Celastrol reduces lung inflammation induced by multiwalled carbon nanotubes in mice via NF-κb-signaling pathway.

Multiwalled carbon nanotubes (MWCNTs) have numerous applications in the field of carbon nanomaterials. However, the associated toxicity concerns have increased significantly because of their widespread use. The inhalation of MWCNTs can lead to nanoparticle deposition in the lung tissue, causing inflammation and health risks. In this study, celastrol, a natural plant medicine with potent anti-inflammatory properties, effectively reduced the number of inflammatory cells, including white blood cells, neutrophils, and lymphocytes, and levels of inflammatory cytokines, such as IL-1ß, IL-6, and TNF-α, in mice lungs exposed to MWCNTs. Moreover, celastrol inhibited the activation of the NF-κB-signaling pathway. This study confirmed these findings by demonstrating comparable reductions in inflammation upon exposure to MWCNTs in mice with the deletion of NF-κB (P50-/-). These results indicate the utility of celastrol as a promising pharmacological agent for preventing MWCNT-induced lung tissue inflammation.

Enhancement of zinc-ion storage capability by synergistic effects on dual-ion adsorption in hierarchical porous carbon for high-performance aqueous zinc-ion hybrid capacitors.

Aqueous zinc-ion capacitors (AZICs) are considered potential energy storage devices thanks to their ultrahigh power density, high safety, and extended cycling life. Carbon-based materials widely used as cathodes in AZICs face challenges, such as inappropriate pore sizes, poor electrolyte-electrode wettability, and insufficient vacancy defects and active sites. These limitations hinder efficient energy storage capacity and long-term stability. To address these issues, the B and F co-doped hierarchical porous carbon cathode materials (BFPC) are constructed through a facile annealing treatment process. The BFPC-2//Zn device exhibited high capacities of 222.4 and 118.3 mAh g-1 at current densities of 0.2 and 10 A g-1, respectively. Notably, the BFPC-2//Zn device demonstrated long-term cycling stability with a high capacity retention of 96.9 % after 20,000 cycles at 10 A g-1. Additionally, the assembled BFPC-2 based AZICs displayed a maximum energy density of 175.8 Wh kg-1 and an ultrahigh power density of 17.3 kW kg-1. Mechanism studies revealed that the exceptional energy storage ability and charge-transfer process of the BFPC cathode are attributed to the synergistic effect of B and F heteroatoms and the coupling effect between vacancy defects and pore size. This work presents a novel design strategy by incorporating B and F active sites into hierarchical porous carbon materials, providing enhanced energy storage capabilities for practical application in AZICs.

Exploration of Novel Meso-C═N-BODIPY-Based AIE Fluorescent Rotors with Large Stokes Shifts for Organelle-Viscosity Imaging.

The research on fluorescent rotors for viscosity has attracted extensive interest to better comprehend the close relationships of microviscosity variations with related diseases. Although scientists have made great efforts, fluorescent probes for cellular viscosity with both aggregation-induced emissions (AIEs) and large Stokes shifts to improve sensing properties have rarely been reported. Herein, we first report four new meso-C═N-substituted BODIPY-based rotors with large Stokes shifts, investigate their viscosity/AIE characteristics, and perform cellular imaging of the viscosity in subcellular organelles. Interestingly, the meso-C═N-phenyl group-substituted probe 6 showed an obvious 594 nm fluorescence enhancement in glycerol and a moderate 650 nm red AIE emission in water. Further, on attaching CF3 to the phenyl group, a similar phenomenon was observed for 7 with red-shifted emissions, attributed to the introduction of a phenyl group, which plays a key role in the red AIE emissions and large Stokes shifts. Comparatively, for phenyl-group-free probes, both the meso-C═N-trifluoroethyl group and thiazole-substituted probes (8 and 9) exhibited good viscosity-responsive properties, while no AIE was observed due to the absence of phenyl groups. For cellular experiments, 6 and 9 showed good lysosomal and mitochondrial targeting properties, respectively, and were further successfully used for imaging viscosity through the preincubation of monensin and lipopolysaccharide (LPS), indicating that C═N polar groups potentially work as rotatable moieties and organelle-targeting groups, and the targeting difference might be ascribed to increased charges of thiazole. Therefore, in this study, we investigated the structural relationships of four meso-C═N BODIPY-based rotors with respect to their viscosity/AIE characteristics, subcellular-targeting ability, and cellular imaging for viscosity, potentially serving as AIE fluorescent probes with large Stokes shifts for subcellular viscosity imaging.

