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CYP76AH1 is the key enzyme in the biosynthesis pathway of tanshinones in Salvia miltiorrhiza, which are famous natural products with activities against various heart diseases and others. CYP76AH1 is a membrane-associated typical plant class II cytochrome P450 enzyme and its catalytic mechanism has not to be clearly elucidated. Structural determination of eukaryotic P450 enzymes is extremely challenging. Recently, we solved the crystal structures of CYP76AH1 and CYP76AH1 in complex with its natural substrate miltiradiene. The structure of CYP76AH1 complexed with miltiradiene is the first plant cytochrome P450 structure in complex with natural substrate. The studies revealed a unique array pattern of amino acid residues, which may play an important role in orienting and stabilizing the substrate for catalysis. This work would provide structural insights into CYP76AH1 and related P450s and the basis to efficiently improve tanshinone production by synthetic biology techniques.

Persistent cardiac Ca2+/calmodulin‐dependent Kinase II (CaMKII) activation was considered to promote heart failure (HF) development, some studies believed that CaMKII was a target for therapy of HF. However, CaMKII was an important mediator for the ischaemia‐induced coronary angiogenesis, and new evidence confirmed that angiogenesis inhibited cardiac remodelling and improved heart function, and some conditions which impaired angiogenesis aggravated ventricular remodelling. This study aimed to investigate the roles and the underlying mechanisms of CaMKII inhibitor in cardiac remodelling. First, we induced cardiac remodelling rat model by ISO, pre‐treated by CaMKII inhibitor KN‐93, evaluated heart function by echocardiography measurements, and performed HE staining, Masson staining, Tunel staining, Western blot and RT‐PCR to test cardiac remodelling and myocardial microvessel density; we also observed ultrastructure of cardiac tissue with transmission electron microscope. Second, we cultured HUVECs, pre‐treated by ISO and KN‐93, detected cell proliferation, migration, tubule formation and apoptosis, and carried out Western blot to determine the expression of NOX2, NOX4, VEGF, VEGFR2, p‐VEGFR2 and STAT3; mtROS level was also measured. In vivo, we found KN‐93 severely reduced myocardial microvessel density, caused apoptosis of vascular endothelial cells, enhanced cardiac hypertrophy, myocardial apoptosis, collagen deposition, aggravated the deterioration of myocardial ultrastructure and heart function. In vitro, KN‐93 inhibited HUVECs proliferation, migration and tubule formation, and promoted apoptosis of HUVECs. The expression of NOX2, NOX4, p‐VEGFR2 and STAT3 were down‐regulated by KN‐93; mtROS level was severely reduced by KN‐93. We concluded that KN‐93 impaired angiogenesis and aggravated cardiac remodelling and heart failure via inhibiting NOX2/mtROS/p‐VEGFR2 and STAT3 pathways.

The dry reforming of methane (DRM) reaction is an attractive approach to convert two greenhouse gases into valuable syngas. However, the DRM reaction remains a great challenge due to catalyst deact...

Cellular senescence is a key mechanism of age-related vascular endothelial dysfunction. Interleukin-17A (IL-17A) is an inflammatory cytokine produced by Th17 cells (a subgroup of helper T cells), which is a key factor in the development of atherosclerosis. However, the effect of IL-17A on the senescence of vascular endothelial cells is still unclear. In this study, we aimed to explore the role of IL-17A on endothelial cell senescence and its signaling pathways associated with senescence. The proportion of Th17 cells in the spleen and the expression levels of IL-17A, IL-6, and vascular cell adhesion molecule-1 (VCAM-1) in mice of different ages were increased with aging. In vitro experiments showed that proliferation was inhibited, senescent β-galactosidase and senescence-associated proteins (p16, p19, p21, and p53) of mouse aortic endothelial cells (MAECs) were increased with IL-17A treatment. Blocking the NF-κB pathway with ammonium pyrrolidinedithiocarbamate (PDTC) successfully inhibited IL-17A-induced expression of senescence-associated proteins. In conclusion, our data reveal a previously unsuspected link between IL-17A and endothelial cell senescence, which was mediated by the NF-κB /p53/Rb pathway. Cellular senescence is a key mechanism of age-related vascular endothelial dysfunction. The authors explored the role of IL-17A on endothelial cell senescence and its associated signaling pathways. Their data reveals a previously unsuspected link between IL-17A and endothelial cell senescence, mediated by the NF-κB /p53/Rb signaling pathway.

