Functional Liquid Metal Nanoparticles Produced by Liquid-Based Nebulization

Functional liquid metal nanoparticles (NPs), produced from eutectic alloys of gallium, promise new horizons in the fields of sensors, microfluidics, flexible electronics, catalysis, and biomedicine. Here, the development of a vapor cavity generating ultrasonic platform for nebulizing liquid metal within aqueous media for the one-step production of stable and functional liquid metal NPs is shown. The size distribution of the NPs is fully characterized and it is demonstrated that various macro and small molecules can also be grafted onto these liquid metal NPs during the liquid-based nebulization process. The cytotoxicity of the NPs grafted with different molecules is further explored. Moreover, it is shown that it is possible to control the thickness of the oxide layer on the produced NPs using electrochemistry that can be embedded within the platform. It is envisaged that this platform can be adapted as a cost-effective and versatile device for the rapid production of functional liquid metal NPs for future liquid metal-based optical, electronic, catalytic, and biomedical applications

Activation of EDTA-resistant gelatinases in malignant human tumors

Among the many proteases associated with human cancer, seprase or fibroblast activation protein alpha, a type II transmembrane glycoprotein, has two types of EDTA-resistant protease activities: dipeptidyl peptidase and a 170-kDa gelatinase activity. To test if activation of gelatinases associated with seprase could be involved in malignant tumors, we used a mammalian expression system to generate a soluble recombinant seprase (r-seprase). In the presence of putative EDTA-sensitive activators, r-seprase was converted into 70- to 50-kDa shortened forms of seprase (s-seprase), which exhibited a 7-fold increase in gelatinase activity, whereas levels of dipeptidyl peptidase activity remained unchanged. In malignant human tumors, seprase is expressed predominantly in tumor cells as shown by in situ hybridization and immunohistochemistry. Proteins purified from experimental xenografts and malignant tumors using antibody- or lectin-affinity columns in the presence of 5 mmol/L EDTA were assayed for seprase activation in vivo. Seprase expression and activation occur most prevalently in ovarian carcinoma but were also detected in four other malignant tumor types, including adenocarcinoma of the colon and stomach, invasive ductal carcinoma of the breast, and malignant melanoma. Together, these data show that, in malignant tumors, seprase is proteolytically activated to confer its substrate specificity in collagen proteolysis and tumor invasion

BMP-6 promotes E-cadherin expression through repressing δEF1 in breast cancer cells

<p>Abstract</p> <p>Background</p> <p>Bone morphogenetic protein-6 (BMP-6) is critically involved in many developmental processes. Recent studies indicate that BMP-6 is closely related to tumor differentiation and metastasis.</p> <p>Methods</p> <p>Quantitative RT-PCR was used to determine the expression of BMP-6, E-cadherin, and δEF1 at the mRNA level in MCF-7 and MDA-MB-231 breast cancer cells, as well as in 16 breast cancer specimens. Immunoblot analysis was used to measure the expression of δEF1 at the protein level in δEF1-overexpressing and δEF1-interfered MDA-MB-231 cells. Luciferase assay was used to determine the rhBMP-6 or δEF1 driven transcriptional activity of the E-cadherin promoter in MDA-MB-231 cells. Quantitative CHIP assay was used to detect the direct association of δEF1 with the E-cadherin proximal promoter in MDA-MB-231 cells.</p> <p>Results</p> <p>MCF-7 breast cancer cells, an ER⁺cell line that expressed high levels of BMP-6 and E-cadherin exhibited very low levels of δEF1 transcript. In contrast, MDA-MB-231 cells, an ER^-cell line had significantly reduced BMP-6 and E-cadherin mRNA levels, suggesting an inverse correlation between BMP-6/E-cadherin and δEF1. To determine if the same relationship exists in human tumors, we examined tissue samples of breast cancer from human subjects. In 16 breast cancer specimens, the inverse correlation between BMP-6/E-cadherin and δEF1 was observed in both ER⁺cases (4 of 8 cases) and ER^-cases (7 of 8 cases). Further, we found that BMP-6 inhibited δEF1 transcription, resulting in an up-regulation of E-cadherin mRNA expression. This is consistent with our analysis of the E-cadherin promoter demonstrating that BMP-6 was a potent transcriptional activator. Interestingly, ectopic expression of δEF1 was able to block BMP-6-induced transactivation of E-cadherin, whereas RNA interference-mediated down-regulation of endogenous δEF1 in breast cancer cells abolished E-cadherin transactivation by BMP-6. In addition to down-regulating the expression of δEF1, BMP-6 also physically dislodged δEF1 from E-cadherin promoter to allow the activation of E-cadherin transcription.</p> <p>Conclusion</p> <p>We conclude that repression of δEF1 plays a key role in mediating BMP-6-induced transcriptional activation of E-cadherin in breast cancer cells. Consistent with the fact that higher level of δEF1 expression is associated with more invasive phenotype of breast cancer cells, our collective data suggests that δEF1 is likely the switch through which BMP-6 restores E-cadherin-mediated cell-to-cell adhesion and prevents breast cancer metastasis.</p

