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Background: Natural products (NPs) are important sources for the design of new drugs and agrochemicals. Neopeltolide, a marine NP, has been identified as a potent Qo-site inhibitor of cytochrome bc1 complex. Methods: In this study, a series of neopeltolide derivatives was designed and synthesized by the simplification of its 14-membered macrolactone ring with a diphenyl ether fragment. The enzymatic inhibition bioassays and mycelium growth inhibition experiments against a range of fungi were performed to determine their fungicidal activities. Results: The derivatives have potent activity against the porcine bc1 complex. Compound 8q showed the best activity with an IC50 value of 24.41 nM, which was 8-fold more effective than that of positive control azoxystrobin. Compound 8a exhibited a 100% inhibitory rate against Zymoseptoria tritici and Alternaria solani at a 20 mg/L dose. Conclusion: Computational results indicated that compounds with suitable physicochemical properties, as well as those forming a hydrogen bond with His161, would have good fungicidal activity. These data could be useful for the design of bc1 complex inhibitors in the future.

An iron-catalyzed coupling reaction of difluoroenol silyl ethers and cyclobutanone oxime esters is described. This protocol provides a convenient access to various previously unknown and potentially useful gem-difluoromethylenated ketonitriles inmoderate to good yields. The transformations of resulting products to other fluorinecontaining products is also documented.

Eight square-pyramidal dysprosium complexes of the type [Dy(X)(DBP)2{TMG(H)}2] were synthesized, where TMG(H) denotes 1,1,3,3-tetramethylguanidine, X denotes an alkoxide ligand or anionic guanidina...

The steviol glycosides (SGs) in stevia (Stevia rebaudiana Bertoni) leaves are becoming increasingly valuable due to its high sweetness but low calorific value, which is driving the development of stevia commercial cultivation. Optimizing fertilization management can effectively increase SGs productivity, but knowledge on the relationship between potassium (K) fertilization and SGs production is still lacking. In this study, pot experiments were conducted in order to investigate the effect of K deficiency on SGs synthesis in stevia leaves, as well as the underlying mechanisms. Our results showed that when compared with standard K fertilization, K deficiency treatment has no significant effect on the biomass of stevia plant grown in a given soil with high K contents. However, K deficiency critically decreased leaf SGs contents as well as the expression of SGs synthesis-related genes. The contents of different sugar components decreased and the activities of sugar metabolism-related enzymes were inhibited under the K deficiency condition. Moreover, spraying sucrose on the leaves of stevia seedlings diminished the inhibitory effect caused by K deficiency. Our results also revealed the significant positive correlations between sucrose, glucose and SGs contents. Overall, our results suggest that K deficiency would suppress the synthesis of SGs in stevia leaves, and this effect may be mediated by the leaf sugar metabolism. Our findings provide new insights into the improvement of SGs production potential.

Background Acylcarnitine is an intermediate product of fatty acid oxidation. It is reported to be closely associated with the occurrence of diabetic cardiomyopathy (DCM). However, the mechanism of acylcarnitine affecting myocardial disorders is yet to be explored. This current research explores the different chain lengths of acylcarnitines as biomarkers for the early diagnosis of DCM and the mechanism of acylcarnitines for the development of DCM in-vitro. Methods In a retrospective non-interventional study, 50 simple type 2 diabetes mellitus patients and 50 DCM patients were recruited. Plasma samples from both groups were analyzed by high throughput metabolomics and cluster heat map using mass spectrometry. Principal component analysis was used to compare the changes occurring in the studied 25 acylcarnitines. Multivariable binary logistic regression was used to analyze the odds ratio of each group for factors and the 95% confidence interval in DCM. Myristoylcarnitine (C14) exogenous intervention was given to H9c2 cells to verify the expression of lipid metabolism-related protein, inflammation-related protein expression, apoptosis-related protein expression, and cardiomyocyte hypertrophy and fibrosis-related protein expression. Results Factor 1 (C14, lauroylcarnitine, tetradecanoyldiacylcarnitine, 3-hydroxyl-tetradecanoylcarnitine, arachidic carnitine, octadecanoylcarnitine, 3-hydroxypalmitoleylcarnitine) and factor 4 (octanoylcarnitine, hexanoylcarnitine, decanoylcarnitine) were positively correlated with the risk of DCM. Exogenous C14 supplementation to cardiomyocytes led to increased lipid deposition in cardiomyocytes along with the obstacles in adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) signaling pathways and affecting fatty acid oxidation. This further caused myocardial lipotoxicity, ultimately leading to cardiomyocyte hypertrophy, fibrotic remodeling, and increased apoptosis. However, this effect was mitigated by the AMPK agonist acadesine. Conclusions The increased plasma levels in medium and long-chain acylcarnitine extracted from factors 1 and 4 are closely related to the risk of DCM, indicating that these factors can be an important tool for DCM risk assessment. C14 supplementation associated lipid accumulation by inhibiting the AMPK/ACC/CPT1 signaling pathway, aggravated myocardial lipotoxicity, increased apoptosis apart from cardiomyocyte hypertrophy and fibrosis were alleviated by the acadesine.

