Abstract Dengue fever is a mosquito‐borne viral disease caused by the dengue virus (DENV). It poses a public health threat globally and, while most people with dengue have mild symptoms or are ...asymptomatic, approximately 5% of affected individuals develop severe disease and need hospital care. However, knowledge of the molecular mechanisms underlying dengue infection and the interaction between the virus and its host remains limited. In the present study, we performed a quantitative proteomic and N‐glycoproteomic analysis of serum from 19 patients with dengue and 11 healthy people. The results revealed distinct proteomic and N‐glycoproteomic landscapes between the two groups. Notably, we report for the first time the changes in the serum N glycosylation pattern following dengue infection and provide abundant information on glycoproteins, glycosylation sites, and intact N‐glycopeptides using recently developed site‐specific glycoproteomic approaches. Furthermore, a series of key functional pathways in proteomic and N‐glycoproteomic were identified. Collectively, our findings significantly improve understanding of host and DENV interactions and the general pathogenesis and pathology of DENV, laying a foundation for functional studies of glycosylation and glycan structures in dengue infection.
The settlement of microorganisms is an unwanted process in various practical fields, where also the first attaching microorganisms could promote other bacterial adhesion, causing an acceleration of ...bioaccumulation on the solid surface and damage to the surface functions. Developing an advanced composite coating with anti-microorganism attachment features is still a big challenge, and the critical element in any such method is to find an efficient functional agent for use in the coating system that could extend the service period. MXenes have received increasing attentions owing to their unique layer structure and large specific surface area. Increasing studies have been devoted to the development of MXene/polymer composites with creatively designed structures to realize various specific functions. Herein, two-dimensional (2D) transition metal carbide material MXene as a carrier was etched and decorated with cellulose to enhance the anchor points to grasp functional Ag nanoparticles via a simple method. The MXene nanosheets (Ti3C2Tx) were modified by cellulose to graft hydroxy groups on their surface, and then they were incorporated into silver nanoparticles (Ag NPs). The results showed that the cellulose could increase the loading content of the Ag NPs on the MXene surface, and also could act as a stabilized material to form the composite filler MXene@cellulose@Ag NPs (MAC), which could serve as a functional agent. Furthermore, the obtained product MAC filler exhibited excellent dispersibility and stability among all the tested fillers (MXene and MA), and it could help avoid aggregation and promote homogenous dispersal in the coating network. Besides, MAC displayed outstanding antibacterial activities against E. coli and S. aureus at the same concentration among all the fillers. When the filler was embedded into the coating system, the composite coating PCB-MAC possessed abundant active Ag+ ions released by the Ag NPs, which could work against bacterial growth and achieve a favorable antibacterial inhibition effect. Therefore, we believe that the active MAC filler maintained high antibacterial efficiency, evincing its potential as a desirable agent for obtaining an excellent anti-adhesive behavior in numerous broad applications, such as the environment field or medical area.
The settlement of microorganisms is an unwanted process in various practical fields, where also the first attaching microorganisms could promote other bacterial adhesion, causing an acceleration of ...bioaccumulation on the solid surface and damage to the surface functions. Developing an advanced composite coating with anti-microorganism attachment features is still a big challenge, and the critical element in any such method is to find an efficient functional agent for use in the coating system that could extend the service period. MXenes have received increasing attentions owing to their unique layer structure and large specific surface area. Increasing studies have been devoted to the development of MXene/polymer composites with creatively designed structures to realize various specific functions. Herein, two-dimensional (2D) transition metal carbide material MXene as a carrier was etched and decorated with cellulose to enhance the anchor points to grasp functional Ag nanoparticles via a simple method. The MXene nanosheets (Ti 3 C 2 T x ) were modified by cellulose to graft hydroxy groups on their surface, and then they were incorporated into silver nanoparticles (Ag NPs). The results showed that the cellulose could increase the loading content of the Ag NPs on the MXene surface, and also could act as a stabilized material to form the composite filler MXene@cellulose@Ag NPs (MAC), which could serve as a functional agent. Furthermore, the obtained product MAC filler exhibited excellent dispersibility and stability among all the tested fillers (MXene and MA), and it could help avoid aggregation and promote homogenous dispersal in the coating network. Besides, MAC displayed outstanding antibacterial activities against E. coli and S. aureus at the same concentration among all the fillers. When the filler was embedded into the coating system, the composite coating PCB-MAC possessed abundant active Ag + ions released by the Ag NPs, which could work against bacterial growth and achieve a favorable antibacterial inhibition effect. Therefore, we believe that the active MAC filler maintained high antibacterial efficiency, evincing its potential as a desirable agent for obtaining an excellent anti-adhesive behavior in numerous broad applications, such as the environment field or medical area.