Analysis of the Cause of Household Carbon Lock-In for Chinese Urban Households

Household energy conservation is an important contributor to achieve the carbon emission reduction target. However, the actual energy-saving effect of Chinese households is under expectation. One reason for this is because household energy consumption is locked in at a certain level, which has become an obstacle to household carbon emission reduction. In order to reduce this obstacle, this study explored the cause of household carbon lock-in based on grounded theory, targeting newly furnished households. A theoretical model was developed to reveal the formation mechanism of carbon lock-in effect in the purchasing process of household energy-using appliances. NVivo 12 software was used to analyze the decoration diaries of 616 sample households, and the results showed that (1) the direct antecedent of the household carbon lock-in effect was the lock-in of purchasing behavior, and the household carbon lock-in effect was mainly exhibited in the consumption path dependence (of energy-using appliances) and the solidification of energy structure; (2) the willingness to purchase household appliances was the direct antecedent of purchasing behavioral lock-in, and the cost had a moderating effect on the transformation from purchase willingness to behavioral lock-in; and (3) in the process of purchasing household appliances, reference groups, value perception, and ecological awareness can promote purchasing behavioral lock-in by affecting willingness of purchase. Suggestions to promote unlocking of household carbon were also proposed

Engineering organic/inorganic nanohybrids through RAFT polymerization for biomedical applications

Despite many early accomplishments in nano material design and synthesis, there remains a significant requirement for novel inorganic and organic nanohybrids with the potential to act as efficacious molecular imaging agents and theranostic vectors. The functionalization of surfactant coated inorganic nanoparticles with polymer shells represents one of the most suitable and popular methods to synthesize polymer/inorganic nanohybrids for theranostic applications. Key requirements for effective imaging agent design include water dispersibility, biocompatibility and functionality to enable enhanced contrast magnetic resonance imaging (MRI), positron-emission tomography (PET), computed tomography (CT), or ultrasound modalities. In this Perspective, we highlight recent advances in the fabrication of organic/inorganic nanohybrids exploiting functionalized polymers prepared using reversible addition-fragmentation chain transfer (RAFT) polymerization. The polymer shells can imbue favorable traits to the nanoparticles such as stealth, image enhancement, storage (and release) of therapeutics, and sensitivity to biological stimuli. In this Perspective, we discuss the design and synthesis of hybrid nanoparticles and discuss current trends and future opportunities

Polymer-assisted magnetic nanoparticle assemblies for biomedical applications

Magnetic nanoparticle (MNP) assemblies have demonstrated great potential in biomedical applications due to their controllable magnetic properties and collective functions. Among the versatile approaches to obtaining MNP assemblies, polymer-assisted assembling methods offer unique advances, by which the assembled nanostructures could exert the merits of both the inorganic magnetic nanoparticles and organic polymeric materials to realize combined advantages for medical diagnosis and treatment. Precise control over the interactions among different building moieties and spatial organization of magnetic nanoparticles with the aid of polymers provides promising strategies in manipulating the physical, chemical, and biological properties of nanoassemblies for biomedical applications. In this review, we summarize the recent progress of polymer-assisted MNP assemblies, which include the mutual interactions between building blocks, architectural diversity of the assemblies, and their synthetic strategies along with biomedical applications. The current review provides a comprehensive insight into controlled and intelligent nanomedicines, which shall facilitate the development of next-generation high-performance theranostic agents based on MNP assemblies