Succinate dehydrogenase (SDH, EC 1.3.5.1) has proven to be an important fungicidal target, and the inhibition of SDH is useful in the treatment of plant pathogens. The discovery of a novel active SDH inhibitor is of high value. Herein, we disclose the discovery of a potent, highly active inhibitor as a fungicide candidate by using a computational substitution optimization method, a fast drug design method developed in our laboratory. The greenhouse experiments showed that compound 17c exhibited high protective activity against south corn rust, soybean rust (SBR), and rice sheath blight at a very low dosage of 0.781 mg/L. Moreover, the field trials indicated that compound 17c is comparable to and even better than commercial fungicides against SBR and cucumber powdery mildew at 50 mg/L concentration. Most surprisingly, compound 17c resulted to be strictly better in curative activity than the commercial fungicide benzovindiflupyr. The computation results indicated that 17c could form another hydrogen bond with C_S42 and then lead to strong van der Waals and electronic interactions with SDH. Our results suggested that 17c is a potential fungicide candidate for SDH.

Novel insecticidal targets are always in demand due to the development of resistance. OfHex1, a β-N-acetyl-d-hexosaminidase identified in Ostrinia furnacalis (Asian corn borer), is involved in insect chitin catabolism and has proven an ideal target for insecticide development. In this study, structure-based virtual screening, structure simplification, and biological evaluation are used to show that compounds with a biphenyl-sulfonamide skeleton have great potential as OfHex1 inhibitors. Specifically, compounds 10k, 10u, and 10v have Ki values of 4.30, 3.72, and 4.56 μM, respectively, and thus, they are more potent than some reported nonglycosyl-based inhibitors such as phlegmacin B1 (Ki = 26 μM), berberine (Ki = 12 μM), 2 (Ki = 11.2 μM), and 3 (Ki = 28.9 μM). Furthermore, inhibitory kinetic assessments reveal that the target compounds are competitive inhibitors with respect substrate, and based on toxicity predictions, most of them have potent drug properties. The obtained results indicate that the biphenyl-sulfonamide skeleton characterized by simple chemical structure, synthetic tractability, potent activity, and low toxicity has potential for further development in pest management targeting OfHex1.

Electrocatalytic reduction of carbon dioxide by metal-organic framework (MOF) catalysts has been widely investigated in recent years, but the poor conductivity strongly limits the application of most MOFs catalysts. In order to overcome the above obstacles, we tried to use a gentle strategy to uniformly introduce highly dispersed carbon nanoparticles into the framework to improve the catalytic activity. Herein, a porous 3D In-MOF {(Me2NH2)[In(BCP)]·2DMF}n (V11) with good stability was constructed, and there are two types of large 1D channels with a diameter of 1.6 and 1.2 nm in the framework. Experimental results show that V11 exhibits a moderate catalytic activity in CO2 electroreduction with 76.0% of Faradaic efficiency for formate. To improve the catalytic activity of V11, methylene blue molecules were introduced into the framework as a carbon source due to its suitable size and carbonization temperature. After calcination at an appropriate temperature, carbon nanoparticles (CPs) with an average diameter of 3.85 nm were anchored in V11 and the framework can keep stable during the synthesis process. The obtained catalyst CPs@V11 was also applied in the CO2 electroreduction, and the maximum Faradaic efficiency of formate increases from 76.0% to 90.1% and the current density increased by 2.2 times. Control experiments and catalytic characterizations demonstrate that the introduced carbon nanoparticles can serve as accelerant to promote the charges and mass transfer in framework, and benefit to sufficiently expose active sites. Furthermore, this strategy can also work on other In-MOFs to improve the catalytic performance in selectivity and current density, demonstrating the good universality of this facile method and giving inspiration to construct more effective catalysts for electroreduction of CO2.

