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In order to solve the oxidation problem of the Ni-based solid oxide electrolysis cells (SOECs), SOECs with symmetrical electrode Sm0.5Sr0.5FeO3-δ- Gd0.1Ce0.9O2-δ (SSF-GDC) were systematically investigated, including the steam partial pressure, the working temperature, the electrolysis voltage. The reversible symmetrical cells with SSF-GDC electrode under humidified hydrogen presented good reversibility, and the maximum electrolysis current density was 1025 mA cm−2 at 800 °C with the applied voltage of 2V. In the case of direct N2 with 20% steam partial pressure as fuel, the symmetrical cells generated the maximum electrolysis current density increased from 267 to 1560 mA cm−2 at 650–800 °C. The influence of the steam partial pressure on the steam electrolysis showed that the maximum electrolysis current densities increased with the increase of the steam partial pressure from 3% to 20%, and the steam electrolysis with 3% steam partial pressure showed obvious concentration polarization due to insufficient steam partial pressure at high electrolysis current density. Finally, the short-term stability at different electrolysis voltages and long-term stability at the electrolysis voltage of 1.5V showed that there was no attenuation after 25 h operation, indicating that SSF-based symmetrical electrodes cab be an alternative to Ni-based fuel electrode materials for high-temperature steam electrolysis.

High-temperature proton-exchange membrane fuel cells (HT-PEMFCs) have shown a broad prospect of applications due to the enhanced reaction kinetics and simplified supporting system. However, the proton conductor, phosphoric acid, tends to poison the active sites of Pt, resulting in high Pt consumption. Herein, Pt nanoparticles anchored on SiO2-modified carbon nanotubes (CNT@SiO2-Pt) are prepared as high-performance cathode catalysts for HT-PEMFCs. The SiO2 in CNT@SiO2-Pt can induce the adsorption of phosphoric acid transferring from Pt active sites in the catalytic layer, avoiding the poisoning of the Pt, and the phosphate fixed by SiO2 provide a high-speed proton conduction highway for oxygen reduction reactions. Accordingly, The CNT@SiO2-Pt cathode achieve superior power density of 765 mW cm−2 (160 °C) and 1,061 mW cm−2 (220 °C) due to the rapid proton-coupled electron process and outstanding stability in HT-PEMFCs. This result provides a new road to resolve the phosphate poisoning for the commercialization of HT-PEMFCs.

Nickel hydroxide (Ni(OH)2 ) is a promising electrocatalyst for the 5-hydroxymethylfurfural oxidation reaction (HMFOR) and the dehydronated intermediates Ni(OH)O species are proved to be active sites for HMFOR. In this study, Ni(OH)2 is modified by platinum to adjust the electronic structure and the current density of HMFOR improves 8.2 times at the Pt/Ni(OH)2 electrode compared with that on Ni(OH)2 electrode. Operando methods reveal that the introduction of Pt optimized the redox property of Ni(OH)2 and accelerate the formation of Ni(OH)O during the catalytic process. Theoretical studies demonstrate that the enhanced Ni(OH)O formation kinetics originates from the reduced dehydrogenation energy of Ni(OH)2 . The product analysis and transition state simulation prove that the Pt also reduces adsorption energy of HMF with optimized adsorption behavior as Pt can act as the adsorption site of HMF. Overall, this work here provides a strategy to design an efficient and universal nickel-based catalyst for HMF electro-oxidation, which can also be extended to other Ni-based catalysts such as Ni(HCO3 )2 and NiO.

With the continuous development of nuclear energy, radioactive iodine in nuclear waste is becoming increasingly harmful to the environment and human health. Herein, we synthesized two cationic covalent organic frameworks (C-TP-PDA-COFs and C-TP-BPDA-COFs) via a post-function process for an exceptional iodine capture. Compared to that of neutral COFs, the iodine uptake capacities of cationic COFs were improved 1.3 times due to electrostatic interactions between COF networks and iodine molecules. Interestingly, C-TP-BPDA-COF possessed high-density ionic units to realize a high iodine uptake value of 6.11 g g−1, which is higher than most neutral COFs and ionic porous adsorbents. This study demonstrates an effective way to construct cationic COF materials and further employ them as scaffolds for iodine capture.

Ni–La2O3 cermet hydrogen electrode having almost no ionic conductivity still exhibits excellent electrochemical performance owing to the hydrogen spillover process from high hydrogen adsorption capability on the La2O3 surface. In this work, we develop Ni–La2O3 cermet hydrogen electrode originating from the in-situ decomposition of the La2NiO4+δ(LNO) oxide, and then perform the electrochemical properties for quasi-symmetrical solid oxide fuel cells (Q-SSOFCs), which own YSZ electrolyte support wrapped GDC barrier layer. The area specific resistance (ASR) of LNO air electrode increases from 2.09 to 7.41 Ω cm2, with the temperature of decreasing from 800 to 600 °C. The electrochemical performances of Q-SSOFCs with Ni–La2O3 cermet hydrogen electrode and LNO air electrode are characterized, and the values of the peak power density and the electrode polarization resistance (Rp) of the symmetrical electrodes measured at 800 °C are 245.18 mW cm−2 and 0.61 Ω cm2. These results indicate that the hydrogen spillover process of Ni–La2O3 cermet hydrogen electrode can greatly promote the hydrogen oxidation reaction.

