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Aim: The high incidence and prevalence of fungal infections call for new antifungal drugs. This work was to develop naphthalimide thiazoles as potential antifungal agents. Results & methodology: These compounds showed significant antifungal potency toward some tested fungi. Especially, naphthalimide thiazole 4h with excellent anti- Candida tropicalis efficacy possessed good hemolysis level, low toxicity and no obvious resistance. Deciphering the mechanism showed that 4h interacted with DNA and disrupted the antioxidant defense system of C. tropicalis. Compound 4h also triggered membrane depolarization, leakage of cytoplasmic contents and LDH inhibition. Simultaneously, 4h rendered metabolic inactivation and eradicated the formed biofilms of C. tropicalis. Conclusion: The multifaceted synergistic effect initiated by naphthalimide thiazoles is a reasonable treatment window for prospective development.

An interesting β-isoquinidine catalyzed divergent reaction was developed to produce either spirocyclopentene oxindoles, spirocyclopentadiene oxindoles or bisoxindoles in a high enantioselective fashion. The utility of this protocol was demonstrated by the versatile transformations of the products. This work not only represents the first highly stereoselective intermolecular catalytic asymmetric allylic alkylation reaction between two isatin-derived MBH carbonate molecules but also constitutes a rare example of isatin-derived MBH carbonate-based enantioselective and α-regioselective [3+2] cycloaddition reactions.

Zinc tin oxide (ZTO) thin films can be deposited by atomic layer deposition (ALD) with adjustable electrical, optical and structural properties. However, the ternary ALD processes usually suffer from low growth rate and difficulty in controlling film thickness and elemental composition, due to the interaction of ZnO and SnO2 processes. In this work, ZTO thin films with different Sn levels are prepared by ALD super cycles using diethylzinc, tetrakis(dimethylamido)tin, and water. It is observed that both the film growth rate and atom composition show nonlinear variation versus [Sn]/([Sn]+[Zn]) cycle ratio. The experimental thickness measured by spectroscopic ellipsometry and X-ray reflectivity are much lower than the expected thickness linearly interpolated from pure ZnO and SnOx films. The [Sn]/([Sn]+[Zn]) atom ratios estimated by X-ray photoelectron spectroscopy have higher values than that expected from the cycle ratios. Hence, to characterize the film growth behavior versus cycle ratio, a numerical method is proposed by simulating the effect of reduced density and reactivity of surface hydroxyls and surface etching reactions. The structure, electrical and optical properties of ZTO with different Sn levels are also examined by X-ray diffraction, atomic force microscope, Hall measurements and ultraviolet–visible–infrared transmittance spectroscopy. The ZTO turns out to be transparent nanocrystalline or amorphous films with smooth surface. With more Sn contents, the film resistivity gets higher (>1 Ω cm) and the optical bandgap rises from 3.47 to 3.83 eV.

Natural berberine-hybridized benzimidazoles as potential antibacterial agents were constructed to treat Staphylococcus aureus infection in the livestock industry. Bioassay showed that some new berberine-benzimidazole hybrids exhibited potent antibacterial efficacies, especially, the 2,4-dichlorobenzyl derivative 7d not only showed strong activity against S. aureus ATCC 29213 with the MIC value of 0.006 mM but also effectively eradicated bacterial biofilm and exhibited low toxicity toward mammalian cells. The drug combination experiments showed that compound 7d together with norfloxacin could enhance the antibacterial efficacy. Moreover, the 2,4-dichlorobenzyl derivative 7d did not show obvious propensity to develop bacterial resistance. Preliminary mechanism studies revealed that the active molecule 7d could damage the membrane integrity, stimulate ROS generation, and bind with DNA as well as S. aureus sortase A, thus exerting powerful antibacterial ability. In light of these facts, berberine-benzimidazole hybrid 7d showed a large potentiality as a new bactericide for treating S. aureus in the livestock industry.

In the niches that Staphylococcus aureus and Pseudomonas aeruginosa coinhabit, the later pathogen produces phenazine antibiotics to inhibit the growth of S. aureus. Recently, a group of halogenated phenazines (HPs) has been shown to have potent antimicrobial activities against Staphylococci; however, no HP-resistant mutant has been reported. Here, we demonstrate that S. aureus develops HP-resistance via single amino acid change (Arg116Cys) in a transcriptional repressor TetR21. RNA-seq analysis showed that the TetR21R116C variation caused drastic up-regulation of an adjacent gene hprS (halogenated phenazine resistance protein of S. aureus). Deletion of the hprS in the TetR21R116C background restored bacterial susceptibility to HP, while hprS overexpression in S. aureus conferred HP-resistance. The expression of HprS is under tight transcriptional control of the TetR21 via direct binding to the promoter region of hprS. The R116C mutation in TetR21 significantly reduced its DNA binding affinity. Moreover, natural phenazine antibiotics (phenazine-1-carboxylic acid and pyocyanin) and a HP analog (HP-22) are ligands for the TetR21, regulating its repressor activity. Combining homology analysis and LC-MS/MS assay we demonstrated that HprS is a phenazine efflux pump. To the best of our knowledge, we provide the first report of phenazine efflux pump in S. aureus. Interestingly, the TetR21R116C variation has been found in some clinical S. aureus isolates, and a laboratory strain of S. aureus with TetR21R116C variation showed enhanced growth competitiveness toward P. aeruginosa and promoted coinfection with P. aeruginosa in the host environment, demonstrating significance of the mutation in host infections.

The ability to access structurally diverse and complex compounds efficiently and economically from readily available starting materials is an important goal in organic synthesis and medicinal chemistry. Herein, DABCO-catalyzed reactions between isatin-derived MBH carbonates and 3-formylchromones selectively leading to either benzopyrone fused spirocyclopentene oxindoles or spirocyclopentadiene 2-oxindoles incorporating a 2-hydroxybenzoyl moiety are described. Interestingly, in the absence of 3-formylchromones, the first synthesis of bisoxindoles containing highly functionalized tri- and tetra-substituted alkene groups can be achieved using the same catalytic system. In this case, the in situ generated tert-butyl carbonate anion (BocO−), which is usually produced as a precursor of the tert-butoxide anion (tBuO−) or as waste, could be finely merged into the products as an efficient nucleophilic partner. Importantly, this tunable approach not only represents a rare example of isatin-derived MBH carbonate-based α-regioselective [3 + 2] annulations, but also constitutes the first intermolecular allylic alkylation reaction between two isatin-derived MBH carbonate molecules.