Cyclization of propargylamines with CO2 to obtain 2-oxazolidone heterocyclic compounds is an essential reaction in industry but it is usually catalyzed by noble-metal catalysts with organic bases as co-catalysts under harsh conditions. We have synthesized a unique CuI /CuII mixed valence copper-based framework {[(CuI6 I5 )Cu3II L6 (DMA)3 ](NO3 )⋅9DMA}n (1) with good solvent and thermal stability, as well as a high density of uncoordinated amino groups evenly distributed in the large nanoscopic channels. Catalytic experiments show that 1 can effectively catalyze the reaction of propargylamines with CO2 , and the yield can reach 99 %. The turnover frequency (TOF) reaches a record value of 230 h-1 , which is much higher than that of reported noble-metal catalysts. Importantly, this is the first report of heterogeneously catalyzed green conversion of propargylamines with CO2 without solvents and co-catalysts under low temperature and atmospheric pressure. A mechanistic study reveals that a triply synergistic catalytic effect between CuI /CuII and uncoordinated amino groups promotes highly efficient and green conversion of CO2 . Furthermore, 1 directly catalyzes this reaction with high efficiency when using simulated flue gas as a CO2 source.

The glutathione S-transferase P1(GSTP1) is an isoenzyme in the glutathione-S transferases (GSTs) enzyme system, which is the most abundant GSTs expressed in adult lungs. Recent research shows that GSTP1 is closely related to the regulation of cell oxidative stress, inhibition of cell apoptosis and promotion of cytotoxic metabolism. Interestingly, there is evidence that GSTP1 single nucleotide polymorphisms (SNP) 105Ile/Val related to the risk of radiation induced lung injury (RILI) development, which strongly suggests that GSTP1 is closely associated with the occurrence and development of RILI. In this review, we discuss our understanding of the role of GSTP1 in RILI and its possible mechanism.

Design and synthesis of air-stable and easily tailored high-performance single-molecule magnets (SMMs) are of great significance toward the implementation of SMMs in molecular-based magneto-electronic devices. Here, by introducing electron-withdrawing fluorinated substituents on equatorial ligand, two chiral Dy(III) macrocyclic complexes, RRRR-Dy-D6hF12 (1) and SSSS-Dy-D6hF12 (2), with a record anisotropy barrier exceeding 1800 K and the longest relaxation time approaching 2500 s at 2.0 K for all known air-stable SMMs, were obtained. The nearly perfect axiality of the ground Kramers doublet (KD) enables the open hysteresis loops up to 20 K in the magnetically diluted sample. It is notable that they are structurally rigid with high thermal stability and the apical ligand can be tailored to carry proper surface-binding groups. This finding not only improves the magnetic properties for air-stable SMMs but also provides a new avenue for deposition of SMMs on surfaces.

Objectives Xanthohumol (XAN) is a unique component of Humulus lupulus L. and is known for its diverse biological activities. In this study, we investigated whether Xanthohumol could ameliorate memory impairment of APP/PS1 mice, and explored its potential mechanism of action. Methods APP/PS1 mice were used for in vivo test and were treated with N-acetylcysteine and Xanthohumol for 2 months. Learning and memory levels were evaluated by the Morris water maze. Inflammatory and oxidative markers in serum and hippocampus and the deposition of Aβ in the hippocampus were determined. Moreover, the expression of autophagy and apoptosis proteins was also evaluated by western blot. Key findings Xanthohumol significantly reduced the latency and increased the residence time of mice in the target quadrant. Additionally, Xanthohumol increased superoxide dismutase level and reduced Interleukin-6 and Interleukin-1β levels both in serum and hippocampus. Xanthohumol also significantly reduced Aβ deposition in the hippocampus and activated autophagy and anti-apoptotic signals. Conclusions Xanthohumol effectively ameliorates memory impairment of APP/PS1 mice by activating mTOR/LC3 and Bax/Bcl-2 signalling pathways, which provides new insight into the neuroprotective effects of Xanthohumol.