Development of meso-Five-Membered Heterocycle BODIPY-Based AIE Fluorescent Probes for Dual-Organelle Viscosity Imaging.

Fluorescent rotors with aggregation-induced emission (AIE) and organelle-targeting properties have attracted great attention for sensing subcellular viscosity changes, which could help understand the relationships of abnormal fluctuations with many associated diseases. Despite the numerous efforts spent, it remains rare and urgent to explore the dual-organelle targeting probes and their structural relationships with viscosity-responsive and AIE properties. Therefore, in this work, we reported four meso-five-membered heterocycle-substituted BODIPY-based fluorescent probes, explored their viscosity-responsive and AIE properties, and further investigated their subcellular localization and viscosity-sensing applications in living cells. Interestingly, the meso-thiazole probe 1 showed both good viscosity-responsive and AIE (in pure water) properties and could successfully target both mitochondria and lysosomes, further imaging cellular viscosity changes by treating lipopolysaccharide and nystatin, attributing to the free rotation and potential dual-organelle targeting ability of the meso-thiazole group. The meso-benzothiophene probe 3 with a saturated sulfur only showed good viscosity-responsive properties in living cells with the aggregation-caused quenching effect and no subcellular localization. The meso-imidazole probe 2 showed the AIE phenomenon without an obvious viscosity-responsive property with a C═N bond, while the meso-benzopyrrole probe 4 displayed fluorescence quenching in polar solvents. Therefore, for the first time, we investigated the structure-property relationships of four meso-five-membered heterocycle-substituted BODIPY-based fluorescent rotors with viscosity-responsive and AIE properties, and among these, 1 with a C═N bond and a saturated sulfur on the meso-thiazole, potentially contributing to their corresponding AIE and viscosity-responsive properties, served as a sensitive AIE fluorescent rotor for imaging dual-organelle viscosity in both mitochondria and lysosomes.

Fabrication of dual heteroatom-doped graphitic carbon from waste sponge with "killing two birds with one stone" strategy for advanced aqueous zinc-ion hybrid capacitors.

Emerging aqueous zinc-ion hybrid capacitors (AZICs) are considered a promising energy storage because of their superior electrochemical performance. The pore structure, suitable heteroatom content, and graphitization degree (GD) of carbon-based cathodes significantly influence the electrochemical performance of AZICs. The N, S dual-doped porous graphitic carbon materials (LC-750) with the combined characteristics of high GD (1.11) and large specific surface area (1678.38 m2 g-1) are successfully developed by a facile "killing two birds with one stone" strategy using K3Fe(C2O4)3·3H2O as the activating and graphitizing agent, and waste sponge (WS) and coal tar pitch (CTP) as the heteroatom and carbon resource, respectively. Results show that the LC-750 cathode displays high capacities of 185.3 and 95.2 mAh g-1 at 0.2 and 10 A g-1. Specifically, the assembled LC-750//Zn capacitor can offer a maximal energy density of 119.5 Wh kg-1, a power density of 20.3 kW kg-1, and a capacity retention of 87.8% after 15,000 cycles at 10 A g-1. Density functional theory simulations demonstrate that N and S dual-doping can promote the adsorption kinetics of Zn ions. This design strategy is a feasible and cost-effective method for the preparation of dual heteroatom-doped graphitic carbon electrodes, which enables recycling of WS and CTP into high-valued products.

GhbZIP30-GhCCCH17 module accelerates corm dormancy release by reducing endogenous ABA under cold storage in Gladiolus.

