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1.
Food Chem ; 459: 140328, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38981386

ABSTRACT

In this study, we examined multiple endocrine-disrupting ultraviolet-absorbing compounds (UVACs) in marine invertebrates used in personal care products and packaging. Modified QuEChERS and liquid chromatography UniSpray ionization tandem mass spectrometry were used to identify 16 UVACs in marine invertebrates. Matrix-matched calibration curves revealed high linearity (r ≥ 0.9929), with limits of detection and quantification of 0.006-1.000 and 0.020-3.000 ng/g w.w., respectively. In oysters, intraday and interday analyses revealed acceptable accuracy (93%-120%) and precision (≤18%), except for benzophenone (BP) and ethylhexyl 4-(dimethylamino) benzoate. Analysis of 100 marine invertebrate samples revealed detection frequencies of 100%, 98%, 89%, 64%, and 100% for BP, 4-hydroxybenzophenone, 4-methylbenzophenone, 4-methylbenzylidene camphor, and benzophenone-3 (BP-3), respectively. BP and BP-3 were detected at concentrations of 4.40-27.39 and < 0.020-0.560 ng/g w.w., respectively, indicating their widespread presence. Overall, our proposed method successfully detected UVACs in marine invertebrates, raising concerns regarding their potential environmental and health effects.

2.
ACS Nano ; 2024 Jul 14.
Article in English | MEDLINE | ID: mdl-39004841

ABSTRACT

Dynamic control of circularly polarized photoluminescence has aroused great interest in quantum optics and nanophotonics. Chiral plasmonic metasurfaces enable the manipulation of the polarization state via plasmon-photon coupling. However, current plasmonic light-emitting metasurfaces for effective deterministic modulation of spin-dependent emission at near-infrared wavelengths are underexplored in terms of dissymmetry and tunability. Here, we demonstrate a microfluidic hybrid emitting system of a suspended twisted stacking metasurface coated with PbS quantum dots. The suspended metasurface is fabricated with a single step of electron beam exposure, exhibiting a strong optical chirality of 309° µm-1 with a thickness of less than λ/10 at key spectral locations. With significant chiral-selective interactions, enhanced photoluminescence is achieved with strong dissymmetry in circular polarization. The dissymmetry factor of the induced circularly polarized emission can reach 1.54. More importantly, altering the refractive index of the surrounding medium at the bottom surface of the metasurface can effectively manipulate the chiroptical responses of the hybrid system, hence leading to chirality-reversed emission. This active hybrid emitting system could be a resultful platform for chirality-switchable light emission from achiral quantum emitters, holding great potential for anticounterfeiting, biosensing, light sources, imaging, and displays.

3.
Microorganisms ; 12(6)2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38930536

ABSTRACT

Licorice (Glycyrrhiza glabra) is a plant of the genus Glycyrrhiza in the family Fabaceae/Leguminosae and is a renowned natural herb with a long history of medicinal use dating back to ancient times. Glycyrrhizin (GLY), the main active component of licorice, serves as a widely utilized therapeutic agent in clinical practice. GLY exhibits diverse medicinal properties, including anti-inflammatory, antibacterial, antiviral, antitumor, immunomodulatory, intestinal environment maintenance, and liver protection effects. However, current research primarily emphasizes GLY's antiviral activity, while providing limited insight into its antibacterial properties. GLY demonstrates a broad spectrum of antibacterial activity via inhibiting the growth of bacteria by targeting bacterial enzymes, impacting cell membrane formation, and altering membrane permeability. Moreover, GLY can also bolster host immunity by activating pertinent immune pathways, thereby enhancing pathogen clearance. This paper reviews GLY's inhibitory mechanisms against various pathogenic bacteria-induced pathological changes, its role as a high-mobility group box 1 inhibitor in immune regulation, and its efficacy in combating diseases caused by pathogenic bacteria. Furthermore, combining GLY with other antibiotics reduces the minimum inhibitory concentration, potentially aiding in the clinical development of combination therapies against drug-resistant bacteria. Sources of information were searched using PubMed, Web of Science, Science Direct, and GreenMedical for the keywords "licorice", "Glycyrrhizin", "antibacterial", "anti-inflammatory", "HMGB1", and combinations thereof, mainly from articles published from 1979 to 2024, with no language restrictions. Screening was carried out by one author and supplemented by others. Papers with experimental flaws in their experimental design and papers that did not meet expectations (antifungal papers, etc.) were excluded.