Exploring highly active cathode materials with fast cathodic oxygen reduction has been considered as one of the most promising approaches to accelerate the commercialization process of intermediate temperature solid oxide fuel cells (IT -SOFCs). Herein, a highly active hybrid catalyst system with multiphase heterointerfaces consisting of (PrSr)Ni0.5Mn0.5O3-δ, PrOx nanoparticles and (PrSr)2(MnNi)O4-δ is self-assembly formed by substitution of Sr into Pr2Ni0.5Mn0.5O4-δ (S-PNM). Further using S-PNM as cathode materials for IT-SOFCs, S-PNM achieves a remarkable maximum power density of 960 mW cm−2 at 800 °C and an outstanding short-term stability with the discharge voltage of 0.68 V for 80 h. The excellent electrochemical performance by the preliminary experimental results is attributed to the coexistence of multiphase heterointerfaces of (PrSr)Ni0.5Mn0.5O3-δ, (PrSr)2(MnNi)O4-δ and PrOx nanoparticles, which can accelerate cathodic oxygen reduction.

A redox-stable perovskite oxide Sm0.5Sr0.5FeO3-δ (SSF) at reduced temperatures is investigated as a new promising electrode material for symmetric solid oxide fuel cells (SSOFCs). SSF exhibits well structural stability and catalytic activity in redox atmosphere at intermediate temperatures (≤750 °C), and the electrical conductivity exhibits a semiconductor behavior both in cathode and anode atmosphere. To enhance the electrochemical performance of SSF by adding oxygen-ion conductor Gd0.1Ce0.9O2-δ (GDC), the electrode polarization resistances at 750 °C are reduced from 2.86 to 0.67 Ω cm2 in air and from 4.32 to 0.91 Ω cm2 in humidified H2, respectively. Accordingly, the cell performance of SSOFCs with SSF-GDC composite electrode is almost twice (201.74 mW cm−2 at 750 °C) of those with the single-phase one. There preliminary experimental results demonstrate SSF-based electrode materials can be new promising candidates for SSOFCs at low temperatures.

Background Lignin is a complex aromatic heteropolymer comprising 15–30% dry weight of the lignocellulose. The complex structural characteristic of lignin renders it difficult for value-added utilization. Exploring efficient lignin-degrading microorganisms and investigating their lignin-degradation mechanisms would be beneficial for promoting lignin valorization. In this study, a newly isolated white-rot basidiomycete, Trametes hirsuta X-13, with capacity to utilize alkaline lignin as the sole substrate was investigated. Results The analysis of the fermentation properties of T. hirsuta X-13 using alkaline lignin as the sole substrate, including the mycelial growth, activities of ligninolytic enzymes and the rates of lignin degradation and decolorization confirmed its great ligninolysis capacity. The maximum lignin degradation rate reached 39.8% after 11 days of T. hirsuta X-13 treatment, which was higher than that of reported fungi under the same condition. Fourier transform infrared spectrometry (FTIR), gas chromatography–mass spectrometry (GC–MS) scanning electron micrographs (SEM), two-dimensional heteronuclear single quantum coherence NMR analysis (2D-HSQC NMR) collaborated with pyrolysis gas chromatography–mass spectrometry (py-GC/MS) analyses proved that lignin structure was severely deconstructed along with amounts of monomer aromatics generated. Furthermore, according to those chemical analysis, in addition to canonical Cα–Cβ breakage, the cleavage of lignin interunit linkages of β–β might also occur by T. hirsuta X-13. Conclusions This study characterized a newly isolated white-rot basidiomycete T. hirsuta X-13 with impressive alkaline lignin degradation ability and provided mechanistic insight into its ligninolysis mechanism, which will be valuable for the development of lignin valorization strategies.

Ethanol can induce acute stimulant responses in animals and human beings. Moreover, repeated exposure to ethanol may produce increased sensitivity to its acute locomotor stimulant actions, a process referred to as locomotor sensitization. The molecular mechanism of the development of acute stimulant responses and locomotor sensitization by ethanol is not fully understood. Sodium leak channel (NALCN) is widely expressed in central nervous system and controls the basal excitability of neurons. The present study aims to determine whether NALCN is implicated in the ethanol-induced acute responses and locomotor sensitization in mice. Here, our results showed that ethanol caused acute stimulant responses in DBA/2 mice. Locomotor sensitization was successfully induced following the sensitization procedure. Accordingly, the expression levels of NALCN mRNA and protein in the nucleus accumbens (NAc) were markedly increased in the sensitization mice compared to the control mice. Knockdown the expression levels of NALCN in the NAc alleviated both the ethanol-induced acute responses and locomotor sensitization. Our findings indicate that upregulation of NALCN expression in the NAc contributes to the ethanol-induced acute stimulant responses and locomotor sensitization in DBA/2 mice.

The electrooxidation of 5-hydroxymethylfurfural (HMF) offers a promising green route to attain high-value chemicals from biomass. The HMF electrooxidation reaction (HMFOR) is a complicated process involving the combined adsorption and coupling of organic molecules and OH- on the electrode surface. An in-depth understanding of these cooperative adsorption behaviors and reaction processes is fundamentally essential. Herein, the adsorption behavior of HMF and OH-, and the role of oxygen vacancy on Co3O4 are initially unraveled. Correspondingly, instead of the competitive adsorption of OH- and HMF on the metal sites, it is observed that the OH- could fill into oxygen vacancy (Vo) before couple with organic molecules through the lattice oxygen oxidation reaction process, which could accelerate the rate-determining step of the dehydrogenation of 5-hydroxymethyl-2-furancarboxylic acid (HMFCA) and enhance the overall conversion of HMF on Vo-Co3O4. This work sheds a depth insight on the catalytic mechanism of oxygen vacancy, which benefits designing a novel strategy to modulate the multi-molecules combined adsorption behaviors.