Two-component systems (TCS), which typically consist of a membrane-embedded histidine kinase and a cytoplasmic response regulator, are the dominant signaling proteins for transduction of environmental stimuli into cellular response pathways in prokaryotic cells. HptRSA is a recently identified TCS consisting of the G6P-associated sensor protein (HptA), transmembrane histidine kinase (HptS), and cytoplasmic effector (HptR). HptRSA mediates glucose-6-phosphate (G6P) uptake to support Staphylococcus aureus growth and multiplication within various host cells. How the mechanism by which HptRSA perceives G6P and triggers a downstream response has remained elusive. Here, we solved the HptA structures in apo and G6P-bound states. G6P binding in the cleft between two HptA domains caused a conformational closing movement. The solved structures of HptA in complex with the periplasmic domain of HptS showed that HptA interacts with HptS through both constitutive and switchable interfaces. The G6P-free form of HptA binds to the membrane-distal side of the HptS periplasmic domain (HptSp), resulting in a parallel conformation of the HptSp protomer pair. However, once HptA associates with G6P, its intramolecular domain closure switches the HptA-HptSp contact region into the membrane-proximal domain, which causes rotation and closure of the C termini of each HptSp protomer. Through biochemical and growth assays of HptA and HptS mutant variants, we proposed a distinct mechanism of interface switch-mediated signaling transduction. Our results provide mechanistic insights into bacterial nutrient sensing and expand our understanding of the activation modes by which TCS communicates external signals.

Significance of unstable species leaching was for the first time demonstrated on MOF-derived catalysts by taking PtNi-C as an example, that was instructive for the relevant catalyst fabrication and performance study. PtNi-C catalyst was synthesized by combining Pt nanoparticles with Ni-BTC after annealing in the tube furnace and the unstable Ni species can be easily leached out in nitric acid, and the stable PtNi nanoparticles trapped in the graphite carbon layer were obtained. The greatly improved catalytic ability for alcohol fuels oxidation was verified by comparing the fresh and acid leached catalysts in terms of the high peak current density, specific and mass activity and rapid charge transfer kinetics and high catalytic stability. The current work guides the importance of unstable assistant promoter removal for the MOF derived catalysts.

Graphene oxide (GO), an important chemical precursor of graphene, can stably disperse in aqueous surrounding and undergo aggregation as metal cations introduced. The usual instability of GO with ions is caused by the shielding effect of ions and crosslinking between GO and ions. However, the dynamic stability of GO under ions exchange still remains unclear. Here, we investigated the dynamic dispersion stability of GO with metal ions and observed a redispersion behavior in concentrated Fe3+ solution, other than permanent aggregation. The exchange with Fe3+ ions drives the reversion of Zeta (ζ) potential and enables the redispersion to individual GO-Fe3+ complex sheets, following a dynamic electric double layer (EDL) mechanism. It is found that the specifically strong electrostatic shielding effect and coordination attraction between Fe3+ and functional oxygen groups allows the selective redispersion of GO in concentrated Fe3+ solution. The revealed dynamic dispersion stability complements our understanding on the dispersive stability of GO and can be utilized to fabricate graphene-metal hybrids for rich applications.

Separators are key materials to ensure the safety of lithium-ion batteries and improve their performance. Currently, commercial lithium-ion battery separators are mainly polyolefin organic diaphragms, but their temperature instability leads to battery short circuit and fire risk. A flexible SiO2 nanofiber membrane combined with a poly(vinylidene fluoride-hexafluoropropylene) (PVDF-HFP) nanofiber membrane is prepared by an electrospinning method. The mechanical strength of the SiO2/PVDF-HFP composite nanofiber membrane (SPF) is twice as high as the pure SiO2 nanofiber membrane and at 200°C, there are almost no dimensional changes of the SPF separators. Compared to commercial polyethylene (PE) separators, SPF shows excellent thermal stability and large-area closed cells at 180°C when used in lithium-ion battery separators. The porosity of SPF is 89.7%, which is more than twice than that of an ordinary PE separator. The liquid absorption rate of SPF is much higher than an ordinary PE separator and has reached 483%. Furthermore, the cycle and rate performance of lithium-ion batteries prepared by SPF has been improved significantly. These excellent properties, as well as the potential for large-scale production of electrospinning technology, make SPF an ideal choice for high-power battery separators.

Tangshan city in Hebei Province is one of the most heavily polluted cities in China, with substantial industrial emissions. The development of effective air pollution emission reduction policies requires knowledge of the sources and health risks of polycyclic aromatic hydrocarbon (PAH)-enriched fine particulate matter (PM2.5 ). We investigated the seasonal variation and source apportionment of 16 priority PAH-enriched PM2.5 samples in Tangshan during 2014 and 2015, and we assessed the health risks associated with inhalation exposure to PAHs. The PM2.5 samples were collected from April 2014 to February 2015. We analyzed the concentrations of PM2.5 and PAH-enriched PM2.5 , and used principal component analysis and molecular diagnostic ratios to identify potential sources. We explored the relationship between distribution and meteorological conditions, and used an incremental lifetime cancer risk (ILCR) model to quantitatively evaluate exposure from the inhalation risk of PAHs. The average mass concentration of PM2.5 was 196 µg/m3 , with a range 34.0 to 586 µg/m3 . The median ∑16 PAH values in PM2.5 were 190 ng/m3 , with a range of 60.2 to 862 ng/m3 over the sampling period. The order of ∑16 PAHs concentration was winter > autumn > summer > spring. The results show that the primary sources of PAH-enriched PM2.5 are coal combustion, vehicle exhaust, and biomass burning. The annual mean of benzo[a]pyrene (BaP) was 8.37 ng/m3 , more than 8-fold greater than the BaP annual standard (1 ng/m3 ) set by the Chinese State Environmental Protection Agency. The ILCR values for 3 groups (children, teenagers, and adults) over the 4 seasons were between 10-6 and 10-4 , indicating a potential health risk from PAHs in Tangshan. Environ Toxicol Chem 2020;39:458-467. © 2019 SETAC.