4.
ACS Appl Mater Interfaces ; 16(24): 31776-31787, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38858834

ABSTRACT

Stimuli-responsive materials have garnered substantial interest in recent years, particularly liquid crystal networks (LCNs) with sophisticatedly designed structures and morphing capabilities. Extensive efforts have been devoted to LCN structural designs spanning from two-dimensional (2D) to three-dimensional (3D) configurations and their intricate morphing behaviors through designed alignment. However, achieving microscale structures and large-area preparation necessitates the development of novel techniques capable of facilely fabricating LCN microstructures with precise control over both overall shape and alignment, enabling a 3D-to-3D shape change. Herein, a simple and cost-effective in-cell soft lithography (ICSL) technique is proposed to create LCN microstructures with customized shapes and predesigned morphing. The ICSL technique involves two sequential steps: fabricating the desired microstructure as the template by using the photopolymerization-induced phase separation (PIPS) method and reproducing the LCN microstructures through templating. Meanwhile, surface anchoring is employed to design and achieve molecular alignment, accommodating different deformation modes. With the proposed ICSL technique, cylindrical and spherical microlens arrays (CMLAs and SMLAs) have been successfully fabricated with stimulus-driven polarization-dependent focusing effects. This technique offers distinct advantages including high customizability, large-area production, and cost-effectiveness, which pave a new avenue for extensive applications in different fields, exemplified by adaptive soft micro-optics and photonics.

5.
Talanta ; 277: 126415, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38878513

ABSTRACT

Endothelial cells (ECs) migration is a crucial early step in vascular repair and tissue neovascularization. While extensive research has elucidated the biochemical drivers of endothelial motility, the impact of biophysical cues, including vessel geometry and topography, remains unclear. Herein, we present a novel approach to reconstruct 3D self-assembly blood vessels-on-a-chip that accurately replicates real vessel geometry and topography, surpassing conventional 2D flat tube formation models. This vessels-on-a-chip system enables real-time monitoring of vasculogenesis and ECs migration at high spatiotemporal resolution. Our findings reveal that ECs exhibit increased migration speed and directionality in response to narrower vessel geometries, transitioning from a rounded to a polarized morphology. These observations underscore the critical influence of vessel size in regulating ECs migration and morphology. Overall, our study highlights the importance of biophysical factors in shaping ECs behavior, emphasizing the need to consider such factors in future studies of endothelial function and vessel biology.

6.
Front Cell Dev Biol ; 12: 1385991, 2024.
Article in English | MEDLINE | ID: mdl-38887515

ABSTRACT

Cellular movement is essential for many vital biological functions where it plays a pivotal role both at the single cell level, such as during division or differentiation, and at the macroscopic level within tissues, where coordinated migration is crucial for proper morphogenesis. It also has an impact on various pathological processes, one for all, cancer spreading. Cell migration is a complex phenomenon and diverse experimental methods have been developed aimed at dissecting and analysing its distinct facets independently. In parallel, corresponding analytical procedures and tools have been devised to gain deep insight and interpret experimental results. Here we review established experimental techniques designed to investigate specific aspects of cell migration and present a broad collection of historical as well as cutting-edge computational tools used in quantitative analysis of cell motion.