Gladiolus hybridus is one of the most popular flowers worldwide. However, its corm dormancy characteristic largely limits its off-season production. Long-term cold treatment (LT), which increases sugar content and reduces abscisic acid (ABA), is an efficient approach to accelerate corm dormancy release (CDR). Here, we identified a GhbZIP30-GhCCCH17 module that mediates the antagonism between sugars and ABA during CDR. We showed that sugars promoted CDR by reducing ABA levels in Gladiolus. Our data demonstrated that GhbZIP30 transcription factor directly binds the GhCCCH17 zinc finger promoter and activates its transcription, confirmed by yeast one-hybrid, dual-luciferase (Dual-LUC), chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR) and electrophoretic mobility shift assay (EMSA). GhCCCH17 is a transcriptional activator, and its nuclear localisation is altered by surcose and cytokinin treatments. Both GhbZIP30 and GhCCCH17 positively respond to LT, sugars, and cytokinin treatments. Silencing GhbZIP30 or GhCCCH17 resulted in delayed CDR by regulating ABA metabolic genes, while their overexpression promoted CDR. Taken together, we propose that the GhbZIP30-GhCCCH17 module is involved in cold- and glucose-induced CDR by regulating ABA metabolic genes.

GFP-based red-emissive fluorescent probes for dual imaging of ß-amyloid plaques and mitochondrial viscosity.

Alzheimer's disease (AD), with incurable neurodegenerative damage, has attracted growing interest in exploration of better AD biomarkers in its early diagnosis. Among various biomarkers, amyloid-ß (Aß) aggregates and mitochondrial viscosity are closely related to AD and their dual imaging might provide a potential and feasible strategy. In this work, five GFP-based red-emissive fluorescent probes were rationally designed and synthesized for selective detection of ß-amyloid plaques and viscosity, among which C25e exhibited superior properties and could successfully image ß-amyloid plaques and mitochondrial viscosity with different fluorescence wavelength signals "turn-on" at around 624 and 640 nm, respectively. Moreover, the staining of brain sections from a transgenic AD mouse showed that probe C25e showed higher selectivity and signal-to-noise ratio towards Aß plaques than commercially-available Thio-S. In addition, the probe C25e was, for the first time, employed for monitoring amyloid-ß induced mitochondrial viscosity changes. Therefore, this GFP-based red-emissive fluorescent probe C25e could serve as a dual-functional tool for imaging ß-amyloid plaques and mitochondrial viscosity, which might provide a unique strategy for the early diagnosis of Alzheimer's disease.

Celastrol alleviates oxidative stress induced by multi-walled carbon nanotubes through the Keap1/Nrf2/HO-1 signaling pathway.

Multi-walled carbon nanotubes (MWCNTs) mainly induce oxidative stress through the overproduction of reactive oxygen species (ROS), which can lead to cytotoxicity. Celastrol, a plant-derived compound, can exert antioxidant effects by reducing ROS production. Our results indicated that exposure to MWCNTs decreased cell viability and increased ROS production. Nrf2 knockdown (kd) led to increased ROS production and enhanced MWCNT-induced cytotoxicity. Keap1-kd led to decreased ROS production and attenuated cytotoxicity. Treatment with celastrol significantly decreased ROS production and promoted Keap1 protein degradation through the lysosomal pathway, thereby enhancing the translocation of Nrf2 from the cytoplasm to the nucleus and increasing HO-1 expression. The in vivo results showed that celastrol could alleviate the inflammatory damage of lung tissues, increase the levels of the antioxidants, GSH and SOD, as well as promote the expression of the antioxidant protein, HO-1 in MWCNT-treated mice. Celastrol can alleviate MWCNT-induced oxidative stress through the Keap1/Nrf2/HO-1 signaling pathway.

Pt Nanoparticles Confined in a 3D Porous FeNC Matrix as Efficient Catalysts for Rechargeable Li-CO2/O2 Batteries.

