Andrographolide derivatives or analogs exhibit potent anti-inflammatory effects in several disease models through NF-κB activity. In this study, we synthesized different andrographolide derivatives ...and investigated their effects on the toll-like receptor (TLR)-induced production of pro-inflammatory cytokines. Among these compounds, 3b, 5a, and 5b inhibited both TNF-α/NF-κB and TLR4/NF-κB signaling pathways. Treatment with compounds 3b, 5a, and 5b and their structural analogs, 3a and 6b, suppressed the expression of pro-inflammatory cytokines upon the activation of TLR3 and TLR4 ligands. Compounds 3b and 5a, but not 3a, 5b, or 6b, inhibited the nuclear translocation of the NF-κB p65 subunit. Treatment with compounds 3b, 5a, 3a, 5b, and 6b attenuated the phosphorylation of p65 and IκBα. Compounds 6b suppressed the expression of the NF-κB p65 subunit. However, these compounds, except for 5b, did not affect the TLR9-induced NF-κB-independent production of the pro-inflammatory cytokines, TNF-α, and IFN-β. Compound 3b potentially protected mice from LPS-induced acute pulmonary inflammation through the inhibition of p65 phosphorylation and the decrease of serum pro-inflammatory cytokines and chemokine. Our study revealed a functional structure-activity relationship between andrographolide derivatives and innate immunity. We identified compound 3b as a potent immune suppressive agent with the potential to protect acute pulmonary infection.
Hexagonal boron nitride (hBN) has recently been demonstrated to contain optically polarized and detected electron spins that can be utilized for implementing qubits and quantum sensors in ...nanolayered-devices. Understanding the coherent dynamics ofmicrowave driven spins in hBN is of crucial importance for advancing these emerging new technologies. Here, we demonstrate and study the Rabi oscillation and related phenomena of a negatively charged boron vacancy (V-B(-)) spin ensemble in hBN. We report on different dynamics of the V-B(-) spins at weak and strong magnetic fields. In the former case the defect behaves like a single electron spin system, while in the latter case it behaves like a multi-spin system exhibiting multiple-frequency dynamical oscillation as beat in the Ramsey fringes. We also carry out theoretical simulations for the spin dynamics of V-B(-) and reveal that the nuclear spins can be driven via the strong electron nuclear coupling existing in V-B(-) center, which can be modulated by the magnetic field and microwave field.
Integrated microstructures composed of organic micro/nanocrystals have gained impressive interest recently as probable candidate for constructing optoelectronic circuits. However, the fabrication of ...these designed composite structures remains a huge challenge. Herein, the sequentially self‐assembled branched homostructures based on 1D single‐crystalline organic microrods of 1,4‐bis((E)‐4‐iodostyryl)‐2,5‐dimethoxybenzene through the facile solution‐processing approach are demonstrated. The growth mechanism of these dendritic microcrystals with an angle of 75° between trunk and branch is attributed to the facet‐selective growth principle between the (020) and (110) crystal planes, for which the interplanar spacing mismatch rate is as low as 6.1%. More significantly, this branched microstructure exhibits an asymmetric optical waveguide and can function as an optical logic gate with an ON/OFF ratio of 10.5. Therefore, the approach to build this organized multilevel structure could provide further applications as building blocks in integrated optoelectronic circuits.
Sequential self‐assembly of branched 1,4‐bis((E)‐4‐iodostyryl)‐2,5‐dimethoxybenzene organic microrods is successfully achieved through the facile solution process that follows the facet‐selective growth principle. The homostructures with an angle of 75° between trunk and branch exhibit an asymmetric optical waveguide, which can further serve as an optical logic gate with an ON/OFF ratio of 10.5.