7.
Mol Ther ; 2024 May 31.
Article in English | MEDLINE | ID: mdl-38822524

ABSTRACT

Dysregulated T cell activation underpins the immunopathology of rheumatoid arthritis (RA), yet the machineries that orchestrate T cell effector program remain incompletely understood. Herein, we leveraged bulk and single-cell RNA sequencing data from RA patients and validated protein disulfide isomerase family A member 3 (PDIA3) as a potential therapeutic target. PDIA3 is remarkably upregulated in pathogenic CD4 T cells derived from RA patients and positively correlates with C-reactive protein level and disease activity score 28. Pharmacological inhibition or genetic ablation of PDIA3 alleviates RA-associated articular pathology and autoimmune responses. Mechanistically, T cell receptor signaling triggers intracellular calcium flux to activate NFAT1, a process that is further potentiated by Wnt5a under RA settings. Activated NFAT1 then directly binds to the Pdia3 promoter to enhance the expression of PDIA3, which complexes with STAT1 or PKM2 to facilitate their nuclear import for transcribing T helper 1 (Th1) and Th17 lineage-related genes, respectively. This non-canonical regulatory mechanism likely occurs under pathological conditions, as PDIA3 could only be highly induced following aberrant external stimuli. Together, our data support that targeting PDIA3 is a vital strategy to mitigate autoimmune diseases, such as RA, in clinical settings.

8.
Biomolecules ; 14(5)2024 May 12.
Article in English | MEDLINE | ID: mdl-38785979

ABSTRACT

The balance between ubiquitination and deubiquitination is instrumental in the regulation of protein stability and maintenance of cellular homeostasis. The deubiquitinating enzyme, ubiquitin-specific protease 36 (USP36), a member of the USP family, plays a crucial role in this dynamic equilibrium by hydrolyzing and removing ubiquitin chains from target proteins and facilitating their proteasome-dependent degradation. The multifaceted functions of USP36 have been implicated in various disease processes, including cancer, infections, and inflammation, via the modulation of numerous cellular events, including gene transcription regulation, cell cycle regulation, immune responses, signal transduction, tumor growth, and inflammatory processes. The objective of this review is to provide a comprehensive summary of the current state of research on the roles of USP36 in different pathological conditions. By synthesizing the findings from previous studies, we have aimed to increase our understanding of the mechanisms underlying these diseases and identify potential therapeutic targets for their treatment.


Subject(s)
Neoplasms , Ubiquitin Thiolesterase , Humans , Neoplasms/metabolism , Neoplasms/genetics , Neoplasms/enzymology , Neoplasms/pathology , Ubiquitin Thiolesterase/metabolism , Ubiquitin Thiolesterase/genetics , Animals , Ubiquitination , Inflammation/metabolism , Signal Transduction , Ubiquitin/metabolism
9.
J Phys Condens Matter ; 36(34)2024 May 30.
Article in English | MEDLINE | ID: mdl-38729174

ABSTRACT

Resonant exchange of the chiral Majorana fermions (MFs) that is coupled to two parallel Majorana zero modes (MZMs) or two parallel quantum dots (QDs) is investigated. We find that, in the two QDs coupling case, the resonant exchange for the chiral MFs is analogous to that in the MZM coupling case. We further propose a circuit based on topological superconductor, which is formed by the proximity coupling of a quantum anomalous Hall insulator and a s-wave superconductor, to observe the resonant exchange of chiral MFs pairs. The numerical calculations show that the resonant transmission of the chiral MFs can be adjusted by varying the coupling parameters at superconductor phase differenceΔφ=π. It is particularly noteworthy that, by only modulating the coupling strength between the two QDs, the resonant exchange may be switched on or off. By adding another MZM, the non-Abelian braiding like operation can be realized. Therefore, our design scheme may provide another way for non-Abelian braiding operation of MFs and the findings may have potential application value in the realization of topological quantum computers.

10.
Article in English | MEDLINE | ID: mdl-38648128

ABSTRACT

In this article, a novel adaptive control method based on neural networks is proposed for a class of multiagent systems (MASs) with nonlinear functions and external disturbances. First, the approximation properties of neural networks are used to approximate the MAS partial differential equation (PDE) model with nonlinear terms containing two variables, time t, and spatial variable x. Second, an adaptive controller is constructed to actuate the parabolic MAS to reach consensus under external disturbances. Based on this, the finite-time theorem and special inequalities are applied to prove the stability of the closed-loop system. Thus, MAS that have nonlinear functions and external disturbances are enabled with finite-time consensus. Finally, the effectiveness of the proposed control method is demonstrated by numerical simulations.

