Single Ru Sites on Covalent Organic Framework-Coated Carbon Nanotubes for Highly Efficient Electrocatalytic Hydrogen Evolution.

Covalent organic frameworks (COFs) with precisely controllable structures and highly ordered porosity possess great potential as electrocatalysts for hydrogen evolution reaction (HER). However, the catalytic performance of pristine COFs is limited by the poor active sites and low electron transfer. Herein, to address these issues, the conductive carbon nanotubes (CNTs) are coated by a defined structure RuBpy(H2 O)(OH)Cl2 in bipyridine-based COF (TpBpy). And this composite with single site Ru incorporated can be used as HER electrocatalyst in alkaline conditions. A series of crucial issues are carefully discussed through experiments and density functional theory (DFT) calculations, such as the coordination structure of the atomically dispersion Ru ions, the catalytic mechanism of the embedded catalytic site, and the effect of COF and CNTs on the electrocatalytic properties. According to DFT calculations, the embedded single sites Ru act as catalytic sites for H2 generation. Benefitting from increasing the catalyst conductivity and the charge transfer, the as-prepared c-CNT-0.68@TpBpy-Ru shows an excellent HER overpotential of 112 mV at 10 mA cm-2 under alkaline conditions as well as an excellent durability up to 12 h, which is superior to that of most of the reported COFs electrocatalysts in alkaline solution.

Coiled-coil domain containing 159 is required for spermatid head and tail assembly in mice†.

The centrosome is critical for maintaining the sperm head-tail connection and the formation of flagellar microtubules. In this study, we found that in mouse testes, CCDC159 (coiled-coil domain-containing protein 159) is specifically localized to the head-tail coupling apparatus (HTCA) of spermatids, a structure that ensures sperm head-tail tight conjunction. CCDC159 contains a C-terminal coiled-coil domain that functions as the centrosomal localization signal. Gene knockout (KO) of Ccdc159 in mice resulted in acephalic spermatozoa, abnormal flagella, and male infertility. To explore the mechanism behind CCDC159 regulating spermatogenesis, we identified CCDC159-binding proteins using a yeast two-hybrid screen and speculated that CCDC159 participates in HTCA assembly by regulating protein phosphatase PP1 activity. Further RNA-sequencing analyses of Ccdc159 KO testes revealed numerous genes involved in male gamete generation that were downregulated. Together, our results show that CCDC159 in spermatids is a novel centrosomal protein anchoring the sperm head to the tail. Considering the limitation of KO mouse model in clarifying the biological function of CCDC159 in spermatogenesis, a gene-rescue experiment will be performed in the future.

Arsenic up-regulates PD-L1 and enhances lung tumorigenesis through activation of STAT3 in alveolar epithelial type 2 cells.

Arsenic is a carcinogen and chronic exposure to arsenic increases the risk of many cancers, including lung cancer. However, the underlying mechanism is not clear. Using A/J mice as a model, our previous animal study has shown that chronic arsenic exposure up-regulates PD-L1 on lung tumor cells which interacts with PD-1 on T cells and inhibits T cell anti-tumor function resulting in increased lung tumorigenesis. In a subsequent in vitro study, we further found that arsenic up-regulated PD-L1 by activating STAT3 at tyrosine 705 in lung epithelial cells, and inhibition of STAT3 mitigated arsenic-induced PD-L1 up-regulation. The present study aims to determine whether STAT3 regulates PD-L1 in the lung of A/J mice and the type of cells from which lung tumor develops upon arsenic exposure. For that purpose, a mouse line with STAT3 conditional knockout in alveolar type 2 (AT2) cells was developed. Our results indicate that arsenic exposure up-regulates PD-L1 in AT2 cells through activating STAT3 in A/J mice. Conditional knockout of STAT3 in AT2 cells inhibited arsenic-induced PD-L1 up-regulation and lung tumor formation. Thus, our findings reveal that STAT3 is the upstream regulator of arsenic-induced PD-L1 up-regulation in AT2 cells and the inhibition of T cell anti-tumor function in the lung, and that AT2 cells are sensitive to arsenic exposure and from which arsenic-enhanced lung tumor formation in A/J mice.

Selective Integrating Molecular Catalytic Units into Bipyridine-Based Covalent Organic Frameworks for Specific Photocatalytic Fuel Production.