C24H17NO5, triclinic, P1̄ (no. 2), a = 8.5858(2) Å, b = 9.2397(4) Å, c = 13.7831(8) Å, α = 97.11(3)°, β = 103.23(3)°, γ = 113.33(3)°, V = 948.8(2) Å3, Z = 2, R gt(F) = 0.0545, wR ref(F 2) = 0.1669, T = 296(2) K.

Occurring in hops (Humulus lupulus) and beer as a racemic mixture, (2R,2S)-8-prenylnaringenin (8-PN) is a potent phytoestrogen in hop dietary supplements used by women as alternatives to conventional hormone therapy. With a half-life exceeding 20 h, 8-PN is excreted primarily as 8-PN-7-O-glucuronide or 8-PN-4'-O-glucuronide. Human liver microsomes and 11 recombinant human UDP-glucuronosyltransferases (UGTs) were used to catalyze the formation of the two oxygen-linked glucuronides of purified (2R)-8-PN and (2S)-8-PN, which were subsequently identified using mass spectrometry and nuclear magnetic resonance spectroscopy. Formation of (2R)- and (2S)-8-PN-7-O-glucuronides predominated over the 8-PN-4'-O-glucuronides except for intestinal UGT1A10, which formed more (2S)-8-PN-4'-O-glucuronide. (2R)-8-PN was a better substrate for all 11 UGTs except for UGT1A1, which formed more of both (2S)-8-PN glucuronides than (2R)-8-PN glucuronides. Although several UGTs conjugated both enantiomers of 8-PN, some conjugated just one enantiomer, suggesting that human phenotypic variation might affect the routes of metabolism of this chiral estrogenic constituent of hops.

The biomonitoring of hydroxy polycyclic aromatic hydrocarbons in urine, as a direct way to access multiple exposures to polycyclic aromatic hydrocarbons, has raised great concerns due to their increasing hazardous health effects on humans. Solid-phase extraction is an effective and useful technique to preconcentrate trace analytes from biological samples. Here, we report a novel solid-phase extraction method using a graphene oxide incorporated monolithic syringe for the determination of six hydroxy polycyclic aromatic hydrocarbons in urine coupled with liquid chromatography-tandem mass spectrometry. The effect of graphene oxide amount, washing solvent, eluting solvent, and its volume on the extraction performance were investigated. The fabricated monoliths gave higher adsorption efficiency and capacity than the neat polymer monolith and commercial C18 sorbent. Under the optimum conditions, the developed method provided the detection limits (S/N = 3) of 0.02-0.1 ng/mL and the linear ranges of 0.1-1500 ng/mL for six analytes in urine sample. The recoveries at three spiked levels ranged from 77.5 to 97.1%. Besides, the intra column-to-column (n = 3) and inter batch-to-batch (n = 3) precisions were ≤ 9.8%. The developed method was successfully applied for the determination of hydroxy polycyclic aromatic hydrocarbons in urine samples of coke oven workers.

The known chalcone (±)-sanjuanolide (1) can be isolated from Dalea frutescens. This study presents a convergent strategy for the first total synthesis of ( R)-, ( S)-, and (±)-sanjuanolide (1). The key step for synthesizing ( R)- and ( S)-1 was a Corey-Bakshi-Shibata enantioselective carbonyl reduction to construct the C-2″ configuration. ( R)-1 efficiently inhibited the lipopolysaccharides (LPS)-induced expression of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), while ( S)-1 produced no significant anti-inflammatory effect. ( R)-1 also effectively inhibited the mRNA expression of several inflammatory cytokines after the LPS challenge in vitro. The synthesis and biological properties of these compounds have confirmed ( R)-sanjuanolide and (±)-sanjuanolide as promising new leads for developing anti-inflammatory agents.

Ultrafine Pt nanocrystals with an average particle size of 2.2 ± 1 nm coupled over the petaloid Fe2P surface are proposed as a novel, efficient, and robust catalyst for alcohol fuel electro-oxidation. The strong coupling effect of metal-support imparts a strong electronic interaction between the Fe2P and Pt interface that can weaken the adsorption of poisoning CO species according to the d-band theory. Defects and increased surface area of the petaloid Fe2P are beneficial to the Pt nanoparticle anchoring and dispersion as well as the charge transfer and reactant transportation during the electrochemical reaction. These features make the Pt-Fe2P catalyst system exhibit excellent catalytic activity, antipoisoning ability, and catalytic stability for alcohol fuel of methanol and ethanol electro-oxidation compared with a controlled Pt/C catalyst. The high catalytic efficiency is proposed to come from the strong coupling effect of Pt and petaloid Fe2P interface that can maintain the mechanical and chemical stability of the catalyst system. This kind of phosphide-supported ultrafine Pt nanocrystals will be a promising catalyst in fuel cells.