Carotenoids are important natural pigments that give bright colors to plants. The difference in the accumulation of carotenoids is one of the key factors in the formation of various colors in carrot taproots. Carotenoid cleavage dioxygenases (CCDs), including CCD and nine-cis epoxycarotenoid dioxygenase (NCED), are the main enzymes involved in the cleavage of carotenoids in plants. Seven CCD genes have been annotated from the carrot genome. In this study, through expression analysis, we found that the expression level of DcCCD4 was significantly higher in the taproot of white carrot (low carotenoid content) than orange carrot (high carotenoid content). The overexpression of DcCCD4 in orange carrots caused the taproot color to be pale yellow, and the contents of α-carotene and s-carotene decreased sharply. Mutant carrot with loss of DcCCD4 function exhibited yellow color (the taproot of the control carrot was white). The accumulation of s-carotene was also detected in taproot. Functional analysis of the DcCCD4 enzyme in vitro showed that it was able to cleave α-carotene and s-carotene at the 9, 10 (9', 10') double bonds. In addition, the number of colored chromoplasts in the taproot cells of transgenic carrots overexpressing DcCCD4 was significantly reduced compared with that in normal orange carrots. Results demonstrated that DcCCD4 affects the accumulation of carotenoids through cleavage of α-carotene and s-carotene in carrot taproot.

A base-free catalytic system for the aerobic oxidation of 5-hydroxymethyl-2-furfural was exploited by using Pt nanoparticles immobilized onto a thermoresponsive poly(acrylamide-co-acrylonitrile)-b-poly(N-vinylimidazole) block copolymer, with an upper critical solution temperature of about 45 °C. The Pt nanocatalysts were well-dispersed and highly active for the base-free oxidation of 5-hydroxymethyl-2-furfural by molecular oxygen in water, affording high yields of 2,5-furandicarboxylic acid (up to >99.9%). The imidazole groups in the block copolymer were conducive to the improvement of catalytic performance. Moreover, the catalysts could be easily separated and recovered based on their thermosensitivity by cooling the reaction system below the upper critical solution temperature. Good stability and reusability were observed over these copolymer-immobilized catalysts with no obvious decrease in catalytic activity in the five consecutive cycles.

Background Carrot (Daucus carota L.), an important root vegetable, is very popular among consumers as its taproot is rich in various nutrients. Abiotic stresses, such as drought, salt, and low temperature, are the main factors that restrict the growth and development of carrots. Non-heme carotene hydroxylase (BCH) is a key regulatory enzyme in the β-branch of the carotenoid biosynthesis pathway, upstream of the abscisic acid (ABA) synthesis pathway. Results In this study, we characterized a carrot BCH encoding gene, DcBCH1. The expression of DcBCH1 was induced by drought treatment. The overexpression of DcBCH1 in Arabidopsis thaliana resulted in enhanced tolerance to drought, as demonstrated by higher antioxidant capacity and lower malondialdehyde content after drought treatment. Under drought stress, the endogenous ABA level in transgenic A. thaliana was higher than that in wild-type (WT) plants. Additionally, the contents of lutein and β-carotene in transgenic A. thaliana were lower than those in WT, whereas the expression levels of most endogenous carotenogenic genes were significantly increased after drought treatment. Conclusions DcBCH1 can increase the antioxidant capacity and promote endogenous ABA levels of plants by regulating the synthesis rate of carotenoids, thereby regulating the drought resistance of plants. These results will help to provide potential candidate genes for plant drought tolerance breeding.

A new Cs-γ-CD-MOF material obtained in colourless large crystals and with a three-dimensional porous structure containing coordinated by cesium ions and γ-cyclodextrin was synthesised by an improved vapour diffusion method. The chemical formula of the Cs-γ-CD-MOF material was C24H34CsO20, with the I4 space group. Compared with the traditional solvent vapour diffusion method (7 days), this method is advantageous for rapid crystal formation (1 day). Simultaneously, the drug adsortion capacity of γ-CD and Cs-γ-CD-MOFs for myricetin was compared and the results indicated that Cs-γ-CD-MOFs (280.05 mg g−1) have a higher drug adsorption capacity than γ-CD (142.92 mg g−1). Finally, the energy and conformation of the Cs-γ-CD-MOF material for adsorbing the drug myricetin were obtained through molecular docking.

A copper-catalyzed C-3 functionalization of imidazo[1,2-a]pyridines with 3-indoleacetic acids through an aerobic oxidative decarboxylative process has been developed. The protocol provided a series of 3-(1H-indol-3-ylmethyl)-imidazo[1,2-a]pyridines in moderate to good yields under simple reaction conditions. Importantly, some products exhibited potent antiproliferative activity in cancer cell lines.

Controllable ternary Pt–Cu–Mn lamellar oxides with different amounts of Pt were synthesized using a facile and expeditious self-propagating flaming technique for catalytic oxidation of toluene. The surface structure, composition, and structure–performance relationship were investigated by combining X-ray diffraction (XRD), Brunauer–Emmett–Teller (BET) surface area, scanning electron microscopy (SEM), transmission electron microscopy (TEM), hydrogen temperature-programmed reduction (H2-TPR), and X-ray photoelectron spectroscopy (XPS). The catalytic performance of the as-produced catalysts toward the catalytic oxidation of toluene was investigated. Among the catalysts, the 0.5Pt-MnCu catalyst has shown 90% toluene removal at 228 °C with excellent cyclic stability, which is a significant achievement for MnCu binary nanosheet-like catalysts containing low amounts of Pt (0.5 wt %). This study has also inferred the degradation activity of modulated MnCu composite catalysts, which greatly hinges on the doping level of Pt. The lattice oxygen species are dominating according to the Mn–O bond strength, local environment, and reducibility. Moreover, Pt can increase the covalency of surface metal–oxygen bonds and electron affinity of surface metal-coordinated oxygen centers, thereby expediting the adsorption/activation of the gaseous oxygen molecules on oxide surfaces, which can step up the lattice oxygen as well as oxygen vacancy-involved reactions to invoke the Mars–van Krevelen and Langmuir–Hinshelwood mechanisms for boosting the overall toluene oxidation performance of PtCuMnOx catalytic materials. Based on the obtained results, this study proposes a vital insight into manipulating the nanoscale catalytic functions, which could also promise pivotal potential toward engineering the state-of-the-art transition-metal nanostructure for environmental catalysis.

