Two-Orders-of-Magnitude Enhancement of SERS Activity via a Simple Surface Engineering of Quasi-Metal Single-Crystal Frameworks.

Beyond noble metals and semiconductors, quasi-metals have recently been shown to be noteworthy substrates for surface enhanced Raman spectroscopy, and their excellent quasi-metal surface-enhanced Raman spectroscopy (SERS) sensing has demonstrated a wider range of application scenarios. However, the underlying mechanism behind the enhanced Raman activity is still unclear. Here, we demonstrate that surface hydroxyls play a crucial role in the enhancement of the SERS activity of quasi-metal nanostructures. As a demonstration material, quasi-metallic MoO2 single-crystal frameworks rich in surface hydroxyls have been shown to have 100 times higher SERS activity than MoO2 single-crystal frameworks without hydroxyl functionalization, with a Raman enhancement factor of up to 7.6 × 107. Experimental and first-principles density-functional theory calculation results show that the enhanced Raman activity can be attributed to an effective interfacial charge transfer within the MoO2/OH/molecule system.

Fenamates: Forgotten treasure for cancer treatment and prevention: Mechanisms of action, structural modification, and bright future.

Fenamates as classical nonsteroidal anti-inflammatory agents are widely used for relieving pain. Preclinical studies and epidemiological data highlight their chemo-preventive and chemotherapeutic potential for cancer. However, comprehensive reviews of fenamates in cancer are limited. To accelerate the repurposing of fenamates, this review summarizes the results of fenamates alone or in combination with existing chemotherapeutic agents. This paper also explores targets of fenamates in cancer therapy, including COX, AKR family, AR, gap junction, FTO, TEAD, DHODH, TAS2R14, ion channels, and DNA. Besides, this paper discusses other mechanisms, such as regulating Wnt/ß-catenin, TGF-ß, p38 MAPK, and NF-κB pathway, and the regulation of the expressions of Sp, EGR-1, NAG-1, ATF-3, ErbB2, AR, as well as the modulation of the tumor immune microenvironment. Furthermore, this paper outlined the structural modifications of fenamates, highlighting their potential as promising leads for anticancer drugs.

Synthesis of Graphdiyne Hollow Spheres and Multiwalled Nanotubes and Applications in Water Purification and Raman Sensing.

Controlling the structure of graphdiyne (GDY) is crucial for the discovery of new properties and the development of new applications. Herein, the microemulsion synthesis of GDY hollow spheres (HSs) and multiwalled nanotubes composed of ultrathin nanosheets is reported for the first time. The formation of an oil-in-water (O/W) microemulsion is found to be a key factor controlling the growth of GDY. These GDY HSs have fully exposed surfaces because of the avoidance of overlapping between nanosheets, thereby showing an ultrahigh specific surface area of 1246 m2 g-1 and potential applications in the fields of water purification and Raman sensing.

Exploring the Fate of Copper Ions in the Synthesis of Graphdiyne.

Copper is a crucial catalyst in the synthesis of graphdiyne (GDY). However, as catalysts, the final fate of the copper ions has hardly been concerned, which are usually treated as impurities. Here, it is observed that after simple washing with water and ethanol, GDY still contains a certain amount of copper ions, and demonstrated that the copper ions are adsorbed at the atomic layers of GDY. Furthermore, we transformed in situ the copper ions into ultrathin Cu nanocrystals, and the obtained Cu/GDY hybrids can be generally converted into a series of metal/GDY hybrid materials, such as Ag/GDY, Au/GDY, Pt/GDY, Pd/GDY, and Rh/GDY. The Cu/GDY hybrids exhibit extraordinary surface enhanced Raman scattering effect and can be applied in pollutant efficient enrichment and detection.

Ultrathin Graphdiyne Nanowires with Diameters below 3 nm: Synthesis, Photoelectric Effect, and Enhanced Raman Sensing.