Association of soft tissue infection in the extremity with glucose and lipid metabolism as well as inflammatory factors was investigated. One hundred and twenty-six patients with diabetes mellitus (DM) complicated with soft tissue infection in the lower extremity admitted and treated in Dongying People's Hospital from March 2016 to February 2017 were selected and divided into mild (n=46), moderate (n=43) and severe group (n=37) according to the severity of the soft tissue infection in the lower extremity. The glucose and lipid metabolism, inflammatory factors and influencing factors were compared among different groups of patients before treatment, and the changes in glucose and lipid metabolism as well as inflammatory factors were observed after treatment. Before treatment, the levels of free fatty acid (FFA), fasting plasma glucose (FPG), fasting insulin (FINS), vascular cell adhesion molecule-1 (VCAM-1), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in mild group were remarkably lower than those in moderate and severe groups, while the serum adiponectin (APN) level was obviously higher (P

Toll-like receptor 4 (TLR4) and TLR4 interactor with leucine-rich repeats (TRIL) play a crucial role in the inflammatory response. This study investigated the role of long noncoding RNA taurine-upregulated gene 1 (lncRNA TUG1) in TRIL/TLR4 signaling in spinal cord ischemia reperfusion (IR) injury. IR injury was induced in experimental rats; knockdown of TUG1 and TRIL was induced by intrathecal injection of siRNAs and overexpression of TRIL was induced by pcDNA3.3-TRIL. The results showed that the mRNA levels of TUG1 were increased at 12 hours after IR; this was accompanied by increased expression of the TRIL- and TLR4-mediated NF-κB/IL-1β signaling pathway. Activated microglia, detected with increased ionized calcium-binding adapter molecule 1 as a marker, exacerbated the hind-limb neurological impairment and blood-spinal cord barrier (BSCB) leakage after IR. TUG1 knockdown inhibited expression of TRIL and TLR4 signaling proinflammatory cytokines and microglial activation, and attenuated neurological deficit and BSCB leakage. TRIL knockdown inhibited the TLR4-mediated inflammatory response, while TRIL expression reversed the inhibited inflammatory effect caused by TUG1 knockdown. These data suggest that TUG1 knockdown inhibited inflammatory damage of the TLR4-mediated NF-κB/IL-1β signaling pathway after IR via suppressing TRIL expression.

Engineering graphene into a particular shape is vital for potential industrial applications. To this end, better understanding of the growth mechanism is needed to control the growth behavior of graphene on a substrate surface with a specific shape. In this work, a tetragon-shaped graphene single crystal (TS_GSC) with millimeter-scale grain size was achieved on copper foil, which was annealed at oxygen-free conditions (AOF) prior to graphene growth. The TS_GSC grains are featured by two dendritic Frontiers at the shorter-edge (SE) sides and two sharp Frontiers at the longer-edge (LE) sides of graphene grain. By combining scanning electron microscopy, optical microscopy, and Raman mapping with carbon isotope labeling, we revealed for the first time an asymmetric growth behavior of TS_GSC grains on an AOF-treated copper substrate. It was supposed that the growth of graphene was determined by the diffusion-limited aggregation mechanism at the SE side, whereas it was governed by the edge-determined atom-attac...

Plenty of biological materials are constructed from repeated unit cells with handed configurations, wherein the hierarchical self-assembly of handed units confers optimized mechanical properties and environmental adaptability to bulk biological materials. Inspired by biological handed architectures, we propose handedness-controlled and solvent-driven actuators by programming twisted fibers, such as twisted graphene oxide fibers (TGFs), with mirrored handedness, mechanical robustness and superb flexibility. The large twists (beyond 4800 turns per meter), hair-like diameter (down to 63 μm), large tensile strain (29%) and light weight (1.49 g cm−3) of TGFs enable them to provide a large start-up torque of 2.7 × 10−7 N m, and to deliver a record rotor kinetic power of 89.3 W kg−1 when stimulated by polar solvents such as acetone and water. By assembling handed TGF units, we achieve precise outputting of rotor kinetic energy (from 0.78 W kg−1 to 12.5 W kg−1), controllable harvesting of electrical energy (from 2.37 W kg−1 to 11.5 W kg−1), and free handling of a heavy object. The activeness, inertness and operation of all the actuating systems are well controlled by the handedness of TGF units. They are highly stable and reversible, and maintain a high energy output efficiency over multiple operation cycles. These handedness-controlled systems are also extended to hybrid twisted fibers containing nanocomposites and polymers, indicating their general practicability. Handedness-controlled actuators open an alternative avenue for fabricating energy harvesters, responsive textiles, electronic skins and soft robots.

A Gram-stain-positive, rod-shaped bacterial strain, 22-7T, was isolated from ocean sediment of Laizhou Bay, China, and was characterized by using a polyphasic approach. Optimal growth was observed at 33 °C on a 2216E agar plate of pH 7.5 and with 2 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences identified it as a member of the genus Jeotgalibacillus , most similar to Jeotgalibacillus campisalis SF-57T (98.7 % similarity), Jeotgalibacillus marinus DSM 1297T (98.2 %) and Jeotgalibacillus soli P9T (97.1 %). Average nucleotide identity values and digital DNA–DNA hybridization values were less than 74.2 and 18.1 %, respectively, between strain 22-7T and the type strains of closely related species. The major polar lipids were aminophospholipid, phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol; the major fatty acids (>10 %) were anteiso-C15 : 0 and iso-C15 : 0; and the major menaquinone was MK-7. The peptidoglycan type of the cell wall was A1α linked through l-lysine as the diamino acid. Combined data from phenotypic, chemotaxonomic and genotypic characterizations demonstrated that strain 22-7T represents a novel Jeotgalibacillus species, for which the name Jeotgalibacillus proteolyticus sp. nov. is proposed. The type strain is 22-7T(=MCCC 1H00228T=KCTC 33930T).

An unprecedented amount of fungal and fungal-like infections has recently brought about some of the most severe die-offs and extinctions due to fungal drug resistance. Aimed to alleviate the situation, new effort was made to develop novel purinylthiazolylethanone derivatives, which were expected to combat the fungal drug resistance. Some prepared purinylthiazolylethanone derivatives possessed satisfactory inhibitory action towards the tested fungi, among which compound 8c gave a MIC value of 1 μg/mL against C. albicans. The active molecule 8c was able to kill C. albicans with undetectable resistance as well as low hematotoxicity and cytotoxicity. Furthermore, it could hinder the growth of C. albicans biofilm, thus avoiding the occurrence of drug resistance. Mechanism research manifested that purinylthiazolylethanone derivative 8c led to damage of cell wall and membrane disruption, so protein leakage and the cytoplasmic membrane depolarization were observed. On this account, the activity of fungal lactate dehydrogenase was reduced and metabolism was impeded. Meanwhile, the increased levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) disordered redox equilibrium, giving rise to oxidative damage to fungal cells and fungicidal effect.