Au Nanoparticles-Decorated BiOI Nanosheet Arrays for Cathodic Photoelectrochemical Dopamine Sensors

Photocathode-based photoelectrochemical (PEC) sensors can well evade the intrinsic hole oxidation reactions occurring at the photoelectrode–electrolyte interface and expand the application of PEC sensors in the field of bioanalysis. Herein, a cathodic PEC sensor based on p-type semiconductor bismuth oxyiodide nanosheet arrays (BiOI NSAs) integrated with gold nanoparticles (AuNPs) on indium-doped tin oxide (ITO) electrode (ITO/BiOI NSAs/AuNPs) is fabricated by a two-step electrodeposition method. The local surface plasmon resonance (LSPR) effect of AuNPs facilitates the capability of visible light absorption of the BiOI NSAs. Meanwhile, AuNPs, as an electron reservoir, improve the charge separation efficiency of carriers by forming a Schottky barrier, allowing more electrons to be transferred to O2 dissolved in the electrolyte, consequently promoting the PEC activity of the photoactive materials. Furthermore, dopamine (DA) can enhance the photocurrent of the ITO/BiOI NSAs/AuNPs photoelectrode by binding to Bi3+ on the BiOI NSAs surface to in-situ-form a charge-transfer complex (CTC). Based on this phenomenon, a PEC sensor was designed for the determination of DA, and the PEC sensor showed acceptable results for DA detection in real samples. The PEC sensor demonstrates the prospect of BiOI-based materials in cathodic PEC biosensing

Recent advances in molecular imaging of atherosclerotic plaques and thrombosis

As the complications of atherosclerosis such as myocardial infarction and stroke are still one of the leading causes of mortality worldwide, the development of new diagnostic tools for the early detection of plaque instability and thrombosis is urgently needed. Advanced molecular imaging probes based on functional nanomaterials in combination with cutting edge imaging techniques are now paving the way for novel and unique approaches to monitor the inflammatory progress in atherosclerosis. This review focuses on the development of various molecular probes for the diagnosis of plaques and thrombosis in atherosclerosis, along with perspectives of their diagnostic applications in cardiovascular diseases. Specifically, we summarize the biological targets that can be used for atherosclerosis and thrombosis imaging. Then we describe the emerging molecular imaging techniques based on the utilization of engineered nanoprobes together with their challenges in clinical translation

Functionalization of NaGdF4 nanoparticles with a dibromomaleimide-terminated polymer for MR/optical imaging of thrombosis

Herein, we report the development of a thrombosis-targeted molecular imaging probe with magnetic resonance (MR) and optical dual-modality capacity using dibromomaleimide (DBM)-bearing polymer-grafted NaGdF nanoparticles. The random copolymer of bisphosphonic ester (BPE)-P(OEGA-co-DBM) was first synthesized through reversible addition-fragmentation chain transfer (RAFT) copolymerization of oligo(ethylene glycol)methyl ether acrylate (OEGA) and DBM-based monomers using a BPE-terminated RAFT agent. The resulting polymers were subjected to deprotection with the formation of bisphosphonic acid (BPA) terminals, allowing for the attachment of the as-synthesized BPA-P(OEGA-co-DBM) chains onto the surface of paramagnetic NaGdF nanoparticles through the ligand exchange reaction. Azide moieties could be readily incorporated into the hybrid nanoparticles by the coupling reaction between the highly reactive DBM moieties and amine derivatives. Intriguingly, the coupling reaction was characterized by a unique fluorescence turn-on even in aqueous media, which subsequently enabled the fluorescence imaging applications of the resulting hybrid nanoparticle. Furthermore, a single-chain antibody (scFv), which is specifically used for the active conformation of the GPIIb/IIIa integrin, was successfully attached onto the nanoparticles by a strain-promoted copper-free "click" reaction, allowing the targeting of activated platelets in acute thrombosis. The hybrid nanoparticles prepared through this new surface functionalization protocol possessed not only high colloidal stability under physiological conditions but also potential MR/optical imaging capacity. The thrombosis targeting capacity of the hybrid nanoparticle-based probe was then demonstrated by exploiting DBM conjugation-induced fluorescence in living cells