Oxidative Nickel-Catalyzed ortho-C-H Amination of (Iso)quinolines with Alicyclic Amines Directed by a Sacrificial N-Oxide Group.

Transition metal (TM)-catalyzed direct amination of C-H bonds on free or fused pyridine (Py) rings with free amines still remains scarce because amines and the Py ring tend to adopt a nonproductive N-bound coordination with many TMs, leading to a significant decrease of catalytic reactivity. We herein disclose a nickel-catalyzed and a sacrificial N-oxide group directed oxidative coupling of (iso)quinolyl C-H bonds and alicyclic amines, which furnishes bioimportant amino(iso)quinolines efficiently and selectively in a single step. Noteworthy, this protocol avoids the use of aggressive reactants and very strong bases usually required when aminating on nonoxidized Py rings.

Selective edge etching of Pd metallene for enhanced formic acid electrooxidation.

We develop a facile, selective edge etching strategy to create edge sites in Pd metallene using acetic acid. The created edge sites remarkably increase the electrochemically active surface area but reduce the charge transfer resistance, resulting in significant enhancement of catalytic activity and stability toward formic acid oxidation.

Effects of elevated CO2 concentration and experimental warming on morphological, physiological, and biochemical responses of winter wheat under soil water deficiency.

Global climate change and freshwater scarcity have become two major environmental issues that constrain the sustainable development of the world economy. Climate warming caused by increasing atmospheric CO2 concentration can change global/regional rainfall patterns, leading to uneven global seasonal precipitation distribution and frequent regional extreme drought events, resulting in a drastic reduction of available water resources during the critical crop reproduction period, thus causing many important food-producing regions to face severe water deficiency problems. Understanding the potential processes and mechanisms of crops in response to elevated CO2 concentration and temperature under soil water deficiency may further shed lights on the potential risks of climate change on the primary productivity and grain yield of agriculture. We examined the effects of elevated CO2 concentration (e[CO2]) and temperature (experimental warming) on plant biomass and leaf area, stomatal morphology and distribution, leaf gas exchange and mesophyll anatomy, rubisco activity and gene expression level of winter wheat grown at soil water deficiency with environmental growth chambers. We found that e[CO2] × water × warming sharply reduced plant biomass by 57% and leaf photosynthesis (P n) 50%, although elevated [CO2] could alleviated the stress from water × warming at the amount of gene expression in RbcL3 (128%) and RbcS2 (215%). At ambient [CO2], the combined stress of warming and water deficiency resulted in a significant decrease in biomass (52%), leaf area (50%), P n (71%), and G s (90%) of winter wheat. Furthermore, the total nonstructural carbohydrates were accumulated 10% and 27% and increased R d by 127% and 99% when subjected to water × warming and e[CO2] × water × warming. These results suggest that water × warming may cause irreversible damage in winter wheat and thus the effect of "CO2 fertilization effect" may be overestimated by the current process-based ecological model.

Gravity-driven membrane system treating heavy metals-containing secondary effluent: Improved removal of heavy metals and mechanism.

This study aimed at investigating the removal performance of the gravity-driven membrane (GDM) system in treating the heavy metals-containing secondary effluent, as well as evaluating the respective roles of Fe and Mn addition on the removal of heavy metals. GDM process with the formation of biocake layer exerted effective removals of Cr, Pb and Cd, with an average removal efficiency of 98%, 95% and 40%, respectively, however, after removing the biocake layer, the removal efficiencies of Cr, Pb and Cd reduced to 59%, 85% and 19%, respectively, indicating that the biocake layer played a fundamental role in removing heavy metals. With the assistance of Fe, the removal efficiency of heavy metals increased, and exhibited a positive response to the Fe dosage, due to the adsorption by the freshly generated iron oxides. On the contrary, the Mn involvement would result in the reduction of Cd removal due to the competitive adsorption of residual dissolved Mn2+ and Cd. Furthermore, the addition of a high dosage of Fe increased the diversity of eukaryotic communities and facilitated the elimination of heavy metals, however, the involvement of Mn would lead to a reduction in microbial diversity, resulting in a decrease of heavy metal removal efficiency. These findings are expected to develop new tactics to enhance heavy metal removal and promote widespread application of GDM technology in the fields of deep treatment of heavy metals-containing wastewater and reclamation of secondary effluent.