Directed evolution (DE) inspired by natural evolution (NE) has been achieving tremendous successes in protein/enzyme engineering. However, the conventional ‘one-protein-for-one-task’ DE cannot match the ‘multi-proteins-for-multi-tasks’ NE in terms of screening throughput and efficiency, thus often failing to meet the fast-growing demands for biocatalysts with desired properties. In this study, we design a novel ‘multi-enzyme-for-multi-substrate’ (MEMS) DE model and establish the proof-of-concept by running a NE-mimicking and higher-throughput screening on the basis of ‘two-P450s-against-seven-substrates’ (2P×7S) in one pot. With the significantly improved throughput and hit-rate, we witness a series of convergent evolution events of the two archetypal cytochrome P450 enzymes (P450 BM3 and P450cam) in laboratory. Further structural analysis of the two functionally convergent P450 variants provide important insights into how distinct active-sites can reach a common catalytic goal.

BackgroundNeuroinflammation and cellular apoptosis caused by spinal cord ischemia/reperfusion (I/R) injury result in neurological dysfunction. MicroRNAs (miRs) have crucial functions in spinal cord I/R injury pathogenesis according to previous evidences. Herein, whether miR-128-3p contributes to spinal cord I/R injury by regulating specificity protein 1 (SP1) was assessed.MethodsA rat model of spinal cord I/R injury was established by occluding the aortic arch for 14 min. Then, miR-128-3p’s interaction with SP1 was detected by dual-luciferase reporter assays. Next, miR-128-3p mimic and inhibitor, as well as adenovirus-delivered shRNA specific for SP1 were injected intrathecally for assessing the effects of miR-128-3p and SP1 on rats with spinal cord I/R injury. SP1, Bax and Bcl-2 expression levels in I/R injured spinal cord tissues were evaluated by Western blotting, while IL-1β, TNF-α, and IL-6 were quantitated by ELISA. Tarlov scores were obtained to detect hind-limb motor function. Evans blue (EB) dye extravasation was utilized to examine blood–spinal cord barrier (BSCB) permeability. Terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) staining was performed for neuronal apoptosis assessment.ResultsMiR-128-3p expression was decreased, while SP1 amounts were increased in rat spinal cord tissue specimens following I/R. SP1 was identified as a miR-128-3p target and downregulated by miR-128-3p. MiR-128-3p overexpression or SP1 silencing alleviated I/R-induced neuroinflammation and cell apoptosis, and improved Tarlov scores, whereas pretreatment with miR-128-3p inhibitor aggravated the above injuries.ConclusionOverexpression of miR-128-3p protects neurons from neuroinflammation and apoptosis during spinal cord I/R injury partially by downregulating SP1.

Cadmium (Cd) is a toxic nonessential metal that poses a health risk for humans. Cd is easily accumulated in leaf vegetables than in other vegetables. Leafy vegetables are one of the major dietary Cd sources for the human body. In this study, pak choi was used as our experimental material as it is an important leafy vegetable, especially in Asia. A NRAMP transporter - BcNRAMP1 was identified in pak choi, which is involved in manganese (Mn) and Cd uptake in yeast and in planta. BcNRAMP1 is expressed in the whole plant body of pak choi, with a higher abundance in root tissues than in shoots. Mn deficiency and Cd exposure strongly induced BcNRAMP1 transcription levels. Through transient expression of BcNRAMP1-GFP fusion protein in tobacco leaf epidermal cells, BcNRAMP1 was revealed as a plasma membrane protein. Expressing BcNRAMP1 in yeast enhanced yeast cells to absorb Mn, Cd, and iron (Fe). Overexpression of BcNRAMP1 in Arabidopsis wild-type and nramp1 mutant increased and complemented Mn and Cd transportation and accumulation, respectively. Using noninvasive microelectrode ion flux measurements, a direct evidence that BcNRAMP1 acts on Cd influx in Arabidopsis root cells was provided. The results of this study reveal that BcNRAMP1 functions as a NRAMP protein in planta, absorbing nutrient metal Mn and the toxic metal Cd.

Background Spinal cord ischemia/reperfusion injury (SCII) is one of the most serious spinal cord complications that stem from varied spine injuries or thoracoabdominal aortic surgery. Nevertheless, the molecular mechanisms underlying the SCII remain unclear. Methods Male Sprague-Dawley (SD) rats were randomly divided into 5 groups of sham, SCII 24 h, SCII 72 h, sevoflurane preconditioning SCII 24 h (SCII 24 h+sevo), and sevoflurane preconditioning SCII 72 h (SCII 72 h+sevo) group. We then analyzed the expression of differentially expressed micro RNAs (DEmiRNAs) in these groups and their target genes. Functional enrichment analysis of their target genes was further performed using Metascape software. The microRNA-messenger RNA-pathway (miRNA-mRNA-pathway) network and the sevoflurane-miRNA-mRNA-pathway integrative network were further constructed to explore the molecular mechanisms underlying SCII and neuroprotective effects of sevoflurane against SCII. Molecular docking was also performed to evaluate the interactions between hub targets and sevoflurane. Finally, the expression levels of miR-21-5p and its target genes [mitogen-activated protein kinase kinase 3 and protein phosphatase 1 regulatory subunit 3B (MAP2K3 and PPP1R3B)] were measured using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot analyses. Results We found that sevoflurane alters several miRNA expression following SCII at 24 and 72 h after reperfusion. It was shown that miR-221-3p, miR-181a-1-3p, and miR-21-5p were upregulated both at 24 and 72 h in the sevoflurane pre-treatment reperfusion groups. Functional enrichment analysis revealed that target genes for the above co-DEmiRNAs at 24 and 72 h in the SCII group with sevoflurane pretreatment participated in the mitogen-activated protein kinase (MAPK), ErbB, apoptosis, and transforming growth factor-beta (TGF-beta) signaling pathways. Both MAP2K3 and PPP1R3B were found to be common targets for sevoflurane and miRNA-mRNA-pathway (rno-miR-21-5p). It was shown that MAP2K3 regulates the MAPK signaling and the T cell receptor signaling pathways, whereas PPP1R3B regulates the ErbB signaling pathway. Molecular docking further revealed that sevoflurane strongly binds the MAP2K3 and PPP1R3B proteins. Compared to the sham group, SCII induced significant under-expression of miR-21-5p but upregulated PPP1R3B and MAP2K3 proteins; sevoflurane pretreatment increased the expression of miR-21-5p but decreased those of PPP1R3B and MAP2K3 proteins. Conclusions In general, sevoflurane regulates the expression of several miRNAs following SCII. In particular, sevoflurane might protect against SCII via regulating the expression of miR-21-5p, its target genes (MAP2K3 and PPP1R3B), and related signaling pathways.