Combustion characteristics of hydrogen-containing syngas are distinct from those of traditional hydrocarbon fuels. However, the efficiency for any fire extinguishant on syngas/air flame suppression has not been validated up to now. In this study, we developed novel core-shell microstructured nanocomposites (CSMNs) with inner seawater for syngas/air fire extinguishing. To optimize the preparation conditions, we adopted a three-factor three-level Box-Behnken design (BBD). The corrosion rate and minimum extinguishing concentration of CSMNs were determined by corrosion tests and Cup-burner experiments, respectively. Results showed that the BBD method exhibits good agreement between experimental data and fitted models. By applying numerical optimization, we determined that solid mass fraction, rotation speed, and rotation time in a range of 2–10%, 4000–8000 rpm, and 60–180 s, respectively, are the optimal preparation conditions for the CSMN preparation. The degree of corrosion rate and mass concentration in co-flow gaseous fuel/air fire suppression were reduced by more than 50% compared to an aqueous seawater solution. The updated methods can be used to study the fire inhibition efficiency of the emerging class of composite materials with the core-shell structure. This does not only provide solutions for syngas/air flame inhibition, but it also gives new insight into the application of seawater for fire extinguishment.

Nickel-based superalloy thin-walled components have been used in aerospace equipments requiring high reliability and durability at high-temperature condition. To overcome the problem of severe thinning occurs in conventional one-step hydroforming, this paper proposes an innovative multi-step hydroforming process for manufacturing complex T-shaped tubular parts of nickel-based superalloy. The appropriate process parameters in every step for preventing undesirable wrinkling and splitting defects, including internal pressure, axial feeding length, axial feeding ratio, and retreating displacement of middle punch, have been determined through a detailed numerical simulation investigation. The results show that manufacturing of a GH4169 T-shaped tubular part with expanded diameter can be successfully implemented using a four-step hydroforming. Moreover, the four-step hydroforming process, as well as the forming defects and the thickness distribution of several typical sections on the hydroformed GH4169 T-shaped tubular part, are all discussed. Finally, the complex GH4169 T-shaped tubular part with a thickness more than 3 mm can be obtained successfully after the top of the side branch is removed. These results provide insights for the manufacturing of T-shaped tubular part with expanded diameter, and contribute to the development of superalloy tube forming process at room temperature.

Catalyst-dependent oxidative cyclization of diynes with pyridine N-oxides is achieved using an amide directing group. Non-polarized and aminated alkyne could be selectively activated by copper and gold, thus leading to divergent synthesis of a range of pyrroles and dihydroindeno[1,2-c]pyrrol-3(2H)-ones. It should be noted that this difference might be attributed to the multicoordinated Cu center and the linearly aligned dicoordinated Au center.