Highly active triple-conducting (proton-, oxygen-ion-, and electron-conducting) perovskite oxide BaCo0.4Fe0.4Zr0.1Y0.1O3-δ need to further optimize the electrochemical performance and chemical stability in carbon dioxide and water containing atmospheres, greatly limiting its widespread use in protonic ceramics fuel cells (PCFCs). Here, Ba-site deficient Ba0.9Co0.4Fe0.4Zr0.1Y0.1O3-δ (B9CFZY) was synthesized and investigated as a promising candidate concerning the chemical and structural stability, electrical conductivity and electrochemical performance. Anode-supported button cells with the prevalent BaZr0.1Ce0.7Y0.2O3-δ (BZCY) as electrolyte using B9CFZY and B9CFZY-BZCY cathodes, respectively, were fabricated and then measured at 700-550 °C. The maximum power density of the cells with B9CFZY-based cathodes increase from 452 mW cm−2 to 537 mW cm−2 at 700 °C, however, the corresponding polarization loss decreases from 0.30 to 0.15 Ω cm2 by adding proton-conducting BZCY. Importantly, to better explore the reasons for the improved electrochemical performance, the distribution function of relaxation time (DRT) is used to distinguish different electrode polarization processes of both cells. The results indicate the polarization peaks (P3) of cells with composite cathode resulting from oxygen gas adsorption and dissociation can be greatly accelerated as well as the polarization peaks (P2) resulting from oxygen species diffusion to three phase boundaries or active sites in the cathode. The dramatic improvements demonstrate Ba deficient B9CFZY-BZCY material can be a very competitive cathode material for PCFCs.

Improvements to the degradation of NO by photocatalysts requires enhanced oxidation activity. In this work, the heterostructural photocatalyst BiOBr0.5I0.5/BiOBr/BiOI was prepared and showed enhanced photocatalytic efficiency for the removal of NO. We examined the photocatalytic removal of NO and confirmed that the improved efficiency of NO removal in our systems was due to the synergic effect of enhanced carrier and exciton photocatalysis. The superoxide and singlet oxygen generated from these two processes lead to the highly efficient removal of NO. Meanwhile, the photocatalytic NO removal mechanism of BiOBr0.5I0.5/BiOBr/BiOI was explored by in-situ FT-IR. This investigation provides a new approach to the design of efficient photocatalysts and an increased understanding of the NO removal mechanism through photocatalytic technology.

The Type VI secretion system (T6SS) is a membrane protein complex related to inter-bacterial competitions and host-pathogen interactions in Pseudomonas aeruginosa. The T6SS is regulated by a great variety of regulatory mechanisms at multiple levels, including post-translational modification with threonine phosphorylation mediated by Ser/Thr protein kinase PpkA and phosphatase PppA. The T6SS is activated by PpkA via Thr phosphorylation of Fha, and PppA can antagonize PpkA. PppA is a PP2C-family protein phosphatase and plays a key role in the disassembly and reassembly of T6SS organelles. Herein, we report the first crystal structure of PppA from Pseudomonas aeruginosa, which was determined at a resolution of 2.10 A. The overall structure consists of a bacteria PPM structural core and a flexible flap subdomain. PppA harbors a catalytic pocket containing two manganese ions which correspond to the canonical dinuclear metal center of Ser/Thr protein phosphatases including the bacterial PPM phosphatases and human PP2C. The flexibility and the diversity of the sequence of flap subdomain across the homologues might provide clues for substrates specific recognition of phosphatases.

Ceria-based solid oxide fuel cells (SOFCs) are the promising candidates for the low- and intermediate-temperature SOFCs. However, the Ce4+ in the ceria-based electrolyte materials is likely reduced to Ce3+ under low oxygen partial pressure, leading to high electronic conductivity. Therefore, ceria-based SOFCs commonly show low open-circuit voltage and low efficiency due to the leakage current. While extensive studies of the electron transport mechanism and the methods for the prevention of leakage current in ceria-based electrolytes have been conducted, systematic reviews of the relevant literature have been notably rare. In this review, the formation mechanism and factors affecting electronic conductivity in doped ceria are clearly described. Additionally, two kinds of methods including the optimization of the single ceria-doped electrolyte and the use of the various electron blocking layers (e.g., ZrO2-based, doped BaCeO3/SrCeO3 and doped Bi2O3 materials) are systematically summarized. Finally, mathematical models describing the electrochemical characteristics of ceria-based SOFCs based on different assumptions are reviewed. This review can provide useful guidance for the further development and application of internal short-circuit-free ceria-based SOFCs.

The exposure to ambient fine particulate matter (PM2.5) can induce oxidative stress, contributing to global burden of diseases. The evaluation of the oxidative potential (OP) of PM2.5 is thus critical for the health risk assessment. We collected ambient PM2.5 samples in Hangzhou city, China for four consecutive quarters in the year 2017 and investigated the oxidation property of PM2.5 components by the dithiothreitol (DTT) assay. The annual mean of ambient PM2.5 mass concentrations in 2017 was 63.05 μg m−3 (median: 57.34, range: 6.67–214.33 μg m−3) with the significant seasonal variations ranking as winter > spring > summer > autumn. Secondary inorganic aerosol (SIA) species including SO42−, NO3− and NH4+ totally account for >50% of PM2.5 mass. The annual mean volume-normalized DTT activity (DTTv) showed a relatively high value of 0.62 nmol/min/m3 (median: 0.62, range: 0.11–1.66 nmol/min/m3) and DTTv of four seasons was roughly at the same level, indicating a high annual exposure level of ambient PM2.5. SIA species were correlated well with the corresponding DTTv and showed significant diurnal variations with strong or moderate correlations at day and weak correlations at night, suggesting strong secondary formation in daytime with contribution to the particulate OP. The annual mean mass-normalized DTT activity (DTTm) had a relatively low value of 6.39 pmol/min/μg (median: 5.63, range: 1.99–22.70 pmol/min/μg), indicating low intrinsic oxidative toxicity. The DTTm of four seasons ranked as autumn > winter > spring > summer, indicating seasonal variations of the DTT-active components. The PM2.5 mass concentration is more related to exposure levels than intrinsic properties of components, while OP is determined by the components rather than PM2.5 mass concentration. Our results provide an insight into reactive oxygen species-induced health risk of PM2.5 exposure and decision for subsequent emission control.