Long noncoding RNAs and microRNAs (miRNAs) play a vital role in spinal cord ischemia reperfusion (IR) injury. The aim of this study was to identify the potential interactions between taurine upregulated gene 1 (TUG1) and miRNA-29b-1-5p in a rat model of spinal cord IR. The IR injury was established by 14-minute occlusion of aortic arch. TUG1 and metadherin (MTDH) knockdown were induced by respective siRNAs, and miR-29b-1-5p expression was modulated using specific inhibitor or mimics. The interactions between TUG1, miR-29b-1-5p, and the target genes were determined using the dual-luciferase reporter assay. We found that IR respectively downregulated and upregulated miR-29b-1-5p and TUG1, and significantly increased MTDH expression. MTDH was predicted as a target of miR-29b-1-5p and its knockdown downregulated NF-κB and IL-1β levels. A direct interaction was observed between TUG1 and miR-29b-1-5p, and knocking down TUG1 upregulated the latter. Furthermore, overexpression of miR-29b-1-5p or knockdown of TUG1 alleviated blood-spinal cord barrier leakage and improved hind-limb motor function by suppressing MTDH and its downstream pro-inflammatory cytokines. Knocking down TUG1 also alleviated MTDH/NF-κB/IL-1β pathway-mediated inflammatory damage after IR by targeting miR-29b-1-5p, whereas blocking the latter reversed the neuroprotective effect of TUG1 knockdown and restored MTDH/NF-κB/IL-1β levels.

A method for the intermolecular annulation of benzynes with allenes is disclosed. This protocol utilized allenes as an unconventional diene component for the selective synthesis of phenanthrenes and dihydrophenanthrenes under the control of different benzyne precursors, featuring high atom-economy and good functional group compatibility. Density functional theory (DFT) calculations reveal that different migratory routes of the aromatic C-H bond are crucial for the observed selectivity.

MicroRNAs (miRNAs) regulate protein expression by antagonizing the translation of mRNAs and are effective regulators of normal nervous system development, function, and disease. MicroRNA-29b (miR-29b) plays a broad and critical role in brain homeostasis. In this study, we tested the function of miR-29b in animal and cell models by inhibiting miR-29b expression. Mouse models of middle cerebral artery occlusion were established using the modified Zea-Longa suture method. Prior to modeling, 50 nmol/kg miR-29b antagomir was injected via the tail vein. MiR-29b expression was found to be abnormally increased in ischemic brain tissue. The inhibition of miR-29b expression decreased the neurological function score and reduced the cerebral infarction volume and cell apoptosis. In addition, the inhibition of miR-29b significantly decreased the malondialdehyde level, increased superoxide dismutase activity, and Bcl-2 expression, and inhibited Bax and Caspase3 expression. PC12 cells were treated with glutamate for 12 hours to establish in vitro cell models of ischemic stroke and then treated with the miR-29 antagomir for 48 hours. The results revealed that miR-29b inhibition in PC12 cells increased Bcl-2 expression and inhibited cell apoptosis and oxidative damage. These findings suggest that the inhibition of miR-29b inhibits oxidative stress and cell apoptosis in ischemic stroke, producing therapeutic effects in ischemic stroke. This study was approved by the Laboratory Animal Care and Use Committee of the First Affiliated Hospital of Zhengzhou University (approval No. 201709276S) on September 27, 2017.

Excessive fructose (Fru) consumption has been reported to favor nonalcoholic fatty liver disease (NAFLD). However, the molecular mechanism is still elusive, lacking effective therapeutic strategies. Carminic acid (CA), a glucosylated anthraquinone found in scale insects like Dactylopius coccus, exerts anti-tumor and anti-oxidant activities. Nevertheless, its regulatory role in Fru-induced NAFLD is still obscure. Here, the effects of CA on NAFLD in Fru-challenged mice and the underlying molecular mechanisms were explored. We found that Fru intake significantly led to insulin resistance and dyslipidemia in liver of mice, which were considerably attenuated by CA treatment through repressing endoplasmic reticulum (ER) stress. Additionally, inflammatory response induced by Fru was also attenuated by CA via the blockage of nuclear factor-κB (NF-κB), mitogen-activated protein kinases (MAPKs) and tumor necrosis factor α/TNF-α receptor (TNF-α/TNFRs) signaling pathways. Moreover, Fru-provoked oxidative stress in liver tissues was remarkably attenuated by CA mainly through improving the activation of nuclear factor erythroid 2-related factor 2 (Nrf-2). These anti-dyslipidemias, anti-inflammatory and anti-oxidant activities regulated by CA were confirmed in the isolated primary hepatocytes with Fru stimulation. Importantly, the in vitro experiments demonstrated that Fru-induced lipid accumulation was closely associated with inflammatory response and reactive oxygen species (ROS) production regulated by TNF-α and Nrf-2 signaling pathways, respectively. In conclusion, these results demonstrated that CA could be considered as a potential therapeutic strategy to attenuate metabolic disorder and NAFLD in Fru-challenged mice mainly through suppressing inflammatory response and oxidative stress.