11.
Opt Express ; 32(7): 12528-12536, 2024 Mar 25.
Article in English | MEDLINE | ID: mdl-38571073

ABSTRACT

Diffractive optical element is advantageous for miniaturization, arraying and integration of optical systems. They have been widely used in beam shaping, diffractive imaging, generating beam arrays, spectral optimization and other aspects. Currently, the vast majority of diffractive optics are not tunable. This limits the applicability and functionality of these devices. Here we report a tunable diffractive optical element controlled by light in the visible band. The diffractive optical element consists of a square gold microarray deposited on a deformable substrate. The substrate is made of a liquid crystal elastomer. When pumped by a 532 nm laser, the substrate is deformed to change the crystal lattice. This changes the far-field diffraction pattern of the device. The proposed concept establishes a light-controlled soft platform with great potential for tunable/reconfigurable photonic devices, such as filters, couplers, holograms and structural color displays.

12.
Bioorg Chem ; 147: 107377, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38653150

ABSTRACT

The first systematic acylated diversification of naturally scarce premyrsinane diterpenes, together with their biosynthetic precursors lathyrane diterpene were carried out. Two new series of premyrsinane derivates (1a-32a) and lathyrane derivates (1-32) were synthesized from the naturally abundant lathyrane diterpene Euphorbia factor L3 through a bioinspired approach. The cholinesterase inhibitory and neuroprotective activities of these diterpenes were investigated to explore potential anti-Alzheimer's disease (AD) bioactive lead compounds. In general, the lathyrane diterpenes showed the better acetylcholinesterase (AChE) inhibitory activity than that of premyrsinanes. The lathyrane derivative 17 bearing a 3-dimethylaminobenzoyl moiety showed the best AChE inhibition effect with the IC50 value of 7.1 µM. Molecular docking demonstrated that 17 could bond with AChE well (-8 kal/mol). On the other hand, premyrsinanes showed a better neuroprotection profile against H2O2-induced injury in SH-SY5Y cells. Among them, the premyrsinane diterpene 16a had significant neuroprotective effect with the cell viability rate of 113.5 % at 12.5 µM (the model group with 51.2 %). The immunofluorescence, western blot and reactive oxygen species (ROS) analysis were conducted to demonstrate the mechanism of 16a. Furthermore, a preliminary SAR analysis of the two categories of diterpenes was performed to provide the insights for anti-AD drug development.


Subject(s)
Acetylcholinesterase , Alzheimer Disease , Cholinesterase Inhibitors , Diterpenes , Euphorbia , Neuroprotective Agents , Diterpenes/pharmacology , Diterpenes/chemistry , Diterpenes/chemical synthesis , Alzheimer Disease/drug therapy , Cholinesterase Inhibitors/pharmacology , Cholinesterase Inhibitors/chemical synthesis , Cholinesterase Inhibitors/chemistry , Neuroprotective Agents/pharmacology , Neuroprotective Agents/chemistry , Neuroprotective Agents/chemical synthesis , Euphorbia/chemistry , Humans , Acetylcholinesterase/metabolism , Structure-Activity Relationship , Molecular Structure , Molecular Docking Simulation , Dose-Response Relationship, Drug , Cell Survival/drug effects
13.
Bioorg Chem ; 147: 107400, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38688196

ABSTRACT

Although certain members of the Ubiquitin-specific peptidases (USPs) have been recognized as promising therapeutic targets for various diseases, research progress regarding USP21 has been relatively sluggish in its early stages. USP21 is a crucial member of the USPs subfamily, involved in diverse cellular processes such as apoptosis, DNA repair, and signal transduction. Research findings from the past decade demonstrate that USP21 mediates the deubiquitination of multiple well-known target proteins associated with critical cellular processes relevant to both disease and homeostasis, particularly in various cancers.This reviewcomprehensively summarizes the structure and biological functions of USP21 with an emphasis on its role in tumorigenesis, and elucidates the advances on the discovery of tens of small-molecule inhibitors targeting USP21, which suggests that targeting USP21 may represent a potential strategy for cancer therapy.