The radical S-adenosylmethionine (SAM) superfamily is currently the largest known enzyme family. These enzymes reductively cleave SAM to produce a highly reactive 5'-deoxyadenosyl (dAdo) radical, which abstracts a hydrogen from the substrate and initiates diverse reactions. The canonic dAdo radical-mediated hydrogen abstraction can be changed to radical addition reactions by using olefin-containing substrate analogues, which result in adenosylation reactions. Here we report investigation of the adenosylation reactions catalyzed by four radical SAM l-Tyr lyases (RSTLs), including HydG, FbiC, and two ThiH enzymes from different organisms. We show RSTLs have diverse substrate specificity, and ThiH from E. coli exhibits the highest substrate tolerance toward the tested substrates. We also show ThiH from Clostridium berjerinckii does not act on 4-amino-l-phenylalanine, but catalyzes adenosylation of the corresponding olefin-containing analogue, suggesting adenosylation may occur more easily than the canonic radical SAM reactions. Our study highlights the remarkable catalytic promiscuity of radical SAM enzyme and the potential in using these enzymes for the synthesis of nucleotide-containing compounds.

Naringenin (NAR) is a natural flavonoid which exerts extensive biological activity, including anti-oxidation, anti-inflammation, anti-cancer, immune regulation and so on. However, the effect and mechanism of NAR in the alveolar bone regeneration are still unclear, which limits its clinical use. Hence, we investigated the effects of NAR in the proliferation, osteogenic and endothelial differentiation of human periodontal ligament stem cells (hPDLSCs) and explore the possible mechanism. The results showed that the proper concentrations (100 nM–10 μM) of NAR can promote the proliferation rate, osteogenic and endothelial differentiation of hPDLSCs. And the 1 μM NAR had the best proliferation promoting effect, while the 10 μM NAR had the best ability of promoting osteogenic and endothelial differentiation. NAR also promoted the mRNA expression of SDF-1 in a concentration dependent manner in PDLSCs. After adding the selective CXCR4 antagonist AMD3100, the osteogenic effect of NAR on PDLSCs is slightly enhanced, while the endothelial differentiation effect of NAR on hPDLSCs is attenuated. In summary, these results indicated that NAR promoted the proliferation of hPDLSCs, and promoted endothelial differentiation of hPDLSCs via SDF-1 to activate SDF-1/CXCR4 signaling pathway. However, the mechanism of which SDF-1 related signaling pathway is activated by NAR to enhance the osteogenic differentiation of hPDLSCs still needs to be investigated.

Background Depressive patients show less altruistic behavior. While, older adults present higher tendencies for altruism than younger adults. Depression and age are two of the influencing factors of altruism, kynurenine (KYN), and its metabolites. However, the characteristics of altruism in late-life depression (LLD) and its possible underlying mechanism have not been studied. Objective We aimed to explore the characteristics of altruism in LLD patients and its neurobiological mechanism and structural brain network. We investigated whether the levels of metabolites in kynurenine pathway (KP) and white matter (WM) network topological features would influence the altruistic behavior in LLD patients. Methods Thirty-four LLD patients and 36 heathy controls (HCs) were included. Altruism was evaluated by the Dictator Game (DG) paradigm. Serum concentrations of KP metabolites were detected by the liquid chromatography-tandem mass spectrometry method. The topological features of the WM network were calculated from diffusion tensor imaging data in conjunction with graph-theoretical analysis. Results The LLD participants exhibited a higher level of altruism and WM global network properties than the HCs. Kynurenic acid to kynurenine (KYNA/KYN) ratio was associated with the DG performance in LLD group. KYNA/KYN ratio was associated with the WM network properties in HC group. Conclusions KYN metabolism played an important role in altruistic behavior in LLD.

Injectable hydrogels with pH-sensitive and self-healing properties have great application potential in the field of anti-cancer drug carriers. In this work, an injectable hydrogel is prepared using 4armPEG-benzaldehyde (4armPEGDA) and N-carboxyethyl chitosan (CEC) as a new drug carrier. The gelation time, equilibrium swelling rate, degradation time, and dynamic modulus of the injectable hydrogels can be adjusted by merely changing the concentration of 4armPEGDA. The volume of the hydrogel shrinks at pH 5.6 and expands at pH 7.4, which helps to control the release of anti-cancer drug. At pH 5.6, the hydrogels show a fast and substantial Dox release effect, which is five times higher than that at pH 7.4. In vitro cumulative drug release of all the hydrogels reached equilibrium on about the fourth day, and the hydrogel is completely degraded within five days, which contributes to the Dox-loaded hydrogel to further release the remaining Dox. Moreover, the Dox-loaded hydrogel shows a strong inhibitory effect on the growth of human hepatocellular carcinoma cells (HepG2). Finally, the anti-tumor model experiment in vivo demonstrated that the Dox-loaded hydrogel can significantly inhibit tumor growth within five days. Therefore, such injectable hydrogels are excellent carriers for the potential treatment of hepatocellular carcinoma.

