Rapid Selenoprotein Activation by Selenium Nanoparticles to Suppresses Osteoclastogenesis and Pathological Bone Loss.

Osteoclast hyperactivation stands as a significant pathological factor contributing to the emergence of bone disorders driven by heightened oxidative stress levels. The modulation of the redox balance to scavenge reactive oxygen species emerges as a viable approach to addressing this concern. Selenoproteins, characterized by selenocysteine (SeCys2) as the active center, are crucial for selenium-based antioxidative stress therapy for inflammatory diseases. This study reveals that surface-active elemental selenium (Se) nanoparticles, particularly lentinan-Se (LNT-Se), exhibit enhanced cellular accumulation and accelerated metabolism to SeCys2, the primary active Se form in biological systems. Consequently, LNT-Se demonstrates significant inhibition of osteoclastogenesis. Furthermore, in vivo studies underscore the superior therapeutic efficacy of LNT-Se over SeCys2, potentially attributable to the enhanced stability and safety profile of LNT-Se. Specifically, LNT-Se effectively modulates the expression of the selenoprotein GPx1, thereby exerting regulatory control over osteoclastogenesis inhibition, and the prevention of osteolysis. In summary, these results suggest that the prompt activation of selenoproteins by Se nanoparticles serves to suppress osteoclastogenesis and pathological bone loss by upregulating GPx1. Moreover, the utilization of bioactive Se species presents a promising avenue for effectively managing bone disorders.

Engineering cancer cell membrane-camouflaged metal complex for efficient targeting therapy of breast cancer.

BACKGROUND: Cancer cell membrane-camouflaged nanotechnology for metal complex can enhance its biocompatibility and extend the effective circulation time in body. The ruthenium polypyridyl complex (RuPOP) has extensive antitumor activity, but it still has disadvantages such as poor biocompatibility, lack of targeting, and being easily metabolized by the organism. Cancer cell membranes retain a large number of surface antigens and tumor adhesion molecules CD47, which can be used to camouflage the metal complex and give it tumor homing ability and high biocompatibility. RESULTS: Therefore, this study provides an electrostatic adsorption method, which uses the electrostatic interaction of positive and negative charges between RuPOP and cell membranes to construct a cancer cell membrane-camouflaged nano-platform (RuPOP@CM). Interestingly, RuPOP@CM maintains the expression of surface antigens and tumor adhesion molecules, which can inhibit the phagocytosis of macrophage, reduce the clearance rate of RuPOP, and increase effective circulation time, thus enhancing the accumulation in tumor sites. Besides, RuPOP@CM can enhance the activity of cellular immune response and promote the production of inflammatory cytokines including TNF-α, IL-12 and IL-6, which is of great significance in treatment of tumor. On the other hand, RuPOP@MCM can produce intracellular ROS overproduction, thereby accelerating the apoptosis and cell cycle arrest of tumor cells to play an excellent antitumor effect in vitro and in vivo. CONCLUSION: In brief, engineering cancer cell membrane-camouflaged metal complex is a potential strategy to improve its biocompatibility, biological safety and antitumor effects.

Mesoporous silica nanoparticle-embedded lanthanide organic polyhedra for enhanced stability, luminescence and cell imaging.

We report here a simple but efficient "ship-in-a-bottle" synthetic strategy for increasing the stability and luminescence performance of LOPs by embedding them into mesoporous silica nanoparticles (MSNs). Three types of hybrid materials, i.e. Eu8L12@MSNs, Eu8L12@MSNs-NH2 and Eu8L12@MSNs-biotin, have been prepared and characterized by FT-IR, TGA, SEM and TEM. Photo-optical measurements confirmed that the photoluminescence quantum yields in water have been greatly improved from 5.50% for pristine Eu8L12 to 44.04% for Eu8L12@MSNs-biotin, along with fast disassembly for the former and the optical performance has been maintained for the latter under acidic conditions (pH = 4). Moreover, compared to Eu8L12, Eu8L12@MSNs and Eu8L12@MSNs-NH2, the biotin-modified hybrid material Eu8L12@MSNs-biotin has exhibited much enhanced fluorescence-imaging ability toward the MDA-MB-231 human breast cancer cells, with significantly reduced dosage of the complex. Our work provides a useful strategy for the functionalization of multinuclear lanthanide organic assemblies toward their biosocial applications.