Subject(s)
Neoplasms , Ubiquitin Thiolesterase , Humans , Neoplasms/drug therapy , Neoplasms/pathology , Neoplasms/metabolism , Ubiquitin Thiolesterase/antagonists & inhibitors , Ubiquitin Thiolesterase/metabolism , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Animals , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/chemistry , Molecular Structure
14.
Plant Physiol ; 195(2): 970-985, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38478469

ABSTRACT

The Xishuangbanna (XIS) cucumber (Cucumis sativus var. xishuangbannanesis) is a semiwild variety that has many distinct agronomic traits. Here, long reads generated by Nanopore sequencing technology helped assembling a high-quality genome (contig N50 = 8.7 Mb) of landrace XIS49. A total of 10,036 structural/sequence variations (SVs) were identified when comparing with Chinese Long (CL), and known SVs controlling spines, tubercles, and carpel number were confirmed in XIS49 genome. Two QTLs of hypocotyl elongation under low light, SH3.1 and SH6.1, were fine-mapped using introgression lines (donor parent, XIS49; recurrent parent, CL). SH3.1 encodes a red-light receptor Phytochrome B (PhyB, CsaV3_3G015190). A ∼4 kb region with large deletion and highly divergent regions (HDRs) were identified in the promoter of the PhyB gene in XIS49. Loss of function of this PhyB caused a super-long hypocotyl phenotype. SH6.1 encodes a CCCH-type zinc finger protein FRIGIDA-ESSENTIAL LIKE (FEL, CsaV3_6G050300). FEL negatively regulated hypocotyl elongation but it was transcriptionally suppressed by long terminal repeats retrotransposon insertion in CL cucumber. Mechanistically, FEL physically binds to the promoter of CONSTITUTIVE PHOTOMORPHOGENIC 1a (COP1a), regulating the expression of COP1a and the downstream hypocotyl elongation. These above results demonstrate the genetic mechanism of cucumber hypocotyl elongation under low light.


Subject(s)
Cucumis sativus , Genome, Plant , Hypocotyl , Quantitative Trait Loci , Hypocotyl/growth & development , Hypocotyl/genetics , Cucumis sativus/genetics , Cucumis sativus/growth & development , Quantitative Trait Loci/genetics , Phytochrome B/genetics , Phytochrome B/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Light
15.
Huan Jing Ke Xue ; 45(3): 1577-1585, 2024 Mar 08.
Article in Chinese | MEDLINE | ID: mdl-38471871

ABSTRACT

The adsorption characteristics of ammonia nitrogen for constructed wetland were studied with ceramsite, quartz sand, and gravel. The material was characterized using scanning electron microscopy and a BET-specific surface area analyzer. It was found that the surface of ceramide was coarser than that of quartz sand and gravel, and the internal pores were more developed. The specific surface area of ceramide (18.97 m2·g-1) was higher than that of quartz sand and gravel. In the pure ammonia nitrogen solution and Grade I B standard for the wastewater treatment plant effluent ammonia nitrogen solution of the effluent from the simulated sewage plant, the adsorption capacity of the three substrates was as follows:ceramsite > gravel > quartz sand. The saturated adsorption capacity (63.55 m2·g-1) of ceramides was the highest in the mixed solution. The adsorption process of ammonia nitrogen by ceramides accorded with the pseudo-second-order kinetic model (R2 of 0.99 in the pure ammonia nitrogen solution and 0.98 in the mixed solution). The Freundlich and Langmuir models were used to fit the isothermal adsorption results in a pure ammonia nitrogen solution. It was found that the Freundlich model described the adsorption characteristics of the ceramics more accurately than the Langmuir model (R2=0.93), indicating that the adsorption of ammonia nitrogen by the ceramics was multilayer adsorption. In conclusion, the adsorption capacity of ceramide was strong, and the adsorption capacity of ceramide in the mixed solution was 31% higher than that in the pure ammonia nitrogen solution, which was suitable to be used as the matrix filler of constructed wetland.