Although phosphate rock has been considered as a potential new rare earth elements (REEs) resource, the recovery of REEs from phosphate rock is impeded by technical challenges and cost issues. This study investigated the effects of operation conditions on the leaching efficiencies of REEs and phosphorus from Zhijin phosphate ore, a large phosphate deposit in China. The leaching process overtime was also studied by chemical analysis, scanning electron microscope with energy dispersive spectroscopy (SEM-EDS), and X-ray diffraction (XRD). The results indicated that the REEs from Zhijin phosphate ore were mainly present in fluorapatite and dolomite, and REEs had similar trends of leaching efficiency to those of phosphorus and magnesium. Under the conditions of 25 wt% phosphoric acid concentration in the initial pulp, a weight ratio of liquid to solid of 12 mL/g, a temperature of 60°C, an agitation speed of 220 rpm, and leaching time of 120 min, REEs and phosphorus leaching efficiencies of 97.8% and 99.7% were obtained. Most parts of dissoluble substances were decomposed within 30 min. Chemical analysis, SEM-EDS, and XRD results indicated that leaching efficiencies of minerals in Zhijin phosphate ore increased following the order: quartz, aluminosilicate, pyrite, fluorapatite, dolomite, and calcite.

Secretory pore-forming proteins (PFPs) have been identified in organisms from all kingdoms of life. Our studies with the toad species Bombina maxima found an interaction network among aerolysin family PFPs (af-PFPs) and trefoil factors (TFFs). As a toad af-PFP, BmALP1 can be reversibly regulated between active and inactive forms, with its paralog BmALP3 acting as a negative regulator. BmALP1 interacts with BmTFF3 to form a cellular active complex called βγ-CAT. This PFP complex is characterized by acting on endocytic pathways and forming pores on endolysosomes, including stimulating cell macropinocytosis. In addition, cell exocytosis can be induced and/or modulated in the presence of βγ-CAT. Depending on cell contexts and surroundings, these effects can facilitate the toad in material uptake and vesicular transport, while maintaining mucosal barrier function as well as immune defense. Based on experimental evidence, we hereby propose a secretory endolysosome channel (SELC) pathway conducted by a secreted PFP in cell endocytic and exocytic systems, with βγ-CAT being the first example of a SELC protein. With essential roles in cell interactions and environmental adaptations, the proposed SELC protein pathway should be conserved in other living organisms.

Periodontitis is an infection-driven inflammatory disease with a complex etiology that is associated with spontaneous tooth loosening. The remediation of periodontitis requires the activation of osteogenesis and regeneration of the lost tissue that is currently not possible through existing clinical practice. The present study has examined the effects of Astragaloside I on the osteogenesis and osteogenic differentiation of periodontal ligament stem cells. The results show increased cell viability and alkaline phosphatase activity in the periodontal ligament stem cells by Astragaloside I treatment. Astragaloside I stimulated the expression of ALP, RUNX2, β-catenin, and OPN in PDLSCs suggesting that Astragaloside I enhances osteoblastic differentiation by modulating Wnt/β-catenin signaling pathway. Further support for involvement of the Wnt/β-catenin signaling pathway comes from the reversal of Astragaloside I stimulation by inhibition of this pathway by a specific inhibitor. In summary the results presented here suggest Astragaloside I as a promising candidate drug for bone remodeling and periodontal tissue engineering.

In this work, we reported a in situ synthesizing strategy for flexible TiO2 films by one-step hydrothermal treatment of Ti films deposited on the stainless steel (StS) substrate by direct current magnetron sputtering (DCMS) in tetramethylammonium hydroxide (TMAOH) solution. The structure and morphology of the films were characterized by field emission scanning electron microscopy (FESEM), X-Ray diffraction (XRD), transmission electron microscopy (TEM), and high-resolution transmission electron microscopy (HRTEM). Results show that the as-prepared TiO2 is anatase nano-pillar with tetrahedral and biconical-tip, and its elongated direction is [110] and the circumferential faces is {101} planes on tips. Higher substrate temperature is favorable to improve the density, adhesion and crystallinity of deposited Ti films. The microstructure of the deposited titanium films and the concentration of TMAOH solution can affect the morphologies of the TiO2 films, and then affect their photoelectrochemical properties. Photoelectrochemical analyses by transient photocurrent response and linear sweep voltammogram show that TiO2 film obtained in 1 M TMAOH solution from Ti film deposited at room temperature has the best photoelectrochemical property, followed by TiO2 film obtained in 1.5 M TMAOH solution from Ti film deposited at 600 °C, which is attributed to their larger surface area. This work provides further insights into conveniently in situ synthesize anatase nano-pillar film on non-Ti and acid nonresistant substrates.