Blocking tumor necrosis factor-α delays progression of chronic obstructive pulmonary disease in rats through inhibiting MAPK signaling pathway and activating SOCS3/TRAF1.

The present study was conducted in order to study the detailed molecular mechanism of tumor necrosis factor (TNF)-α in chronic obstructive pulmonary disease (COPD). The rats were treated with cigarette smoke (CS) and lipopolysaccharide (LPS) to establish the COPD model. Next, the changes in lung injury in COPD rats with TNF-α knockdown was tested. Meanwhile, the regulation of TNF-α on MAPK pathway and its downstream molecules (SOCS3/TRAF1) was determined by western blotting. On this basis, the activation of MAPK and inhibition of SOCS3/TRAF1 was also examined. Subsequently, the lung function was tested with the plethysmograph, the cells of bronchoalveolar lavage fluid was counted and classified. Furthermore, lung tissue sections were stained with hematoxylin and eosin to verify whether the treatment of MAPK pathway and downstream molecules affected the effect of TNF-α knockdown on COPD. The present study showed that TNF-α knockdown could alleviate the decrease in the function and inflammatory injury of the lungs of rats with COPD. Western blot analysis verified that TNF-α knockdown could inhibit the activation of MAPK pathway and increase the expression of SOCS3/TRAF1. The following experimental results showed that the relief of lung injury caused by TNF-α knockdown could be deteriorated by activating MAPK pathway. It was also found that the symptom of COPD was decreased following transfection with sh-TNF-α but worsened by SOCS3/TRAF1 knockdown. Overall, TNF-α knockdown inhibited the activation of MAPK pathway and increased the expression of SOCS3/TRAF1, thus delaying the process of COPD.

Dehydration impeding ionic conductance through two-dimensional angstrom-scale slits.

There has been long-standing academic interest in the study of ion transport in nanochannel systems, owing to its vast implications in understanding the nature of numerous environmental, biological and chemical processes. Here, we investigate ion transport through two-dimensional slits using molecular dynamics simulations. These slits with angstrom-scale height dimensions can be realistically replicated in the simulation, which leads to direct comparisons between simulations and experiments. In particular, this new confining geometry allows the size exclusion effect to be unambiguously decoupled from other mechanisms. As the slit size approaches the ultimate scale, dehydration at the entry impedes the ionic conductance significantly, and even induces a complete ion rejection. We demonstrate that energy barriers required to accomplish the ion permeation can be theoretically connected to the partial dehydration process. The proposed model is further validated by simulations. Our results offer insights into the atomistic details of ion permeation, which may also shed light on developing effective ways for water filtration and desalination.

Shuttle Suppression by Polymer-Sealed Graphene-Coated Polypropylene Separator.

"Shuttle effect" of lithium polysulfides (LiPS) leads to a poor performance and a short cycle life of the Li-S battery, thus limiting their practical application. We demonstrate here that after coating polypropylene (PP) separator with a continuous monolayer graphene, the shuttle effect can be significantly suppressed by limiting the passage of long-chain LiPS. The graphene/PP separator can be further modified by sealing the big holes or pores on graphene with in situ polymerized nylon-66 via an interfacial polymerization reaction between diamine and adipoyl chloride supplied by the aqueous and oil phase, respectively, from each side of the membrane. With this engineered membrane, an initial specific capacity of 1128.4 mAh g-1 at 0.05C is achieved after test in a coin cell, higher than that of 983.2 mAh g-1 with pristine PP, along with increased Coulombic efficiency from 96.0 to 99.9% and enhanced cycling durability. Molecular dynamics simulations attest that the nanopores with appropriate size and structure are effective in acting as a "sieve" to selectively allow only Li+ ions to pass through but prevent LiPS from migrating to the anode, consequently alleviating the shuttle effect. Our method provides a facile solution toward the mitigated shuttle effect and eventually contributes to the high performance of Li-S battery.