Wireless Gold/Boron-Nitrogen-Codoped Graphene-Based Antenna Immunosensor for the Rapid Detection of Neuron-Specific Enolase.

Tumor-marker immunosensors for rapid on-site detection have not yet been developed because of immunoreaction bottlenecks, such as shortening the reaction time and facilitating incubation. In this study, a gold-boron-nitrogen-codoped graphene (Au-BNG)-based immunosensor antenna was constructed for the rapid detection of neuron-specific enolase (NSE). A Au-BNG radiation electrode with dual functions of antibody protein fixation and signal transmission was developed for the first time. A radiation sample cell was constructed by embedding a radiation electrode into the groove of a poly(dimethylsiloxane) dielectric substrate. The constructed sense antenna achieves accurate detection of NSE with a range from 50 fg mL-1 to 40,000 pg mL-1 and a limit of detection of 10.99 fg mL-1, demonstrating excellent selectivity, stability, and reliability. The tumor-marker detection meter can provide NSE detection results as rapidly as within 2 min by using the new strategy of the microwave self-incubation of tumor markers. This antenna immunosensor is suitable for rapid detection in outpatient clinics and can be developed into household tumor-marker detectors, which would be significant in the early detection, long-term monitoring, and efficacy evaluation of tumors.

Light-Initiated Imprinted Membrane-Based Biomimetic SERS Sensor toward Selective Detection of Trace MC-LR.

Microcystin-LR (MC-LR) is a severe threat to human and animal health; thus, monitoring it in the environment is essential, especially in water quality protections. Herein, in this work, we synthesize PVDF/CNT/Ag molecular imprinted membranes (PCA-MIMs) via an innovative combination of surface-enhanced Raman spectroscopy (SERS) detection, membrane separation, and molecular-imprinted technique toward the analysis of MC-LR in water. In particular, a light-initiated imprint is employed to protect the chemical structure of the MC-LR molecules. Furthermore, in order to ensure the detection sensitivity, the SERS substrates are combined with the membrane via the assistance of magnetism. The effect of synthesis conditions on the SERS sensitivity was investigated in detail. It is demonstrated from the characteristic results that the PCA-MIMs present high sensitivity to the MC-LR molecules with excellent selectivity against the interfere molecules. Results clearly show that the as-prepared PCA-MIMs hold great potential applications to detect trace MC-LR for the protection of water quality.

Photocatalytic Production of Ethanolamines and Ethylenediamines from Bio-Polyols over a Cu/TiO2 Catalyst.

Valorization of biomass-derived polyols into high-value-added ethanolamines and ethylenediamines is highly attractive. Herein, we report a one-step photocatalytic protocol to convert bio-polyols into a 60 % yield of ethanolamines and ethylenediamines over a multifunctional Cu/TiO2 catalyst. This catalyst enables a tandem process of photocatalytic polyol C-C bond cleavage and reductive amination in one pot at room temperature, and also allows the selective conversion of various bio-polyols and amines. Mechanistic studies revealed that photogenerated holes in TiO2 promote the retro-aldol C-C bond cleavage or oxidative dehydrogenation of polyols, and photogenerated electrons accumulate on small-sized Cu clusters, which facilitate the reductive amination via hydrogen transfer and prevent the H2 generation. This strategy provides new opportunities for the development of non-noble metal photocatalysts and methods of biomass conversion under mild conditions.

Natural Enfumafungin Analogues from Hormonema carpetanum and Their Antifungal Activities.

Ibrexafungerp, an inhibitor of fungal ß-(1,3)-d-glucan synthase, represents the first new class of antifungals to be approved in the last 20 years. Ibrexafungerp is a semisynthetic derivative of the naturally occurring triterpene glycoside enfumafungin. In order to search for new analogues of enfumafungin and to probe its biosynthesis, we undertook a reinvestigation of Hormonema carpetanum, which led to the isolation of two new analogues, enfumafungins B and C, together with enfumafungin. Due to the presence of a hemiacetal moiety in the structure, the enfumafungins appear as a mixture of two interconverting epimers during both the purification process and NMR data acquisition. The structure elucidation, including the differentiation of 25S* and 25R* epimers, was completed by combined analyses of NMR and MS spectroscopic data. The discovery of enfumafungins B and C may have implications for enfumafungin biosynthesis. The antifungal activity of enfumafungins B and C was significantly lower than that of enfumafungin, suggesting that the C-2 substituents and the C-19 carboxy acid are important for activity. Molecular docking simulations revealed significant hydrogen bond interactions between enfumafungins and ß-(1,3)-d-glucan synthase, which may be useful for developing new antifungal agents.