Due to the intrinsic layered structure, graphdiyne (GDY) strongly tends to form 2D materials, therefore, most of the current research are based on GDY 2D structures. Up to now, the synthesis of its ultrathin nanowires with a high aspect ratio has not been reported. Here, the ultrathin GDY nanowires with diameters below 3 nm are reported for the first time by a two-phase interface synthesis method, which has excellent crystallinity and an aspect ratio of more than 2500. Evidence shows that the GDY ultrathin nanowires are formed by the oriented-attachment mechanism of nanoparticles. The GDY ultrathin nanowires exhibit a significant quantum confinement effect, enhanced photoelectric effect, and promising applications in surface-enhanced Raman sensing.

Rapid on-site detection of persistent organic pollutants using multiwalled carbon nanotube-modified paper spray ionization and a miniature mass spectrometer.

RATIONALE: Rapid on-site detection of persistent organic pollutants (POP) is highly desirable for environmental protection. METHODS: Herein, a rapid on-site analytical workflow was developed for the investigation of polycyclic aromatic hydrocarbons and perfluorinated compounds using multiwalled carbon nanotube-modified paper spray ionization (PSI) coupled with a miniature ion trap mass spectrometer. Critical parameters regarding PSI and miniature mass spectrometry analysis were optimized. RESULTS: The analytical performance of the developed method was evaluated under optimized conditions, obtaining a short analysis duration of less than 1 min, sufficient linearity with correlation coefficients greater than 0.99, acceptable recovery rates of 93.1%-105.8% with relative standard deviations of between 3.5% and 10.3%, and reasonable sensitivity with limits of detection and quantitation of 2-200 and 5-500 µg/L, respectively. CONCLUSIONS: Considering these aspects, it was concluded that the present approach demonstrated a promising solution for rapid on-site detection of emerging POPs.

A Metallic Niobium Nitride with Open Nanocavities for Surface-Enhanced Raman Spectroscopy.

The construction of open hot-spot structures that facilitate the entry of analytes is crucial for surface-enhanced Raman spectroscopy. Here, metallic niobium nitride (NbN) three-dimensional (3D) hierarchical networks with open nanocavity structure are first found to exhibit a strong visible-light localized surface plasmon resonance (LSPR) effect and extraordinary surface-enhanced Raman scattering (SERS) performance. The unique nanocavity structure allows easy entry of molecules, promoting the utilization of electromagnetic hot spots. The NbN substrate has a lowest detection limit of 1.0 × 10-12 M and a Raman enhancement factor (EF) of 1.4 × 108 for contaminants. Furthermore, the NbN hierarchical networks possess outstanding environmental durability, high signal reproducibility, and detection universality. The remarkable SERS sensitivity of the NbN substrate can be attributed to the joint effect of LSPR and interfacial charge transport (CT).

Directly Convert Carbonaceous Microspheres to Three-Dimensional Porous Carbon Microspheres with a Robust Self-Supporting Structure as a Metal-Free SERS Substrate for Online High-Throughput Analysis.

It is of great significance for practical applications to directly convert readily available biomass carbon into three-dimensional (3D) porous carbon microspheres with a self-supporting structure. Herein, we report the convenient conversion of biomass carbon microspheres to hierarchical porous carbon microspheres (HP-CMSs) with a robust self-supporting framework structure. A general SiO2-induced etching mechanism is proposed for the formation of the HP-CMSs. Benefiting from this robust 3D self-supporting frame structure, these HP-CMSs have outstanding mechanical, chemical, and thermal stability. As a metal-free surface-enhanced Raman scattering (SERS) substrate with an ultrahigh specific surface area (4216 m2 g-1) and a high density of active sites, the HP-CMSs exhibit high sensitivity with a detection limit of 10-10 M and a Raman enhancement factor of 3.5 × 106. By integrating the enrichment and sensing functions of the HP-CMSs in a microfluidic channel, online high-throughput SERS detection of 20 samples within 5 min is achieved in a single channel, and the relative standard deviation of the signals between samples is only 5.1%. The current work develops a convenient preparation method that converts sustainable biomass carbon to 3D hierarchical porous carbon and provides a potential material for sensing, energy, catalysis, and other fields.