The cathodic product Li2CO3, due to its high decomposition potential, has hindered the practical application of rechargeable Li-CO2/O2 batteries. To overcome this bottleneck, a Pt/FeNC cathodic catalyst is fabricated by dispersing Pt nanoparticles (NPs) with a uniform size of 2.4 nm and 8.3 wt % loading amount into a porous microcube FeNC support for high-performance rechargeable Li-CO2/O2 batteries. The FeNC matrix is composed of numerous two-dimensional (2D) carbon nanosheets, which is derived from an Fe-doping zinc metal-organic framework (Zn-MOF). Importantly, using Pt/FeNC as the cathodic catalyst, the Li-CO2/O2 (VCO2/VO2 = 4:1) battery displays the lowest overpotential of 0.54 V and a long-term stability of 142 cycles, which is superior to batteries with FeNC (1.67 V, 47 cycles) and NC (1.87 V, 23 cycles) catalysts. The FeNC matrix and Pt NPs can exert a synergetic effect to decrease the decomposition potential of Li2CO3 and thus enhance the battery performance. In situ Fourier transform infrared (FTIR) spectroscopy further confirms that Li2CO3 can be completely decomposed under a low potential of 3.3 V using the Pt/FeNC catalyst. Impressively, Li2CO3 exhibits a film structure on the surface of the Pt/FeNC catalysts by scanning electron microscopy (SEM), and its size can be limited by the confined space between the carbon sheets in Pt/FeNC, which enlarges the better contacting interface. In addition, density functional theory (DFT) calculations reveal that the Pt and FeNC catalysts show a higher adsorption energy for Li2CO3 and Li2CO4 intermediates compared to the NC catalyst, and the possible discharge pathways are deeply investigated. The synergetic effect between the FeNC support and Pt active sites makes the Li-CO2/O2 battery achieve optimal performance.

Novel Meso-Benzothiazole-Substituted BODIPY-Based AIE Fluorescent Rotor for Imaging Lysosomal Viscosity and Monitoring Autophagy.

Meso-substituted boron dipyrromethenes (BODIPYs) provide a potential and innovative strategy for the synergistic construction of aggregation-induced emission (AIE) probes and fluorescent rotors for monitoring cellular viscosity changes, which play critical roles in understanding the function of viscosity in its closely associated diseases. Therefore, for the first time, a BODIPY-based fluorescent probe (1) with a rotatable meso-benzothiazole group was rationally designed and synthesized, showing both good viscosity-responsive and AIE properties. Probe 1 through direct linkage with the thiazole group, showed nearly no emission in low viscous solvents; however, a strong emission at 534 nm appeared and increased gradually with the increase in viscosity, attributing to the efficient restriction of the rotatable meso-benzothiazole group. The intensity (log I534) displayed a good linear relationship with viscosity (log η) in the viscous range of 0.59-945 cP in methanol/glycerol mixtures. Interestingly, 1 showed enhanced emission at 534 nm in 70% water compared to pure acetonitrile due to the aggregation-induced inhibited rotations. Cellular imaging suggested that 1 could successfully sense lysosomal viscosity changes induced by lipopolysaccharide, nystatin, low temperature, and dexamethasone in living cells, which could be further applied in autophagy monitoring by tracing viscosity changes. As a comparison, its analogue 2 directly linking with the phenyl group showed no viscosity-responsive or AIE properties. Therefore, for the first time, we reported a meso-benzothiazole-BODIPY-based fluorescent rotor with AIE and lysosomal viscosity-responsive properties in nervous cells, which was further applied in monitoring autophagy, and this work thus could provide an innovative strategy for the design of potential AIE and viscosity-responsive probes.

Vascular toxicity of multi-walled carbon nanotubes targeting vascular endothelial growth factor.

