Core-Shell Gold Nanoparticles@Pd-Loaded Covalent Organic Framework for In Situ Surface-Enhanced Raman Spectroscopy Monitoring of Catalytic Reactions.

A core-shell nanostructure of gold nanoparticles@covalent organic framework (COF) loaded with palladium nanoparticles (AuNPs@COF-PdNPs) was designed for the rapid monitoring of catalytic reactions with surface-enhanced Raman spectroscopy (SERS). The nanostructure was prepared by coating the COF layer on AuNPs and then in situ synthesizing PdNPs within the COF shell. With the respective SERS activity and catalytic performance of the AuNP core and COF-PdNPs shell, the nanostructure can be directly used in the SERS study of the catalytic reaction processes. It was shown that the confinement effect of COF resulted in the high dispersity of PdNPs and outstanding catalytic activity of AuNPs@COF-PdNPs, thus improving the reaction rate constant of the AuNPs@COF-PdNPs-catalyzed hydrogenation reduction by 10 times higher than that obtained with Au/Pd NPs. In addition, the COF layer can serve as a protective shell to make AuNPs@COF-PdNPs possess excellent reusability. Moreover, the loading of PdNPs within the COF layer was found to be in favor of avoiding intermediate products to achieve a high total conversion rate. AuNPs@COF-PdNPs also showed great catalytic activities toward the Suzuki-Miyaura coupling reaction. Taken together, the proposed core-shell nanostructure has great potential in monitoring and exploring catalytic processes and interfacial reactions.

Cell membrane-targeted surface enhanced Raman scattering nanoprobes for the monitoring of hydrogen sulfide secreted from living cells.

Hydrogen sulfide (H2S), an important gas signal molecule, participates in intercellular signal transmission and plays a considerable role in physiology and pathology. However, in-situ monitoring of H2S level during the processes of material transport between cells remains considerably challenging. Herein, a cell membrane-targeted surface-enhanced Raman scattering (SERS) nanoprobe was designed to quantitatively detect H2S secreted from living cells. The nanoprobes were fabricated by assembling cholesterol-functionalized DNA strands and dithiobis(phenylazide) (DTBPA) molecules on core-shell gold nanostars embedded with 4-mercaptoacetonitrile (4-MBN) (AuNPs@4-MBN@Au). Thus, three functions including cell-membrane targeted via cholesterol, internal standard calibration, and responsiveness to H2S through reduction of azide group in DTBPA molecules were integrated into the nanoprobes. In addition, the nanoprobes can quickly respond to H2S within 90 s and sensitively, selectively, and reliably detect H2S with a limit of detection as low as 37 nM due to internal standard-assisted calibration and reaction specificity. Moreover, the nanoprobes can effectively target on cell membrane and realize SERS visualization of dynamic H2S released from HeLa cells. By employing the proposed approach, an intriguing phenomenon was observed: the other two major endogenous gas transmitters, carbon monoxide (CO) and nitric oxide (NO), exhibited opposite effect on H2S production in living cells stimulated by related gas release molecules. In particular, the introduction of CO inhibited the generation of H2S in HeLa cells, while NO promoted its output. Thus, the nanoprobes can provide a robust method for investigating H2S-related extracellular metabolism and intercellular signaling transmission.

Schiff Base Reaction in a Living Cell: In Situ Synthesis of a Hollow Covalent Organic Polymer To Regulate Biological Functions.

Artificially performing chemical reactions in living biosystems to attain various physiological aims remains an intriguing but very challenging task. In this study, the Schiff base reaction was conducted in cells using Sc(OTf)3 as a catalyst, enabling the in situ synthesis of a hollow covalent organic polymer (HCOP) without external stimuli. The reversible Schiff base reaction mediated intracellular Oswald ripening endows the HCOP with a spherical, hollow porous structure and a large specific surface area. The intracellularly generated HCOP reduced cellular motility by restraining actin polymerization, which consequently induced mitochondrial deactivation, apoptosis, and necroptosis. The presented intracellular synthesis system inspired by the Schiff base reaction has strong potential to regulate cell fate and biological functions, opening up a new strategic possibility for intervening in cellular behavior.

Smart Nanoplatform for Visualizing Hydrogen Sulfide and Amplifying Oxidative Stress to Tumor Apoptosis.