JNK regulates the Nrf2/NQO1-ARE pathway against Microcystins-Induced oxidative stress in freshwater mussel Cristaria plicata.

In response to stress, cells can utilize several processes, such as the activation of the Nrf2/Keap1 pathway as a critical regulator of oxidative stress to protect against oxidative damage. C-Jun N-terminal kinase (JNK), a member of the mitogen-activated protein kinase (MAPK) family, is involved in regulating the NF-E2-related nuclear factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway. NAD(P)H quinone redox enzyme-1 (NQO1), a downstream target gene of the Nrf2 pathway, plays a vital role in removing peroxide and providing resistance to oxidative injury. We found that microcystins (MCs) stimulated CpNrf2 to express and increase anti-oxidative enzyme activities in a previous experiment. In our current study, the full-length cDNAs of JNK and NQO1 from Cristaria plicata (designated CpJNK and CpNQO1) were cloned. The relative levels of CpJNK and CpNQO1 were high in hepatopancreas. Upon MCs induction, the relative level of CpNQO1 was increased, whereas that of CpJNK was decreased significantly. In contrast, CpNrf2 knockdown upregulated the expression of CpJNK mRNA and phosphorylation of CpJNK protein (Cpp-JNK), but inhibited CpNQO1 expression. Additionally, we found that JNK inhibitor SP600125 stimulated expression of CpNQO1 and CpNrf2 upon exposure to MCs, and we further confirmed that CpNrf2 protein combined with the ARE element in CpNQO1 gene promoter in vitro, and increased CpNQO1-ARE-luciferase activity in a CpNrf2-dependent manner. These findings indicated C. plicata effectively alleviated MC-induced oxidative injury through JNK participated in regulating the Nrf2/NQO1-ARE pathway.

Identification of Nrf2/Keap1 pathway and its transcriptional regulation of antioxidant genes after exposure to microcystins in freshwater mussel Cristaria plicata.

Microcystins (MC) are one of the most abundant and widely distributed cyanotoxins in aquatic systems. MC inhibits the functions of protein phosphatase 1 and 2A (PP1/2A), which can seriously affect ecosystem integrity. The NF-E2-related nuclear factor 2 (Nrf2)/Kelch-like epichlorohydrin-related protein-1 (Keap1) signaling pathway protects against oxidative damage by activating phase II detoxification/antioxidant enzymes. Our previous study revealed that MC upregulates the expression and enhances the activities of the antioxidant enzymes by stimulating the CpNrf2 signaling pathway. In the current study, to further clarify the regulatory role of Keap1 in response to MC-induced oxidative stress in shellfish, we cloned the full-length cDNA of Keap1a and Keap1b from Cristaria plicata (designated CpKeap1a and CpKeap1b), which are 2952 and 3710 bp peptides, respectively. The amino acid sequence of CpKeap1a and CpKeap1b contained Tram-track and Bric-a-brac (BTB), Intervening region (IVR), and Double glycine repeat (DGR) domain. Additionally, CpKeap1a contained two cysteine residues analogous to Cys-273 and -288 in zebrafish, but CpKeap1b did not. Moreover, CpKeap1a and -1b formed a homodimer and heterodimer, respectively, and also formed a heterodimer with CpNrf2. In the hepatopancreas, the expression levels of CpKeap1a and -1b were the highest, but MC treatment down-regulated the expression of these proteins. Moreover, the transcription of antioxidant enzymes with antioxidant response element (ARE-driven enzymes), including CpMnSOD, CpCu/ZnSOD, CpTRX, CpPrx, CpSe-GPx, and Cpsigma-GST was upregulated by CpNrf2 in the hepatopancreas. Compared with the MC-induced group, CpKeap1a-siRNA1117 injection significantly increased the transcription of mRNAs for ARE-driven enzymes and Nrf2. CpKeap1a-siRNA1117 also enhanced the activities of antioxidation enzymes. These findings demonstrated that Keap1a negatively regulated the expression of Nrf2 protein and MC-induced oxidative stress response in C. plicata. Therefore, we speculated that CpKeap1a promoted CpNrf2 by recognizing and binding MC. These events then protected molluscs from MC-induced oxidative damage.

P62/SQSTM1 upregulates NQO1 transcription via Nrf2/Keap1a signaling pathway to resist microcystins-induced oxidative stress in freshwater mussel Cristaria plicata.