Moving MoO2/C Nanospheres with the Functions of Enrichment and Sensing for Online-High-Throughput SERS Detection.

The development of online surface-enhanced Raman spectroscopy (SERS) detection methods is crucial to achieving high-throughput efficiency. Herein, a non-noble-metal moving substrate that integrates the functions of enrichment and sensing is developed for the microfluidic online-high-throughput detection of pollutants. The lowest limit of detection of 1 × 10-12 M and a Raman enhancement factor of 6.3 × 108 are obtained on the nanospheres. In a single detection channel, the analysis of 20 samples is achieved within 5 min, and the relative standard deviation of the signals is less than 6.8%. Compared with static SERS detection of fixed substrates, this dynamic SERS detection method greatly reduces the contamination memory effect of the analyte residue, enabling it to perform the sequential quantitative detection of samples with large concentration differences. Moreover, the current online SERS platform realizes the rapid quantitative detection of multicomponent samples.

Disruption of C/EBPß-Clec7a axis exacerbates neuroinflammatory injury via NLRP3 inflammasome-mediated pyroptosis in experimental neuropathic pain.

BACKGROUND: Growing evidence shows that C-Type Lectin Domain Containing 7A (Clec7a) may be involved into neuroinflammatory injury of various neurological diseases. However, its roles in neuropathic pain remain unclear. METHODS: A chronic constriction injury (CCI) rat model was constructed, and gene expression profilings in spinal cord tissues of CCI-insulted rats were detected by both microarray and RNA-seq studies. A series of bioinformatics analyses identified C/EBPß-Clec7a to be a candidate axis involved into neuropathic pain. Then, its roles in mechanical allodynia, and pathological and molecular changes during CCI progression were determined by various gain-of-function and loss-of-function experiments in vivo and in vitro. RESULTS: Significant upregulation of Clec7a at both mRNA and protein levels were verified in spinal cord tissues of CCI-insulted rats. Clec7a knockdown markedly attenuated CCI-induced mechanical allodynia, obstructed Syk, ERK and JNK phosphorylation, inhibited NLRP3 inflammasome and caspase-1 activation, GSDMD cleavage, and consequently reduced the release of pro-inflammatory cytokines (all P < 0.05). Mechanically, the rat Clec7a promoter was predicted to bind with transcription factor C/EBPß, confirmed by Luciferase assay and ChIP-qPCR. Both in vivo and in vitro assays demonstrated that C/EBPß knockdown significantly suppressed CCI- or LPS/ATP-induced Clec7a upregulation, and subsequently reduced Syk, ERK and JNK phosphorylation, NLRP3 oligomerization, caspase-1 activation, GSDMD expression and pyroptosis, which were markedly reversed by the co-transfection of Clec7a expression vector. CONCLUSIONS: This pre-clinical investigation reveals that C/EBPß-Clec7a axis may be a potential target for relieving neuropathic pain through alleviating neuroinflammation, paving its way for clinical translation as a promising approach for neuropathic pain therapy.

Exploring Pathways and Mechanisms for Dichloroacetonitrile Formation from Typical Amino Compounds during UV/Chlorine Treatment.