Oxidative stress is involved in various signaling pathways and serves a key role in inducing cell apoptosis. Therefore, it is significant to monitor oxidative stress upon drug release for the assessment of therapeutic effects in cancer cells. Herein, a glutathione (GSH)-responsive surface-enhanced Raman scattering (SERS) nanoplatform is proposed for ultra-sensitively monitoring the substance related with oxidative stress (hydrogen sulfide, H2S), depleting reactive sulfur species and releasing anticancer drugs to amplify oxidative stress for tumor apoptosis. The Au@Raman reporter@Ag (Au@M@Ag) nanoparticles, where a 4-mercaptobenzonitrile molecule as a Raman reporter was embedded between layers of gold and silver to obtain sensitive SERS response, were coated with a covalent organic framework (COF) shell to form a core-shell structure (Au@M@Ag@COFs) as the SERS nanoplatform. The COF shell loading doxorubicin (DOX) of Au@M@Ag@COFs exhibited the GSH-responsive degradation capacity to release DOX, and its Ag layer as the sensing agent was oxidized to Ag2S by H2S to result in its prominent changes in SERS signals with a low detection limit of 0.33 nM. Moreover, the releasing DOX can inhibit the generation of H2S to promote the production of reactive oxygen species, and the depletion of reactive sulfur species (GSH and H2S) in cancer cells can further enhance the oxidative stress to induce tumor apoptosis. Overall, the SERS strategy could provide a powerful tool to monitor the dynamic changes of oxidative stress during therapeutic processes in a tumor microenvironment.

Dual-Modal Apoptosis Assay Enabling Dynamic Visualization of ATP and Reactive Oxygen Species in Living Cells.

ATP and reactive oxygen species (ROS) are considered significant indicators of cell apoptosis. However, visualizing the interplay between apoptosis-related ATP and ROS is challenging. Herein, we developed a metal-organic framework (MOF)-based nanoprobe for an apoptosis assay using duplex imaging of cellular ATP and ROS. The nanoprobe was fabricated through controlled encapsulation of gold nanorods with a thin zirconium-based MOF layer, followed by modification of the ROS-responsive molecules 2-mercaptohydroquinone and 6-carboxyfluorescein-labeled ATP aptamer. The nanoprobe enables ATP and ROS visualization via fluorescence and surface-enhanced Raman spectroscopy, respectively, avoiding the mutual interference that often occurs in single-mode methods. Moreover, the dual-modal assay effectively showed dynamic imaging of ATP and ROS in cancer cells treated with various drugs, revealing their apoptosis-related pathways and interactions that differ from those under normal conditions. This study provides a method for studying the relationship between energy metabolism and redox homeostasis in cell apoptosis processes.

Self-Assembled Plasmonic Nanojunctions Mediated by Host-Guest Interaction for Ultrasensitive Dual-Mode Detection of Cholesterol.

Herein, a fluorescence and surface-enhanced Raman spectroscopy dual-mode system was designed for cholesterol detection based on self-assembled plasmonic nanojunctions mediated by the competition of rhodamine 6G (R6G) and cholesterol with ß-cyclodextrin modified on gold nanoparticles (HS-ß-CD@Au). The fluorescence of R6G was quenched by HS-ß-CD@Au due to the fluorescence resonance energy transfer effect. When cholesterol was introduced as the competitive guest, R6G in the cavities of HS-ß-CD@Au was displaced to recover its fluorescence. Moreover, two of HS-ß-CD@Au can be linked by one cholesterol to form a more stable 2:1 complex, and then, plasmonic nanojunctions were generated, which resulted in the increasing SERS signal of R6G. In addition, fluorescence and SERS intensity of R6G increased linearly with the increase in the cholesterol concentrations with the limits of detection of 95 and 74 nM, respectively. Furthermore, the dual-mode strategy can realize the reliable and sensitive detection of cholesterol in the serum with good accuracy, and two sets of data can mutually validate each other, which demonstrated great application prospects in the surveillance of diseases related with cholesterol.

AuNPs-COFs Core-Shell Reversible SERS Nanosensor for Monitoring Intracellular Redox Dynamics.