Present study prepared curcumin-loaded nanoliposomes using bovine milk, krill phospholipids and cholesterol; and investigated the effects of cholesterol on membrane characteristics, storage stability and antibacterial properties of the curcumin nanoliposomes. Bovine milk phospholipids which have higher saturation than krill phospholipids resulted in formation of curcumin-loaded nanoliposomes with higher encapsulation efficiency (84.78%), larger absolute value of zeta potential and vesicle size (size: 159.15 ± 5.27 nm, zeta potential: −28.3 ± 0.62 mV). Cholesterol helps to formation of a more hydrophobic, compact and tighter bilayer membrane structure which improved the storage stability of nanoliposomes under alkaline (66.25 ± 0.46%), heat (43.25 ± 0.69%) and sunlight (49.44 ± 1.78%) conditions. In addition, curcumin-loaded nanoliposomes can effectively target infectious bacteria which secrete pore-forming toxins such as Staphylococcus aureus by causing the bacterial cell wall to lysis. Findings from present work can guide future development of novel antibacterial agents for use in food preservation.

Insulin-degrading enzyme (IDE) plays a critical role in both the proteolytic degradation and inactivation of insulin. The exploration of novel IDE inhibitors could aid in the study of novel therapeutics for type-2 diabetes. Herein, we report a hypothesized stabilized β-hairpin peptide that can efficiently inhibit the enzymatic activity of IDE. The resulting stabilized peptide B35 is demonstrated to activate the AKT phosphorylation pathway in skeletal muscle cells and is shown to slow insulin degradation. An 80 mg kg–1 intraperitoneal (i.p.) injection of the stabilized β-hairpin peptide B35 is demonstrated to improve glucose tolerance during an oral glucose tolerance test in obese mouse model. We note that this stabilized peptide exhibited negligible cytotoxicity in both in vitro and in vivo assays, even at high concentrations (300 μM). This study suggests that IDE peptide inhibitors could function as potentially meaningful candidates for the development of type-2 diabetes therapeutics.

Uniform close-packed superlattice self-assembled from colloidal nanocrystals usually exhibit different chemical and physical properties compared with the homologous bulk materials. Herein, c-oriented NiFe-LDH films (NiFe-LDH-F) and Ni(OH)2 films (Ni(OH)2-F) were successfully fabricated by a colloid self-assembly method. The electrocatalytic oxidation properties of the resulting c-oriented NiFe-LDH-F and Ni(OH)2-F were studied towards the oxygen evolution reaction (OER) and the ethanol electrooxidation reaction (EOR), respectively. Due to orderly stacking c-oriented superlattices, the NiFe-LDH-F and Ni(OH)2-F both showed high proton diffusion coefficients, which significantly improved the electrocatalytic activities. The NiFe-LDH-F on the glassy carbon electrode showed an excellent OER electrocatalytic activity with a small overpotential of 220 mV at 10 mA cm−2 and a low Tafel slope of 53.3 mV dec−1. The Ni(OH)2-F showed a superior EOR performance without obvious passivation. This study may open up a new insight into designing efficient and robust materials for superior electrocatalysis..

Thanks to their large binding interfaces, peptides are attractive ligands targeting protein-protein interactions compared with small molecules. Various strategies to improve peptides' pharmaceutical properties have been developed to constrain peptides into their functional three-dimensional structures. In our previous work, we reported that an in-tether chiral center could modulate peptides' biophysical properties. Herein, we applied this concept to construct a chiral sulfoxide center into the N-terminal end-cap system. We proved that this in-tether sulfoxide chiral center influences the structure of this N-capped template. In addition, longer peptides targeting estrogen receptor were also synthesized and we revealed that this chiral center could also modulate binding affinity to estrogen receptor alpha with enhanced protease resistance.

Although our recent study indicated that imidacloprid, a widely used neonicotinoid insecticide, inhibited IgE-mediated rat mast cell RBL-2H3 activation, little information is available on the relationship between imidacloprid and IgE-mediated human mast cell activation, and the inhibition mechanism still remains unclear. In the present work, the IgE-sensitized RBL-2H3 cells and human basophilic cell KU812 were incubated with imidacloprid or methyllycaconitine (MLA, the antagonist of α7-nAChRs) prior to the treatment of imidacloprid, followed by challenging the cells with dinitrophenyl–human serum albumin and β-lactoglobulin, respectively. The allergic mediator release, Ca2+ influx in cells, cPLA2 activity, the phosphorylation contents of PLC-γ and NF-κB in FceRI signaling pathway were tested. The results indicated that imidacloprid could suppress the production of allergic mediators, Ca2+ mobilization, cPLA2 activity and the expression of the phosphorylated antibodies of PLC-γ and NF-κB in the RBL-2H3 and KU812 cells. Moreover, an IgE-dependent passive cutaneous anaphylaxis model was used to determine whether α7-nAChRs involved the suppressive effects of imidacloprid in vivo. It was shown that MLA alleviated the imidacloprid-induced inhibition on the absorbance value of vascular extravasation in mice. It is the first time it has been demonstrated that α7-nAChRs involve the inhibitory effects of imidacloprid on the IgE-mediated activation of mast cells.

