Latest ArticlesThe fluorescence lifetime of nicotinamide adenine dinucleotide (NADH), a key endogenous coenzyme and metabolic biomarker, can reflect the metabolic state of cells. To implement metabolic imaging of brain tissue at high resolution, we assembled a two-photon fluorescence lifetime imaging microscopy (FLIM) platform and verified the feasibility and stability of NADH-based two-photon FLIM in paraformaldehyde-fixed mouse cerebral slices. Furthermore, NADH based metabolic state oscillation was observed in cerebral nuclei suprachiasmatic nucleus (SCN). The free NADH fraction displayed a relatively lower level in the daytime than at the onset of night, and an ultradian oscillation at night was observed. Through the combination of high-resolution imaging and immunostaining data, the metabolic tendency of different cell types was detected after the first two hours of the day and at night. Thus, two-photon FLIM analysis of NADH in paraformaldehyde-fixed cerebral slices provides a high-resolution and label-free method to explore the metabolic state of deep brain regions.
We found compound 12N-p-trifluoromethylbenzenesulfonyl matrinane (1) was a potent anti-diabetic agent. Thirty-five tricyclic matrinic derivatives were synthesized and determined for their stimulatory effects on glucose consumption in L6 myotubes, taking 1 as the lead. In high-fat diet (HFD) and STZ induced diabetic mice, 9a significantly lowers blood glucose, improves glucose tolerance, and especially alleviates diabetic nephropathy and islet damage. Mechanism study indicates that 9a simultaneously targets mitochondrial complex I to increase AMP/ATP ratio, as well as liver kinase B1 (LKB1) and calcium/calmodulin-dependent protein kinase (CaMKK), which synergistically activates AMPKα and then stimulates glucose transporter 4 (GLUT4) membrane translocation and 2-deoxyglucose (2-DG) uptake to exert anti-diabetic efficacy. Therefore, compound 9a with a novel structure is a promising anti-diabetic candidate with the advantage of multiple-target mechanism, worthy of further investigation.
Target discovery, involving target identification and validation, is the prerequisite for drug discovery and screening. Novel methodologies and technologies for the precise discovery and confirmation of drug targets are powerful tools in understanding the disease, looking for a drug and elucidating the mechanism of drug treatment. Among the common target identification and confirmation methods, the modified method is time-consuming and laborious, which may reduce or change the activity of natural products. The unmodified methods developed in recent years without chemical modification have gradually become an important means of studying drug targets. A wide range of unmodified approaches have been reported, introducing and analyzing the recent emerging methodologies and technologies. This review highlights the advantages and limitations of these methods for the application of drug target discovery and presents an overview of their contributions to the target discovery of small molecule drugs. The application and future development trends of methodologies in target discovery are also prospected to provide a reference for drug target research.
Hydrogen peroxide (H2O2) synthesis generally involves the energy-intensive anthraquinone process. Alternatively, electrochemical synthesis provides a green, economical, and environmentally friendly route to prepare H2O2 via the two-electron oxygen reduction reaction, but this process requires efficient catalysts with high activity and selectivity simultaneously. Here, we report an N, O co-doped carbon xerogel-based electrocatalyst (NO-CX) prepared by a simple and economical method. The NO-CX catalyst exhibits a high H2O2 selectivity over 90% in a potential range of 0.2–0.6 V and a high H2O2 production rate of 1410 mmol gcat−1 h−1. The density functional theory calculations demonstrate that the coupling effect between N and O can effectively induce the redistribution of surface charge and the edge carbon atom adjacent to an ether group and a graphite nitrogen atom is the active site. This work provides a straightforward and low-cost process to produce highly selective H2O2 catalysts, which is in place for the expansion of electrocatalytic synthesis of useful chemicals.
Nanoscale low-dimensional chiral architectures are increasingly receiving scientific interest, because of their potential applications in many fields such as chiral recognition, separation and transformation. Using 6, 12-dibromochrysene (DBCh), we successfully constructed and characterized the large-area two-dimensional chiral networks on Au(111) and one-dimensional metal-liganded chiral chains on Cu(111) respectively. The reasons and processes of chiral transformation of chiral networks on Au(111) were analyzed. We used scanning tunneling spectroscopy (STS) to analyze the electronic state information of this chiral structure. This work combines scanning tunneling microscopy (STM) with non-contact atomic force microscopy (nc-AFM) techniques to achieve ultra-high-resolution characterization of chiral structures on low-dimensional surfaces, which may be applied to the bond analysis of functional nanofilms. Density functional theory (DFT) was used to simulate the adsorption behavior of the molecular and energy analysis in order to verify the experimental results.