International audience; A family of four mononuclear DyIII complexes of the guanidine-based ligand L [L = tris(2-hydroxybenzylidene)triaminoguanidine] with formulas [DyLCl2(DMF)2]·DMF·CH3OH (1), [DyL2(CH3OH)2]Br·H2O·3CH3OH (2), [DyL2(H2O)2]SCN·3H2O·CH3OH (3) and [DyL2(CH3OH)2]SCN·CH3CN·CH3OH (4) were successfully prepared by varying reaction conditions. Complex 1 is seven-coordinate, with three N2O from ligand L along with two equatorially trapped DMF molecules and two axial Cl- anions, adopting pentagonal bipyramidal D5h symmetry. Complexes 2-4 have somewhat similar structures with six donor N4O2 sites from two ligands and two O from corresponding solvent molecules, featuring a N4O4 octa-coordinate environment with triangular dodecahedron D2d symmetry. Magnetic investigations indicated that complex 1 did not demonstrate single-molecule magnetic behavior, while complexes 2-4 were single-ion magnets (SIMs) under zero applied DC field with the effective energy barriers (Ueff) of 207.3 (2), 222.5 (3) and 311.7 K (4), respectively. The different types of coordinated solvent molecules and counter anions caused changes in intermolecular interactions and coordination geometries that severely affected their magnetic dynamics. The magnetic behaviors of these complexes were investigated through complete-active space self-consistent field (CASSCF) calculations with the inclusion of spin-orbit effects. Calculations revealed that the measured differences in magnetic behaviors originated mainly from intermolecular and crystal-packing effects as isolated complexes 1-4 have almost identical electronic and magnetic properties.

In recent years, transition-metal-catalyzed tandem cyclization reactions of alkynes, especially those involving a metal carbene intermediate, have received worthwhile interest, as this type of reaction does not require the use of risky and potentially explosive diazo compounds as starting materials for carbene generation. A significant and general strategy for the stereospecific synthesis of 5-membered cycles is Nazarov cyclization based on the 4π-conrotatory electrocyclization of a conjugated pentadienyl cation to afford a cyclopentenyl cation. In this review, we introduce an overview of recent advances in the transition-metal-catalyzed Nazarov cyclization of alkynes via a metal carbene intermediate, and categorize these reactions according to the structure of the metal carbene. Our aim is to accelerate advancements in this enchanting area of research.

Objectives: Chronic myeloid leukemia (CML) is a malignant tumor of the blood system. Go6976, as a type of indolocarbazole and shows strong antitumor effects, but there have been no reports on the effect of Go6976 on CML. The objectives of this research were: (1) to explore the impact of Go6976 on CML in vitro and in vivo; and (2) to explore the drug toxicity of Go6976 to normal cells and animals.Methods:K562 cells and CML mice were used to explore the effect of Go6976 on CML. Peripheral blood mononuclear cells (PBMCs), CD34+ cells, and healthy mice were used to explore the drug toxicity of Go6976.Results: Cell experiments showed that Go6976 could inhibit the proliferation of K562 cells and enhance the inhibitory effects of imatinib at 5 μM and 10 μM, but it had little effect on CD34+ cells or PBMCs at concentrations less than 5 μM. Animal experiments showed that 2.5 mg/kg Go6976 could effectively inhibit the development of CML in mice, and it had almost no effects on healthy mice at 2.5 mg/kg and 10 mg/kg.Discussion: Because of the direct inhibitory effect of Go6976 on CML and its pharmacological enhancement effect on imatinib, it is foreseeable that Go6976 could become a new type of anti-CML medicine. And the further research is needed.Conclusion: Our findings verified that Go6976 could effectively inhibit CML in vitro and in vivo, and it is almost nontoxic to hematopoietic cells, immune cells, and healthy mice.

Owing to the high synthetic value of deuteration in the pharmaceutical industry, we describe herein the conversion of a range of aromatic ketones to deuterium-labeled products in good to excellent yields. Efficient and site-selective deuteration of benzyl alcohols by D2O with visible light irradiation of quantum dots (QDs), together with gram-scale synthesis and photocatalyst recycling experiments indicated the potential of the developed method in practical organic synthesis.

Cortisol is a reliable biomarker to evaluate human stress, as excessive stress can lead to an increased risk of cardiovascular diseases, neurogenic diseases, and sudden death. Therefore, it is necessary and important to seek a convenient and fast approach to detect cortisol, which is a great challenge. Herein, a novel four-fold interpenetrated framework {[Eu(BTB)(H2O)3]·1.5DMA·5H2O}n (MHT-1) was constructed and structurally characterized. The highly interpenetrated framework of MHT-1 endows it with high thermal, solvent and pH stabilities. Notably, MHT-1 can selectively detect cortisol with a wide concentration range from 10−9 M to 4 × 10−3 M in artificial human sweat. The corresponding sensitivity limit of MHT-1 can reach 10−9 M, which is a comparable value among those of other reported studies. In addition, MHT-1 can repeatedly detect cortisol at least 20 times without an obvious loss of sensing sensitivity. More importantly, an intelligent logic gate has been designed, providing a simple approach to detect cortisol levels in human sweat with the naked eye. This work offers a novel luminescent MOF and a technique to achieve the visual and simple detection of cortisol in human sweat with a promising practical application.