Molecular metal compounds have demonstrated excellent catalytic activity and product selectivity in the H2 evolution reaction (HER) and the CO2 reduction reaction (CO2RR). The heterogenization of molecular catalysts is regarded as an effective approach to improve their applicability. In this work, the molecular catalytic units [Cp*Ir(Bpy)Cl]+ and [Ru(Bpy)(CO)2Cl2] are constructed in situ on the bipyridine sites of the covalent organic framework for photocatalytic HER and CO2RR, respectively. Inheriting the impressive performance of molecular catalysts, the functionalized TpBpy-M exhibits excellent catalytic activity and product selectivity. Under visible light irradiation, the H2 production rate of TpBpy-Ir is about 760 µmol g-1 h-1, which is 6.7 times higher than that of TpBpy without built-in catalytic sites. Also, the HCOOH production rate of TpBpy-Ru is 271 µmol g-1 h-1, with an impressive selectivity of 88%. Control experiments validated that this improvement is attributed to the incorporation of molecular catalytic units into the framework. Photoluminescence spectroscopy measurements and theoretical calculation consistently demonstrate that, under illumination, the photosensitizer [Ru(Bpy)3]Cl2 is excited and transfers electrons to the catalytic sites in TpBpy-M, which then catalyzes the reduction of H+ and CO2.

Synthesizing high performance LNMO cathode materials with porous structure by manipulating reynolds number in a microreactor.

The demand for Lithium-ion batteries (LIBs) has significantly grown in the last decade due to their extensive use electric vehicles. To further advance the commercialization of LIBs for various applications, there is a pressing need to develop electrode materials with enhanced performance. The porous microsphere morphology LiNixMn2-xO4(LNMO) is considered to be an effective material with both high energy density and excellent rate performance. Nevertheless, LNMO synthesis technology still has problem such as long reaction time, high energy consumption and environmental pollution. Herein, LNMO microsphere was successfully synthesized with short precursors reaction time (18 s) at 40 °C without using chelating agent by microreaction technology combined solid-state lithiation. The optimized LNMO cathode shows microsphere (∼8µm) morphology stacked by nano primary particles, with abundant mesoporous and fully exposed low-energy plane. The electrochemical analysis indicates that the optimized LNMO cathode demonstrates 97.33% capacity retention even after 200 cycles at 1C. Additionally, the material shows a highly satisfactory discharge capacity of 92.3 mAh·g-1at 10C. Overall, microreaction technology is anticipated to offer a novel approach in the synthesis of LNMO cathode materials with excellent performance.

Anion-Coordination Foldamer-Based Polymer Network: from Molecular Spring to Elastomer.

Foldamer is a scaled-down version of coil spring, which can absorb and release energy by conformational change. Here, polymer networks with high density of molecular springs were developed by employing anion-coordination-based foldamers as the monomer. The coiling of the foldamer is controlled by oligo(urea) ligands coordinating to chloride ions; subsequently, the folding and unfolding of foldamer conformations endow the polymer network with excellent energy dissipation and toughness. The mechanical performance of the corresponding polymer networks shows a dramatic increase from P-L2UCl (non-folding), to P-L4UCl (a full turn), and then to P-L6UCl (1.5 turns), in terms of strength (2.62 MPa; 14.26 MPa; 22.93 MPa), elongation at break (70 %; 325 %; 352 %), Young's modulus (2.69 MPa; 63.61 MPa; 141.50 MPa), and toughness (1.12 MJ/m3; 21.39 MJ/m3; 49.62 MJ/m3), respectively, which is also better than those without anion centers and the non-foldamer based counterparts. Moreover, P-L6UCl shows enhanced strength and toughness than most of the molecular-spring based polymer networks. Thus, an effective strategy for designing high-performance anion-coordination-based materials is presented.

SSELM-neg: spherical search-based extreme learning machine for drug-target interaction prediction.

