Search

Two series of novel NLRP3 inflammasome inhibitors are designed, synthesized, and evaluated in an effort to develop diversified analogs based on the N-(phenylcarbamoyl)benzenesulfonamide scaffold. SAR studies reveal that the sulfonylurea linker can tolerate chemical modifications with either simply changing over the position of carbonyl and sulfonyl group or structurally flexibly inserting a cyclopropyl group, leading to identification of several more potent and diversified NLRP3 antagonists (e.g., 9) with low nanomolar inhibitory activities. Further studies indicate that these two series of compounds with low cytotoxicity exhibited weak effects on the generation of NO and TNF-a. The findings may serve as good starting points for the development of more potent NLRP3 inflammasome inhibitors as valuable pharmacological probes or potential drug candidates.

The single-atom enzyme (SAE) is a novel type of nanozyme that exhibits extraordinary catalytic activity. Here, we constructed a PEGylated manganese-based SAE (Mn/PSAE) by coordination of single-atom manganese to nitrogen atoms in hollow zeolitic imidazolate frameworks. Mn/PSAE catalyzes the conversion of cellular H2 O2 to . OH through a Fenton-like reaction; it also promotes the decomposition of H2 O2 to O2 and continuously catalyzes the conversion of O2 to cytotoxic . O2 - via oxidase-like activity. The catalytic activity of Mn/PSAE is more pronounced in the weak acidic tumor environment; therefore, these cascade reactions enable the sufficient generation of reactive oxygen species (ROS) and effectively kill tumor cells. The prominent photothermal conversion property of the amorphous carbon can be utilized for photothermal therapy. Hence, Mn/PSAE exhibits significant therapeutic efficacy through tumor microenvironment stimulated generation of multiple ROS and photothermal activity.

5,6,12,13-Tetraazaperopyrenes with different number of tert-butyl groups (c-TAPP-T, c-TAPP-H) were synthesized, via four-fold Bischler-Napieralski cyclization as the key step. As deduced from the single-crystal structures and optical properties, N-doping and substitution type allow for a precise control of intermolecular interactions. Compared to the reported 1,3,8,10-tetraazaperopyrenes, significantly different packing modes were found in 5,6,12,13-tetraazaperopyrenes. Going from c-TAPP-T to c-TAPP-H, two additional tert-butyl groups lead to different preferential growth directions, affording 1D and 2D microcrystals, respectively. Most importantly, both microcrystals exhibit excellent optical waveguide properties with extraordinarily low loss coefficients and unique polarization features. Although c-TAPP-H possesses a rigid and planar core, its crystals display an exceptional mechanochromic fluorescence, which, again, depends on the mode of molecular packing.

Background: Ferroptosis is a form of iron-dependent programmed cell death that differs from apoptosis with regards to both mechanism and cell morphology. Therefore, ferroptotic-based cancer therapy has shown significant potential to overcome the weaknesses of conventional therapeutics mediated by apoptosis pathways. Effective ferroptosis can be induced by the intracellular Fenton reaction that is dependent on the adequate supply of iron ions and H2O2 in cells. However, these are often insufficient due to intrinsic cellular regulation. Methods: In this study, we designed a cisplatin prodrug-loaded manganese-deposited iron oxide nanoplatform (Pt-FMO) to trigger intracellular cascade reactions that lead to generation of reactive oxygen species (ROS) to enhance ferroptotic effect. The Pt-FMO causes the tumor microenvironment responsive to release manganese, iron ions and Pt-drugs. As manganese is an element that is able to catalyze the Fenton reaction more effectively than iron, coupled with the Pt-drugs that can promote generation of H2O2 in cells, the Pt-FMO is expected to significantly strengthen catalysis of the Fenton reaction, which favors the ferroptotic effect. Moreover, the Pt-drugs will eventually function as cisplatin. Thus, Pt-FMO is an ideal candidate for tumor ferroptotic combined with apoptotic treatment. Results: In vivo results demonstrated that, at a dosage of only 8.89% Pt content, Pt-FMO is able to achieve a similar treatment effect as cisplatin. Hence, Pt-FMO exhibited significantly lower systemic toxicity compared to cisplatin. Additionally, Pt-FMO exhibits effective T2 -weighted MRI enhancement for tumor imaging. Conclusion: The Pt-FMO nanoplatform is designed to introduce mutual beneficial cascade reactions for promoting ferroptosis and apoptosis in combination with tumor MRI. The Pt-FMO system, which causes ferroptosis combined with apoptosis, can efficiently induce tumor cell death.