Self-assembly flexible SERS imprinted membrane based on Ag nanocubes for selective detection of microcystin-LR.

Silver nanocubes monolayer-modified polydimethylsiloxane (Ag NC/PDMS) flexible SERS substrates have been prepared by a three-phase interface self-assembly procedure. The combination of this method with membrane technology brings nanoparticles in close proximity, densely, and regularly arranged in monolayers over a large area, leading to excellent SERS properties. Considering the complexity of practical detection, molecular imprinted polymers (MIPs) were anchored on the surface of SERS substrate and applied to selective detection of microcystin-LR (MC-LR). It is worth mentioning that the SERS imprinted membranes (AP-MIMs) were still clearly detected at a concentration of 0.1 µg·L-1 of MC-LR in drinking water, and the detection limit was as low as 0.0067 µg·L-1. The substrate exhibited excellent uniformity with a relative standard deviation (RSD) of 6.1%. In the presence of interference molecules, AP-MIMs exhibited excellent selectivity for MC-LR. Furthermore, in the spiking and recovery tests of practical lake water samples, the method showed excellent recoveries ranging from 96.47 to 105.31%. It has been demonstrated that the prepared AP-MIMs can be applied to sensitive and specific detection of trace amounts of MC-LR in drinking water.

Tuning Benzylic C-H Functionalization of (Thio)xanthenes with Electrochemistry.

Here, we report a tunable electrochemical benzylic C-H functionalization of (thio)xanthenes with terminal alkynes and nitriles in the absence of any catalyst or external chemical oxidant. The benzylic C-H functionalization can be well controlled by varying the electrochemical conditions, affording the specific coupling products via C-C and C-N bond formation.

Electrochemical Regioselective Cross-Dehydrogenative Coupling of Indoles with Xanthenes.

An electrochemical cross-dehydrogenative coupling of indoles with xanthenes has been established at room temperature. This coupling reaction could proceed in the absence of any catalyst or external oxidant, and generate the indole derivatives in moderate yields. Mechanistic experiments support that a radical pathway maybe involved in this reaction system.

A label-free electrochemical immunosensor based on a gold-vertical graphene/TiO2 nanotube electrode for CA125 detection in oxidation/reduction dual channels.

A label-free immunosensor was constructed in oxidation and reduction dual channel mode for the trace detection of cancer antigen 125 (CA125) in serum. The gold-vertical graphene/titanium dioxide (Au-VG/TiO2) electrode was used as the signal-amplification platform, and cytosine and dopamine were used as probes in the oxidation and reduction channels, respectively. VG nanosheets were synthesized on a TiO2 nanotube array via chemical vapor deposition (CVD), and Au nanoparticles were deeply embedded on the surface and in the root of the VG nanosheets via electrodeposition. The CA125 antibody was then directly immobilized onto the electrode surface, benefitting from its natural affinity for Au nanoparticles. In the oxidation and reduction channels the CA125 antibody-Au-VG/TiO2 immune electrode had the same response concentration range (0.01-1000 mU∙mL-1) for the determination of the CA125 antigen. However, the oxidation channel had a higher sensitivity (14.82 µA•(log(mU•mL-1))-1 at a working potential of ~ 1.25 V vs. SCE), lower detection limit (0.0001 mU∙mL-1), higher stability, and lower performance deviation than the reduction channel. This immunosensor was successfully used for CA125 detection in human serum. The recoveries of spiked serum samples ranged from 99.8 ± 0.5 to 100 ± 0.4%. The study on the difference in the sensing performance between oxidation and reduction channels provides a preliminary experimental reference for exploring dual-channel synchronous detection immunosensors and verifying the accuracy of the assay based on dual-channel data, which will promote the development of reliable electrochemical immunosensor technology.

Hydrophilic modification of PVDF-based SERS imprinted membrane for the selective detection of L-tyrosine.