Engineering microbes to produce terpenes from renewable feedstock is a promising alternative to traditional production approaches. Generally, terpenes are not readily secreted by microbial cells, and ...their distribution within cells is usually obscure and often a restricting factor for the overproduction of terpenes due to the storage limitation. Here, we determined that squalene overproduced in the cytoplasm of Saccharomyces cerevisiae was distributed in a form similar to oil droplets. Interestingly, these suspected oil droplets were confirmed to be inflated peroxisomes that were swollen along with the production of squalene, indicating that peroxisomes in S. cerevisiae are dynamic depots for the storage of squalene. In view of this, harnessing peroxisomes as subcellular compartments for squalene synthesis was performed, achieving a 138-fold improvement in squalene titer (1312.82 mg/L) relative to the parent strain, suggesting that the peroxisome of S. cerevisiae is an efficient subcellular factory for the synthesis of terpenes. By dual modulation of cytoplasmic and peroxisomal engineering, the squalene titer was further improved to 1698.02 mg/L. After optimizing a two-stage fed-batch fermentation method, the squalene titer reached 11.00 g/L, the highest ever reported. This provides new insight into the synthesis and storage of squalene in peroxisomes and reveals the potential of harnessing peroxisomes to overproduce terpenes in S. cerevisiae through dual cytoplasmic-peroxisomal engineering.
•Yeast peroxisome is a dynamic storage depot for squalene.•Yeast peroxisome is an efficient subcellular factory for squalene synthesis.•Dual cytoplasmic and peroxisomal engineering is favorable to high yield of squalene.
Monitoring interparticle chemical communication plays a critical role in the nanomaterial synthesis as this communication controls the final structure and stability of global nanoparticles (NPs). Yet ...most ensemble analytical techniques, which could only reveal average macroscopic information, are unable to elucidate NP‐to‐NP interactions. Herein, we employ stochastic collision electrochemistry to track the morphology transformation of Ag NPs in photochemical process at the single NP level. By further statistical analysis of time‐resolved current transients, we quantitatively determine the dynamic chemical potential difference and interparticle communication between populations of large and small Ag NPs. The high sensitivity of stochastic collision electrochemistry enables the in situ investigation of chemical communication‐dependent transformation kinetics of NPs in photochemical process, shedding light on designing nanomaterials.
In situ monitoring of photoinduced chemical communication between single Ag nanoparticles is achieved via the stochastic collision electrochemistry. The superior sensitivity enables to investigate the dynamic chemical potential difference at the single‐nanoparticle level, indicating the cooperative interparticle communication controls the morphology transformation kinetics, thereby determining the final structure of collective Ag nanoparticles.
Computed tomography (CT) is a widely utilized noninvasive diagnostic tool in clinical practice. However, the commonly employed small molecular iodinated contrast agents (ICAs) in clinical CT imaging ...have limitations such as nonspecific distribution in body, rapid clearance through kidneys, etc., leading to a narrow imaging time window. In contrast, existing nano‐sized ICAs face challenges like structural uncertainty, poor reproducibility, low iodine content, and uniformity issues. In this study, a novel approach is presented utilizing the aggregation‐induced emission luminogen (AIEgen) to design and fabricate a kind of monocomponent nano‐sized ICA (namely, BioDHU‐CT NPs) that exhibits a unique aggregation effect upon activation. The small sized BioDHU‐CT nanoparticles exhibit excellent tumor targeting capabilities and can release ICA modified with AIEgen with a high release efficiency up to 88.45%, under the activation of reactive oxygen species highly expressed in tumor regions. The released ICA performs in situ aggregation capability in the tumor region, which can enhance the retention efficiency of CT contrast agents, extending the imaging time window and improving the imaging quality in tumor regions.
A monocomponent and size‐adjustable nano‐computed tomography (CT) contrast agent is developed by utilizing a reactive oxygen species‐responsive platform and a fluorogen with aggregation function for improved in vivo tumor CT imaging. The nano‐CT contrast agent displays tumor‐targeting property and can rapidly aggregate in tumor regions after activation, enhancing its retention efficiency and extending the imaging time window.