Discotic π-conjugated supramolecular assemblies, especially with chiral supramolecular nanostructures, have been attracting growing research interest due to their significant optoelectronic properties and the possibilities of their applications in the new generation of organic semiconductors. However, the impact of supramolecular chirality on their mechanical and electrical performances remains poorly understood. Herein, a series of optically active supramolecular gels were formed from achiral triphenylene derivatives by introducing limonene as the chiral source. Owing to the well-ordered supramolecular packing, the homochiral supramolecular gels exhibited greater mechanical strength and higher conductivity, compared to heterochiral architectures. The impact of supramolecular packing in homochiral or heterochiral assemblies on their resulting mechanical and electrical performances was investigated in detail, which might be of great fundamental value for the rational design of chiral π-conjugated supramolecular nanostructures for applications in chiral optoelectronics.

Participatory sensing uses both local devices for data collection and cloud-based servers for processing. However, transferring the collected data to the cloud can lead to draining device battery power and cause network bandwidth bottlenecks, especially for large multimedia files. In this paper, we investigate how the processing resources at the edge of the network can be leveraged to enable efficient participatory sensing that avoids heavy network traffic. In particular, we report on the experiences of designing, implementing, and evaluating a sensing system that constructs indoor maps by recognizing door signs. A distinguishing characteristic of our system is an almost exclusive use of edge-based processing for tasks that include ML-based image recognition, human-assisted data verification, data model retraining, and administrative data flow aggregation. Our evaluation shows that our system architecture effectively leverages the available edge resources, while greatly reducing network traffic. Based on our experiences of implementing and evaluating our system prototype, we identify several open research directions for further advancing edge-based participatory sensing.

Here, we present a novel PDA microtube waveguide platform by combining heterogeneous CHA amplification with competitive inhibition. The heterogeneous CHA amplification system can preferentially amplify the signal of the correct target, while the competitive inhibition system will preferentially bind with the mutant targets and inactivate their signal.

Chiral discrimination of amino acid enantomers could give us a better understanding of the fundamental processes in organisms since enantiomers may have opposite biological effects. However, most of the reported chiral discrimination methods were based on different interaction between the chiral host platform and amino acid enantiomers, the chiral discrimination probes using achiral host platform have not been explored yet. Herein we reported the development of an easy, rapid and sensitive discrimination methodology of amino acid enantiomers using achiral materials, which relied on the different coordination between Cu 2+ ions and amino acid enantiomers. These coordinations could result in different pH values of samples containing the same amount of l - or d -amino acid enantiomers and Cu 2+ . By introduction of pH-responsive fluorophore 5(6)-Carboxyfluorescein (CF), above pH variation could be easily detected through fluorescence (FL) spectrometter, which could be utilized to determine the variety of amino acid enantiomers (including basic and acidic amino acids). Moreover, a more convenient achiral polyacrylamide (PAM) hydrogel containing CF and Cu 2+ has also been successfully fabricated to discriminate amino acid enantiomers and even the enantiomeric excess (ee) of mixtures at the designed concentration ranges.