Two sulfonated diterpenoid alkaloids possessing different but related novel carbon skeletons, named aconidenusulfonine A (1) and 12, 16-secoaconidenusulfonine A (2), respectively, were isolated as minor components from an aqueous extract of the lateral roots of Aconitum carmichaelii ("Fu Zi"). The structures of 1 and 2, representing the first two C21-diterpenoid alkaloids from nature, were determined by analysis of various spectroscopic data and chemical transformation, of which 1 was further proved by single-crystal X-ray diffraction. Especially, 1 exhibited dose-depended analgesic activity consistent with the clinical function of Fu Zi.
Two-dimensional polymers (2DPs) are emerging crystalline 2D organic material comprising free-standing, single-atom/monomer-thick, planar, and covalent networks with long-ranging structural order. Benefiting from their intrinsic porosity, crystallinity, and electrical properties, 2DPs have displayed great potential for separation, energy conversion and electronic fields. In this mini review, we aim to provide the recent progress in crystalline 2DPs films form synthesis strategies to characterization methods, as well as the future trends. We first present the synthesis strategy of single-crystalline 2DPs films including crystal engineering approaches and surface science. Also, we summarize the characterization methods of 2DPs films and highlight the advantages and limitations of different methods focusing on chemical bonding, morphology, and crystal structure. Finally, we will present the current challenges and trends regarding the future developments of crystallinity, monomer design, synthesis strategy and characterization.
Understanding and establishing the structure-activity relation of nanoparticles is a prerequisite for rational design of high-performance electrocatalysts. Cu2O nanoparticles enclosed with different crystal facets, namely, o-Cu2O NPs with {111} facets, c-Cu2O NPs with {100} facets are prepared and their electrocatalytic properties for oxygen evolution reaction (OER) in alkaline condition are evaluated at single nanoparticle level with a combination of scanning electrochemical cell microscopy and scanning electron microscopy. It is found that the o-Cu2O NPs have significantly superior OER electrocatalytic activity compared to c-Cu2O, which is almost inert. The estimated turnover frequency (TOF) at 1.97 V vs. RHE on {111} facet increases from 4 s−1 to 115 s−1 with the octahedron edge length decreasing from 1.3 µm to 100 nm. Deposition of carbon on c-Cu2O surface barely promotes the activity, suggesting the inherent poor electric conductivity within the nanocrystal is most likely the reason for low activity. This work provides direct probing to single transition metal oxide crystals with dramatically different activity.
Recently, exploiting a novel supramolecular fabrication pathway have drawn great attention. To this endeavor, we firstly designed and reported an original light-activated platform based on the internal-driven forces of macrocyclic host by hiring the pillar[5]arene as the host molecule (H) and phenazine derivatives acting as an energetic guest molecule (G). Surprisingly, after adding the H solution into G system, the intensive fluorescence emission of the G molecule rapidly decreased under the irradiation of the UV-light (254 nm) until absolutely quenching. Delightfully, different from the traditional supramolecular host-guest interaction, the fluorescent emission of G molecule could be recovered after irradiating under the nature light. In view of this interesting observations, the interaction mechanism was carefully investigated by a series of characterizations. Those results suggested that the G molecule was easily threaded into the macrocyclic cavity (H) under the internal-driven forces induced by the UV-light irradiation, forming a 1:1 host-guest complex. Moreover, taking advantage of this especial feature, the light-activated platform of host–guest complex was further applied for ink-free light-driven printing materials, exhibiting great potential in the real application.
By using a perylene diimine (PDI) syn-atropisomer as highly preorganized precursor, we successfully constructed a visible-light-active organic macrocycle PDI-M. The formation of macrocyclic structure effectively avoids self-aggregation of PDI cores and enhances the absorption in visible region. As a photocatalyst, PDI-M exhibits excellent activity on aerobic selective oxidation of sulfide into sulfoxide under visible light irradiation at room temperature. Mechanism studies show that both superoxide and singlet oxygen act as reactive oxygen species. This work provides a typical case toward the maximum utilization of photosensitive groups under mild conditions.
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