The anti-tumor and anti-inflammatory effects of limonin have been established, here, we aim to explore whether limonin can induce protective effects against doxorubicin (DOX)-mediated cardiotoxicity which limits its clinical application. We found that limonin attenuated DOX-mediated cytoxicology of myocardial cell line H9C2 by measuring cell viability and reactive oxygen species (ROS) level. Additionally, limonin ameliorates DOX-induced cardiac injury in rat by examining the activity of lactate dehydrogenase (LDH), superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) concentration, and histopathological changes. Mechanistically, it was shown that limonin partially abrogated the inhibition of Nuclear factor – like 2 and Sirtuin 2 signaling induced by DOX. Furthermore, limonin-mediated protective effects on DOX-mediated cytoxicology of H9C2 were rescued by a Sirt2-specific inhibitor or siRNA against Sirt2. Thus, this work reveals that limonin can suppress DOX-mediated cardiotoxicity by activating Nrf2 and Sirt2 signaling., Graphical abstract

Nickel-catalyzed regioselective electrocarboxylation of allylic halides with CO2 at atmospheric pressure has been developed by adjusting reaction parameters, including catalyst, solvent, temperature and additive. β,γ-Unsaturated carboxylic acids were obtained in moderate to good yields and with high chain selectivity. This reaction shows tolerance to functional groups. In addition, cyclic voltammetry was performed to provide the possible mechanism of nickel-catalyzed CO2 allylation.

The lower-temperature thermal treatment of PTFE/ACET composites created a novel F-doped ACET catalyst with excellent ORR activity for the flexible solid-state ZAB. It delivered a high discharge-voltage of 1.10 V and a small voltage gap of 0.8 V at a current density of 2 mA cm−2 for over 1080 cycles (180 hours).

Using synthetic zeolite from fly ash to treat high concentration phosphorus wastewater does not only improve the utilization of fly ash as solid waste but also reduce the environmental pressure caused by eutrophication. A synthetic zeolite was prepared from coal fly ash by one-step hydrothermal synthesis and applied for phosphorus adsorption from industrial wastewater (∼8,000 mg-P/L), and its adsorption characteristics and performance were studied. The results indicated that the product was a well-crystallized Na-P1 zeolite with typical morphology of plate- and rod-shaped crystals. Compared with the original fly ash, the specific surface area and average pore volume of the synthetic zeolite were nine and six times larger than the fly ash, reaching 43.817 m2/g and 0.122 cm3/g. The results from phosphorus adsorption onto the synthetic zeolite showed that the synthetic zeolite had good phosphorus adsorption properties. The adsorption process highly conformed to the pseudo-second-order kinetic model with the regression coefficient R 2 of 0.998. Phosphorus adsorption on the synthetic zeolite was fitted to the Langmuir monolayer adsorption model, and the regression coefficient R 2 was 0.989. The maximum phosphorus adsorption capacity was 84.4 mg-P/g-zeolite.

Novel surface-microporous graphene (SMG), which was synthesized directly from CO2via its reaction with a Na/K liquid alloy, was demonstrated as a robust metal-free electrocatalyst for the air cathode of ZABs. The SMG-based ZAB (SMG-ZAB) exhibited an excellent peak power density of 65 mW cm−2 at a current density of 83 mA cm−2, which is comparable to that of the ZAB with a commercial 20% Pt/C cathode (65 mW cm−2 at 84 mA cm−2). Furthermore, the SMG-ZAB delivered an unprecedented small charge–discharge voltage gap of 0.25 V at 2 mA cm−2 with excellent durability, which is not only superior to that (0.75 V) of the 20% Pt/C-based ZAB, but also better than any reported values of all-solid-state ZABs. The excellent performance of the SMG electrocatalyst can be attributed to the synergistic effect of its defects and oxygen-containing surface functional groups as well as its unique pore structure of interconnected macropores and surface micropores. This provides a promising route to develop excellent metal-free air cathodes for secondary metal–air batteries from a greenhouse gas.

Cysteine represents an attractive target for peptide/protein modification due to the intrinsic high nucleophilicity of the thiol group and low natural abundance. Herein, a cleavable and tunable covalent modification approach for cysteine containing peptides/proteins with our newly designed aryl thioethers via a SNAr approach was developed. Highly efficient and selective bioconjugation reactions can be carried out under mild and biocompatible conditions. A series of aryl groups bearing different bioconjugation handles, affinity or fluorescent tags are well tolerated. By adjusting the skeleton and steric hindrance of aryl thioethers slightly, the modified products showed a tunable profile for the regeneration of the native peptides., A cleavable and tunable covalent modification approach for cysteine by aryl thioethers via a SNAr approach was developed. The highly efficient and selective bioconjugation reactions can proceed under the mild and biocompatible conditions.