The polyvinylidene difluoride (PVDF) membrane has received considerable attention as a flexible surface enhanced Raman scattering (SERS) substrate due to its excellent mechanical and physicochemical properties. However, the poor fouling resistance of PVDF membrane due to its intrinsic hydrophobic property limits its practical application. To address this, in this investigation, a SERS imprinted membrane is synthesized based on W18O49/Ag composites. Firstly, to promote hydrophilicity, N-vinyl-2-pyrrolidone (NVP) and triethoxyvinylsilane (VTES) are copolymerized by hydrolysis condensation and linked with engineered polyvinypyrrolidone (PVP) chains exposed on the surface of membrane. Furthermore, W18O49/Ag composites are dispersed on the membrane under the assistance of polydopamine (pDA) to promote the pollution resistance. Subsequently, in order to demonstrate the practical detection property, W18O49/Ag/PVDF membrane is selected as the SERS substrate to synthesize SERS imprinted membrane by precipitation polymerization for the selective detection of L-tyrosine. The characteristic results reveal that the SERS-imprinted membrane exhibits satisfactory hydrophilicity, and it can effectively degrade the pollutant molecules absorbed on its surface under ultraviolet light illumination. It is proved from the detection results that the LOD of WADP-MIMs for L-tyrosine reached 10-9 mol L-1 when the concentration of L-tyrosine changed between 10-3-10-9 mol L-1. The correlation coefficient (R2) is 0.994 and the limit of detection is 10-9 mol L-1. Meanwhile, it can be applied for the selective detection of L-tyrosine in mixture samples. Overall, this study presents a novel approach for the hydrophilic modification and pollution resistance enhancement of PVDF-based SERS imprinted membrane, which can be effectively utilized for the selective detection of practical samples.

Electrochemical Site-Selective Alkylation of Azobenzenes with (Thio)Xanthenes.

Herein, we first report an electrochemical methodology for the site-selective alkylation of azobenzenes with (thio)xanthenes in the absence of any transition metal catalyst or external oxidant. A variety of groups are compatible with this electrochemical alkylation, which furnishes the products in moderate to good yields.

Discovery of Venturicidin Congeners and Identification of the Biosynthetic Gene Cluster from Streptomyces sp. NRRL S-4.

Chemical screening of Streptomyces sp. NRRL S-4 with liquid chromatography-mass spectrometry (LC-MS) and the following chromatographic isolation led to the discovery of four 20-membered macrolides, venturicidin A (4) and three new congeners venturicidins D-F (1-3). Genome sequencing of strain S-4 revealed the presence of a biosynthetic gene cluster (BGC) encoding glycosylated type I polyketides (PKS). The BGC designated to venturicidin biosynthesis (ven) was supported by the proposed biosynthetic pathway and confirmed by inactivation of the core PKS gene of venK. Bioinformatic analyses on the conserved motifs and known stereospecificities in PKS modules are consistent with the structure and absolute configuration. This is the first report of venturicidin BGC since the discovery of the macrolide in 1961. In the biological assays, venturicidin A (4) and E (2) displayed a high selective cytotoxicity against acute monocytic leukemia MV-4-11 cells with IC50 values of 0.09 and 0.94 µM, respectively. Venturicidin A (4) also showed a weak inhibitory activity on FMS-like-tyrosine kinase.

Heteroatom-participated lignin cleavage to functionalized aromatics.

Lignin, the most abundant aromatic polymer in nature, enables sustainable supply of miscellaneous aromatics as green fuels and chemicals. Obtaining the value-added aromatics from lignin, though subjected to enormous research efforts, mainly relies on depolymerization induced by activated hydrogen species or oxygen species, delivering hydrocarbons and oxygenates. The future bio-refinery demands a broad spectrum of fine chemicals, especially those containing elements other than C, H and O. Heteroatom-containing compounds have emerged as powerful reagents to participate in the bond cleavage in lignin; meanwhile, the obtained heteroatom-containing aromatics, which could be used as dye precursors, pharmaceutical precursors, hydrogen storage materials, etc., extend the application of lignin-derived products. This tutorial review updates recent advances in the lignin C-C and C-O bond cleavages induced by heteroatoms X (N, Si, I and Li), which also lead to functionalized products containing C-X and O-X bonds. The representative reaction pathways and feasibilities in lignin models and extracts are summarized. Potential applications of functionalized monomers in synthetic transformations, pharmaceuticals, dyes and energy storage are also discussed.