The redox homeostasis in living cells is greatly crucial for maintaining the redox biological function, whereas accurate and dynamic detection of intracellular redox states still remains challenging. Herein, a reversible surface-enhanced Raman scattering (SERS) nanosensor based on covalent organic frameworks (COFs) was prepared to dynamically monitor the redox processes in living cells. The nanosensor was fabricated by modifying the redox-responsive Raman reporter molecule, 2-Mercaptobenzoquione (2-MBQ), on the surface of gold nanoparticles (AuNPs), followed by the in situ coating of COFs shell. 2-MBQ molecules can repeatedly and quickly undergo reduction and oxidation when successively treated with ascorbic acid (AA) and hypochlorite (ClO-) (as models of reductive and oxidative species, respectively), which resulted in the reciprocating changes of SERS spectra at 900 cm-1. The construction of the COFs shell provided the nanosensor with great stability and anti-interference capability, thus reliably visualizing the dynamics of intracellular redox species like AA and ClO- by SERS nanosensor. Taken together, the proposed SERS strategy opens up the prospects to investigate the signal transduction pathways and pathological processes related with redox dynamics.

[Comparative study on effect of acupoint heat-sensitive moxibustion and Seretide on the symptoms of bronchial asthma at chronic persistent stage].

OBJECTIVE: To observe the difference in the efficacy on the symptoms of bronchial asthma at the chronic persistent stage between acupoint heat-sensitive moxibustion and western medicine with Seretide. METHODS: Sixty-four cases were randomly divided into a heat-sensitive moxibustion group (32 cases) and a western medication group (32 cases). In the heat-sensitive moxibustion group, the sensitized points located between Feishu (BL 13) and Geshu (BL 17) or in the region 6-cun lateral from the 1st and the 2nd intercostal spaces of the chest were selected. The heat-sensitive moxibustion was adopted, continuously for 8 days, once per day. In the later 22 days of the 1st month, 12 treatments should be ensured. Two months later, 15 treatments should be guaranteed each month. The time of each treatment was 30 to 90 min. Totally 50 treatments were required. In the western medication group, Seretide inhaler was adopted, one inhalation each time, twice per day, for 3 months totally. The asthmatic symptoms were scored for the patients in two groups and the comparison was made between the two groups. RESULTS: After 3 months of treatment, the asthmatic symptom scores were all improved for the patients in the heat-sensitive moxibustion group and the western medication group as compared with those before treatment (both P < 0.05). In 6 months of follow-up visit, the asthmatic symptom scores in the heat-sensitive moxibustion group were stable, but those in the western medication group were reduced, there was significant difference between the two groups (P < 0.05). CONCLUSION: The acupoint heat-sensitive moxibustion effectively relieves the clinical symptoms for the patients with bronchial asthma at the chronic persistent stage. Its efficacy is similar to that of Seretide inhaler. But the long-term efficacy of the heat-sensitive moxibustion is much better.

[Observation on therapeutic effect of muscular needling combined with scarring moxibustion on active stage of rheumatoid arthritis].

OBJECTIVE: To observe the therapeutic effect of muscular needling combined with scarring moxibustion on active stage of rheumatoid arthritis (RA). METHODS: Sixty cases of RA were randomly divided into a muscular needling group and a medication group, 30 cases in each group. The muscular needling group was treated by muscular needling on Quchi (LI 11), Sanyinjiao (SP 6), etc. combined with scarring moxibustion on Dazhui (GV 14), Zusanli (ST 36) etc., while the medication group was treated by oral administration of Diclofenac sodium and intramuscular injection of Methotrexate. The therapeutic effects, main symptoms and signs, erythrocyte sedimentation rate (ESR) and rheumatoid factor were observed in two groups before and after treatment. RESULTS: The total effective rate of muscular needling group was 76.7%, and that of medication group was 73.3%, there was no significant difference between two groups (P > 0.05). The clinical symptoms, signs, and E8R of two groups were improved obviously compared with those before treatment (P < 0.01, P < 0.05), however there were no significant differences between the two groups after treatment (all P > 0.05). The adverse reactions of medication group were more eminent compared to the muscular needling group. CONCLUSION: Muscular needling can obviously relieve the symptoms and signs of active stage rheumatoid arthritis and the effect is equivalent to oral administration of western medicine, the incidence of adverse reactions in the muscular needling group is obviously lower than that of western medication. Muscular needling is a safe and effective method for treatment of RA.