The formation of disinfection byproducts (DBPs) during UV/chlorine treatment, especially nitrogenous DBPs, is not well understood. This study investigated the formation mechanisms for dichloroacetonitrile (DCAN) from typical amino compounds during UV/chlorine treatment. Compared to chlorination, the yields of DCAN increase by 88-240% during UV/chlorine treatment from real waters, while the yields of DCAN from amino compounds increase by 3.3-5724 times. Amino compounds with electron-withdrawing side chains show much higher DCAN formation than those with electron-donating side chains. Phenylethylamine, l- phenylalanine, and l-phenylalanyl-l-phenylalanine were selected to represent amines, amino acids, and peptides, respectively, to investigate the formation pathways for DCAN during UV/chlorine treatment. First, chlorination of amines, amino acids, and peptides rapidly forms N-chloramines via chlorine substitution. Then, UV photolysis but not radicals promotes the transformation from N-chloramines to N-chloroaldimines and then to phenylacetonitrile, with yields of 5.4, 51.0, and 19.8% from chlorinated phenylethylamine, l-phenylalanine, and l-phenylalanyl-l-phenylalanine to phenylacetonitrile, respectively. Finally, phenylacetonitrile is transformed to DCAN with conversion ratios of 14.2-25.6%, which is attributed to radical oxidation, as indicated by scavenging experiments and density functional theory calculations. This study elucidates the pathways and mechanisms for DCAN formation from typical amino compounds during UV/chlorine treatment.

Carbamate-based N-Substituted tryptamine derivatives as novel pleiotropic molecules for Alzheimer's disease.

A novel series of carbamate-based N-substituted tryptamine derivatives were designed and synthesized based on functional group combination strategy, and possessed both cholinesterase inhibition and neuroprotective effects. After systematically evaluating the cholinesterase inhibitory activity of 24 synthesized compounds, compound 6H6, bearing n-heptyl residue as carbamate moiety, was highlighted due to its great BChE-selective inhibition (eeAChE IC50 > 100 µM; eqBChE IC50 = 7 nM), neuronal protection, antioxidation and anti-neuroinflammation efficacy. Cytotoxicity and acute toxicity assays confirmed the safety-efficacy profiles of compound 6H6. Besides, pharmacokinetic properties and blood-brain barrier (BBB) permeability of compound 6H6 were favorable and suitable for further study in vivo. The behavioral tests revealed that compound 6H6 could remarkably improve the scop-induced ethological changes and memory impairment, suggesting compound 6H6, as an attractive pleiotropic molecule, had great promise in treating Alzheimer's disease.

Consistent Optimization of Blast Furnace Ironmaking Process Based on Controllability Assurance Soft Sensor Modeling.

The blast furnace ironmaking process is the core of steel manufacturing, and the optimization of this process can bring enormous economic and environmental benefits. However, previous data-driven optimization methods neglect the uncontrollability of part of the variables in the predictive modeling process, which brings great uncertainty to the optimization results and adversely affects the optimization effect. To address this problem, a consistency optimization framework based on controllability assurance soft sensor modeling is proposed. The method achieves the information extraction of uncontrollable variables in a process-supervised way, and improves the posterior distribution prediction accuracy. The method also proposes an integrated self-encoder regression module, which uses the regression to guide the encoding, realize the construction of latent features, and further improve the prediction accuracy of the model. Integrating the prediction module and the multi-objective gray wolf optimizer, the proposed model achieves the optimization of the blast furnace ironmaking process with only controllable variables as prediction model inputs while being capable of giving uncertainty estimates of the solutions. Empirical data validated the optimization model and demonstrated the effectiveness of the proposed algorithm.

Selective Preparation of Mo2N and MoN with High Surface Area for Flexible SERS Sensing.

γ-Mo2N and δ-MoN are the two most important molybdenum nitrides, but controllable preparation of them with high surface area has not been achieved. Herein, we achieved selective preparation of γ-Mo2N and δ-MoN. The key factor for the selective preparation of γ-Mo2N and δ-MoN is to control the crystal phase of the precursor MoO3. In H2O and NH3 mixed gas, the α-MoO3 nanoribbons are nitridated to obtain γ-Mo2N single-crystal porous nanobelts, while the h-MoO3 prisms are nitrided to obtain δ-MoN hierarchical porous columns. The corrosion effect of H2O plays a key role in the formation of single-crystal porous structure. The γ-Mo2N flexible membrane composed of the single-crystal porous nanobelts exhibits strong localized surface plasmon resonance and surface enhanced Raman scattering effect, which show highly sensitive response to polychlorinated phenol.