The total OH reactivity (kOH′) is an important parameter for quantitative assessment of the atmospheric oxidation capacity. Although laboratory measurement of kOH′ has been achieved 20 years ago, the instruments required are often costly and complex. Long-term atmospheric observations remain challenging and elusive. In this work, a novel instrument combining laser-flash photolysis with a mid-infrared Faraday rotation spectrometer (LFP-FRS) has been developed for the measurement of kOH′ and for studying gas phase free radical kinetics. The reactor is composed of a Herriott-type optical multipass cell, and OH radicals were generated by flash photolysis of ozone with a 266 nm pulsed Nd:YAG laser. The decay of the OH signal was directly measured with a time-resolved FRS spectrometer at 2.8 μm. The overlapping path length between the pump beam and probe beam was 25 m. High performance was achieved by subtracting the signals before and after flash photolysis to eliminate interferences caused by H2O absorption and background drift. The optimum precisions (1σ) of OH concentration and kOH′ measurement were 4 × 106 molecules cm–3 and 0.09 s–1 over data acquisition times of 56 and 112 s, respectively. The performance of the system was evaluated by the reaction of OH with CO and NO. The measured rate coefficients (kOH+CO and kOH+NO) were in good agreement with values reported in the literature. The developed LFP-FRS provides a new, high precision, and highly selective tool for atmospheric chemistry research of OH radicals and other transient paramagnetic free radicals such as HO2 radicals. 92;6

Exposure to polycyclic aromatic hydrocarbons (PAHs) may lead to adverse health risks. To understand the potential sources and carcinogenic risks of PAHs in Tangshan, 40 PM2.5 samples were collected for analysis of eighteen PM2.5-bound PAHs during non-heating period and heating period. The results display a significant variation. The median concentration of &sum, 18PAHs during the heating period (282 ng/m3) was higher than during the non-heating period (185 ng/m3). Especially, the median concentration of Benzopyrene (BaP) during the heating period (61.6 ng/m3) was 16.9-fold that during the non-heating period (3.64 ng/m3). It exceeded BaP annual average limit of China (1 ng/m3). Diagnostic ratios (DRs) and principal component analysis (PCA) both indicated that vehicle emissions and coal and biomass combustion were the dominant contributors of PAHs pollution in Tangshan. The incremental lifetime cancer risk (ILCR) of three age groups (children, teenagers, and adults) ranged from 2.56 &times, 10&minus, 6 to 5.26 &times, 5 during the entire sampling periods. The 95% risk values of adults exceeded 10&minus, 4 during the heating periods, indicating a potential health risk from PAHs.

BackgroundCannabinoid-2 receptor (CB2R) plays an important role in the cascading inflammation following ischemic injury. The toll-like receptors 4 (TLR4)/matrix metalloproteinase 9 (MMP9) signal pathway is involved in blood-brain barrier dysfunction induced by ischemia stroke. The aim of this study is to investigate the roles of exogenous activation of CB2R on attenuating neurological deficit and blood-spinal cord barrier (BSCB) disruption during rat spinal cord ischemia reperfusion (I/R) injury, through modulation of the TLR4/MMP9 axis.MethodsAnimals were intraperitoneally pretreated with TLR4 inhibitor TAK-242, CB2R agonist JWH-133 with or without CB2R antagonist AM630, or equivalent volume of vehicle 1 h before undergoing 14-min occlusion of descending aorta or sham operation. One, two, three, and 7 days after reperfusion, hindlimb locomotor function was evaluated with Basso, Beattie, and Bresnahan (BBB) Locomotor Scale, BSCB integrity was detected by measurement of Evans blue (EB) extravasation and spinal cord edema. The protein expression levels of CB2R, tight junction protein Zonula occluden-1 (ZO-1), TLR4, MMP9, MyD88, NF-κB p65, and NF-κB p-p65 were determined by western blot. The MMP9 activity was analyzed by gelatin zymography. Double immunofluorescence staining was used to identify the perivascular localization of CB2R, TLR4, MMP9, and reactive astrocytes, as well as the colocalization of CB2R, TLR4, and MMP9 with reactive astrocytes.ResultsJWH-133 pretreatment attenuated hindlimb motor functional deficit and BSCB leakage, along with preventing downregulation of ZO-1 and upregulation of TLR4/MMP9, similar to the effects of TAK-242 preconditioning. JWH-133 or TAK-242 pretreatment reduced the perivascular expression of TLR4/MMP9 and reactive astrocytes following injury. JWH-133 pretreatment also downregulated MyD88/NF-κB level, MMP9 activity, and the astrocytic TLR4/MMP9 after I/R injury.ConclusionsExogenous activation of CB2R by JWH-133 attenuated neurological deficit and BSCB disruption after spinal cord I/R injury via inhibition of TLR4/MMP9 expression.

Every year, the harvesting of Eucalyptus generates a large amount of abandoned Eucalyptus leaves (ELs), which may release dissolved organic matter (DOM) when immersed in water. If these substances are carried by surface runoff directly to the source of drinking water, some components in the DOM tend to form disinfection byproducts (DBPs) within the water-supply system, posing risk to human health. In this study, the characteristics of DOM released from leaves of Eucalyptus urophylla were studied and the potential of DBPs formation of the EL-released DOM during the chlorination process was investigated. The results showed that the EL-released DOM was mainly composed of small molecules and hydrophobic substances. Of the total EL-released DOM, the proportion with molecular weight less than 10 kDa accounted for over 80% and the hydrophobic substances took up over 62%. The DOM showed strong absorbance at UV254 and the fluorescence response corresponding to humic acid-like (HA-like) fractions, soluble microbial byproduct-like, aromatic protein and fulvic acid-like (FA-like) material, which have been considered to be related to the potential precursors of chlorinated DBPs. Non-targeted screening demonstrated the presence of phenolics, carbohydrates, and amino acids. The analysis of products generated in chlorination process revealed the formation of trichloromethane (TCM) and the total organic halogen (TOX). The present study fully confirms that the DOM released from Eucalyptus urophylla leaves has great potential for the generation of chlorinated DBPs.