BACKGROUND: The experimental verification of a drug discovery process is expensive and time-consuming. Therefore, efficiently and effectively identifying drug-target interactions (DTIs) has been the focus of research. At present, many machine learning algorithms are used for predicting DTIs. The key idea is to train the classifier using an existing DTI to predict a new or unknown DTI. However, there are various challenges, such as class imbalance and the parameter optimization of many classifiers, that need to be solved before an optimal DTI model is developed. METHODS: In this study, we propose a framework called SSELM-neg for DTI prediction, in which we use a screening approach to choose high-quality negative samples and a spherical search approach to optimize the parameters of the extreme learning machine. RESULTS: The results demonstrated that the proposed technique outperformed other state-of-the-art methods in 10-fold cross-validation experiments in terms of the area under the receiver operating characteristic curve (0.986, 0.993, 0.988, and 0.969) and AUPR (0.982, 0.991, 0.982, and 0.946) for the enzyme dataset, G-protein coupled receptor dataset, ion channel dataset, and nuclear receptor dataset, respectively. CONCLUSION: The screening approach produced high-quality negative samples with the same number of positive samples, which solved the class imbalance problem. We optimized an extreme learning machine using a spherical search approach to identify DTIs. Therefore, our models performed better than other state-of-the-art methods.

Efficient Fabrication of Micro/Nanostructured Polyethylene/Carbon Nanotubes Foam with Robust Superhydrophobicity, Excellent Photothermality, and Sufficient Adaptability for All-Weather Freshwater Harvesting.

The integration of fog collection and solar-driven evaporation has great significance in addressing the challenge of the global freshwater crisis. Herein, a micro/nanostructured polyethylene/carbon nanotubes foam with interconnected open-cell structure (MN-PCG) is fabricated using an industrialized micro extrusion compression molding technology. The 3D surface micro/nanostructure provides sufficient nucleation points for tiny water droplets to harvest moisture from humid air and a fog harvesting efficiency of 1451 mg cm-2 h-1 is achieved at night. The homogeneously dispersed carbon nanotubes and the graphite oxide@carbon nanotubes coating endow the MN-PCG foam with excellent photothermal properties. Benefitting from the excellent photothermal property and sufficient steam escape channels, the MN-PCG foam attains a superior evaporation rate of 2.42 kg m-2 h-1 under 1 Sun illumination. Consequently, a daily yield of ≈35 kg m-2 is realized by the integration of fog collection and solar-driven evaporation. Moreover, the robust superhydrophobicity, acid/alkali tolerance, thermal resistance, and passive/active de-icing properties provide a guarantee for the long-term work of the MN-PCG foam during practical outdoor applications. The large-scale fabrication method for an all-weather freshwater harvester offers an excellent solution to address the global water scarcity.

Stress Induces Prolonged Pain Recovery After Surgery: Involvement of Glucocorticoid-Related Pathway.

BACKGROUND: Increasing evidence suggests that chronic stress increases pain sensitivity and exacerbates existing pain. However, whether and how chronic unpredictable stress (CUS) affects surgical pain is unclear. METHODS: A postsurgical pain model was performed by longitudinal incision from 0.3 cm of the proximal edge of the heel toward the toes. The skin was sutured, and the wound site was covered. Sham surgery groups underwent the same procedure without an incision. The short-term CUS procedure was conducted by exposure of mice to 2 different stressors each day for 7 days. The behavior tests were conducted between 9:00 am and 4:00 pm. Mice were killed on day 19, and the mouse bilateral L4/5 dorsal root ganglia, spinal cord, anterior cingulate and insular cortex, and amygdala were collected for immunoblot analyses. RESULTS: Presurgical exposure of mice to CUS every day for 1-7 days showed significant depression-like behavior as evidenced by reduced sucrose preference in the sucrose consumption test and prolonged immobility time in the forced swimming task. This short-term CUS procedure did not affect the basal nociceptive response to mechanical and cold stimuli in the Von Frey and acetone-induced allodynia tests, but it delayed pain recovery after surgery, as indicated by the prolonged hypersensitivity in mechanical and cold stimuli by 12 days. The subsequent studies demonstrated that this CUS caused an increase in adrenal gland index. The abnormalities in pain recovery and adrenal gland index after surgery were reversed by a glucocorticoid receptor (GR) antagonist RU38486. Moreover, the prolonged pain recovery after surgery induced by CUS seemed to involve an increase in GR expression and decreases in cyclic adenosine monophosphate, phosphorylated cAMP response element binding protein, and brain-derived neurotrophic factor levels in emotion-related brain regions, such as anterior cingulate and insular cortex, amygdala, dorsal horn, and dorsal root ganglion. CONCLUSIONS: This finding indicates that stress-induced GR change may result in dysfunction of GR-related neuroprotective pathway.