Ionic liquids (ILs) are potential green solvents with very broad application prospects. Their toxicity and other biological effects are largely related to their hydrophobic properties. In this work, the effects of two imidazolium-based ILs with either a butyl or a hexyl chain, [C4mim][OAc] or [C6mim][OAc], on the phase behaviours of a representative phospholipid, dipalmitoylphosphatidylcholine (DPPC), were examined using synchrotron small- and wide-angle X-ray scattering and differential scanning calorimetry techniques. A series of samples with a lipid : IL molar ratio ranging from 1 : 0 to 1 : 4/1 : 5 were prepared as aqueous dispersions in the form of multi-lamellar vesicles. The two ILs were found to have distinct effects on the phase behaviours of DPPC. For [C4mim][OAc], its effect is very limited. In contrast, for [C6mim][OAc], it could eliminate the pre-transition of DPPC, markedly affect the main phase transition of the lipid, and insert into the DPPC bilayer at gel state to form an interdigitated gel phase. The findings increased our understanding on the biological effects of imidazolium-based ILs and might shed light on the design of novel IL-based antimicrobials.

Objective: To observe the effects of total flavonoids of chrysanthemum and medicated serum on the expression of related proteins in the lacrimal tissue and dry-eye cell models of male rabbits with dry eye caused by castration. Methods: (1) 150 male Japanese rabbits were randomly divided into five groups, with 30 rabbits in each group: normal control group (group A), sham group (group B), model group (group C), androgen control group (group D) and total flavonoids of chrysanthemum treatment group (group E). The androgen deficiency dry-eye model was established by bilateral castration in groups C, D and E. Normal saline was administered to groups A, B and C by gavage; androgen (testosterone propionate) was injected into muscle in group D; and group E was given total flavonoids of chrysanthemum by gavage. All white rabbits were tested the Schirmer I test (SIT) and tear break-up time (BUT). After euthanasia, tear gland tissue was harvested so that we could observe pathological changes in the expression of related inflammatory factors in the lacrimal gland tissue. The expression of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1) was detected in the lacrimal gland tissue by immunohistochemistry. Reverse transcription PCR was used to quantitatively detect expression of TGF-β1 mRNA. (2) Male Wistar rat lacrimal epithelial cells were used to establish a model of eye stem cell apoptosis caused by androgen levels. The blank control group was set up without androgen culture, the control group with androgen culture, and the total flavonoids of chrysanthemum group without androgen. The MTT method was used to determine the optimal intervention dosage of drug-containing plasma. Western blot and QPCR were used to detect the expression of AR mRNA, NF-κB phosphorylated protein and TGF-β1 in lacrimal epithelial cells, and the androgen-like effect of total flavonoids of chrysanthemum was observed. Results: (1) Immunohistochemistry showed that groups A, B, D and E had significantly lower expression of IL-1β and TNF-α than group C (P < 0.05); among these, group E had slightly higher expression than group D (P > 0.05). RT-PCR results showed that the relative expression of TGF-β1 mRNA in groups A, B, D and E was significantly higher than in group C (P < 0.05), and the relative expression of TGF-β1 mRNA in groups D and E was higher than that in groups A and B (P < 0.05). (2) Using the MTT method, the final concentration of interfering cells was calculated to be 13.2%. The expression of AR protein, NF-κB and TGF-β1 in the chrysanthemum flavonoid plasma intervention and testosterone propionate intervention groups was enhanced, and there were significant differences relative to the blank group (P < 0.01). The expression level of NF-κB in the total flavonoid containing plasma intervention group was lower than that in the testosterone propionate intervention group (P < 0.01). Conclusions: The total flavonoids of chrysanthemum can inhibit IL-1β and TNF-α expression in the lacrimal gland tissue of castrated male rabbits with dry eye to increase synthesis of TGF-β1 mRNA and TGF-β1, thereby inhibiting the inflammatory response. The medicated plasma with total flavonoids of chrysanthemum promotes expression of AR mRNA, upregulating expression of NF-κB, further promoting upregulation of TGF-β1 protein expression in lacrimal epithelial cells, inhibiting inflammation by regulating related proteins, and ultimately alleviating the symptoms of dry eye.