16.
Cell Mol Biol Lett ; 29(1): 32, 2024 Mar 05.
Article in English | MEDLINE | ID: mdl-38443798

ABSTRACT

RNA-binding proteins (RBPs) are kinds of proteins with either singular or multiple RNA-binding domains (RBDs), and they can assembly into ribonucleic acid-protein complexes, which mediate transportation, editing, splicing, stabilization, translational efficiency, or epigenetic modifications of their binding RNA partners, and thereby modulate various physiological and pathological processes. CUG-BP, Elav-like family 1 (CELF1) is a member of the CELF family of RBPs with high affinity to the GU-rich elements in mRNA, and thus exerting control over critical processes including mRNA splicing, translation, and decay. Mounting studies support that CELF1 is correlated with occurrence, genesis and development and represents a potential therapeutical target for these malignant diseases. Herein, we present the structure and function of CELF1, outline its role and regulatory mechanisms in varieties of homeostasis and diseases, summarize the identified CELF1 regulators and their structure-activity relationships, and prospect the current challenges and their solutions during studies on CELF1 functions and corresponding drug discovery, which will facilitate the establishment of a targeted regulatory network for CELF1 in diseases and advance CELF1 as a potential drug target for disease therapy.


Subject(s)
Drug Discovery , Epigenesis, Genetic , Homeostasis , RNA , RNA, Messenger
17.
Proc Natl Acad Sci U S A ; 121(14): e2317492121, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38547056

ABSTRACT

Energy metabolism is highly interdependent with adaptive cell migration in vivo. Mechanical confinement is a critical physical cue that induces switchable migration modes of the mesenchymal-to-amoeboid transition (MAT). However, the energy states in distinct migration modes, especially amoeboid-like stable bleb (A2) movement, remain unclear. In this report, we developed multivalent DNA framework-based nanomachines to explore strategical mitochondrial trafficking and differential ATP levels during cell migration in mechanically heterogeneous microenvironments. Through single-particle tracking and metabolomic analysis, we revealed that fast A2-moving cells driven by biomimetic confinement recruited back-end positioning of mitochondria for powering highly polarized cytoskeletal networks, preferentially adopting an energy-saving mode compared with a mesenchymal mode of cell migration. We present a versatile DNA nanotool for cellular energy exploration and highlight that adaptive energy strategies coordinately support switchable migration modes for facilitating efficient metastatic escape, offering a unique perspective for therapeutic interventions in cancer metastasis.


Subject(s)
Amoeba , Cell Line, Tumor , Cell Movement , Physical Phenomena
18.
Adv Sci (Weinh) ; 11(19): e2401254, 2024 May.
Article in English | MEDLINE | ID: mdl-38483920

ABSTRACT

Pancreatic fibrosis (PF) is primarily characterized by aberrant production and degradation modes of extracellular matrix (ECM) components, resulting from the activation of pancreatic stellate cells (PSCs) and the pathological cross-linking of ECM mediated by lysyl oxidase (LOX) family members. The excessively deposited ECM increases matrix stiffness, and the over-accumulated reactive oxygen species (ROS) induces oxidative stress, which further stimulates the continuous activation of PSCs and advancing PF; challenging the strategy toward normalizing ECM homeostasis for the regression of PF. Herein, ROS-responsive and Vitamin A (VA) decorated micelles (named LR-SSVA) to reverse the imbalanced ECM homeostasis for ameliorating PF are designed and synthesized. Specifically, LR-SSVA selectively targets PSCs via VA, thereby effectively delivering siLOXL1 and resveratrol (RES) into the pancreas. The ROS-responsive released RES inhibits the overproduction of ECM by eliminating ROS and inactivating PSCs, meanwhile, the decreased expression of LOXL1 ameliorates the cross-linked collagen for easier degradation by collagenase which jointly normalizes ECM homeostasis and alleviates PF. This research shows that LR-SSVA is a safe and efficient ROS-response and PSC-targeted drug-delivery system for ECM normalization, which will propose an innovative and ideal platform for the reversal of PF.