Diverse Reactions of α-Diimine-Ligated MgI -MgI -Bonded Compound with Carbodiimides.

The α-diimine-ligated dimagnesium(I) compound [K(thf)3 ]2 [LMg-MgL] (1, L=[(2,6-iPr2 C6 H3 )NC(Me)]2 2- ) displays diverse reactivities toward carbodiimides (RN=C=NR) with different R substituents. In the reaction of 1 with Me3 SiNCNSiMe3 , one of the easily leaving trimethylsilyl groups is lost to yield the Me3 SiNCN- moiety that either bridges two MgII centers (2) or terminally coordinated (3). In contrast, with the similarly bulky tBuNCNtBu, the carbodiimide inserts into Mg-Mg bond with accompanying C-H activation of a ligand or solvent (products 4 and 5). In the case of dicyclohexyl or diisopropyl carbodiimide, reductive C-C coupling of two RNCNR molecules occurs to form the [C2 (NR)4 ]2- diamido moiety, which bridges two Mg centers, giving complexes [{K(dme)2 }2 LMg(µ-{C2 (NR)4 })MgL] (6, R=Cy; 7, R=iPr) and [L⋅- Mg(µ-{C2 (NR)4 })MgL⋅- ] (8). Most interestingly, upon treating 1 with Me3 SiC≡CSiMe3 , the acetylide complex [K(dme)][LMg(C≡CSiMe3 )(dme)] (9) was prepared, which undergoes a rare "double insertion" with CyNCNCy to afford [K(solv)][K(dme)2 LMg(NCy)2 C-C≡C-C(NCy)2 MgL] (10) containing an acetylenediide-coupled bis(amidinate) ligand that bridges two Mg atoms.

The relationship between illness perceptions and fluid-control adherence among Chinese hemodialysis patients: a cross-sectional study.

Fluid-control adherence was important for hemodialysis (HD) patients, and while significant correlations between treatment adherence and illness perceptions have been found, there is limited research that explored the relationship between illness perceptions and fluid-control adherence. We sought to assess illness perceptions and fluid-control adherence and to explore the relationship between them among Chinese hemodialysis patients. A cross-sectional study of 253 Chinese HD patients was conducted. We recorded sociodemographic and disease characteristics, Revised Illness Perception Questionnaire (IPQ-R) responses, Fluid Control in Hemodialysis Patients Scale (FCHPS) scores and the interdialytic weight gain (IDWG). The total FCHPS score of hemodialysis patients was of a moderate level, and 45.85% hemodialysis patients' IDWG exceeded 3.0 kg. Regression analysis revealed that sex, academic level, marital status, treatment control dimension and causal (physical) factors of illness perceptions explained 12.7% variance in the total FCHPS score. Age, normalized whole-body urea clearance (Kt/V), dry weight (DW) residual urine volume (mL/24 h) and consequence dimension of illness perceptions explained 29.0% variance in IDWG. About mediating effect analysis, positive indirect effects on IDWG were found for identity, consequences and emotional representations through the attitude dimension of FCHPS, and negative indirect effects on IDWG were found for treatment control and illness coherence through the attitude dimension of FCHPS. The results demonstrated that some sociodemographic and clinical characteristics and illness perceptions were associated with fluid-control adherence, and the patient's attitude toward fluid control is an important mediator between illness perceptions and IDWG, implying that attitude can be a focus of intervention programs based on illness perceptions to improve Chinese HD patients' fluid-control adherence.

The educational quality perception, professional interest, and career choices among hospitality postgraduate students.

Brain drain has become an important issue throughout the health service sector, with gender imbalance and employment discrimination leading to an increasing number of master's graduates opting to leave the profession. To explore this issue, the study examines the impact of both internal and external factors on the employment choices of postgraduate students, which starting from the core factor of the quality of higher education and combined with the professional interest as personal factor. The study adopts the questionnaire survey method to collect questionnaire data from 338 hospitality postgraduate students in China's institutions of higher education. The study adopts Multiple Linear Regression analysis to draw the following conclusions: 1) there is a significant influence of educational quality perception on career choice, the higher the level of educational quality perception, the stronger the students' willingness to choose this field for career development; 2) there is a significant effect of professional interest on career choice, the higher the student's level of interest in the major, the greater the willingness to choose this field for career development. 3) Identity mediates the relationship between educational quality perception (and professional interest) and career choice, which means that educational quality perception and professional interest can contribute to career decisions by promoting students' identity; 4) Future work self positively moderates the relationship between identity and career choice. The clearer the students' goals for their future job development, the stronger the effect of professional identity on career choice. The research conclusions have positive implications for higher education and career guidance for postgraduate students in hospitality management.