Multiple resistance and pH adaptation (Mrp) complexes are sophisticated cation/proton exchangers found in a vast variety of alkaliphilic and/or halophilic microorganisms, and are critical for their survival in highly challenging environments. This family of antiporters is likely to represent the ancestor of cation pumps found in many redox-driven transporter complexes, including the complex I of the respiratory chain. Here, we present the three-dimensional structure of the Mrp complex from a Dietzia sp. strain solved at 3.0-A resolution using the single-particle cryoelectron microscopy method. Our structure-based mutagenesis and functional analyses suggest that the substrate translocation pathways for the driving substance protons and the substrate sodium ions are separated in two modules and that symmetry-restrained conformational change underlies the functional cycle of the transporter. Our findings shed light on mechanisms of redox-driven primary active transporters, and explain how driving substances of different electric charges may drive similar transport processes.

Membrane vesicles (MVs) released from bacteria act as extracellular vehicles carrying various functional cargoes between cells. MVs with different cargoes play multiple roles in stress adaptation, nutrient acquisition and microbial interactions. However, previous studies have primarily focused on MVs from Gram-negative bacteria, while the characteristics of cargoes in MVs from Gram-positive bacteria and their involvement in microbial interactions remain to be elucidated. Here, we used a Gram-positive strain, Dietzia sp. DQ12-45-1b from Corynebacteriales, to analyse the characteristics and functions of MVs. We identified the 'antioxidant' canthaxanthin is stored within MVs by LC-MS/MS. In addition, nearly the entire genomic content of strain DQ12-45-1b are evenly distributed in MVs, suggesting that MVs from DQ12-45-1b might involve in horizontal gene transfer. Finally, the mycobactin-type siderophores were detected in MVs. The iron-loaded MVs effectively mediate iron binding and delivery to homologous bacteria from the order Corynebacteriales, but not to more distantly related species from the orders Pseudomonadales, Bacillales and Enterobacterales. These results revealed that the iron-loaded MVs are shared between homologous species. Together, we report the Gram-positive bacterium Dietzia sp. DQ12-45-1b released MVs that contain canthaxanthin, DNA and siderophores and prove that MVs act as public goods between closely related species.

Microbes spontaneously release membrane vesicles (MVs), which play roles in nutrient acquisition and microbial interactions. Iron is indispensable for microbes, but is a difficult nutrient to acquire. However, whether MVs are also responsible for efficient iron uptake and therefore involved in microbial interaction remains to be elucidated. Here, we used a Gram-positive strain, Dietzia sp. DQ12-45-1b, to analyze the function of its MVs in heme-iron recycling and sharing between species. We determined the structure and constituent of MVs and showed that DQ12-45-1b releases MVs originating from the mycomembrane. When comparing proteomes of MVs between iron-limiting and iron-rich conditions, we found that under iron-limiting conditions, heme-binding proteins are enriched. Next, we proved that MVs participate in extracellular heme capture and transport, especially in heme recycling from environmental hemoproteins. Finally, we found that the heme carried in MVs is utilized by multiple species, and we further verified that membrane fusion efficiency and species evolutionary distance determine heme delivery. Together, our findings strongly suggest that MVs act as a newly identified pathway for heme recycling, and represent a public good shared between phylogenetically closely related species.