Multiwalled carbon nanotubes (MWCNTs) are currently widely used and are expected to be used as drug carriers and contrast agents in clinical practice. Previous studies mainly focused on their lung toxicity; therefore, their effects on the vascular endothelium are unclear. In this study, a human angiogenesis array was used to determine the effect of MWCNTs on the expression profile of angiogenic factors in endothelial cells and to clarify the role of vascular endothelial growth factor (VEGF) in MWCNT-induced endothelial cell injury at the cellular and animal levels. The results indicated that MWCNTs (20-30 nm and 30-50 nm) could enter endothelial cells and disrupt human umbilical vein endothelial cell (HUVECs) activity in a concentration-dependent manner. MWCNTs disrupted the tube formation ability and cell migration function of HUVECs. The results from a Matrigel Plug experiment in mice showed that angiogenesis in the MWCNT experimental group was significantly reduced. The results of a protein chip analysis indicated that VEGF expression in the MWCNT treatment group was decreased, a finding that was validated by ELISA results. The protein expression levels of AKT and eNOS in the MWCNT treatment group were significantly decreased; the administration of recombinant VEGF significantly alleviated the migration ability and tube formation ability of endothelial cells injured by MWCNTs, upregulated the protein expression of AKT and eNOS, and increased the number of neovascularization in mice in the MWCNT treatment group. This study demonstrated that MWCNTs affect angiogenesis via the VEGF-Akt-eNOS axis which can be rescued by VEGF endothelial treatment.

A novel TCF-aza-BODIPY-based near-infrared fluorescent probe for highly selective detection of hypochlorous acid in living cells.

Hypochlorous acid/hypochlorite (HOCl/ClO-) plays important roles in killing bacterial and causing damage to living tissues, and its abnormal levels could lead to many diseases. Although great efforts have been devoted, fluorescent probes for HOCl/ClO- with near-infrared fluorescence, good selectivity/sensitivity, and low background are still important and urgent. In this work, a novel double-bond-linked TCF-aza-BODIPY-based near-infrared fluorescent probe (3) was rationally designed, successfully prepared, and applied for sensing HOCl/ClO- in both solutions and living RAW264.7 cells, showing good selectivity and fluorescence "turn-on" phenomenon at 670 nm with low background. The limit of detection towards ClO- was determined to be 0.36 µM through the linear fluorescence changes at 670 nm in a broad ClO--concentration range of 0-150 µM. Furthermore, the sensing mechanism was investigated by mass spectrometry and compared with 1, suggesting that the remarkable spectroscopic changes could be ascribed to the oxidization of the double bond to the aldehyde group, accompanied with the leaving of the TCF group. Confocal imaging experiments also confirmed the remarkable intracellular fluorescence enhancements through incubation of ClO- and phorbol ester 12-myristate 13-acetate (PMA) in RAW264.7 cells. Therefore, for the first time, we reported a near-infrared TCF-aza-BODIPY-based fluorescent probe for highly sensitive and fluorescence "turn-on" detection of both exogenous and endogenous HOCl in living RAW264.7 cells through the quick oxidation of a conjugated double bond.

Rotor-Tuning Boron Dipyrromethenes for Dual-Functional Imaging of Aß Oligomers and Viscosity.

Alzheimer's disease (AD), known as a common incurable and elderly neurodegenerative disease, has been widely explored for accurate detection of its biomarker (Aß oligomers) for early diagnosis. Although great efforts have been made, it is still of great importance to develop fluorescence probes for Aß oligomers with good selectivity and low background. Herein, starting from BODIPY493/503 (a commercial dye for neutral lipid droplets), which exhibited a small Stokes shift and no response toward Aß peptides, two fluorescence probes 5MB-SZ and B-SZ with a benzothiazole rotor at the 2-position of the BODIPY core and a methyl or benzyl group at the meso position have been designed and synthesized, which exhibited excellent optical properties/stability and could successfully image ß-amyloid fibrils and viscosity. Upon exposure to Aß oligomers, the fluorescence intensity of 5MB-SZ was enhanced by 43.64-fold with the corresponding fluorescence quantum yields changing from 0.85% to 27.43%. Meanwhile, probe 5MB-SZ showed a highly sensitive viscosity response in both solutions and living cells. In vitro and in vivo experiments confirmed that probe 5MB-SZ exhibited an excellent capacity for imaging ß-amyloid fibrils. Therefore, 5MB-SZ, as a rotor-tuning BODIPY analogue, could possibly serve as a highly potential and powerful fluorescence probe for early diagnosis of AD.

Novel cationic meso-CF3 BODIPY-based AIE fluorescent rotors for imaging viscosity in mitochondria.