Microcystins (MCs) are the most frequent and widely distributed type of cyanotoxin in aquatic systems, and they cause an imbalance of the body's oxidative system. In a previous experiment, we demonstrated that the mollusk Cristaria plicata can protect against MC-induced oxidative damage through the nuclear factor erythroid 2-related factor 2(Nrf2)/Kelch-like epichlorohydrin-related protein-1 (Keap1) pathway. Here, we evaluated whether selective autophagy affects the Nrf2/Keap1a anti-oxidative stress pathway in C. plicata. Full-length cDNA sequences of p62/SQSTM1 from C. plicata (Cpp62) were divided into 2484 bp fragments. From N-terminal to C-terminal, the amino acid sequence of Cpp62 contained PB1 (Phox and Bem1p domain), ZNF (zinc finger domain) chain, LIR (LC3 interacting region) and UBA (ubiquitin-associated domain) domains, but not the KIR (Keap1 interacting region) domain. We confirmed that Cpp62 did not bind to CpKeap1a in vitro, and the relative level of Cpp62 was the highest in the hepatopancreas. Moreover, MCs significantly upregulated the mRNA and protein levels of Cpp62 in the hepatopancreas after CpKeap1a knockdown, whereas Nrf2 upregulated the transcription levels of Cpp62, suggesting that MCs increased Cpp62 expression via the Nrf2/Keap1a signaling pathway. Moreover, Cpp62 and CpNrf2 proteins have a strong affinity for the NQO1 promoter, but MCs inhibited the ability of CpNrf2 and Cpp62 to upregulate luciferase activity. The results show that Nrf2 and the p62 protein induced p62 expression by binding to ARE (antioxidant response element) sequences in the p62 promoter of C. plicata, thereby promoting p62 to resist MC-induced oxidative stress. Therefore, we speculate that MCs induce p62-dependent autophagy in C. plicata, resulting in the inhibition of Nrf2 transcription and Cpp62 promoter activity. These findings help to reveal the mechanism by which the p62-Nrf2/Keap1 pathway mitigates MC-induced oxidative damage in mussels.

Influence of operation modes on gravity-driven membrane process in treating the secondary effluent: Flux improvement and biocake layer property.

A low flux level of the gravity-driven membrane (GDM) process constrained its extensive application in treating the secondary effluent. In this study, different operation modes were introduced to the GDM process without aeration, backwashing, and chemical cleanings, hoping to develop simple and economic flux regulating strategies, and their influences on the filtration performances and biocake layer characteristics were systematically investigated. The results indicated that the stable fluxs in the intermittent GDM systems elevated by 40%-100% relative to the continuous GDM case, attributing to the synergetic effects of forming more permeable, mushroom-like structures and reducing the concentrations of EPS and SMP within biocake layers. The quantitative analysis of biocake layer properties suggested that the structural parameters of porosity and absolute roughness were closely related to the flux variation compared to the thickness and relative roughness. Besides, the intermittent GDM system generated an apparent detachment of the biocake layer from the membrane surface along with a persistent flux increase than in the continuous GDM case during long-term filtration, achieving its self-sustained operation in a higher flux level without any interferences. The periodical flux recovery and decline occurred daily in each intermittent GDM system since the biocake layer attached to the membrane surface was mainly reversible. Although there were no significant differences in removing dissolved organic pollutants under different operation modes, the manganese removals decreased by 0%-25% in the intermittent GDM filtrations compared to the continuous GDM scenario. The optimized daily operation mode was 16 h on / 8 h off (operation of 16 h, interruption of 8 h), considering the trade-off effects between membrane flux level and water production. These findings provide a new simply-feasible optimized GDM process operation strategy and benefit promoting the application of the GDM system in the reclamation of wastewater.

Effects of organics concentration on the gravity-driven membrane (GDM) filtration in treating iron- and manganese-containing surface water.