To promote the recycling of agricultural organic wastes (AOWs), e.g., crop straws, and livestock and poultry (LP) manures, it is very important to analyze the demand-supply balance of the nitrogen nutrients converted from AOWs for agricultural utilization on a regional basis. Focusing on Shangshui County in central China’s Henan Province, this paper thoroughly analyzes this demand-supply balance through literature query and field survey. Firstly, the amount of nitrogen nutrients converted from the crop straws, and LP manures were calculated for the study area. Next, the demand for nitrogen nutrients of agricultural planting in the study area was estimated based on the soil properties and agricultural planting area. Based on the calculation results, the demand-supply balance of the nitrogen nutrients converted from AOWs for agricultural utilization in the study area was subject to quantitative analysis. The results show that: In 2017, the agricultural planting in Shangshui County demanded 35.16 kilotons of nitrogen nutrients; the total supply of nitrogen nutrients converted from AOWs stood at 25.86 kilotons, including 12.41 kilotons from crop straws (47.99%) and 13.45 kilotons (52.01%) from LP manures; the demand-supply ratio (amount of demand/supply quantity) of nitrogen nutrients was 1.36, that is, the demand surpassed the supply; therefore, the nitrogen nutrients provided by the AOWs in the study area can be fully utilized by the agricultural soil in the region.

Toehold-mediated DNA strand displacement (DSD) is a powerful strategy to engineer dynamics in DNA-based devices and for molecular computing. However, facile strategies for autonomously self-resettable DSD cascades with programmable lifetimes are still missing. Here, we concatenate an ATP-powered ligation/restriction network with toehold-mediated DSD reactions realizing ATP-driven transient DSD with self-resetting behavior. The ATP-fueled ligation biases strand displacement reactions by increasing the toehold length and increasing the local concentration by covalent fixation, while the concurrent endonuclease restriction eliminates this bias, allowing to reset the system. The lifetimes and adaptive dynamic steady states for the DSD are engineered by the ATP-fueled uphill-driven nonequilibrium ligation/restriction system. By programming the toeholds for downstream DSD reaction networks, we realize ATP-fueled transient DSD cascades. A higher level of fuel-driven automaton is achieved by combining two subsystems for the transient DSD, where the expelled strands are each other's input strands and the restriction-induced double-stranded DNA melting resets the systems.

Summary Multivalency-driven liquid-liquid phase separation (LLPS) is essential for biomolecular condensates to facilitate spatiotemporal regulation of biological functions. Providing programmable model systems would help to better understand the LLPS processes in biology and furnish new types of compartmentalized synthetic reaction crucibles that exploit biological principles. Herein, we demonstrate a concept for programming LLPS using transient multivalency between ATP-driven sequence-defined functionalized nucleic acid polymers (SfNAPs), which serve as simple models for membrane-less organelles. Critically, the prominent programmability of the DNA-based building blocks allows to encode distinct molecular recognitions for multiple multivalent systems, enabling sorted LLPS and, thus, multicomponent DNA coacervates. The ATP-driven coacervates are capable for multivalent trapping of micron-scale colloids and biomolecules to generate functions as emphasized for rate enhancements in enzymatic cascades. This work demonstrates ATP-driven multivalent coacervation as a valuable mechanism for dynamic multicomponent and functional biomolecular condensate mimics and for autonomous materials design in general.

The chemical state of precious metals plays an important role in redox reaction. In order to maintain rhodium (Rh) at metallic state, which is recognized as reactive center in three-way catalytic reactions, we synthesized Rh/CeO2–ZrO2 (Rh/CZ) catalyst by liquid phase reduction adsorption with glycerol as reductant (Rh/CZ-g). Detailed characterizations were conducted to investigate the chemical state of Rh species, and the CO-FTIR and XPS results indicated that Rh species mainly existed in metallic state for Rh/CZ-g. Through CO chemisorption and H2-TPR, it’s proved that the liquid phase reduction treatment would weaken the interaction between Rh species and CeO2–ZrO2 support, avoiding the supply of oxygen species from CeO2–ZrO2 to Rh in some degree. Compared with Rh/CeO2–ZrO2 catalyst prepared by incipient wetness impregnation, Rh/CZ-g exactly had superior activity in three-way catalytic process. Combined with in situ DRIFTS, some important intermediate species, such as Rh–CN, Rh-(NO)2, formates and acetates, preferred to adsorb and transform on Rh/CZ-g with larger proportion of metallic Rh, which determined Rh/CZ-g was more favorable for three-way catalytic reactions, even after aged at 950 °C for 5 h. The purpose of this work is to inspire researchers use simple and valid methods to synthesize highly efficient three-way catalysts.