Construction of Carbon Dots with Wavelength-Tunable Electrochemiluminescence and Enhanced Efficiency.

Tuning the electrochemiluminescence (ECL) wavelength of carbon dots (CDs) with enhanced efficiency is essential for multiplexed biosensing, bioimaging, and energy applications but remains challenging. Herein, we reported a facile route to finely modulate the ECL wavelength of CDs from 425 to 645 nm, the widest range ever reported, along with a more than 5-fold enhancement of ECL efficiency via phosphorous (P) incorporation. The molecular mechanism was explored experimentally and theoretically, which revealed the unusual dual roles of P dopants in the form of P-C and P-O bonding, that is, importing shallow trapping states and promoting an effective intramolecular charge transfer. This work would allow unlocking the key factors of ECL kinetics for heteroatom-doped CDs appearing out of reach and open a new avenue for the rational design of nanocarbon for desirable applications.

Cost-Effective Fabrication of Micro-Nanostructured Superhydrophobic Polyethylene/Graphene Foam with Self-Floating, Optical Trapping, Acid-/Alkali Resistance for Efficient Photothermal Deicing and Interfacial Evaporation.

Solar evaporation is one of the most attractive and sustainable approaches to address worldwide freshwater scarcity. Unfortunately, it is still a crucial challenge that needs to be confronted when the solar evaporator faces harsh application environments. Herein, a promising polymer molding method that combines melt blending and compression molding, namely micro extrusion compression molding, is proposed for the cost-effective fabrication of lightweight polyethylene/graphene nanosheets (PE/GNs) foam with interconnected vapor escape channels and surface micro-nanostructures. A contact angle of 155 ± 2°, a rolling angle of 5 ± 1° and reflectance of ≈1.6% in the wavelength range of 300-2500 nm appears on the micro-nanostructured PE/GNs foam surface. More interestingly, the micro-nanostructured PE/GNs foam surface can maintain a robust superhydrophobic state under dynamic impacting, high temperature and acid-/alkali solutions. These results mean that the micro-nanostructured PE/GNs foam surface possesses self-cleaning, anti-icing and photothermal deicing properties at the same time. Importantly, the foam exhibits an evaporation rate of 1.83 kg m-2 h-1 under 1 Sun illumination and excellent salt rejecting performance when it is used as a self-floating solar evaporator. The proposed method provides an ideal and industrialized approach for the mass production of solar evaporators suitable for practical application environments.

The mechanism underlying arsenic-induced PD-L1 upregulation in transformed BEAS-2B cells.

Chronic exposure to arsenic promotes lung cancer. Human studies have identified immunosuppression as a risk factor for cancer development. The immune checkpoint pathway of Programmed cell death 1 ligand (PD-L1) and its receptor (programmed cell death receptor 1, PD-1) is the most studied mechanism of immunosuppression. We have previously shown that prolonged arsenic exposure induced cell transformation of BEAS-2B cells, a human lung epithelial cell line. More recently our study further showed that arsenic induced PD-L1 up-regulation, inhibited T cell effector function, and enhanced lung tumor formation in the mice. In the current study, using arsenic-induced BEAS-2B transformation as a model system we investigated the mechanism underlying PD-L1 up-regulation by arsenic. Our data suggests that Lnc-DC, a long non-coding RNA, and signal transducer and activator of transcription 3 (STAT3) mediates PD-L1 up-regulation by arsenic.

Reactivity of Transition Metal Gallylene Complexes Toward Substrates with Multiple Carbon-Element Bonds.