Abstract
Nanograined metals have the merit of high strength, but usually suffer from low work hardening capacity and poor thermal stability, causing premature failure and limiting their practical ...utilities. Here we report a “nanodispersion-in-nanograins” strategy to simultaneously strengthen and stabilize nanocrystalline metals such as copper and nickel. Our strategy relies on a uniform dispersion of extremely fine sized carbon nanoparticles (2.6 ± 1.2 nm) inside nanograins. The intragranular dispersion of nanoparticles not only elevates the strength of already-strong nanograins by 35%, but also activates multiple hardening mechanisms via dislocation-nanoparticle interactions, leading to improved work hardening and large tensile ductility. In addition, these finely dispersed nanoparticles result in substantially enhanced thermal stability and electrical conductivity in metal nanocomposites. Our results demonstrate the concurrent improvement of several mutually exclusive properties in metals including strength-ductility, strength-thermal stability, and strength-electrical conductivity, and thus represent a promising route to engineering high-performance nanostructured materials.
Direct, low‐cost, label‐free, and enzyme‐free identification of single nucleobase is a great challenge for genomic studies. Here, this study reports that wild‐type aerolysin can directly identify the ...difference of four types of single nucleobase (adenine, thymine, cytosine, and guanine) in a free DNA oligomer while avoiding the operations of additional DNA immobilization, adapter incorporation, and the use of the processing enzyme. The nanoconfined space of aerolysin enables DNA molecules to be limited in the narrow pore. Moreover, aerolysin exhibits an unexpected capability of detecting DNA oligomers at the femtomolar concentration. In the future, by virtue of the high sensitivity of aerolysin and its high capture ability for DNA oligomers, aerolysin will play an important role in the studies of single nucleobase variations and open up new avenues for a broad range of nucleic‐acid‐based sensing and disease diagnosis.
An aerolysin nanopore directly achieves the identification of four types of single nucleobase (adenine, thymine, cytosine, and guanine) in a free DNA oligomer without the use of additional operations. The high sensitivity of aerolysin nanopores for DNA detection opens up new avenues for nucleic acid analysis and provides opportunities for a wide range of nucleic‐acid‐based sensing.
Malignant ovarian tumors bear the highest mortality rate among all gynecological cancers. Both late tumor diagnosis and tolerance to available chemical therapy increase patient mortality. Therefore, ...it is both urgent and important to identify biomarkers facilitating early identification and novel agents preventing recurrence. Accumulating evidence demonstrates that epigenetic aberrations (particularly histone modifications) are crucial in tumor initiation and development. Histone acetylation and methylation are respectively regulated by acetyltransferases-deacetylases and methyltransferases-demethylases, both of which are implicated in ovarian cancer pathogenesis. In this review, we summarize the most recent discoveries pertaining to ovarian cancer development arising from the imbalance of histone acetylation and methylation, and provide insight into novel therapeutic interventions for the treatment of ovarian carcinoma.
Nanoscale titanium dioxide (nTiO2) has been widely used in cosmetics, catalysts, varnishes, etc., which is raising concerns about its potential hazards to the ecosystem, including the marine ...environment. In this study, the toxicological effect of nTiO2 on the marine phytoplankton Phaeodactylum tricornutum was carefully investigated. The results showed that nTiO2 at concentrations ≥20mg/L could significantly inhibit P. tricornutum growth. The 5-day EC50 of nTiO2 to P. tricornutum growth is 167.71mg/L. Interestingly, nTiO2 was found to exert its most severe inhibition effects on the first day of exposure, at a lower EC50 of 12.65mg/L. During the experiment, nTiO2 aggregates were found to entrap algae cells, which is likely responsible for the observed toxic effects. Direct physical effects such as cell wall damage from the algae entrapment were confirmed by flow cytometry and TEM imaging. Moreover, low indirect effects such as shading and oxidative stress were observed, which supported the idea that direct physical effects could be the dominant factor that causes nTiO2 toxicity in P. tricornutum. Our research provides direct evidence for the toxicological impact of nTiO2 on marine microalgae, which will help us to build a good understanding of the ecological risks of nanoparticles in the marine environment.
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•Toxicological effect of nTiO2 on the marine phytoplankton Phaeodactylum tricornutum was carefully investigated.•nTiO2 showed “high-low” two-step effects on the growth of Phaeodactylum tricornutum.•nTiO2 aggregates were found to entrap algae cells.•Direct physical effects were the dominant factor that caused nTiO2 toxicity on Phaeodactylum tricornutum.
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