Two novel meso-CF3 BODIPY-based fluorescent rotors have been rationally prepared and found to sensitively respond to viscosity in living cells with a fluorescence "turn-on" effect, attributed to the special restricted rotation of meso-CF3 group in viscous environments. Interestingly, a monostyryl probe with one cationic group exhibits good mitochondrial localization and AIE property.

Pyruvate Kinase M2 Mediates Glycolysis Contributes to Psoriasis by Promoting Keratinocyte Proliferation.

Psoriasis is characterized by keratinocyte proliferation and immune cell infiltration. M2 isoform of pyruvate kinase (PKM2) was reported to have an important role in cell proliferation, which is a rate-limiting enzyme that regulates the final step of glycolysis. However, how PKM2 regulates cell metabolism and proliferation in psoriatic keratinocytes is still poorly understood. Interestingly, we found that PKM2 was highly expressed in psoriatic epidermis from patients and mouse models. PKM2 overexpression promoted keratinocyte glycolytic metabolism while knockdown inhibited keratinocyte proliferation and glycolysis. Mice lacking PKM2 specifically in keratinocytes, pharmacological inhibition of PKM2 or glycolysis inhibited keratinocyte proliferation and showed obvious remission in an imiquimod-induced psoriatic mouse model. Moreover, the inhibitor of the EGF-receptor blocked EGF-stimulated PKM2 expression and glycolysis in keratinocytes. We identify PKM2 as an upregulated gene in psoriasis. PKM2 is essential in keratinocyte over-proliferation and may represent a therapeutic target for psoriasis.

Targeted Delivery and Site-Specific Activation of ß-Cyclodextrin-Conjugated Photosensitizers for Photodynamic Therapy through a Supramolecular Bio-orthogonal Approach.

Targeted delivery of photosensitizers using hydrophilic and tumor-directing carriers and site-specific activation of their photocytotoxicity are two common strategies to enhance the specificity of anticancer photodynamic therapy. We report herein a novel supramolecular bio-orthogonal approach to integrate these two functions. A ß-cyclodextrin-substituted aza-boron-dipyrromethene-based photosensitizer was first complexed with a ferrocene-substituted black-hole quencher to inhibit its photosensitizing ability. Upon encountering the adamantane moieties that had been delivered to target cancer cells through specific binding of the conjugated peptide to the overexpressed epidermal growth factor receptor, the ferrocene-based guest species were displaced due to the stronger binding interactions between ß-cyclodextrin and adamantane, thereby restoring the photodynamic activity of the photosensitizer. Hence, this two-step process enabled targeted delivery and site-specific activation of the photosensitizer, as demonstrated through a series of experiments in aqueous media, in a range of cancer cell lines and in tumor-bearing nude mice.

A novel methylenemalononitrile-BODIPY-based fluorescent probe for highly selective detection of hydrogen peroxide in living cells.

Hydrogen peroxide (H2O2) plays vital roles in oxidative stress and signal transduction in living organisms, and its abnormal levels could be linked to many diseases. Despite numerous efforts spent, it is still urgent and of high importance to develop better H2O2 probes with good selectivity, high sensitivity and low backgrounds. To this end, a novel boron dipyrromethene (BODIPY)-based fluorescent probe with an electron-withdrawing methylenemalononitrile at the meso position has been rationally designed, successfully synthesized and investigated for detection of H2O2 in aqueous solutions and living cells, which exhibited high selectivity and sensitivity, fluorescent "turn-on" phenomenon at 540 nm, and ratiometric changes from 506 to 540 nm. Upon exposure to H2O2, a strong fluorescent emission at 540 nm appeared and the corresponding quantum yields changed from 0.009 to 0.13. The detection limit towards H2O2 was calculated to be 31 nM by the linear fluorescence change at 540 nm in the H2O2-concentration ranging from 2 to 10 µM. This probe was applicable in a pH range from 6 to 10. Meanwhile, the sensing mechanism was also confirmed by the 1H NMR and mass spectrometry, suggesting that the above changes might be ascribed to the quick addition and oxidization of the double bond. Furthermore, confocal imaging results also showed great enhancement of intracellular fluorescence upon exposure to H2O2 and PMA in RAW264.7 cells, unambiguously confirming its great potentials as a fluorescent probe for highly sensitive detection of both exogenous and endogenous H2O2 in living cells.