Ferritin is an iron-storage protein nanocage that is assembled from 24 subunits. The hollow cavity of ferritin enables its encapsulation of various therapeutic agents; therefore, ferritin has been intensively investigated for drug delivery. The use of antibody-ferritin conjugates provides an effective approach for targeted drug delivery. However, the complicated preparation and limited protein stability hamper wide applications of this system. Herein, we designed a novel nanobody-ferritin platform (Nb-Ftn) for targeted drug delivery. The site-specific conjugation between nanobody and ferritin is achieved by transglutaminase-catalyzed protein ligation. This ligation strategy allows the Nb conjugation after drug loading in ferritin, which avoids deactivation of the nanobody under the harsh pH environment required for drug encapsulation. To verify the tumor targeting of this Nb-Ftn platform, a photodynamic reagent, manganese phthalocyanine (MnPc), was loaded into the ferritin cavity, and an anti-EGFR nanobody was conjugated to the surface of the ferritin. The ferritin nanocage can encapsulate about 82 MnPc molecules. This MnPc@Nb-Ftn conjugate can be efficiently internalized by EGFR positive A431 cancer cells, but not by EGFR negative MCF-7 cells. Upon 730 nm laser irradiation, MnPc@Nb-Ftn selectively killed EGFR positive A431 cells by generating reactive oxygen species (ROS), whereas no obvious damage was observed on MCF-7 cells. Given that ferritin can be used for encapsulation of various therapeutic agents, this work provides a strategy for facile construction of nanobody-ferritin for targeted drug delivery.

We evaluate the influence of pressure on the thermoelectric power factors PF ≡ S2σ of pristine and Na-doped SnSe crystals by measuring their electrical conductivity σ(T) and Seebeck coefficient S(T) up to ∼22 kbar with a self-clamped piston-cylinder cell. For both cases, σ(T) is enhanced while S(T) reduced with increasing pressure as expected, but their imbalanced variations lead to a monotonic enhancement of PF under pressure. For pristine SnSe, σ(290 K) increases by ∼4 times from ∼10.1 to 38 S cm−1, while S(290 K) decreases by only ∼12% from 474 to 415 μV K−1, leading to about three-fold enhancement of PF from 2.24 to 6.61 μW cm−1 K−2, which is very close to the optimal value of SnSe above the structural transition at ∼800 K at ambient pressure. In comparison, the PF of Na-doped SnSe at 290 K is enhanced moderately by ∼30% up to 20 kbar. In contrast, the PF of isostructural black phosphorus with a simple band structure was found to decrease under pressure. The comparison with black phosphorus indicates that the multi-valley valence band structure of SnSe is beneficial for the enhancement of PF by retaining a large Seebeck coefficient under pressure. Our results also provide experimental confirmation on the previous theoretical prediction that high pressure can be used to optimize the thermoelectric efficiency of SnSe.

Programmable materials and reconfigurable photonic components, which can change their physicochemical properties and functionalities upon external stimuli, are a major topic of interest in modern science. However, most conventional reconfigurable photonic components rely heavily on mechanical deformation, restricting their application. Herein, a novel strategy based on a dynamically tunable fluorescence resonance energy transfer process to design and fabricate programmable fluorescent micropatterns within single polymer microfiber is proposed. A set of reconfigurable photonic components (including optical switchable waveguide systems, photonic analogies of diodes and transistors, as well as one-dimensional (1D) optical encoding) can be achieved within a single polymeric waveguide microfiber straightforwardly, in which such photonic components can be written, erased, and rewritten as 1D binary patterns with tailored external optical stimuli. These results might be of great fundamental value for the rational design of novel reconfigurable photonic devices with numerous potential applications in highly integrated optical communication components and optical computing devices.

Chemoselective hydrogenation of aldehydes with heterogeneous catalysts under mild conditions is of great importance but remains a major challenge. Herein, an efficient strategy was developed for low temperature chemoselective hydrogenation of aldehydes with broad substrate scope over a magnetic material supported palladium catalyst (γ-Fe2O3@HAP-Pd). Aldehydes bearing various reducible functional groups readily underwent hydrogenation to give the corresponding primary alcohols with moderate to excellent yield at room temperature in aqueous solutions. The Hammett equation revealed that the hydrogenation of aromatic aldehydes proceeded via an anionic intermediate. Additionally, when the temperature increased to 70 °C, toluene was obtained by the deoxygenation of benzaldehyde in excellent yield. Furthermore, the γ-Fe2O3@HAP-Pd could be recycled up to six times without loss of activity and metal leaching.

Herein, we study the enantioselective cytotoxicity of vesicles self-assembled by optically active linear polymers (LNPs) and hyperbranched polymers (HBPs). Compared to HBP vesicles, LNP vesicles exhibit properties such as a higher surface charge density and more violent interaction with simulated biomembranes which results in larger cytotoxicity against HeLa cells. Specifically, racemic-LNP vesicles exhibit the largest cytotoxicity of all. More interestingly, there is no significant enantioselective dependence of HBP vesicles on the abovementioned properties. Overall, we proved that the cytotoxicity of vesicles is deeply related to chirality and topological-structures. This research is of great fundamental value for the design of novel bio-interface materials.