Reactivity of transition metal complexes containing the redox-active gallylene (dpp-bian)Ga ligand (dpp-bian = 1,2-bis[(2,6-diisopropylphenyl)imino]acenaphthene) toward isocyanide, isocyanate, isothiocyanate, and ketene substrates is described. The reaction of [(dpp-bian)GaCr(CO)5] (1) with tBuNC results in a dative complex [(dpp-bian)Ga(CNtBu)Cr(CO)5] (2), while compound [(dpp-bian)GaCr(CO)5]2[Na(THF)2]2 (3) reacts with tBuNC to give the coordination polymer [(dpp-bian)GaCr(CO)5][Na(CNtBu)(THF)]n (5). Treatment of [(dpp-bian)GaCr(CO)5]2[Na(THF)2]2 with an excess of PhNCO results in trimerization of the latter and formation of complex [(dpp-bian)GaCr(CO)5][Na(PhNCO)3(Et2O) (DME)] (4). [(dpp-bian)GaFeCp(CO)2] (7) treated with Ph2CCO or PhNCS results in cycloaddition products [(dpp-bian)(Ph2CCO)GaFeCp(CO)2] (8) and [(dpp-bian)(PhNCS)GaFeCp(CO)2] (9). The formation of 2 and 9 was found to be reversible, which offers a means for facile regulation of transition metal center reactivity and cooperative substrate activation. New compounds were characterized by EPR (2), NMR (4, 8, and 9), and IR spectroscopy (2, 4, 5, 8, and 9). The molecular structures of 2, 4, 5, 8, and 9 were established by single-crystal X-ray diffraction analysis. Electronic structures of the compounds have been examined by DFT calculations.

ß-Amyrin ameliorates diabetic nephropathy in mice and regulates the miR-181b-5p/HMGB2 axis in high glucose-stimulated HK-2 cells.

Diabetic nephropathy (DN) is a diabetic complication that can cause renal failure. ß-amyrin has been identified to possess anti-diabetic property. This study was designed to evaluate the potential role of ß-amyrin in DN and its underlying mechanism. Streptozotocin-induced diabetic mice were used as the in vivo model, and high glucose (HG)-stimulated human proximal tubular HK-2 cells were utilized as the in vitro model. Renal histological changes in mice were assessed by hematoxylin-eosin and periodic acid-Schiff staining. HK-2 cell viability and apoptosis were detected by Cell Counting Kit-8 assay and flow cytometry analysis, respectively. ß-amyrin was found to ameliorate kidney injury in DN mice and suppressed inflammatory response as well as apoptosis of HG-stimulated HK-2 cells. miR-181-5p expression in murine renal tissues and HK-2 cells was detected by in situ hybridization (ISH) and fluorescence in situ hybridization (FISH). MiR-181b-5p, a previously identified target for diabetic kidney disease, was downregulated in renal tissues and HG stimulated HK-2 cells, and ß-amyrin induced the upregulation of miR-181b-5p. Binding relationship between miR-181b-5p and high mobility group box 2 (HMGB2) was confirmed by luciferase reporter assay. MiR-181b-5p bound to 3' untranslated region of HMGB2 to suppress its expression. As shown by immunohistochemical staining and immunofluorescence staining, HMGB2 was upregulated in the in vivo and in vitro models of DN, and ß-amyrin induced the downregulation of HMGB2. Moreover, HMGB2 overexpression neutralized the suppressive effects of miR-181b-5p elevation on the inflammatory response and apoptosis of HG-treated HK-2 cells. Overall, ß-amyrin ameliorates DN in mice and suppresses inflammatory response and apoptosis of HG-stimulated HK-2 cells via the miR-181b-5p/HMGB2 axis.

[Anti-oxidative and anti-apoptotic effects and molecular mechanisms of catalpol against H_2O_2-induced oxidative damage in pancreatic ß cells (INS-1 cells)].