A near-infrared-emission aza-BODIPY-based fluorescent probe for fast, selective, and "turn-on" detection of HClO/ClO.

A novel near-infrared-emitting aza-BODIPY-based fluorescent probe with two tellurium atoms at two upper benzyl rings has been prepared and explored for its fluorescent sensing properties towards hypochlorous acid/hypochorite (HClO/ClO-), which showed high selectivity and absolutely fluorescent "turn-on" phenomenon at 738 nm. The fluorescence of this probe was sufficiently quenched due to photoindued electron transfer by two tellurium atoms. Upon exposure to HClO/ClO-, a strong near-infrared emission at 738 nm appeared with fluorescence quantum yields changing from 0 to 0.11. This remarkable fluorescence change was ascribed to the oxidation of both electron-rich tellurium atoms. The detection limit of this probe towards HClO/ClO- was calculated to 0.09 µM in acetonitrile aqueous solution by the linear fluorescence change at 738 nm in the HClO/ClO--concentration range of 0-30 µM. Interestingly, this probe was found to be applicable in a broad pH range (2-10). Meanwhile, the oxidized probe could be further responsive to biothiols with substantial fluorescence disappearance. The bioimaging experiments in RAW264.7 cells showed the appearance of intracellular near-infrared fluorescence after addition of HClO/ClO- and PMA, and the fluorescence could also be reversed to be silenced by further introduction of GSH, confirming its potential application for exogenous and endogenous detection of HClO/ClO- in living cells.

Endothelium-Specific GTP Cyclohydrolase I Overexpression Restores Endothelial Function in Aged Mice.

This study tested the hypothesis that endothelium-specific GTP cyclohydrolase I (GTPCH I) overexpression (Tg-GCH) restores age-associated endothelial dysfunction in vivo. Aortic GTPCH I expression and serum nitric oxide (NO) release were measured in young and aged mice. Aortic rings from young and aged wild-type (WT) mice and aged Tg-GCH mice were suspended for isometric tension recording. A hind limb ischemia model was used to measure blood flow recovery. Aged mice showed reduced GTPCH I expression in the aorta and decreased NO levels in serum. Compared with aged WT mice, Tg-GCH significantly elevated NO levels in serum in aged Tg-GCH mice, restored the impaired aortic relaxation in response to acetylcholine, and significantly elevated aortic constriction in response to L-NAME. Importantly, aged Tg-GCH mice displayed a significant increase in blood flow recovery compared with aged WT mice. GTPCH I reduction contributes to aging-associated endothelial dysfunction, which can be retarded by Tg-GCH.

A theoretical investigation into the cooperativity effect on the TNT melting point under external electric field.

External electric field has been regarded as an effective tool to induce the variation of melting points of molecular crystals. The melting point of 2,4,6-trinitrotoluene (TNT) was calculated by molecular dynamics simulations under external electric field, and the electric field effects on the cooperativity effects of the ternary (TNT)3 were investigated at the M06-2X/6-311+G(d) and ωB97X-D/6-311++G(2d,p) levels. The results show that the melting points are decreased while the intermolecular interactions are strengthened under the external electric fields, suggesting that the intermolecular interactions cannot be used to explain the decreased melting points. A deduction based on the cooperativity effect is put forward: the enhanced cooperativity effects create the more serious defects in the melting process of the molecular crystal under the external electric fields, and simultaneously the local order parameters are decreased, leading to the decreased melting point. Thus, the cooperativity effect stemmed from the intermolecular C-H∙∙∙O H-bonding interactions controls the change of TNT melting point under the external electric field. Employing the information-theoretic approach (ITA), the origin of the cooperativity effects on the melting points of molecular crystal is revealed. This study opens a new way to challenge the problems involving the melting points for the molecular crystal under the external electric fields. However, note that above deduction needs to be improved; after all, the simple (TNT)3 model cannot replace the crystal structure.