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.

Methods for characterizing the structure of starch in relation to its applications: a comprehensive review.

Starch is a major part of the human diet and an important material for industrial utilization. The structure of starch granules is the subject of intensive research because it determines functionality, and hence suitability for specific applications. Starch granules are made up of a hierarchy of complex structural elements, from lamellae and amorphous regions to blocklets, growth rings and granules, which increase in scale from nanometers to microns. The complexity of these native structures changes with the processing of starch-rich ingredients into foods and other products. This review aims to provide a comprehensive review of analytical methods developed to characterize structure of starch granules, and their applications in analyzing the changes in starch structure as a result of processing, with particular consideration of the poorly understood short-range ordered structures in amorphous regions of granules.

Sirtuin 2 up-regulation suppresses the anti-tumour activity of exhausted natural killer cells in mesenteric lymph nodes in murine colorectal carcinoma.

Natural killer (NK) cells inhibit colorectal carcinoma (CRC) initiation and progression through their tumoricidal activity. However, cumulative evidence suggests that NK cells become functionally exhausted in patients with CRC. To deepen the understanding of the mechanisms underlying CRC-associated NK cell exhaustion, we explored the expression and effect of Sirtuin 2 (Sirt2) in mesenteric lymph node (mLN) NK cells in a murine colitis-associated CRC model. Sirt2 was remarkably up-regulated in mLN NK cells after CRC induction. Particularly, Sirt2 was increased in mLN NK cells expressing high T cell immunoglobulin and mucin domain-3 (TIM3), high lymphocyte activation protein-3 (LAG3), high programmed death-1 (PD-1), high T cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT), high NK group 2 member A (NKG2A), but low tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), low interferon-gamma and low granzyme B. In addition, Sirt2 was also increased in NK cells after induction of exhaustion in vitro. Lentivirus-mediated Sirt2 silencing did not affect the acute activation and cytotoxicity of non-exhausted NK cells. However, Sirt2 silencing partially restored the expression of interferon-gamma, granzyme B and CD107a in exhausted NK cells. Meanwhile, Sirt2 silencing down-regulated TIM3, LAG3, TIGIT and NKG2A while up-regulated TRAIL on exhausted NK cells. Consequently, Sirt2 silencing restored the cytotoxicity of exhausted NK cells. Moreover, Sirt2 silencing partially ameliorates the defects in glycolysis and mitochondrial respiration of exhausted NK cells, as evidenced by increases in glycolytic capacity, glycolytic reserve, basal respiration, maximal respiration and spare respiration capacity. Accordingly, Sirt2 negatively regulates the tumoricidal activity of exhausted NK cells in CRC.

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.

Down-regulation of PR/SET domain 10 underlies natural killer cell dysfunction in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the world's leading cause of tumor-related mortalities. Natural killer (NK) cells play a critical role at the first immunological defense line against HCC initiation and progression. NK cell dysfunction is therefore an important mechanism for immune evasion of HCC cells. In the present study using a murine HCC model, we revealed the down-regulation of PR/SET Domain 10 (PRDM10) in hepatic NK cells that were phenotypically and functionally exhausted. PRDM10 silencing diminished the expression of natural killer group 2 member D (NKG2D) and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), augmented T cell immunoglobulin and ITIM domain (TIGIT) expression, and decreased the expression of interferon (IFN)-γ, perforin and granzyme B in normal hepatic NK cells in vitro. Consistently, PRDM10-deficient NK cells exhibited impaired cytotoxicity on target cells. In contrast, PRDM10 over-expression promoted NKG2D and Fas ligand (FasL) expression, reduced CD96 expression and enhanced transcripts of IFN-γ, perforin and granzyme B in NK cells in vivo. Moreover, PRDM10 silencing and PRDM10 over-expression down-regulated and up-regulated Eomesodermin (Eomes) expression, respectively. In summary, this study reveals PRDM10 down-regulation as a novel mechanism underlying NK cell dysfunction and identifies PRDM10 as a supporting factor of NK cell function.