Iron and manganese contamination in the surface water is posing great challenges to the drinking water treatment supply, especially in the complex cases of organics involvement. Gravity-driven membrane (GDM) filtration equipped with the dual functions of ultrafiltration and biocake layer, conferred promising potentials in the removals of iron and manganese. This study evaluated the effects of organics concentrations on the removal performance of iron and manganese, as well as on the flux stabilization during GDM long-term filtration. The results indicated that stable flux level and the removal efficiency of manganese initially increased with the increase of organics concentration in the feed water, and then decreased. The moderate concentration of organic compounds in the feed water would positively facilitate the microbial activities and benefit to engineering a heterogeneous and porous biocake layer on the membrane surface, contributing to the highest improvements of stable flux (6.3 L m-2 h-1), while high concentration of organic compounds in the feed water would result in the increase in the thickness and EPS concentration of the biocake layer, leading to a flux reduction. Furthermore, the moderate concentration of organic compounds in the feed water was also beneficial to the manganese removal (> 94.6%) due to the more accumulation of auto-catalytic oxidation manganese oxides (MnOx) within the biocake layer and the improved biological degradation, however, further increase of organics concentration would deliver a negative impact on the manganese removal owing to the wrapping of MnOx by the organic substances. Overall, these findings provide practical and acceptable strategies to the selections of pre-treatments prior to GDM and promote its extensive application in treating the iron- and manganese-containing surface water.

Ultrafine antimony (Sb) nanoparticles encapsulated into a carbon microfiber framework as an excellent LIB anode with a superlong life of more than 5000 cycles.

Antimony (Sb) anode has attracted increasing attention given its high theoretical capacity and suitable working potential. Nonetheless, its practical application is largely hindered by huge volume changes during the cyclic process, resulting in unsatisfactory long-term cycled stabilities at high current density. In this work, large-scale ultrafine Sb nanoparticles are functionally designed to encapsulate into a 3D carbon microfiber framework (CMF) via a scalable electrospinning approach followed by a thermal treatment process. This fabrication strategy effectively avoids the change in the volume of the Sb anode and provides a fast conductive network to serve as an efficient 3D e/Li+ transport pathway. Benefiting from this novel structural design, an ultrafine Sb nanoparticles@carbon microfiber framework (U-Sb-NPs@CMF) composite anode used for lithium-ion batteries (LIBs) delivers a high reversible capacity of 622 mAh g-1 after 200 cycles at 0.5 A g-1 and 507 mAh g-1 after 2000 cycles at 2 Ag-1 and a high-capacity retention of 350 mAh g-1 even after 5000 long-term cycles. These outstanding charge-discharge performances suggest that the U-Sb-NPs@CMF composite is a promising candidate for an anode material in the application of LIBs.

The excitotoxity of NMDA receptor NR2D subtype mediates human fetal lung fibroblasts proliferation and collagen production.

Studies have suggested that endogenous glutamate and N-methyl-d-aspartate (NMDA) receptor have an excitotoxity role during acute lung injury. Fibroblasts play a critical role in lung development and chronic lung disease after acute lung injury. This study aims to explore the immediate role of NMDAR activation in human lung fibroblasts. The expression of NMDAR 1 subtype (NR1) and four individual NMDAR 2 (NR2) subtypes (NR 2 A to D) was measured in human fetal lung fibroblasts (HFL-1 and MRC-5). Five NMDARs expression were all detectable in two cell lines. Although the expressions of NMDARs were different between MRC-5 and HFL-1, 1mM NMDA elicited the same trend in the downregulation of NR2A expression, the upregulation of NR2D, and the increase of cells proliferation and collagen production. Glutamate stimulation after 24-h of NMDA exposure resulted in weaker and more delayed but more prolonged iCa2+ elevation in HFL-1 than no NMDA exposed cells. NMDA increased the level of pERK1/2, cells proliferation and collagen production, whereas nonspecific NMDAR antagonist MK-801, NR2D-preferring receptor antagonist UBP141 and ERK1/2 phosphorylation inhibitor U0126 suppressed it, respectively. In conclusion, we found that NMDAR activation, NR2D in particular, is involved in human fetal lung fibroblast proliferation and collagen production through a potential ERK1/2-mediated mechanism.

N-methyl-D-aspartate receptor activation mediates lung fibroblast proliferation and differentiation in hyperoxia-induced chronic lung disease in newborn rats.