Celiac disease (CD) is a T cell-mediated enteropathy of the small intestine and caused by the ingestion of wheat gluten and related prolamins in barley and rye. However, there is no effective therapy to alleviate symptoms of celiac disease except for a life-long gluten-free diet. Recent studies showed that modification by microbial transglutaminase (mTG) could reduce the gliadin-specific immune response. In the present study, different acyl-acceptor substrates in combination with mTG were used to modify the model 33-mer peptide (LQLQPFPQPQLPYPQPQLPYPQPQLPYPQPQPF), which is a particular celiac toxic α-gliadin peptide. RP-HPLC and LC-ESI-MS were performed to test the extent of the modifications. R5 ELISA and G12 ELISA were used to analyze the antigenicity of the modified peptide. The shifts of retention time and molecular weight showed great modification of 33-mer peptide after 2 h of incubation with mTG. When acyl-acceptor substrates were crosslinked with 33-mer peptide, the antigenicity of modified peptide forms was decreased compared to its initial level. In summary, it is demonstrated that mTG is active on a variety of chemically acyl-acceptor substrates. Transamidation by mTG with an appropriate amine donor can be used to block the antigenicity of gliadin peptide related to celiac disease. These findings highlight a potential strategy to prevent cereal toxicity in celiac disease.

Summary Tyrosine kinase receptor of insulin-like growth factor 1 receptor (IGF-1R) and insulin receptor (IR) bind to hormones, such as insulin, IGF-1, and IGF-2, and transduces the signals across the cell membrane. However, the complete structure of the receptor and the signal transduction mechanism remains unclear. Here, we report the cryo-EM structure of the ligand-bound ectodomain in the full-length human IGF-1R. We reconstructed the IGF-1R/insulin complex at 4.7 A and the IGF-1R/IGF-1 complex at 7.7 A. Our structures reveal that only one insulin or one IGF-1 molecule binds to and activates the full-length human IGF-1R receptor.

The mechanical and biodegradable properties of hydrogels are two essential properties for practical biomaterial applications. In this work, a series of biodegradable polyurethane (PU) hydrogels were successfully synthesized using two kinds of triol crosslinkers with different chain structures. One crosslinker is normal glycerol (GC) with short chain length, and the other is biodegradable poly (e-caprolactone)-triol (CAPA) with long chain length. All PU hydrogels showed considerable water uptake around ~60%, excellent strength (above 3 MPa), advisable modulus (0.9~1.7 MPa), high elasticity (above 700%), as well as good biodegradability and biocompatibility. Hydrogen bonds served as reversible sacrificial bonds in the PU hydrogels endow them good toughness with partial hysteresis during deformation. The biodegradable long chain crosslinker CAPA can certainly accelerate the degradation of PU hydrogels compared with the GC crosslinked hydrogels. The degradation of these hydrogels was a process of continuous erosion from the surface to interior, which contributes to the high remain of mechanical properties after 30 days-degradation. Besides, the hydrogels also show excellent antifouling ability of protein and anti-adhesion of cells. Therefore, these hydrogels suggest great potential used as biological anti-adhesive membranes or catheters.

Heteroatom doping has been demonstrated to be an effective strategy for improving the performance of catalysts. In this paper, cobalt carbon catalysts co-doped with nitrogen and sulfur (N and S) were synthesized through a hydrothermal method with chelate composites involving melamine, thioglycolic acid (C2H4O2S), and tetrahydrate cobalt acetate (Co(OAc)2·4H2O). In addition, the selective oxidation of ethylbenzene under solvent-free conditions with molecular oxygen was used as a probe reaction to evaluate the activity of the catalysts. The optimized catalyst shows an ethylbenzene conversion of 48% with an acetophenone selectivity of 85%. Furthermore, the catalysts were systematically characterized by techniques such as TEM, SEM, XRD, Raman, and XPS. The results reveal that the species of cobalt sulfides and synergistic effects between N and S has inserted a key influence on their catalytic performance.

In view of the high catalytic activity, enhanced oxygen-ion transport and good stability, the self-assembled hybrid electrocatalyst can be used for symmetrical and reversible solid oxide cells (RSOCs). Herein, a new Ni-free ceramic fuel electrode can be obtained by in situ annealing the orthorhombic perovskite Pr0.6Sr0.4FeO3-δ (PSF) in H2 at 850 °C for 2 h, consisting of orthorhombic perovskite matrix with nano Ruddlesden–Popper oxide (RP/O-PSF). Symmetrical RSOCs consisting of RP/O-PSF fuel electrode, La0.9Sr0.1Ga0.8Mg0.2O3-δ (LSGM) electrolyte and PSF air electrode (PSF|LSGM|PSF) were fabricated and the electrochemical performance was evaluated. The maximum power density of the cell under solid oxide fuel cell (SOFC) mode is 591 mW/cm2 at 800 °C, and the current density of the cell under solid oxide electrolysis cell (SOEC) mode is -1388 mA/cm2 at 800 °C with an applied electrolysis voltage of 1.6 V. The polarization resistances of cell under SOFC mode and SOEC mode are 0.152 Ω cm2 (OCV-0.2 V) and 0.126 Ω cm2 (OCV + 0.2 V), respectively, demonstrating an excellent catalytic activity of RP/O-PSF towards the water electrolysis process compared with hydrogen oxidation reaction (HOR) owing to the accelerated transfer rate of oxygen ions. In addition, the desirable long-term stability indicates the fact that RP/O-PSF hybrid electrode is such a suitable and prospective candidate for symmetrical and reversible solid oxide cells.