Isolation and Identification of Pentalenolactone Analogs from Streptomyces sp. NRRL S-4.

Terpene synthases are widely distributed in Actinobacteria. Genome sequencing of Streptomyces sp. NRRL S-4 uncovered a biosynthetic gene cluster (BGC) that putatively synthesizes pentalenolactone type terpenes. Guided by genomic information, the S-4 strain was chemically investigated, resulting in the isolation of two new sesquiterpenoids, 1-deoxy-8α-hydroxypentalenic acid (1) and 1-deoxy-9ß-hydroxy-11-oxopentalenic acid (2), as shunt metabolites of the pentalenolactone (3) biosynthesis pathway. Their structures and absolute configurations were elucidated by analyses of HRESIMS and NMR spectroscopic data as well as time-dependent density functional theory/electronic circular dichroism (TDDFT/ECD) calculations. Compounds 1 and 2 exhibited moderate antimicrobial activities against Gram-positive and Gram-negative bacteria. These results confirmed that the pentalenolactone pathway was functional in this organism and will facilitate efforts for exploring Actinobacteria using further genome mining strategies.

HMGB1/RAGE axis mediates stress-induced RVLM neuroinflammation in mice via impairing mitophagy flux in microglia.

BACKGROUND: Microglial mediated neuroinflammation in the rostral ventrolateral medulla (RVLM) plays roles in the etiology of stress-induced hypertension (SIH). It was reported that autophagy influenced inflammation via immunophenotypic switching of microglia. High-mobility group box 1 (HMGB1) acts as a regulator of autophagy and initiates the production of proinflammatory cytokines (PICs), but the underlying mechanisms remain unclear. METHODS: The stressed mice were subjected to intermittent electric foot shocks plus noises administered for 2 h twice daily for 15 consecutive days. In mice, blood pressure (BP) and renal sympathetic nerve activity (RSNA) were monitored by noninvasive tail-cuff method and platinum-iridium electrodes placed respectively. Microinjection of siRNA-HMGB1 (siHMGB1) into the RVLM of mice to study the effect of HMGB1 on microglia M1 activation was done. mRFP-GFP-tandem fluorescent LC3 (tf-LC3) vectors were transfected into the RVLM to evaluate the process of autolysosome formation/autophagy flux. The expression of RAB7, lysosomal-associated membrane protein 1 (LAMP1), and lysosomal pH change were used to evaluate lysosomal function in microglia. Mitophagy was identified by transmission electron microscopic observation or by checking LC3 and MitoTracker colocalization under a confocal microscope. RESULTS: We showed chronic stress increased cytoplasmic translocations of HMGB1 and upregulation of its receptor RAGE expression in microglia. The mitochondria injury, oxidative stress, and M1 polarization were attenuated in the RVLM of stressed Cre-CX3CR1/RAGEfl/fl mice. The HMGB1/RAGE axis increased at the early stage of stress-induced mitophagy flux while impairing the late stages of mitophagy flux in microglia, as revealed by decreased GFP fluorescence quenching of GFP-RFP-LC3-II puncta and decreased colocalization of lysosomes with mitochondria. The expressions of RAB7 and LAMP1 were decreased in the stressed microglia, while knockout of RAGE reversed these effects and caused an increase in acidity of lysosomes. siHMGB1 in the RVLM resulted in BP lowering and RSNA decreasing in SIH mice. When the autophagy inducer, rapamycin, is used to facilitate the mitophagy flux, this treatment results in attenuated NF-κB activation and reduced PIC release in exogenous disulfide HMGB1 (ds-HMGB1)-stimulated microglia. CONCLUSIONS: Collectively, we demonstrated that inhibition of the HMGB1/RAGE axis activation led to increased stress-induced mitophagy flux, hence reducing the activity of microglia-mediated neuroinflammation and consequently reduced the sympathetic vasoconstriction drive in the RVLM.

Visible-Light Photoredox-Catalyzed Regioselective Sulfonylation of Alkenes Assisted by Oximes via [1,5]-H Migration.