Konjac glucomannan (KGM) is a hypoglycemic polysaccharide with a wide range of molecular weights. But study on hypoglycemic effects of KGMs relate to molecular weight is limited. In this study, KGMs with high and medium molecular weights, and the degraded KGMs were analyzed with physicochemical properties, hypoglycemic effects and mechanisms. Results showed that as the molecular weight KGMs decreased, the viscosity decreased, molecular flexibility increased, while chemical groups, crystal structures and main chains showed little change. KGMs with medium molecular weights (KGM-M1, KGM-M2) showed better effects on increasing body weight, decreasing levels of fasting blood glucose, insulin resistance, total cholesterol and low density lipoprotein cholesterol, and enhancing integrity of pancreas and colon, than KGMs with high or low molecular weights (KGM-H, KGM-L) in type 2 diabetic rats. Mechanism analysis suggested that KGM-M1 and KGM-M2 had higher antioxidant and anti-inflammatory activities on elevating superoxide dismutase, decreasing malondialdehyde and tumor necrosis factor-α levels. Moreover, KGM-M1 and KGM-M2 increased gut microbiota diversity, Bacteroidetes/Firmicutes ratio and Muribaculaceae, decreased Romboutsia and Klebsiella, and improved 6 diabetic related metabolites. Combined, KGM-M1 and KGM-M2 showed higher hypoglycemic effects, due to regulatory activities of antioxidant, anti-inflammatory, intestinal microbiota, and relieved metabolic disorders.

The textural properties (specific surface area and pore volume/diameter) of yttria-zirconia (Y2O3-ZrO2) ceramic material are critically important to its application in environmental and industrial catalysis. In this work, we tuned the textural properties of the material by a lauric acid-assisted coprecipitation method with high operability and cost-effectiveness. Lauric acid-modified and non-modified yttrium-zirconium hydroxides were prepared. The two hydroxides were then calcined at 700, 800, 900 and 950 °C, respectively, resulting in eight Y2O3-ZrO2 oxides. The surface properties and thermal decomposition behavior of the hydroxides and the structural and textural properties of the oxides were systematically investigated. It was found that lauric acid was chemically bound to the hydroxide surface, which decreased the crystallite size of the oxides. More importantly, intercrystalline aggregation in the oxides was significantly inhibited during the thermal treatment. As a result, the textural properties of mesoporous Y2O3-ZrO2 solid solution were greatly improved even after the material was calcined at high temperatures. As-prepared materials have higher specific surface area (69 to 24 m2/g) and pore volume (0.24 to 0.18 mL/g) than reported congener materials. This work may stimulate ideas for improved processing techniques which were applied to develop Y2O3-ZrO2 ceramic material with excellent textural properties.

Mycoplasma pneumoniae is a strong infectious pathogen that may cause severe respiratory infections. Since this pathogen may possess a latent period after infection, which sometimes leads to misdiagnosis by traditional diagnosis methods, the establishment of a rapid and sensitive diagnostic method is crucial for transmission prevention and timely treatment. Herein, a novel detection method was established for M. pneumoniae detection. The method, which improves upon a denaturation bubble-mediated strand exchange amplification (SEA) that we developed in 2016, is called accelerated SEA (ASEA). The established ASEA achieved detection of 1% M. pneumoniae genomic DNA in a DNA mixture from multiple pathogens, and the limit of detection (LOD) of ASEA was as low as 1.0 × 10−17 M (approximately 6.0 × 103 copies/mL). Considering that the threshold of an asymptomatic carriage is normally recommended as 1.0 × 104 copies/mL, this method was able to satisfy the requirement for practical diagnosis of M. pneumoniae. Moreover, the detection process was finished within 20.4 min, significantly shorter than real-time PCR and SEA. Furthermore, ASEA exhibited excellent performance in clinical specimen analysis, with sensitivity and specificity of 96.2% and 100%, respectively, compared with the “gold standard” real-time PCR. More importantly, similar to real-time PCR, ASEA requires only one pair of primers and ordinary commercial polymerase, and can be carried out using a conventional fluorescence real-time PCR instrument, which makes this method low-cost and easy to accomplish. Therefore, ASEA has the potential for wide use in the rapid detection of M. pneumoniae or other pathogens in large numbers of specimens. Graphical abstract

Lipopolysaccharide (LPS) is an endotoxin involved in a number of acute and chronic inflammatory syndromes. Although LPS‐induced signalling has been extensively studied, there are still mysteries remaining to be revealed. In the current study, we used high‐throughput phosphoproteomics to profile LPS‐initiated signalling and aimed to find novel mediators. A total of 448 phosphoproteins with 765 phosphorylation sites were identified, and we further validated that the phosphorylation of MARK2 on T208 was important for the regulation on LPS‐induced CXCL15 (human IL‐8 homolog), IL‐1β, IL‐6 and TNF‐α release, in which LKB1 had a significant contribution. In summary, induction of cytokines by LPS in mouse macrophage is regulated by LKB1‐MARK2 signals. Our study provides new clues for further exploring the underlying mechanisms of LPS‐induced diseases, and new therapeutic approaches concerning bacterial infection may be derived from these findings.