Seventeen β-dihydroagarofuran-type sesquiterpenes were isolated from the seeds of Celastrus monospermus, and, among them, 15 (1-15) were identified as new natural products. Nine isolates were ...evaluated for their lifespan-extending effect using the standard model animal nematode Caenorhabditis elegans. As a result, all of the tested compounds prolonged the lifespan of C. elegans when compared to the blank control group (p < 0.0001). Among them, celaspermin E (5) extended the average lifespan and maximum lifespan of C. elegans, with effects similar to those of rapamycin, a positive control that has been found experimentally to delay the aging process of yeasts, worms, fruit flies, and mice.
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•A series of mononuclear/dinuclear copper(II) acylhydrazone complexes were synthesized and characterized.•The anti-lung cancer activity of these complexes were evaluated in ...vitro.•Complex 3A was evaluated for its anti-lung cancer effects in vivo and in vitro.
Non-platinum metal-based complexes have good potential for cancer treatment. Here, we designed and synthesized five hydrazone copper(II) complexes, Cu2(HL)2Cl2 1A, Cu2(HL)2(NO3)H2O·NO3 2A, Cu2(HL)2Br2 3A, Cu(L)pyridine 1B and Cu(HL)(pyridine)Br 3B, and evaluated their anti-lung cancer activities. MTT experiments revealed that these copper(II) complexes exhibit higher anticancer activity than cisplatin. Mechanism studies revealed that complex 3A induced G1 phase cell cycle arrest, and induced cell apoptosis via reactive oxygen species (ROS)-mediated mitochondrial dysfunction. Scratch wound healing assay was also performed, revealing that complex 3A have good anti-cell migration activity. Hemolysis assays showed good blood biocompatibility of complex 3A. Furthermore, complex 3A can significantly inhibit the proliferation of A549 3D tumor spheroid. An in vivo anticancer study showed that complex 3A could delays the growth of A549 tumor xenografts with lower systemic toxicity. These results highlight the great possibility of developing highly active copper complexes as anti-lung cancer agents.
An animation showing the working principle of CeMIC: measuring a flow-through C. elegans worm via electrical impedance spectroscopy, identifying its developmental stage and steering it to the target ...outlet.
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•CeMIC detects the size of flow-through worms via electrical impedance spectroscopy.•Channel geometry is optimized to fit the special morphology and behavior of worms.•Electrode configuration eliminates the influence of worm undulation on impedance.•KDE enables fast calculation of impedance signal variations induced by worms.•Development stages can be accurately identified via impedance measurement in CeMIC.
Microfluidic impedance cytometry allows for label-free detection of cells. But it has not yet been used to detect large organisms, such as Caenorhabditis elegans (C. elegans) worms, due to their variable morphology and strong motility. Here, we report on a C. elegans microfluidic impedance cytometry (CeMIC), which enables the electrical impedance measurement of worms when flowing through a straight microchannel and the identification of their developmental stages based on impedance signals. With the optimized configuration of impedance-sensing structures, namely the microchannel and integrated microelectrodes, the influence of undulation and position variation of worms upon the measured impedance can be eliminated. In signal processing, a kernel density estimation method is employed to extract worm-length-related values that can be directly assigned to the developmental stages of worms. The accuracy for impedance-based identification of worm stages can reach 90%. Additionally, the CeMIC device is developed into a simple and automated system for size-based enrichment of worms. Large and small worms from a mixed population are successfully separated to different outlets after identifying their sizes with impedance measurement. Therefore, our CeMIC system provides a promising platform to measure the worm size, identify developmental stages, and prepare size/stage-homogenized populations for C. elegans experiments.
•A series of mixed-ligand Cu(II) complexes were synthesized and characterized.•The anti-lung cancer activity of these Cu complexes were evaluated in vitro.•We revealed the anticancer mechanism of the ...Cu(II) complex.•The ability of complex 4 to inhibit the growth of A549 tumor spheroids was assessed.
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Here we synthesized five mixed-ligand copper(II) Schiff-base complexes, including Cu(HL1)(pyridine) NO3 1, Cu(HL2)(pyridine)Cl 2, Cu(HL3)(pyridine)Br 3, Cu(HL4)(pyridine)Br 4, and Cu(L5)(pyridine) 5, and performed a series of assays to investigate their anti-lung cancer activities in vitro. The structures of these copper(II) complexes were confirmed by X-ray crystallography and elemental analysis. MTT assay showed that complex 4 exhibited stronger cytotoxicity than other complexes. The wound healing assay showed that complex 4 had the well potential to display anti-metastatic activity. Flow cytometry and fluorescence imaging analysis showed that complex 4 led to cell cycle arrest at the S phase and induced mitochondria-mediated apoptotic. Furthermore, in the 3D A549 spherical model, complex 4 clearly exerts an inhibitory effect.