Efficient and safe intracellular delivery of proteins is highly desired in the development of protein therapeutics. Current methods of protein delivery commonly suffer from low loading efficiency, low stability in serum, and lack of versatility for different proteins. Here, we developed a platform for efficient protein delivery using mesoporous silica nanoparticles (MSN) with lipid fusion. By different surface modifications on MSN, the positively charged MSN (MSN+) and the negatively charged MSN (MSN–), were generated for loading different proteins. The cargo proteins, based on the surface charges, can be selectively loaded in very high efficiency. The protein-loaded MSNs were fused with liposomes to form a protocell-like delivery system (MSN-LP) in order to prevent burst release of proteins. The lipid fusion significantly increases the stability of the nanosystem in physiological conditions, and the MSN-LP protocell can efficiently deliver proteins into cells. The cargo proteins can be released in cells ...

Novel photocurable ternary polymer networks were prepared by incorporating N-(4-hydroxy-3-methoxybenzyl)-acrylamide (HMBA) into a cross-linked thiol–ene network based on poly(ethylene glycol)diacrylate (PEGDA) and (mercaptopropyl)methylsiloxane homopolymers (MSHP). The ternary network materials displayed bactericidal activity against Escherichia coli and Staphylococcus aureus and reduced the attachment of marine organism Phaeodactylum tricornutum. Extensive soaking of the polymer networks in aqueous solution indicated that no active antibacterial component leached out of the materials, and thus the ternary thiol–ene coating killed the bacteria by surface contact. The surface structures of the polymer networks with varied content ratios were studied by sum frequency generation (SFG) vibrational spectroscopy. The results demonstrated that the PDMS Si-CH3 groups and mimic-capsaicine groups are predominantly present at the polymer–air interface of the coatings. Surface reorganization was apparent after polyme...

Chemical synthesized silver nanowires have been proved to be the efficient architecture for Plasmonic waveguides, but the high propagation loss prevents their widely applications. Here, we demonstrate that the propagation distance of the plasmons along the Ag NW can be extended if the Ag NW was placed on a dielectric multilayer substrate containing a photonic band gap, but not placed on a commonly used glass substrate. The propagation distance at 630 nm wavelength can reach 16 um even that the Ag NW is as thin as 90 nm in diameter. Experimental and simulation results further show that the polarization of this propagating plasmon mode was nearly parallel to the surface of the dielectric multilayer, so it was excited by a transverse-electric polarized Bloch surface wave propagating along a polymer nanowire with diameter at only about 170 nm on the same dielectric multilayer. Numerical simulations were also carried out and consistent with the experiment results. Our work provides a platform to extend the propagation distance of plasmonic waveguide and also for the integration between photonic and plasmonic waveguides on the nanometre scale., Comment: 5 pages, 4 figures

Controlled Polarization Sensitivity of an active polymer microfiber has been proposed and realized with the electrospun method. The fluorescence intensity guiding through this active polymer microfiber shows high sensitivity to the polarization state of the excitation light. What is more, the fluorescence out-coupled from tip of the microfiber can be of designed polarization state. Principle of these phenomena lies on the ordered and controlled orientation of the polydiacetylene (PDA) main chains inside polymer microfiber.

A dimeric rhodium(ii) complex catalyses the chemoselective dehydrogenative esterification of aldehydes and alcohols., Dehydrogenative cross-coupling of aldehydes with alcohols as well as dehydrogentive cross-coupling of primary alcohols to produce esters have been developed using a Rh-terpyridine catalyst. The catalyst demonstrates broad substrate scope and good functional group tolerance, affording esters highly selectively. The high chemoselectivity of the catalyst stems from its preference for dehydrogenation of benzylic alcohols over aliphatic ones. Preliminary mechanistic studies suggest that the active catalyst is a dimeric Rh(ii) species, operating via a mechanism involving metal–base–metal cooperativity.