We herein report a visible-light photoredox-catalyzed regioselective sulfonylation of alkenes with sulfonyl hydrazides assisted by oximes at room temperature, which affords a variety of sulfones in good yields. The initial mechanistic experiments demonstrate that the hydroxyl group within oximes plays a crucial role in this sulfonylation.

BF3·OEt2-mediated cyclization of ß,γ-unsaturated oximes and hydrazones with N-(arylthio/arylseleno)succinimides: an efficient approach to synthesize isoxazoles or dihydropyrazoles.

A highly efficient BF3·OEt2-mediated cyclization of ß,γ-unsaturated oximes and tosylhydrazones with N-(arylthio/arylseleno)succinimides has been established for the construction of N-heterocycles in a one-step manner. This metal-free cyclization provides direct access to isoxazoles and dihydropyrazoles in good to excellent yields at room temperature. The mechanistic experiments support the formation of a cationic species PhS+ which plays a critical role in this cyclization process.

Room temperature iron(ii)-catalyzed radical cyclization of unsaturated oximes with hypervalent iodine reagents.

Here, we disclose an iron(ii)-catalyzed I-O bond cleavage of Koser's hypervalent iodine reagents (HIRs) that initiated the radical cyclization of unsaturated oximes at room temperature. This strategy is successfully applied for the construction of the isoxazoline backbone in an efficient manner. In particular, the direct introduction of a TsO group into products facilitates their late-stage transformations in organic synthesis.

Micaryolanes A and B, Two New Caryolane-Type Sesquiterpenoids from Marine Streptomyces sp. AH25.

Caryolanes, known as ß-caryophyllene alcohols, are widely occurring sesquiterpenes in plants. From the cultures of marine Streptomyces sp. AH25, two new caryolane sesquiterpenes, micaryolanes A and B (1 and 2), together with caryolan-1,9ß-diol (3) were isolated. Their structures were elucidated by extensive analyses of HR-MS and NMR spectroscopic data. The absolute configurations were assigned via the CD data of the in situ formed [Rh2 (OCOCF3 )4 ] complex and supported by comparison of experimental and calculated specific rotation values. Compounds 1-3 exhibited no activities against Hep3B or MG-63 cell lines or against Gram-positive and Gram-negative bacteria. The results not only enriched the caryolane family, but also proved bacteria as a productive source of terpene metabolites.

Secondary Metabolites from Marine Micromonospora: Chemistry and Bioactivities.

Marine Micromonospora was revealed to be a rather untapped and a rich source of chemically diverse and unique bioactive natural products. This review is aimed to make a comprehensive survey of secondary metabolites that were derived from marine Micromonospora including chemical diversity and biological activities. A total of 116 compounds from 41 marine Micromonospora species have been reported, covering the literatures from 1997 to 2019. These compounds contain several structural classes such as polyketides (PKS), nonribosomal peptides (NRPS), PKS-NRPS hybrids, terpenes and others, and they present cytotoxic, antibacterial, antiparasitic, chemopreventive or antioxidant activities.

A 433-MHz surface acoustic wave sensor with Ni-TiO2-poly(L-lysine) composite film for dopamine determination.

A ternary hybrid material composed of Ni nanoparticles (NPs), TiO2 NPs, and poly(L-lysine) (Ply) was used as a sensing material. It was electrodeposited in situ onto a commercial 433-MHz surface acoustic wave (SAW) resonator to construct a Ni-TiO2-Ply/SAW sensor. The Ni-TiO2-Ply sensing layer fully covered the resonant cavity of the SAW resonator. As the sensing layer completely covers the interdigital transducer and piezoelectric substrate, the sensing area is significantly increased, and the resonator is protected from damage or contamination. To detect the level of dopamine (DA) in serum, the fabrication of the Ni-TiO2-Ply sensing layer, distributions of various components in the sensing layer, and responses of the SAW biosensor to DA were investigated in detail. In addition, an electric field-assisted liquid-phase oxidation technique was developed for loading analytes onto the SAW sensors. After optimizing the pH value and L-lysine content of the sensing layer electrolyte and the pH value of the DA solution, the SAW biosensor responded to DA with a linear concentration range of 1 to 1000 nM, sensitivity of 5.77 MHz nM-1 cm-2, and limit of detection of 0.067 nM. Moreover, the sensor exhibited good selectivity, reproducibility, and stability at ambient temperature.Graphical abstract.