Cardioprotective effects of sinomenine in myocardial ischemia/reperfusion injury in a rat model.

Background: Ischemia reperfusion (I/R) play an imperative role in the expansion of cardiovascular disease. Sinomenine (SM) has been exhibited to possess antioxidant, anticancer, anti-inflammatory, antiviral and anticarcinogenic properties. The aim of the study was scrutinized the cardioprotective effect of SM against I/R injury in rat. Methods: Rat were randomly divided into normal control (NC), I/R control and I/R + SM (5, 10 and 20 mg/kg), respectively. Ventricular arrhythmias, body weight and heart weight were estimated. Antioxidant, inflammatory cytokines, inflammatory mediators and plasmin system indicator were accessed. Results: Pre-treated SM group rats exhibited the reduction in the duration and incidence of ventricular fibrillation, ventricular ectopic beat (VEB) and ventricular tachycardia along with suppression of arrhythmia score during the ischemia (30 and 120 min). SM treated rats significantly (P < 0.001) altered the level of antioxidant parameters. SM treatment significantly (P < 0.001) repressed the level of creatine kinase MB (CK-MB), creatine kinase (CK) and troponin I (Tnl). SM treated rats significantly (P < 0.001) repressed the tissue factor (TF), thromboxane B2 (TXB2), plasminogen activator inhibitor 1 (PAI-1) and plasma fibrinogen (Fbg) and inflammatory cytokines and inflammatory mediators. Conclusion: Our result clearly indicated that SM plays anti-arrhythmia effect in I/R injury in the rats via alteration of oxidative stress and inflammatory reaction.

δ-MoN Yolk Microspheres with Ultrathin Nanosheets for a Wide-Spectrum, Sensitive, and Durable Surface-Enhanced Raman Scattering Substrate.

Facing the complex environment of on-site detection, the development of active substrates with wide-spectrum surface-enhanced Raman scattering (SERS) activity is essential. Herein, we report on the low temperature and reproducible synthesis of plasmonic δ-MoN yolk microspheres by in situ-nitriding amorphous MoO2 microspheres at 500 °C and 1 atm. The yolk-structured δ-MoN exhibits strong and wide-spectrum surface plasmon resonance and SERS effects and can perform highly selective detection for probes with different absorption wavelengths under excitation of 532, 633, and 785 nm lasers, with a limitation of 10-11 M and an enhanced factor of 3.6 × 107. Moreover, the plasmonic δ-MoN yolk microspheres have high environmental durability, which can maintain high sensitivity in strong acid and alkaline solutions.

Dynamic heterogeneity in homogeneous polymer melts.

Chain entanglement behaviors were studied by 1H Hahn echo nuclear magnetic resonance (NMR) and 1H double-quantum (DQ) NMR experiments. Poly(ethylene oxide) (PEO) was chosen to investigate the chain entanglement behaviors. The 1H Hahn echo NMR results demonstrate that the critical molecular weight of PEO is approximately 6 kg mol-1. Above this critical molecular weight, chain entanglements start to occur in the melts resulting in anisotropic motions of polymer chain. The 1H DQ NMR observations establish that PEO melts with molecular weights above the critical value exhibit dynamical entanglements. The entangled networks, formed by PEO with a molecular weight of 480 kg mol-1 (PEO480), present slow mobility and rather homogeneously distributed chain entanglements, while the entangled networks, formed by PEO with a molecular weight of 255 kg mol-1 (PEO255), present fast mobility and obvious dynamic heterogeneity in the distribution of chain entanglement. Short chain PEOs like that with a molecular weight of 2 kg mol-1 are demonstrated to function like solvents when being added in an appropriate concentration to PEO480, and the dilution effect increases the chain mobility of PEO480. Moreover, properly diluted PEO480 networks exhibit dynamic heterogeneity similar to that observed in PEO255.

Discovery of a novel inhibitor of nitric oxide production with potential therapeutic effect on acute inflammation.