Background Camptothecin (CPT) and matrine (MAT) have potential as botanical pesticides against several pest species. However, the mechanisms of metabolic and physiological changes in pests induced by CPT and MAT are unknown. In this study, a toxicological test, an NMR-based metabolomic study, an enzymatic test, and an RT quantitative PCR (RT-qPCR) experiment were all conducted to examine the effect of CPT and MAT on Spodoptera litura. Results CPT (0.5-1%) exerted high toxicity against larvae of S. litura and caused growth stagnation and high mortality of larvae. A variety of metabolites were significantly influenced by 0.5% CPT, including several energy-related metabolites such as trehalose, lactate, succinate, citrate, malate, and fumarate. In contrast, MAT showed low toxicity against larvae and induced almost no changes in hemolymph metabolites of S. litura. Enzymatic tests showed that trehalase activity was significantly decreased in larvae after feeding with 0.5% CPT. RT-qPCR showed that the transcription levels of alanine aminotransferase, malate dehydrogenase, and isocitrate dehydrogenase were decreased while lactate dehydrogenase was increased in the 0.5% CPT-treated group. Conclusions These data indicate that one of the important mechanisms of CPT against S. litura larvae is via the inhibition of trehalose hydrolysis and glycolysis. Our findings also suggest that CPT exhibits a stronger toxicological effect than MAT against S. litura, which provides basic information for the application of CPT in the control of S. litura or other lepidoptera pests.

Chemotherapy-induced neuropathic pain is a common dose-limiting side effect of cancer treatment but the underlying mechanisms are largely unknown. Here, we used a whole-genome expression microarray and gene ontology analysis to identify the upregulation of a sequence-specific DNA-binding protein, HOXA6, in the spinal dorsal horn on Day 10 after injection of rats with oxaliplatin. Genetic disruption of HOXA6 with siRNAs alleviated mechanical allodynia after oxaliplatin administration. Reduced representation bisulfite sequencing assays indicated that oxaliplatin decreased the methylation levels of the SOX10 promoter but not of HOXA6. TET1 was also upregulated by oxaliplatin. Genetic disruption of TET1 with siRNA blocked the promoter demethylation of SOX10 and the upregulation of HOXA6 and SOX10. Importantly, inhibition of SOX10 by intrathecal application of SOX10 siRNA ameliorated the mechanical allodynia induced by oxaliplatin and downregulated the expression of HOXA6. Consistently, overexpression of SOX10 through intraspinal injection of AAV-SOX10-EGFP produced mechanical allodynia and upregulated the expression of spinal dorsal horn HOXA6. Moreover, chromatin immunoprecipitation assays demonstrated that oxaliplatin increased the binding of SOX10 to the promoter region of HOXA6. Taken together, our data suggest that HOXA6 upregulation through the TET1-mediated promoter demethylation of SOX10 may contribute to oxaliplatin-induced neuropathic pain.

Fuel‐driven self‐assemblies are gaining ground for creating autonomous systems and materials, whose temporal behavior is preprogrammed by a reaction network. However, up to now there has been a lack of simple external control mechanisms of the transient behavior, at best using remote and benign light control. Even more challenging is to use different wavelengths to modulate the reactivity of different components of the system, for example, as fuel or building blocks. Success would enable such systems to navigate along different trajectories in a wavelength‐dependent fashion. Herein, we introduce the first examples of light control in ATP‐fueled, dynamic covalent DNA polymerization systems organized in an enzymatic reaction network of concurrent ATP‐powered ligation and restriction. We demonstrate concepts for light activation and modulation by introducing caged ATP derivatives and caged DNA building blocks, making it possible to realize light‐activated fueling, self‐sorting in structure and behavior, and transition across different wavelength‐dependent dynamic steady states., Tuning on multiple channels: Multiple components of the chemical reaction network in the ATP‐driven transient DNA polymerization systems can be caged by different photocleavable groups that respond to different colors of light. As a result, light can be used to modulate the non‐equilibrium behavior and multiple wavelength‐dependent dynamic steady states.

Cadmium (Cd), a phytotoxic heavy metal accumulated in plants and fruits, has significant adverse effects on plant growth and development as well as human health. In particular, Cd pollution has become a serious agricultural issue in recent years. Apple is one of the most popular fruits consumed at the global scale. Improving apple Cd resistance via reductions in Cd absorption can benefit apple tree growth and ensure fruit safety. In this study, we determined that, under the 200 μM Cd treatment, 35S::MdIAA24 apple plants exhibited more biomass and less Cd accumulation in the tested tissues compared to wild type (WT). Furthermore, the 35S::MdIAA24 apple plants demonstrated more favorable photosynthesis characteristics, less reactive oxygen species (ROS) and a greater amount of active antioxidant enzymes under the Cd condition than WT. The expression levels of the Cd uptake genes were observed to be lower in the 35S::MdIAA24 apple plants compared with those of the WT under the Cd treatment. The results highlight the ability of the overexpression of MdIAA24 to enhance apple Cd resistance by improving antioxidant capacity and reducing Cd absorption.