Present study prepared curcumin liposomes with high encapsulation efficiency (>70%) using bovine milk and krill phospholipids; and investigated the effects of phospholipids composition on storage stability, in-vitro bioavailability, antioxidative and anti-hyperglycemic properties of the curcumin liposomes. Curcumin liposomes prepared from bovine milk phospholipids have smaller particle sizes (163.1 ± 6.42 nm) and greater negative zeta potentials (−26.7 mv) as compared to that prepared from krill phospholipids (particle size: 212.2 ± 4.1 nm, zeta potential: −15.23 mv). In addition, curcumin liposomes from bovine milk phospholipids demonstrated better stability under harsh storage conditions (alkaline conditions, oxygen, high temperature and relative humidity). Nevertheless, curcumin-loaded liposomes prepared from bovine milk phospholipids have inferior bioavailability compared to that prepared from krill phospholipids. No significant differences can be observed in terms of anti-oxidative and anti-hyperglycemic properties of liposomes prepared from both bovine milk and krill phospholipids. Findings from present study will open up new opportunities for development of stable curcumin liposomes with good functional properties (high digestibility, bioavailability and pharmacological effects).

Considering the flexible chemical composition, tunable electronic properties and unique two-dimensional structure of layered double hydroxides (LDHs), we constructed NiFe-LDH/Cu2O heterostructure photocatalysts. The photocatalytic performance of NiFe-LDH/Cu2O heterostructure photocatalysts was evaluated by methyl blue (MB) degradation and CO2 reduction under visible-light illumination. The removal efficiency of MB was improved from 20% for Cu2O and 45% for NiFe-LDH to 93% for NiFe-LDH/Cu2O after 30 min adsorption and 240 min visible-light irradiation. Moreover, CH4 yield from CO2 reduction over NiFe-LDH/Cu2O is about 5.6 and 6.9 times that of NiFe-LDH and Cu2O, respectively. Based on a detailed study of structural, electronic, optical and electrochemical properties, Z-scheme photocatalytic mechanism was proposed to explain the enhanced photocatalytic performance of NiFe-LDH/Cu2O. This work presents an inexpensive and flexible strategy for manufacturing heterostructure photocatalysts using earth-abundant elements.

Large quantity of low-concentration coal mine methane (LC-CMM) has been directly emitted to the air, causing severe greenhouse effect and energy loss. We propose to convert the pollutant gas to clean energy by the anodic electrochemical catalysis of solid oxide fuel cells. In the electrochemical conversion of oxygen-bearing LC-CMM, the Ni-based anode shows high catalytic activity and good stability without severe carbon deposition, Ni oxidation or thermal runaway. High electrochemical performance and good discharging stability were achieved with very flexible O2/CH4 ratio and low CH4 concentration. The high electric efficiency of 38.2 % with the fuel utilization of 72 % and the stable discharging for 400 h can be realized by the stacks using the LC-CMM. Accordingly, a heterogeneous kinetics and electrochemical charge-transfer model was established to study the elementary reaction mechanism of O2 in CH4 conversion and carbon removing, also showing the theoretical thresholds of coking and Ni oxidation.

Low levels of endosulfan are known to stimulate mast cells to release allergic mediators, while imidacloprid can inhibit IgE-mediated mast cell degranulation. However, little information about the effects of both pesticides together on mast cell degranulation is available. To measure the effects, IgE-activated mouse bone marrow-derived mast cells (BMMCs) were treated with imidacloprid and endosulfan, individually, and simultaneously at equi-molar concentrations in tenfold steps ranging from 10−4 to 10−11 M, followed by measuring several allergy-related parameters expressed in BMMCs: the mediator production and influx of Ca2+, the phosphorylation content of NF-κB in the FceRI signaling pathway. Then, the effects of the mixtures on IgE-induced passive systemic anaphylaxis (PSA) of BALB/c was detectded. This study clearly showed that the application of equi-molar mixtures of both pesticides with 10−4–10−5 M significantly inhibited the IgE-mediated mouse bone marrow-derived mast cells degranulation in vitro and 10−4 M of them decreased IgE-mediated PSA in vivo, as the application of imidacloprid at the same concentration alone did. Morever endosulfan alone had no remarkable stimulatory effects on any of the factors measured. In conclusion, simultaneous application of equi-molar concentrations of both pesticides generally showed highly similar responses compared to the responses to imidacloprid alone, suggesting that the effects of the mixture could be solely attributed to the effects of imidacloprid.

Our previous studies have shown that longitudinal reduction in retinal nerve fiber layer (RNFL) thickness is associated with cognitive deterioration. However, whether the combination of longitudinal reduction in RNFL thickness with baseline episodic memory performance can better predict cognitive deterioration remains unknown. Therefore, we set out to re-analyze the data obtained from our previous studies with 78 elderly adults (mean age 74.4 ± 3.83 years, 48.7% male) in the community over a 25-month period. The participants were categorized as either stable participants whose cognitive status did not change (n = 60) or converted participants whose cognitive status deteriorated (n = 18). A logistic regression analysis was applied to determine a conversion score for predicting the cognitive deterioration in the participants. We found that the area under the receiver operating characteristic curve (AUC) for the multivariable model was 0.854 (95% CI 0.762–0.947) using baseline story recall as a predictor, but the AUC increased to 0.915 (95% CI 0.849–0.981) with the addition of the longitudinal reduction of RNFL thickness in the inferior quadrant. The conversion score was significantly higher for the converted participants than the stable participants (0.59 ± 0.30 versus 0.12 ± 0.19, p < 0.001). Finally, the optimal cutoff value of the conversion score (0.134) was determined by the analysis of receiver operating characteristic curve, and this conversion score generated a sensitivity of 0.944 and a specificity of 0.767 in predicting the cognitive deterioration. These findings have established a system to perform a larger scale study to further test whether the longitudinal reduction in RNFL thickness could serve as a biomarker of Alzheimer’s disease.

