol A derivatives and their ability to inhibit HIV-1 protease

Ying Wei,Chao-Mei Ma,Tai-Bai Jiang,Jiang Du,Xing Zhou,Guo-Qing Liu,Masao Hattori

Adenoviral vectors coated with cationic PEG derivatives for intravaginal vaccination against HIV-1

Zhaolu Xie,Zhonghua Ji,Zhirong Zhang,Tao Gong,Xun Sun

Mucus layer coating the vaginal epithelium represents a barrier for intravaginally delivered recombined adenoviral (rAd) vectors, but it could be overcome by proper polyethylene glycol (PEG) modification. Here we synthesized two cationic PEG derivatives, amino-(EO) n /(AGE) m -Cyss (APCs). The polymers contained neutral linear PEG (2–5 kDa) to provide a hydrophilic surface and amine pendants to provide positive charge for coating negatively charged rAd by physical adsorption. Given proper molecular composition, the polymer (5k-APC) could coat rAd without causing aggregation, facilitating its mucus penetrating ability and enhancing gene expression both in vitro and in vivo . With HIVgag as the model antigen, the polymer-rAd complexes were administered intravaginally to elicit both systemic and mucosal immune responses. 5k-APC-rAd immunization elicited robust HIVgag-specific cellular responses and also induced higher antigen-specific serum IgG. More importantly, mice immunized with 5k-APC-rAd showed higher level of IgA in vaginal lavage fluid. These findings suggest that 5k-APC-rAd is a promising system for intravaginal immunization against infectious diseases such as HIV within the vaginal tract.

Highly Potent Phosphinic HIV-1 Protease Inhibitors: Synthesis, In Vitro Evaluation, and Docking Studies

Komal Hayat,Danwen Qiu,Yuanyuan Wang,Palmer Sivoko Imbenzi,Faez Iqbal Khan,Magdalini Matziari

In the search for effective HIV-1 protease inhibitors, the design of symmetrical phosphinic pseudopeptides derived from a dual addition of hypophosphorous acid to acrylates (PACs) has emerged as a promising strategy due to their nonhydrolyzable nature and high affinity for this protease. In this study, we report the synthesis, in vitro evaluation, and docking studies of a series of new symmetrical phosphinic inhibitors, synthesized via simple and cost-effective procedures. This approach overcomes the complexities of previous methods and utilizes commercially or readily available reagents. The synthesized PACs, featuring various P2 and P2’ substituents, have been evaluated for their inhibitory activity against the HIV-1 protease. Among them, the PAC-Phe-Val derivative (9c) demonstrated potent inhibition, with an IC50 value of 33 nM, comparable to the FDA-approved Darunavir. Resolution of the isomers of 9c revealed the most potent candidate, with an IC50 value of 1 nM. Molecular docking studies revealed strong hydrogen bonding interactions between PAC-Phe-Val and key active site residues, suggesting a stable and effective binding profile. The compound’s structure–activity relationship (SAR) was explored, identifying crucial features for its inhibitory potency. This work highlights the potential of symmetrical phosphinic pseudopeptides as HIV-1 protease inhibitors and provides a foundation for further development of these compounds as novel antiretroviral therapies. Future research will focus on optimizing the pharmacokinetic properties and evaluating resistance profiles, aiming to advance the next generation of HIV treatments.

Metabolite Identification of HIV-1 Capsid Modulators PF74 and 11L in Human Liver Microsomes

Shujing Xu,Lin Sun,Dang Ding,Xujie Zhang,Xinyong Liu,Peng Zhan

PF74and11L, as potent modulators of the HIV-1 capsid protein, have been demonstrated to act at both early and late stages in the HIV-1 life cycle. However, their clearance is high in human liver microsomes (HLMs). The main goal of this study was to clarify the metabolism ofPF74and11Lin HLMs, and provide guidance for future structural optimization. To accomplish this, the phase-I metabolites ofPF74and11L, resulting from in vitro incubation with HLMs, were investigated via ultra-performance liquid chromatography–ultraviolet–high-resolution mass spectrometry (UPLC–UV–HRMS). The results show that 17 phase-I metabolites were putatively annotated forPF74, whereas 16 phase-I metabolites were found for11L. The main metabolic pathways ofPF74in HLMs were oxidation and demethylation, and the secondary metabolic pathway was hydrolysis; thus, the di-oxidation and demethylation products (M7,M9,M11, andM14) were found to be major metabolites ofPF74in HLMs. In comparison, the main metabolic pathways of11Lin HLMs were oxidation, demethylation, dehydrogenation, and oxidative deamination, withM6′,M11′,M15′, andM16′as the main metabolites. We suggest that the indole ring andN-methyl group ofPF74, and the aniline group, benzene ring R1′,N-methyl, and methoxy group of11L, were the main metabolic soft spots. Therefore, our research illuminates structural optimization options in seeking improved HIV-1 CA modulators.Keywords:PF74;11L;capsid modulators;human liver microsomes;UPLC–UV–HRMS;metabolite identification

Oligonucleotide-linked gold nanoparticle aggregates for enhanced sensitivity in lateral flow assays

Jie Hu,Lin Wang,Fei Li,Yu Long Han,Min Lin,Tian Jian Lu,Feng Xu

Lateral flow assays (LFAs) as rapid analytical techniques promise to be widely used in point-of-care (POC) diagnostics because of their affordability and simplicity. However, LFAs still suffer from low sensitivity in detection of various biomarkers, e.g., nucleic acids. In this study, we developed a simple and general one-step signal amplification strategy, which employed oligonucleotide-linked gold nanoparticle (AuNP) aggregates to enhance the sensitivity in nucleic acid lateral flow (NALF) assays. Using a nucleic acid sequence of human immunodeficiency virus type 1 (HIV-1) as a model analyte, we observed that the detection limit of the developed NALF assay was 0.1 nM, which was improved by 2.5-fold compared with that of a non-signal amplification approach. The methodology described here could be used to detect a broad range of nucleic acids, and the general signal amplification approach could be potentially adopted in other types of LFAs.