The present study investigated the anti-oxidative and anti-apoptotic effects and molecular mechanisms of catalpol on the H_2O_2-induced pancreatic ß-cells(INS-1 cells).The oxidative damage model of INS-1 cells was induced and optimized by the stimulation of H_2O_2 of different concentrations for different time.CCK-8 assay was used to detect cell viability after catalpol intervention(1, 5, 10, 20, 40, 80, and 160 µmol·L~(-1)) for 24 h.Intracellular reactive oxygen species(ROS), superoxide dismutase(SOD), and lipid peroxide malondialdehyde(MDA) were measured by DCFH-DA fluorescent probe, WST-1, and TBA respectively.Moreover, the apo-ptotic effect was detected by AO-EB and Annexin V-FITC/PI staining.In addition, the protein expression levels were detected by Wes-tern blot, and intracellular insulin concentration was measured by ELISA.The results showed that the oxidative damage model of INS-1 cells was stably induced by 50 µmol·L~(-1) H_2O_2 treatment for 2 h, and catalpol at 1-80 µmol·L~(-1) did not affect cell viability of INS-1 cells.Compared with the conditions in the model group, 1, 5, and 10 µmol·L~(-1) catalpol intervention for 2 h could protect INS-1 cells from oxidative damage(P<0.001), reduce ROS and MDA, increase SOD, and inhibit excessive cell apoptosis.Moreover, 1, 5, and 10 µmol·L~(-1) catalpol could also up-regulate the phosphorylation of nuclear transcription factor NF-E2 related factors, negatively regulate Kelch-like ECH-associated protein 1(Keap1), phosphorylation of extracellular signal-regulated kinase(ERK), and heme oxyge-nase 1(HO-1), and promote the protein expression of pancreatic-duodenal homeobox factor-1(PDX-1) and glucose transporter 2(GLUT2).In addition, 1, 5, and 10 µmol·L~(-1) catalpol increased insulin secretion of INS-1 cells under oxidative damage in the high-glucose culture medium, indicating function recovery of pancreatic ß cells.PDX-1 is a key nuclear transcription factor of pancreatic ß cell function that directly regulates GLUT2 and insulin synthesis, and affects glucose homeostasis.In conclusion, catalpol can reduce the oxidative damage and apoptosis of INS-1 cells, activate antioxidant pathway, protect the function of pancreatic ß cells, and improve insulin synthesis and secretion.

Electrostatic Interactions Accelerating Water Oxidation Catalysis via Intercatalyst O-O Coupling.

Intercatalyst coupling has been widely applied in the functional mimics for binuclear synergy in natural metal enzymes. Herein, we introduce two facile and effective design strategies, which facilitate the coupling of two catalytic units via electrostatic interactions. The first system is based on a catalyst molecule functionalized with both a positively charged and a negatively charged group in the structure being able to pair with each other in an antiparallel manner arranged by electrostatic interactions. The other system consists of a mixture of two different of catalysts modified with either positively or negatively charged groups to generate intermolecular electrostatic interactions. Applying these designs to Ru(bda) (H2bda = 2,2'-bipyridine-6,6'-dicarboxylic acid) water-oxidation catalysts improved the catalytic performance by more than an order of magnitude. The intermolecular electrostatic interactions in these two systems were fully identified by 1H NMR, TEM, SAXS, and electrical conductivity experiments. Molecular dynamics simulations further verified that electrostatic interactions contribute to the formation of prereactive dimers, which were found to play a key role in dramatically improving the catalytic performance. The successful strategies demonstrated here can be used in designing other intercatalyst coupling systems for activation and formation of small molecules and organic synthesis.

Involvement of the BNP/NPR-A/BKCa pathway in rat trigeminal ganglia following chronic constriction injury.

Accumulating evidence indicates that the brain natriuretic peptide (BNP) and its receptor (natriuretic peptide receptor, NPR) are widely distributed in a variety of tissues including trigeminal ganglion (TG). Furthermore, recent studies support the involvement of the BNP-NPR-A pathway in acute and chronic pain. To investigate the role of this pathway in chronic pain, an infraorbital nerve-chronic constriction injury (ION-CCI) model of trigeminal neuralgia (TN) was produced in the rat. The time course of changes in mechanical pain threshold was examined. We observed an upregulation of BNP and NPR-A and a downregulation of large-conductance Ca2+-activated K+ (BKCa) mRNA and protein in rats subjected to ION-CCI. Patch clamping experiments in vitro found that BKCa currents were significantly reduced in rats subjected to ION-CCI. BNP increased BKCa currents in ION-CCI rats. These results suggest that BNP and NPR-A might serve as endogenous pain relievers in ION-CCI rats. Modulation of the BNP/NPR-A/BKCa channel pathway in TG may be a viable strategy for the treatment of TN.NEW & NOTEWORTHY BNP has been known to activate its receptor, NPR-A, to modulate inflammatory pain. However, the potential modulatory roles of BNP in TN have not been investigated in detail. We established an ION-CCI model of TN in the rat and observed an upregulation of BNP and NPR-A and a downregulation of BKCa in rats subjected to ION-CCI. Moreover, BNP can increase BKCa currents in ION-CCI rats. Thus, BNP and NPR-A might have inhibitory effects on trigeminal neuralgia through activating the BNP/NPR-A/BKCa channel pathway.