BACKGROUND: Previous studies have suggested that endogenous glutamate and its N-methyl-D-aspartate receptors (NMDARs) play important roles in hyperoxia-induced acute lung injury in newborn rats. We hypothesized that NMDAR activation also participates in the development of chronic lung injury after withdrawal of hyperoxic conditions. METHODS: In order to rule out the anti-inflammatory effects of NMDAR inhibitor on acute lung injury, the efficacy of MK-801 was evaluated in vivo using newborn Sprague-Dawley rats treated starting 4 days after cessation of hyperoxia exposure (on postnatal day 8). The role of NMDAR activation in hyperoxia-induced lung fibroblast proliferation and differentiation was examined in vitro using primary cells derived from the lungs of 8-day-old Sprague-Dawley rats exposed to hyperoxic conditions. RESULTS: Hyperoxia for 3 days induced acute lung injury in newborn rats. The acute injury almost completely disappeared 4 days after cessation of hyperoxia exposure. However, pulmonary fibrosis, impaired alveolarization, and decreased pulmonary compliance were observed on postnatal days 15 and 22. MK-801 treatment during the recovery period was found to alleviate the chronic damage induced by hyperoxia. Four NMDAR 2 s were found to be upregulated in the lung fibroblasts of newborn rats exposed to hyperoxia. In addition, the proliferation and upregulation of alpha-smooth muscle actin and (pro) collagen I in lung fibroblasts were detected in hyperoxia-exposed rats. MK-801 inhibited these changes. CONCLUSIONS: NMDAR activation mediated lung fibroblast proliferation and differentiation and played a role in the development of hyperoxia-induced chronic lung damage in newborn rats.

Apigenin attenuates copper-mediated ß-amyloid neurotoxicity through antioxidation, mitochondrion protection and MAPK signal inactivation in an AD cell model.

Apigenin, belonging to a less toxic and non-mutagenic flavone subclass of flavonoids, has been reported to possess numerous biological activities beneficial to health. Although evidence has shown apigenin might exert its protective effects by reducing the toxicity induced by amyloid-ß peptides (Aß), the precise mechanism is unclear. In the present study, we investigated the in vitro neuroprotective activity of apigenin interrelated with amyloid toxicity and mental homeostasis in an Alzheimer's disease (AD) cell model and explored its potential signal transduction. Our results showed that apigenin protected neurons against Aß-mediated toxicity induced by copper, which was characterized by increasing neuronal viability and relieving mitochondrial membrane dissipation and neuronal nuclear condensation. Further, we demonstrated that apigenin did not provide sufficient effect on decreasing ß-amyloid precursor protein (AßPP) expression and lowering Aß(1-42) secretion, but conserved redox balance by increasing intracellular glutathione levels and enhancing cellular superoxide dismutase and glutathione peroxidase activities, reduced intracellular reactive oxygen species (ROS) generation, blocked ROS-induced p38 mitogen-activated protein kinases (p38 MAPK)- MAPKAP kinase-2 (MK2)-heat shock protein 27 (Hsp27) and stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK)-c-Jun signaling pathways, preserved mitochondrial function, and then regulated apoptotic pathways. In conclusion, apigenin could exert neuroprotection against Aß-induced toxicity in the presence of copper mainly through the mechanisms that regulate redox imbalance, preserve mitochondrial function, inhibit MAPK pathways, and depress neuronal apoptosis.

[Cell apoptosis and the associated signal expression in epithelial cells from patients with idiopathic pulmonary fibrosis].

OBJECTIVE: To investigate the changes and significance of cell apoptosis, Fas/FasL and P53 protein in epithelial cells from patients with idiopathic pulmonary fibrosis (IPF). METHODS: Cell apoptosis and the expressions of Fas/FasL and P53 protein in lung tissues from 12 patients with IPF (IPF group) and 10 normal controls (control group) were detected by terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling (TUNEL) and immunohistochemistry. RESULTS: Compared with the control group (0/10), the percentage of apoptosis in alveolar epithelial cells and bronchial cells of the IPF group (12/12) was higher. The percentage of Fas, FasL and P53 protein expressions (12/12, 12/12, 11/12) in alveolar epithelial cells of the IPF group were higher than those of the control group (5/10, 2/10, 0/10); and the percentage of Fas, FasL and P53 protein expressions (12/12, 12/12, 11/12) in bronchial cells of the IPF group were also higher than those of the control group (6/10, 3/10, 0/10). There was a significant correlation between the percentage of apoptosis and Fas/FasL and P53 protein expression (r=0.625-0.839, all P<0.01). The correlation of the Fas/FasL and P53 protein expression was also significant (r=0.571-0.760, all P<0.01). CONCLUSION: The apoptosis percentage of epithelial cells and the expression of Fas/FasL and P53 protein are up-regulated in lung tissues of IPF, which may play an important role in the development of the disease.