© 2015 American Chemical Society. Designing tight-binding ligands is a primary objective of small-molecule drug discovery. Over the past few decades, free-energy calculations have benefited from improved force fields and sampling algorithms, as well as the advent of low-cost parallel computing. However, it has proven to be challenging to reliably achieve the level of accuracy that would be needed to guide lead optimization (5× in binding affinity) for a wide range of ligands and protein targets. Not surprisingly, widespread commercial application of free-energy simulations has been limited due to the lack of large-scale validation coupled with the technical challenges traditionally associated with running these types of calculations. Here, we report an approach that achieves an unprecedented level of accuracy across a broad range of target classes and ligands, with retrospective results encompassing 200 ligands and a wide variety of chemical perturbations, many of which involve significant changes in ligand chemical structures. In addition, we have applied the method in prospective drug discovery projects and found a significant improvement in the quality of the compounds synthesized that have been predicted to be potent. Compounds predicted to be potent by this approach have a substantial reduction in false positives relative to compounds synthesized on the basis of other computational or medicinal chemistry approaches. Furthermore, the results are consistent with those obtained from our retrospective studies, demonstrating the robustness and broad range of applicability of this approach, which can be used to drive decisions in lead optimization.

Macrocycles have been emerging as a very important drug class in the past few decades largely due to their expanded chemical diversity benefiting from advances in synthetic methods. Macrocyclization has been recognized as an effective way to restrict the conformational space of acyclic small molecule inhibitors with the hope of improving potency, selectivity, and metabolic stability. Because of their relatively larger size as compared to typical small molecule drugs and the complexity of the structures, efficient sampling of the accessible macrocycle conformational space and accurate prediction of their binding affinities to their target protein receptors poses a great challenge of central importance in computational macrocycle drug design. In this article, we present a novel method for relative binding free energy calculations between macrocycles with different ring sizes and between the macrocycles and their corresponding acyclic counterparts. We have applied the method to seven pharmaceutically interesting data sets taken from recent drug discovery projects including 33 macrocyclic ligands covering a diverse chemical space. The predicted binding free energies are in good agreement with experimental data with an overall root-mean-square error (RMSE) of 0.94 kcal/mol. This is to our knowledge the first time where the free energy of the macrocyclization of linear molecules has been directly calculated with rigorous physics-based free energy calculation methods, and we anticipate the outstanding accuracy demonstrated here across a broad range of target classes may have significant implications for macrocycle drug discovery.

Background Kynurenine pathway (KP) activation is associated with several neuropsychiatric diseases, including major depression disorder (MDD). Although several investigations have been conducted on MDD, these have seldom shed light on KP changes in late-life depression (LLD). Objective We aimed to investigate whether tryptophan (TRP) metabolism and kynurenine (KYN) metabolism are imbalanced in LLD patients and to explore the differences in KP characteristics between early onset depression (EOD) and late onset depression (LOD) patients. Methods We investigated 170 LLD patients (EOD 90, LOD 80) and 135 normal controls. Serum concentrations of TRP, KYN and kynurenic acid (KYNA) were detected by the liquid chromatography-tandem mass spectrometry method. Depressive symptoms were assessed by the 17-item Hamilton Depression Scale (HAMD-17). Results LLD patients exhibited lower levels of TRP, KYN, KYNA and KYNA/KYN ratio and a higher level of KYN/TRY ratio than normal controls. The decrease in TRP and the increase in KYN/TRP ratio were found in LOD patients. A low TRP level without increased KYN/TRP ratio was found in EOD patients. The “Depression” factor, which was extracted from HAMD-17 by the principal component factor analysis, was correlated with the TRP level and KYNA/KYN ratio in the EOD group, but no such correlation was found in the LOD group. Conclusions KP changes were observed in LLD patients; LOD patients showed profound shifts in TRP metabolism, while EOD patients showed low TRP level and a shift in KYN metabolism.

Direct inhibition of the protein–protein interaction of ERα and its endogenous coactivators with a cell permeable stabilized peptide may offer a novel, promising strategy for combating ERα positive breast cancers. Here, we report the co-crystal structure of a helical peptide stabilized by a N-terminal unnatural cross-linked aspartic acid (TD) in complex with the ERα ligand binding domain (LBD). We designed a series of peptides and peptide 6 that showed direct and high-affinity binding to ERα with selective antiproliferative activity in ERα positive breast cancer cells. The co-crystal structure of the TD-stabilized peptide 6 in complex with ERα LBD further demonstrates that it forms an α helical conformation and directly binds at the coactivator binding site of ERα. Further studies showed that peptide 6W could potently inhibit cellular ERα’s transcriptional activity. This approach demonstrates the potential of TD stabilized peptides to modulate various intracellular protein–protein interactions involved in...

The helical peptide KLA (KLAKLAKKLAKLAK) is a well-known inducer of cellular apoptosis, acting to disrupt the mitochondrial membrane. However, its weak cellular uptake impedes development of any further applications. Here, we have utilized a novel in-tether chiral center induced helicity strategy (CIH) to develop a potent apoptosis inducer based on this KLA sequence. Notably, for the two resulting epimers of the CIH-KLA peptide, the CIH-KLA-(R) epimer exhibited superior cellular uptakes and special mitochondrial targeting when compared with its S counterpart. This work provides a promising and versatile method to modify the KLA peptide and a proof-of-concept application for the CIH strategy in modifying bioactive peptides.