A novel affinity peptide-antibody sandwich electrochemical biosensor for PSA based on the signal amplification of MnO2-functionalized covalent organic framework.

This work describes a novel affinity peptide-antibody sandwich electrochemical strategy for the ultrasensitive detection of prostate-specific antigen (PSA). Herein, polydopamine-coated boron-doped carbon nitride (Au@PDA@BCN) was synthesized and used as a sensing platform to anchor gold nanoparticles and immobilize primary antibody. Meanwhile, AuPt metallic nanoparticle and manganese dioxide (MnO2)-functionalized covalent organic frameworks (AuPt@MnO2@COF) was facilely synthesized to serve as a nanocatalyst and ordered nanopore for the enrichment and amplification of signal molecules (methylene blue, MB). PSA affinity peptide was bound to AuPt@MnO2@COF to form Pep/MB/AuPt@MnO2@COF nanocomposites (probe). The peptide-PSA-antibody sandwich biosensor was constructed, and the redox signal of MB was measured with the existence of PSA. The fabricated sensor exhibited a linear response (0.00005-10 ng mL-1) with a low detection limit of 16.7 fg mL-1 under the optimum condition. Additionally, the sensor showed an excellent selectivity, ideal repeatability, and good stability for PSA detection in real samples. Furthermore, the porous structure of COF can enrich more MB molecules and increase the sensitivity of the biosensor. This study provides an efficient and ultrasensitive strategy for PSA detection and broadens the use of organic/inorganic porous nanocomposite in biosensing.

Mechanisms Underlying the Effect of Tea Extracts on In Vitro Digestion of Wheat Starch.

The effect of extracts from four types of tea made from Camelia sinensis (green, white, black, and oolong) on in vitro amylolysis of gelatinized starch and the underlying mechanisms were studied. Of the four extracts, black tea extract (BTE) gave the strongest inhibition of starch digestion and on α-amylase activity. Fluorescence quenching and surface plasmon resonance (SPR) showed compounds in BTE bound to α-amylase more strongly than those in the green, white, and oolong tea extracts. Individual testing of five phenolic compounds abundant in tea extracts showed that theaflavins had a greater inhibitory effect than catechins on α-amylase. SPR showed that theaflavins had much lower equilibrium dissociation constants and therefore bound more tightly to α-amylase than catechins. We conclude that BTE had a stronger inhibitory effect on in vitro enzymatic starch digestion than the other tea extracts, mainly due to the higher content of theaflavins causing stronger inhibition of α-amylase.

Ultrahigh stable lead halide perovskite nanocrystals as bright fluorescent label for the visualization of latent fingerprints.

Fingerprints formed by the raised papillary ridges are one of the most important markers for individual identification. However, the current visualization methods for latent fingerprints (LFPs) suffer from poor resolution, low contrast, and high toxicity. In this work, the CsPbBr3/Cs4PbBr6nanostructured composite crystal (CsPbBr3/Cs4PbBr6NCC) were synthesized via a simple chemical solvent-assisted method. Compared with conventional perovskites, the as-prepared CsPbBr3/Cs4PbBr6NCC present an outstanding long-term environmental and water stability with 42% and 80% photoluminescence intensity remaining after 28 d under water and air conditions, respectively. Moreover, a special response to biomolecules from fingerprints was observed due to the hydrophobic interactions between the CsPbBr3/Cs4PbBr6NCC surface hydrophobic ligands (oleyl amine and oleic acid) and the hydrophobic groups in the biomolecules from the human fingers. Clear LFPs images were visualized in a bright environment illuminating the prepared CsPbBr3/Cs4PbBr6NCC powder under UV light of wavelength 365 nm. The images were also obtained on porous and non-porous surfaces such as metal, plastic, wood, glass, and paper products. These perovskite nanocrystals are expected a stable and bright luminescent labeling agent for LFPs visualization and have potential application in crime scene and personal identifications.