Inflammation as a host's excessive immune response to stimulation, is involved in the development of numerous diseases. To discover novel anti-inflammatory agents and based on our previous synthetic work on marine natural product Chrysamide B, it and a series of derivatives were synthesized and evaluated for their anti-inflammatory activity on inhibition of LPS-induced NO production. Then the preliminary structure-activity relationships were conducted. Among them, Chrysamide B is the most potent anti-inflammatory agent with low cytotoxicity and strong inhibition on the production of NO (IC50 = 0.010 µM) and the activity of iNOS (IC50 = 0.082 µM) in LPS-stimulated RAW 264.7 cells. Primary studies suggested that the mechanism of action may be that it interfered the formation of active dimeric iNOS but not affected transcription and translation. Furthermore, its good performance of anti-inflammatory effect on LPS-induced multiple inflammatory cytokines production, carrageenan-induced paw edema, and endotoxin-induced septic mice, was observed. We believe that these findings would provide an idea for the further modification and research of these analogs in the future.

Design, synthesis and antitumor activity evaluation of Chrysamide B derivatives.

Marine natural products derived from special or extreme environment provide an important source for the development of anti-tumor drugs due to their special skeletons and functional groups. In this study, based on our previous work on the total synthesis and structure revision of the novel marine natural product Chrysamide B, a group of its derivatives were designed, synthesized, and subsequently of which the anti-cancer activity, structure-activity relationships and cellular mechanism were explored for the first time. Compared with Chrysamide B, better anti-cancer performance of some derivatives against five human cancer cell lines (SGC-7901, MGC-803, HepG2, HCT-116, MCF-7) was observed, especially for compound b-9 on MGC-803 and SGC-7901 cells with the IC 50 values of 7.88 ± 0.81 and 10.08 ± 1.08 µM, respectively. Subsequently, cellular mechanism study suggested that compound b-9 treatment could inhibit the cellular proliferation, reduce the migration and invasion ability of cells, and induce mitochondrial-dependent apoptosis in gastric cancer MGC-803 and SGC-7901 cells. Furthermore, the mitochondrial-dependent apoptosis induced by compound b-9 is related with the JAK2/STAT3/Bcl-2 signaling pathway. To conclude, our results offer a new structure for the discovery of anti-tumor lead compounds from marine natural products.

Design, synthesis and bioactivity study of evodiamine derivatives as multifunctional agents for the treatment of hepatocellular carcinoma.

Topoisomerase has been found extremely high level of expression in hepatocellular carcinoma (HCC) and proven to promote the proliferation and survival of HCC. Cancer-associated fibroblasts (CAFs) as a kind of key reactive stromal cell that abundantly present in the microenvironment of HCC, could enhance the metastatic ability and drug resistance of HCC. Therefore, developing new drugs that address the above conundrums would be of the upmost significant in the fight against HCC. Evodiamine, as a multi-target natural product, has been found to exert various biological activities such as anti-cancer and anti-hepatic fibrosis via blocking topoisomerase, NF-κB, TGF-ß/HGF, and Smad2/3. Inspired by these facts, 15 evodiamine derivatives were designed and synthesized for HCC treatment by simultaneously targeting Topo I and CAFs. Most of them displayed preferable anti-HCC activities on three HCC cell lines and low cytotoxicity on one normal hepatic cell. In particular, compound 8 showed the best inhibitory effect on HCC cell lines and a good inhibition on Topo I in vitro. Meanwhile, it also induced obvious G2/M arrest and apoptosis, and significantly decreased the migration and invasion capacity of HCC cells. In addition, compound 8 down-regulated the expression of type I collagen in the activated HSC-T6 cells, and induced the apoptosis of activated HSC-T6 cells. In vivo studies demonstrated that compound 8 markedly decreased the volume and weight of tumor (TGI = 40.53%). In vitro and in vivo studies showed that its effects were superior to those of evodiamine. This preliminary attempt may provide a promising strategy for developing anti-HCC lead compounds taking effect through simultaneous inhibition on Topo I and CAFs.