Jie Deng,1 Lorne M Golub,2 Hsi-Ming Lee,2 Veena Raja,2 Francis Johnson,3 Allan Kucine,4 Wonsae Lee,5 Tian-Min Xu,1 Ying Gu6 1Department of Orthodontics, Peking University School and Hospital of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, Beijing, 100081, People’s Republic of China; 2Department of Oral Biology and Pathology, School of Dental Medicine, Stony Brook University, Stony Brook, NY, 11794, USA; 3Department of Chemistry and Pharmacological Sciences, School of Medicine, Stony Brook University, Stony Brook, NY, 11794, USA; 4Department of Oral & Maxillofacial Surgery, School of Dental Medicine, Stony Brook University, Stony Brook, NY, 11794, USA; 5Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY, 11794, USA; 6Department of General Dentistry, School of Dental Medicine, Stony Brook University, Stony Brook, NY, 11794, USACorrespondence: Jie DengDepartment of Orthodontics, Peking University School and Hospital of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing, 100081, People’s Republic of ChinaTel +1 631 632-3172Fax +1 631 632-9705Email jie.deng917@gmail.comTian-Min Xu Email tmxuortho@163.comPurpose: Clinically, it is challenging to manage diabetic patients with periodontitis. Biochemically, both involve a wide range of inflammatory/collagenolytic conditions which exacerbate each other in a “bi-directional manner.” However, standard treatments for this type of periodontitis rely on reducing the bacterial burden and less on controlling hyper-inflammation/excessive-collagenolysis. Thus, there is a crucial need for new therapeutic strategies to modulate this excessive host response and to promote enhanced resolution of inflammation. The aim of the current study is to evaluate the impact of a novel chemically-modified curcumin 2.24 (CMC2.24) on host inflammatory response in diabetic rats.Methods: Type I diabetes was induced by streptozotocin injection; periodontal breakdown then results as a complication of uncontrolled hyperglycemia. Non-diabetic rats served as controls. CMC2.24, or the vehicle-alone, was administered by oral gavage daily for 3 weeks to the diabetics. Micro-CT was used to analyze morphometric changes and quantify bone loss. MMPs were analyzed by gelatin zymography. Cell function was examined by cell migration assay, and cytokines and resolvins were measured by ELISA.Results: In this severe inflammatory disease model, administration of the pleiotropic CMC2.24 was found to normalize the excessive accumulation and impaired chemotactic activity of macrophages in peritoneal exudates, significantly decrease MMP-9 and pro-inflammatory cytokines to near normal levels, and markedly increase resolvin D1 (RvD1) levels in the thioglycolate-elicited peritoneal exudates (tPE). Similar effects on MMPs and RvD1 were observed in the non-elicited resident peritoneal washes (rPW). Regarding clinical relevance, CMC2.24 significantly inhibited the loss of alveolar bone height, volume and mineral density (ie, diabetes-induced periodontitis and osteoporosis).Conclusion: In conclusion, treating hyperglycemic diabetic rats with CMC2.24 (a tri-ketonic phenylaminocarbonyl curcumin) promotes the resolution of local and systemic inflammation, reduces bone loss, in addition to suppressing collagenolytic MMPs and pro-inflammatory cytokines, suggesting a novel therapeutic strategy for treating periodontitis complicated by other chronic diseases.Keywords: hyperglycemia, periodontitis, matrix metalloproteinases, inflammation, resolvins, host-modulatory therapy

Background WRKY transcription factors (TFs) play vital roles in plant growth and development, secondary metabolite synthesis, and response to biotic and abiotic stresses. In a previous transcriptome sequencing analysis of Lilium regale Wilson, we identified multiple WRKY TFs that respond to exogenous methyl jasmonate treatment and lily Fusarium wilt (Fusarium oxysporum). Results In the present study, the WRKY TF LrWRKY3 was further analyzed to reveal its function in defense response to F. oxysporum. The LrWRKY3 protein was localized in the plant cell nucleus, and LrWRKY3 transgenic tobacco lines showed higher resistance to F. oxysporum compared with wild-type (WT) tobacco. In addition, some genes related to jasmonic acid (JA) biosynthesis, salicylic acid (SA) signal transduction, and disease resistance had higher transcriptional levels in the LrWRKY3 transgenic tobacco lines than in the WT. On the contrary, L. regale scales transiently expressing LrWRKY3 RNA interference fragments showed higher sensitivity to F. oxysporum infection. Moreover, a F. oxysporum-induced defensin gene, Def1, was isolated from L. regale, and the recombinant protein LrDef1 isolated and purified from Escherichia coli possessed antifungal activity to several phytopathogens, including F. oxysporum. Furthermore, co-expression of LrWRKY3 and the LrDef1 promoter in tobacco enhanced the LrDef1 promoter-driven expression activity. Conclusions These results clearly indicate that LrWRKY3 is an important positive regulator in response to F. oxysporum infection, and one of its targets is the antimicrobial peptide gene LrDef1.