Reduced mRNA translation delays aging, but the underlying mechanisms remain underexplored. Mutations in both DAF-2 (IGF-1 receptor) and RSKS-1 (ribosomal S6 kinase/S6K) cause synergistic lifespan ...extension in C. elegans. To understand the roles of translational regulation in this process, we performed polysomal profiling and identified translationally regulated ribosomal and cytochrome c (CYC-2.1) genes as key mediators of longevity. cyc-2.1 knockdown significantly extends lifespan by activating the intestinal mitochondrial unfolded protein response (UPRmt), mitochondrial fission, and AMP-activated kinase (AMPK). The germline serves as the key tissue for cyc-2.1 to regulate lifespan, and germline-specific cyc-2.1 knockdown non-autonomously activates intestinal UPRmt and AMPK. Furthermore, the RNA-binding protein GLD-1-mediated translational repression of cyc-2.1 in the germline is important for the non-autonomous activation of UPRmt and synergistic longevity of the daf-2 rsks-1 mutant. Altogether, these results illustrate a translationally regulated non-autonomous mitochondrial stress response mechanism in the modulation of lifespan by insulin-like signaling and S6K.
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•Longevity of daf-2 rsks-1 is mediated by translational repression of cyc-2.1•Germline inhibition of cyc-2.1 activates intestinal UPRmt and AMPK to extend lifespan•Increased GLD-1 represses germline cyc-2.1 translation in the daf-2 rsks-1 mutant•Translational regulation of cyc-2.1 and UPRmt contribute to longevity of daf-2 rsks-1
To understand how reduced translation delays aging, Lan et al. perform translational profiling in C. elegans and propose that, in the significantly long-lived daf-2 rsks-1 mutant, serial translational regulation leads to reduced cytochrome c in the germline, which non-autonomously activates UPRmt and AMPK in the metabolic tissue to ensure longevity.
The antagonistic pleiotropy theory of aging suggests that genes essential for growth and development are likely to modulate aging later in life. Previous studies in
demonstrate that inhibition of ...certain developmentally essential genes during adulthood leads to significant lifespan extension. PAR-1, a highly conserved serine/threonine kinase, functions as a key cellular polarity regulator during the embryonic development. However, the role of PAR-1 during adulthood remains unknown. Here we show that inhibition of
either by a temperature-sensitive mutant or by RNAi knockdown only during adulthood is sufficient to extend lifespan in
. Inhibition of
also improves healthspan, as indicated by increased stress resistance, enhanced proteotoxicity resistance, as well as reduced muscular function decline over time. Additionally, tissue-enriched RNAi knockdown analysis reveals that PAR-1 mainly functions in the epidermis to regulate lifespan. Further genetic epistatic and molecular studies demonstrate that the effect of
on lifespan requires the AMP-activated protein kinase (AMPK), and RNAi knockdown of
results in age-dependent AMPK activation and reduced lipid accumulation in the metabolic tissue. Taken together, our findings reveal a previously undescribed function of PAR-1 in adulthood, which will help to understand the molecular links between development and aging.
The settlement of microorganisms is an unwanted process in various practical fields, where also the first attaching microorganisms could promote other bacterial adhesion, causing an acceleration of ...bioaccumulation on the solid surface and damage to the surface functions. Developing an advanced composite coating with anti-microorganism attachment features is still a big challenge, and the critical element in any such method is to find an efficient functional agent for use in the coating system that could extend the service period. MXenes have received increasing attentions owing to their unique layer structure and large specific surface area. Increasing studies have been devoted to the development of MXene/polymer composites with creatively designed structures to realize various specific functions. Herein, two-dimensional (2D) transition metal carbide material MXene as a carrier was etched and decorated with cellulose to enhance the anchor points to grasp functional Ag nanoparticles
via
a simple method. The MXene nanosheets (Ti
3
C
2
T
x
) were modified by cellulose to graft hydroxy groups on their surface, and then they were incorporated into silver nanoparticles (Ag NPs). The results showed that the cellulose could increase the loading content of the Ag NPs on the MXene surface, and also could act as a stabilized material to form the composite filler MXene@cellulose@Ag NPs (MAC), which could serve as a functional agent. Furthermore, the obtained product MAC filler exhibited excellent dispersibility and stability among all the tested fillers (MXene and MA), and it could help avoid aggregation and promote homogenous dispersal in the coating network. Besides, MAC displayed outstanding antibacterial activities against
E. coli
and
S. aureus
at the same concentration among all the fillers. When the filler was embedded into the coating system, the composite coating PCB-MAC possessed abundant active Ag
+
ions released by the Ag NPs, which could work against bacterial growth and achieve a favorable antibacterial inhibition effect. Therefore, we believe that the active MAC filler maintained high antibacterial efficiency, evincing its potential as a desirable agent for obtaining an excellent anti-adhesive behavior in numerous broad applications, such as the environment field or medical area.
The settlement of microorganisms is an unwanted process in various practical fields, where also the first attaching microorganisms could promote other bacterial adhesion, causing an acceleration of bioaccumulation on the solid surface and damage to the surface functions.
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