To meet requirements of fracturing fluid thickener, triethanolamine was used to modify carboxymethyl hydroxyethyl cellulose (CMHEC) to obtain product called T-CMHEC of high viscosity. Rheological properties of CMHEC and T-CMHEC solutions were investigated to compare its structure and rheological performance, including viscosity, flow curve, thixotropy and viscoelasticity. Viscosities of CMHEC and T-CMHEC solutions are respectively 19.0 mPa · s and 63.2 mPa · s for the same concentration of 0.3%. Viscosity of T-CMHEC solutions is 3.3 times of CMHEC ones. Besides, the thixotropy and viscoelasticity of T-CMHEC system are both getting stronger than before. In summary, the T-CMHEC system shows better rheological performance after modification. Crosslinking process of T-CMHEC system is investigated under steady shear under different conditions, containing shear rates, concentrations of crosslinking agent, concentrations of pH adjuster and temperature. Viscosity curves changing with time are obtained dur...

Atmospheric simulation chambers play vital roles in the validation of chemical mechanisms and act as a bridge between field measurements and modeling. Chambers operating at atmospheric levels of OH radicals (106–107 molecule/cm3) can significantly enhance the possibility for investigating the discrepancies between the observation and model predications. However, few chambers can directly detect chamber OH radicals at ambient levels. In this paper, we report on the first combination of a superconducting magnet with midinfrared Faraday rotation spectroscopy (FRS) for real time in situ measurement of the OH concentration in an atmospheric simulation chamber. With the use of a multipass enhanced FRS, a detection limit of 3.2 × 106 OH/cm3 (2σ, 4s) was achieved with an absorption path length of 108 m. The developed FRS system provided a unique, self-calibrated analytical instrument for in situ direct measurement of chamber OH concentration.

A surface acoustic wave (SAW) humidity sensor based on AlN/Si (doped) layered structure and graphene oxide (GO) sensing layer is proposed for high sensitivity and low temperature coefficient of frequency. With the GO thin film, the sensitivity of the humidity sensor is increased to 42.08 kHz/RH% when the relative humidity is greater than 80%RH. The humidity sensor performs well even at both very low (≤10%RH) and very high (≥90%RH) detection range of humidity. The present sensor has low hysteresis, excellent short term repeatability and long term stability (variation less than ± 2%). The sensor also shows a fast response and short recovery time. Moreover, using the AlN/Si (doped) layered structure, the thermal stability of the sensor is significantly improved. After being covered with GO thin film, the temperature coefficient of frequency (TCF) of the sensor is further reduced to −22.1 ppm/°C, much smaller than the previously reported SAW humidity sensors.

As an important group of green leaf volatiles (GLVs), C6 hexenyl esters, are found to be widely emitted into the atmosphere by plants and vegetation, especially when they suffer mechanical damage. It is indispensable to understand their atmospheric fate for environmental assessment and model simulation. In this paper, the rate constants for reactions of O3 with four cis-3-hexenyl esters have been measured using an absolute method in a flow tube reactor at 298 K and atmospheric pressure. The measured rate constants (in 10−17 cm3 per molecule per s) were 4.06 ± 0.66 for cis-3-hexenyl formate, 5.77 ± 0.70 for cis-3-hexenyl acetate, 7.62 ± 0.88 for cis-3-hexenyl propionate, and 12.34 ± 1.59 for cis-3-hexenyl butyrate, respectively. Theoretical calculations were also carried out for the title reactions to better understand their kinetics and mechanism using density functional theory (DFT) and transition state theory (TST). Geometry optimizations, energy and harmonic vibrational frequency calculations were performed for all of the stationary points at the BHandHLYP/6-311+G(d,p) level of theory. The calculated rate constants were in good agreement with the experimental values. The results showed that the reactivity of the studied compounds towards O3 was obviously dependent on their chemical structure, such as the nature of the substituent, and the relative positions of the double bond and the substituent. The results were also discussed in terms of their atmospheric importance in the degradation of these unsaturated esters by comparing their lifetimes with respect to their reactions with O3 and other main atmospheric oxidants.

Residuals have rarely been granted attention when employing a hydrothermal approach to prepare binder-free supported catalysts. Using Ni foam supported NiCo2O4 catalyst for oxygen evolution reaction as an example, it was found that the catalytic activity of NiCo2O4 from the residuals loaded on glass carbon is comparable to Ni foam supported NiCo2O4, while the specific activity and turnover frequency value of the former catalyst are many times higher than that of the supported catalyst. In view of sustainability and green development, residuals should be given more attention when catalyst is prepared using the hydrothermal fabrication approach.

C18H14S2, monoclinic, P21/c (no. 14), a = 10.196(3) Å, b = 14.756(4) Å, c = 9.508(3) Å, β = 103.965(14)°, V = 1388.3(7) Å3, Z = 4, R gt(F) = 0.0480, wR ref(F 2) = 0.1207, T = 200(2) K.

C21H15F2N3O2, triclinic, P1̄ (no. 2), a = 7.389(5) Å, b = 14.011(9) Å, c = 16.733(11) Å, α = 96.568(13)°, β = 100.432(13)°, γ = 94.589(13)°, V = 1683.6(19) Å3, Z = 4, R gt(F) = 0.0589, wR ref(F 2) = 0.1621, T = 296 K.

We designed unique acicular or octahedral Fe3O4/rice husk-based activated carbon (AC) composites in electromagnetic wave (EMW) absorption. The key factors included the carbon layer structure and the regular metal oxide (Fe3O4) morphology. Particularly, the experiments involved a thorough ball milling method on biological substrates, which would significantly improve the absorber performance than conventional treated steps. The microstructures were controlled flexibly by adjusting the ratio of activator and magnetizing agent. The formed pores and the regular structures enhanced multiple interface polarizations. The minimum reflectance (RLmin) values of sample H4 reached –52.137, –41.918, –51.733, and –47.614 dB at 1.669, 2.002, 2.393, and 3.000 mm, respectively. The RLmin values were mainly concentrated in C, X and Kμ bands, and the reflectance (RL ≤ –10 dB) values covered a wide frequency range of approximately 13 GHz. In summary, the composites had the characteristics of interface engineering, high specific surface area, strong dielectric, and magnetic loss.