There has been growing interest in preparing silver nanoparticles (AgNPs) under mild conditions in short time and using AgNPs to detect hydrogen peroxide. Here, we report the facile preparation of AgNPs by co-incubating AgNO3 and ionic liquid (IL) 1-carboxymethyl-3-methylimidazolium nitrate (HO2CMIMNO3) modified carbon dots (NO3-CDs) under mild circumstance in 10 s without extra reductant. Mechanism investigations indicate that the strong electronegativity and steric effect of the anionic moiety of IL endow the CDs high affinity toward Ag+ and facilitates the fast fabrication of AgNPs. The resultant NO3-CD/AgNP hybrid exhibits absorbance fading behavior toward H2O2 and the decrease in absorbance at 415 nm provides accurate detection within 0.1–10 µmol L−1, along with a detection limit of 0.087 µmol L−1. The colorimetric method is successfully applied to H2O2 detection in urine and lake water sample with satisfactory recoveries. Moreover, the fluorescence “off–on” phenomena of NO3-CD/AgNP hybrid in the presence of H2O2, offers successful monitor on the fluctuation of H2O2 in human breast cancer (MCF-7) cells. This work provides a fast approach to CD/AgNP hybrid, and demonstrates its potential as sensing probe for H2O2 in lake water, urine, and living cells by making full use of the absorbance and fluorescence of the hybrid. Silver nanoparticles are prepared in 10 s with IL-CDs as reductant and are employed as colorimetric and fluorescent probe for H2O2 in real samples and living cells.

Atherosclerosis (AS) is the leading cause of heart attacks, stroke, and peripheral vascular disease. Berberine (BBR), a botanical medicine, has diversified anti-atherosclerotic effects but with poor absorption. The aim of this study was to develop an effective BBR-entrapped nano-system for treating AS in high-fat diet (HFD)-fed Apoe(−/−) mice, and also explore the possible underlying mechanisms involved. Three d-α-tocopherol polyethylene glycol (PEG) succinate (TPGS) analogues with different PEG chain lengths were synthesized to formulate BBR-entrapped micelles. HFD-fed Apoe(−/−) mice were administered with optimized formula (BBR, 100 mg/kg/day) orally for 5 months. The artery plaque onset and related metabolic disorders were evaluated, and the underlying mechanisms were studied. Our data showed that, BT1500M increased BBR deposition in liver and adipose by 107.6% and 172.3%, respectively. In the Apoe(−/−) mice, BT1500M ameliorated HFD-induced hyperlipidemia and lipid accumulation in liver and adipose. BT1500M also suppressed HFD-induced chronic inflammation as evidenced by the reduced liver and adipose levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β); and decreased plasma level of TNF-α, IL-6, IL-1β, interferon-γ (IFN-γ), monocyte chemotactic protein (MCP), and macrophage inflammatory factor (MIP). The mechanism study showed that BT1500M changed Ampk and Nf-κb gene expression, and interrupted a crosstalk process between adipocytes and macrophages. Further investigation proved that BT1500M decreased endothelial lesion and subsequent macrophage activation, cytokines release, as well as cholesteryl ester gathering in the aortic arch, resulting in ameliorated artery plaque build-up. Our results provide a practical strategy for treating AS using a BBR-entrapped nano-system., Graphical abstract BT1500M, which increased gut-absorption and intra-cellular uptake of berberine, modulated AMPK and NF-κB expression, and improved dyslipidemia and inflammation induced by high fat diet. The endothelial injury and subsequent macrophage infiltration and cholesteryl ester gathering in the aortic arch were decreased, resulting in the inhibition of artery plaque build-up.Image 1

In this work, well-defined two-dimensional metallacycles have been successfully employed for the well-controlled self-assembly of gold nanoparticles (AuNPs) into discrete clusters such as dimers, trimers, tetramers, pentamers and even hexamers at the water-oil interface for the first time. Furthermore, the modular construction of metallacycle molecules allows precise control of spacing between the gold nanoparticles. Interestingly, it was found that interparticle spacing below 5 nm created by molecular metallacycles in the resultant discrete gold nanoparticle clusters led to a strong plasmon coupling, thus inducing great field enhancement inside the gap between the NPs. More importantly, different discrete clusters with precise interparticle spacing provide a well-defined system for studying the hot-spot phenomenon in surface-enhanced Raman scattering (SERS); this revealed that the SERS effects were closely related to the interparticle spacing.