Revealing the mechanisms of starch amylolysis affected by tea catechins using surface plasmon resonance.

The interaction of polyphenolic catechins from Camellia sinensis tea with α-amylase, and the effects of the interactions on the kinetics of starch amylolysis, were investigated. Binding studies using surface plasmon resonance (SPR) and enzyme kinetic analysis indicated that the in vitro digestibility of gelatinized wheat starch was decreased by the addition of catechins present in tea. Tea catechins decreased enzyme activity by reducing the maximum velocity (Vmax) of the α-amylase, but had little effect on the Michaelis-Menten constant (Km). Binding studies by SPR showed that the structure of the catechins influenced their affinity for α-amylase. Pearson correlation analysis showed that the decreased digestibility of starch in the presence of catechins was due to their binding of α-amylase interaction inhibiting the catalytic effectiveness of the enzyme. From this study, we concluded that the faster and stronger the binding of catechins and α-amylase, the greater reduction of starch digestion is.

Ultrasensitive electrochemical sensor for prostate specific antigen detection with a phosphorene platform and magnetic covalent organic framework signal amplifier.

Magnetic covalent organic frameworks (COFs) are useful mesoporous materials for the enrichment and separation of analytes, and are utilized in the pretreatment of samples. However, the use of magnetic COFs in electrochemical immunosensors has rarely reported. Herein, a novel electrochemical assay for the determination of prostate specific antigen (PSA) was developed using black phosphorene (BPene) as a platform and magnetic COFs for signal amplification. BPene was prepared via water-phase exfoliation. BPene nanocomposite (Au@BPene) was prepared by depositing Au nanoparticles (Au NPs) onto BPene. This nanocomposite was utilized as an immunsensing platform to bind primary antibodies and improve electron transfer. Subsequently, an Au NP-loaded magnetic COF was used to immobilize the secondary antibodies and abundant electronic signals of methylene blue (MB). The fabricated sensor exhibited linearity ranging from 0.0001 ng mL-1 to 10 ng mL-1 with the detection limit of 30 fg mL-1. The sensor could determine the PSA in a real sample with excellent specificity, good stability, and desirable reproducibility. The effective signal amplification of the proposed sensor is attributed to the good electron transfer of Au@BPene, excellent enrichment capacity of signal molecules (MB) of the COF, and efficient catalytic activity of Fe3O4. This work not only provides an effective electrochemical assay to detect PSA in real sample, but also broadens the utilization scope of magnetic COFs in immunosensing.

[Experience of SONG Nanchang preventing bronchial asthma by blistering therapy of dog-day moxibustion].

Professor SONG Nanchang owns unique experience of preventing bronchial asthma by the blistering therapy of dog-day moxibustion. He believes that the method has the action of festering moxibustion without its adverse reaction, the pathogenesis of asthma is the impairment of the dispersing and descending of the lung. When the lung,the spleen and the kidney are deficient,pathogenic factors,such as phlegm,damp and the cold,twist in the lung and the air passage is blocked, then asthma happens. Blistering therapy with little but fierce medicines acquires the features of specific but overall acupoints and more big blister. Meanwhile,with the emphasis on communication and nursing service,the therapy is apparently effective and worth widely using.

[Professor SONG Nanchang's experience for treatment of peripheral facial paralysis].

Professor SONG Nanchang's clinical experience and characteristics for treatment of peripheral facial paralysis are introduced. In clinical treatment, professor SONG has adopted staging treatment strategy, and performed acupuncture stimulation with different levels. He attaches great importance to the acupoint selection on distal limbs. For the treatment on the face, he takes temperature as necessity; he inherits from famous Chinese doctor ZONG Ruilin's acupuncture technique of slow-twisting and gentle-pressing. Meanwhile, he excels in combination, of different therapies, using acupuncture, moxibustion, electroacupuncture, auricular point sticking, Chinese herbal medicine, etc. according to individual condition and disease stages. He also emphasizes on psychological counseling and daily life care to achieve rehabilitation within the shortest time.

[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.