Subject(s)
Extracellular Matrix , Fibrosis , Nanoparticles , Reactive Oxygen Species , Reactive Oxygen Species/metabolism , Extracellular Matrix/metabolism , Animals , Fibrosis/metabolism , Resveratrol/pharmacology , Humans , Pancreatic Stellate Cells/metabolism , Pancreatic Stellate Cells/drug effects , Pancreas/metabolism , Pancreas/pathology , Pancreatic Diseases/metabolism , Disease Models, Animal , Oxidative Stress/drug effects , Vitamin A/metabolism , Mice , Rats , Drug Delivery Systems/methods
19.
J Biol Chem ; 300(2): 105660, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38242322

ABSTRACT

Persistent high-risk HPV infection is closely associated with cervical cancer development, and there is no drug targeting HPV on the market at present, so it is particularly important to understand the interaction mechanism between HPV and the host which may provide the novel strategies for treating HPV diseases. HPV can hijack cell surface heparan sulfate proteoglycans (HSPGs) as primary receptors. However, the secondary entry receptors for HPV remain elusive. We identify myosin-9 (NMHC-IIA) as a host factor that interacts with HPV L1 protein and mediates HPV internalization. Efficient HPV entry required myosin-9 redistribution to the cell surface regulated by HPV-hijacked MEK-MLCK signaling. Myosin-9 maldistribution by ML-7 or ML-9 significantly inhibited HPV pseudoviruses infection in vitro and in vivo. Meanwhile, N-glycans, especially the galactose chains, may act as the decoy receptors for HPV, which can block the interaction of HPV to myosin-9 and influence the way of HPV infection. Taken together, we identify myosin-9 as a novel functional entry receptor for high-risk HPV both in vitro and in vivo, and unravel the new roles of myosin-9 and N-glycans in HPV entry, which provides the possibilities for host targets of antiviral drugs.


Subject(s)
Human Papillomavirus Viruses , Papillomavirus Infections , Virus Internalization , Humans , Cytoskeletal Proteins , Heparan Sulfate Proteoglycans/metabolism , Myosins , Cell Line , Animals , Cricetinae , Cricetulus , Polysaccharides/metabolism
20.
ACS Appl Mater Interfaces ; 16(5): 5401-5411, 2024 Feb 07.
Article in English | MEDLINE | ID: mdl-38271201

ABSTRACT

Nanostructure-enhanced biodetection is widely used for early diagnosis and treatment, which plays an essential role in improving the cure rates of cancer patients. ZnO nanostructure-based fluorescence immunoassay has been demonstrated to enable effective and sensitive detection of cancer biomarkers for their excellent biocompatibility, high electrical point, and unique fluorescence enhancement properties. Further optimization of such fluorescence detection technology is still in demand to meet the requirements of highly sensitive, multiplex detection, and user-friendly devices. Droplet microfluidics is a promising platform for high-throughput analysis of biological assays, and they have been intensively used in analytical chemistry and synthesis of nanoparticles. Here, we propose a simple droplet chip, where a static droplet array was successfully obtained for in situ growth of ZnO nanostructures with varied diameters by changing the entire growth time and replenishment interval. This device provides a novel and alternative approach for patterned growth of ZnO nanostructures and understanding the growth condition of ZnO nanostructures in static droplet, which offers some guidance toward the design of multiple fluorescence amplification platforms potentially for biosensing. As a demonstration, we used the patterned grown ZnO nanostructures for multiple detection of cancer biomarkers, achieving a low limit of detection as low as 138 fg/mL in the human α-fetoprotein assay and 218 fg/mL in the carcinoembryonic antigen assay with a large dynamic range of 8 orders. These results suggest that such multifunctional microfluidic devices may be useful tools for efficient fluorescence diagnostic assays.


Subject(s)
Microfluidic Analytical Techniques , Nanoparticles , Nanostructures , Zinc Oxide , Humans , Microfluidics/methods , Zinc Oxide/chemistry , Nanostructures/chemistry , Biomarkers, Tumor
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