Latest ArticlesCarbon monoxide (CO) gas therapy, a novel anti-tumor technique based on the cytotoxicity from the CO released in situ, has become one of the hot topics in cancer treatment. Since the technique is oxygen-independent, it displays promising therapeutic effect for hypoxic tumor where traditional photodynamic therapy shows limited efficacy and insufficient penetration depth. To fully address these limitations of PDT, we propose a synergetic sonodynamic-CO gas releasing strategy for the therapy of hypoxic tumor. In this work, two rhenium(I) tricarbonyl complexes with different substituted ligands are investigated for US-triggered ROS generation and CO release. Our results indicated that the electron-donating NMe2-substituted complex (Re-NMe2) exhibits stronger luminescence intensity and generates more singlet oxygen (1O2) than the electron-withdrawing NO2-substituted complex (Re-NO2). In addition, Re-NMe2 displays release of CO triggered by US, thus showing high sono-cytotoxicity to tumor cells in-vitro and in-vivo. The strong ROS-generating capability combined with rapid CO-releasing feature from Re-NMe2 has made it a powerful tool for the efficient treatment of hypoxic tumor.
The 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.
Phosphorylation plays crucial parts in lenticular biological function. Getting knowledge of region-resolved phosphoproteome contributes to better comprehending the pathogenesis. Here, we prepared the hybrid metal organic frameworks (HMOFs) for probing the region-resolved heterogeneity of phosphoproteome in human lens. 1334 phosphosites corresponding to 564 phosphoproteins, 1160 phosphosites corresponding to 316 phosphoproteins and 517 phosphosites corresponding to 205 phosphoproteins were identified in capsule, cortex and nucleus, respectively, providing the relatively extensive distribution mapping of phosphorylation in human lens for the first time. The label-free quantification experiments and principal component analysis presented differential expression of phopshoproteins in three subregions. For instance, α-crystallin, β-crystallin and fibrillin-1 closely associated with cataract and Marfan syndrome showed disparate spatial distribution. The preferential phosphoproteins in capsule, cortex and nucleus were involved in cytoskeleton organization, metabolic process and lens development in camera-type eye, respectively. This work first provided a general overview of region-resolved phosphoproteome of human lens.
The coupling of bipolar electrode (BPE) arrays and electrofluorochromic (EFC) imaging has exhibited great abilities in bioanalysis. However, the imaging resolution and analytical performance are hampered by the large size of the electrode and the rapid diffusion of EFC molecules on the electrode surface. Here, to address the challenges, bipolar nanoelectrodes (BPnE) array and in situ immobilization strategy of EFC molecules were proposed. Anodized aluminum oxide (AAO) template-assisted Au nanoelectrodes array with high density was fabricated as BPnE array for high spatial imaging resolution. By electrically polymerizing EFC molecules on the surface of single Au nanoelectrode, the rapid diffusion of EFC molecules on the electrode surface was not only avoided, but also realizing electrofluorescent imaging on an individual nanoelectrode. Using dopamine (DA) released from living PC12 cells as a model, the proposed strategy exhibited an ultra-high sensitivity for DA analysis with a detection limit of 0.45 nmol/L and the DA release amount from a single cell was calculated to be 0.13 pmol/L. Moreover, the dynamic change of DA release under the drug stimulation from living PC12 cells could also be monitored.
Due to the abundant sodium reserves and high safety, sodium ion batteries (SIBs) are foreseen a promising future. While, hard carbon materials are very suitable for the anode of SIBs owing to their structure and cost advantages. However, the unsatisfactory initial coulombic efficiency (ICE) is one of the crucial blemishes of hard carbon materials and the slow sodium storage kinetics also hinders their wide application. Herein, with spherical nano SiO2 as pore-forming agent, gelatin and polytetrafluoroethylene as carbon sources, a multi-porous carbon (MPC) material can be easily obtained via a co-pyrolysis method, by which carbonization and template removal can be achieved synchronously without the assistance of strong acids or strong bases. As a result, the MPC anode exhibited remarkable ICE of 83% and a high rate capability (208 mAh/g at 5 A/g) when used in sodium-ion half cells. Additionally, coupling with Na3V2(PO4)3 as the cathode to assemble full cells, the as-fabricated MPC//NVP full cell delivered a good rate capability (146 mAh/g at 5 A/g) as well, implying a good application prospect the MPC anode has
The photocatalyzed synthesis of 9-arylpurines has been developed using 9H-purines and non-activated arenes. This method is highly atom economical using an acridinium photocatalyst induced by visible light under air atmosphere at room temperature. It employs no metal or external oxidant for the synthesis of 9-arylpurine derivatives.
Macrophages play a crucial role in initiating, maintaining, and resolving inflammation through the phenotypic shift, inducing or inhibiting the production of inflammatory cytokines. Therefore, macrophages are potential targets for treating inflammatory diseases. Andrographolide (AND) is a potent anti-inflammatory drug that can reduce pro-inflammatory cytokines and suppress NF-κB /MAPK pathway in activated macrophages. Although AND has many medicinal properties, its lower water solubility and first-pass effect in the liver have hindered its clinical application. In this context, by using a metal phenolic network as a stabilizer, we designed and prepared highly stabilized AND nanocrystals (AND-MPN Ns) with high drug loading capacity to facilitate the clinical application of AND. Our findings showed that AND-MPN Ns could be used to enhance the anti-inflammation in-vitro via macrophage polarization, reducing pro-inflammatory cytokines IL-6 and TNF-α, and suppressing the NF-κB signaling pathway activation. The results demonstrated the potential of AND-MPN Ns to combat inflammatory diseases effectively.
Two chimeric sesterterpene synthases (AaTPS1 and AaTPS2) were functionally characterized from Alternaria alternata MB-30 isolated from the leaves of a sesterterpenoid-producing Lamiaceae plant Leucosceptrum canum. AaTPS1 generated a 5/8/6/5 tetracyclic sesteraltererol (1) and its absolute stereochemistry was determined by X-ray crystallographic analysis of its derivative 10, 11-epoxysesteraltererol (2), which enabled revision of the absolute configuration of C7 of sesterfisherol produced by NfSS and PTTS014 characterized previously and its derivative 10, 11-epoxysesterfisherol. AaTPS2 produced a 5/15 bicyclic preterpestacin I (3). Site-directed mutagenesis suggested that F192 in AaTPS1 was likely involved in controlling of the hydroxylation of C12, and eight amino acids were important for the enzyme activity of AaTPS1 and AaTPS2. The engineered Escherichia coli and Saccharomyces cerevisiae strains were constructed for the productions of compounds 1 and 3, and the highest titer of compound 1 reached 62.3 mg/L in shake-flask culture. Both compounds 1 and 2 showed anti-adipogenic activity.
An aldehyde-reactive probe based on 2-amino benzamidoxime (ABAO) framework was introduced, which can selectively label aldehydes in DNA through intramolecular ring closure under mild aqueous solutions. We screened ABAO derivatives that can undergo a cyclization with the formylated nucleobases to generate a fluorescence nucleoside, and of these derivatives 5-methoxy-ABAO (PMA) emerged as the optimal choice. PMA can sensitively and selectively react with 5fU, 5fC and AP to form fluorogenic dihydroquinazoline derivatives, which also can quantify DNA damages induced by γ-irradiation. PMA-initiated labeling strategy provides great convenience for qualitative and quantitative detection of aldehydes in DNA.
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.
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