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Background: Copper complex has been gaining much attention in anticancer research as a targeted agent since cancer cells uptake more copper than non-cancerous cells. Our group synthesised a ternary copper complex, which is composed of 1,10-phenanthroline and tyrosine [Cu(phen)(L-tyr)Cl].3H20. These two payloads have been designed to cleave DNA and inhibit protein degradation system (proteasome) concurrently in cancer cells, making this copper complex a dual-target compound. Objective: The current study was carried out to investigate the mode of cell death and the role of autophagy induced by [Cu(phen)(L-tyr)Cl].3H20 in MCF-7 and MDA-MB-231 breast cancer cells. Methods: Growth inhibition of [Cu(phen)(L-tyr)Cl].3H20 towards MDA-MB-231 and human non-cancerous MCF10A breast cells was determined by MTT assay. Annexin-V-FITC/PI and cell cycle analysis were evaluated by flow cytometry. The expression of p53, Bax, caspase-9, caspase-7, caspase-3 and LC3 was determined using western blot analysis. The cells were then co-treated with hydroxychloroquine to ascertain the role of autophagy induced by [Cu(phen)(L-tyr)Cl].3H20. Results: [Cu(phen)(L-tyr)Cl].3H20 inhibited the growth of cancer cells dose-dependently with less toxicity towards MCF10A cells. Additionally, [Cu(phen)(L-tyr)Cl].3H20 induced apoptosis and cell cycle arrest towards MCF-7 and MDA-MB-231 breast cancer cells possibly via regulation of p53, Bax, caspase-9, caspase-3 and capase-7. The expression of LC3II was upregulated in both cancer cell lines upon treatment with [Cu(phen)(L-tyr) Cl].3H20, indicating the induction of autophagy. Co-treatment with autophagy inhibitor hydroxychloroquine significantly enhanced growth inhibition of both cell lines, suggesting that autophagy induced by [Cu(phen)(L-tyr) Cl].3H20 in both breast cancer cells promoted cell survival. Conclusion: [Cu(phen)(L-tyr)Cl].3H20 holds great potential to be developed for breast cancer treatment.

Objective: Based on the expression changes in the TGF-β/ALK5/Smad2/3 signal transduction pathway, the repair of cartilage injury in the rabbit knee joint was investigated and evaluated by oral administration of naringin in combination with acellular dermal matrix implantation. Methods: First, twenty New Zealand white rabbits were randomly divided into five groups: a sham operation group (Sham group), a model group (Mod group), a naringin group (Nar group), an acellular dermal matrix group (ADM group), a naringin ​+ ​acellular dermal matrix group (Nar/ADM group). After the 12th week, the repaired tissues were assessed for histomorphology and repair content of the repaired site by observing the morphological characteristics of articular cartilage. The International Cartilage Repair Society (ICRS)'s macroscopic evaluation of the cartilage repair scale and the quantitative scoring repair effect of the modified O'Driscoll grading system were used as evaluation criteria. In addition, the structure of the rabbit knee joint was evaluated by micro-CT scan, histological staining (H & E staining, Alcian blue staining, Safranin-O staining) and immunohistochemical staining (TGF-β2 immunostaining, TGF-β3 immunostaining, Sox-9 immunostaining). Results: ① The observation of the repair morphology of joint defect tissues showed that the repair effects of the Nar and ADM groups were better than that of the Mod group, and the repair effect of Nar/ADM group was the best (P

Evaluating the correlation between hypoxia inducible factor 1 (HIF-1) and nitric oxide (NO) generated under hypoxia is of great significance. In this work, we developed a fluorescent probe for the monitor of HIF-1 activity influenced by NO under hypoxia in hepatoma cells with dual-targeting for hepatocyte and lipid droplet (LD). The probe shows excellent selectivity to NO and high sensitivity with 6000-fold fluorescence enhancement. Live cell imaging experiments revealed the probe's capability of imaging exogenous and endogenous NO with specific in LDs of HepG2 cells. For cells under hypoxia, HIF-1 induced LD level is observed to correlate with NO level. This work provides the in-situ visualization of NO-dependent HIF-1 upregulation through LD accumulation.

The aim of the current study was to evaluate the protective effects and mechanisms of isoliquiritigenin (ISO) on acute renal injury. CCK-8 assays were applied to assess the effects of ISO at different doses (20, 40, and 80 μg/mL) on oxidative damage in human renal HK-2 cells incubated with high glucose. After the diabetic nephropathy (DN) rat model was established, the model animals were randomly assigned to saline-treated control, three model groups received the 10, 20 and 40 mg/kg ISO, respectively, using the healthy Sprague-Dawley (SD) rats as normal control. The blood biochemical indexes, renal functions, oxidative stress, morphological changes, fibrosis- and JAK2/STAT3-related factors in DN model rats were all assessed. The cellular viability of the renal HK-2 cells with oxidative damages were all markedly ameliorated via the incubation of ISO between 10 and 80 μg/mL compared with negative control. In addition, the significantly down-regulated ROS content and up-regulated expression levels of GSH, SOD2, and GPX1 were all observed in ISO-treated groups. Long-term administration of ISO at different doses in DN rats effectively improved general diabetic characteristics and renal morphology. Furthermore, long-term administration of ISO could ameliorate excessive oxidation stress, down-regulate the expression levels of renal fibrosis- and inflammation-related factors, as well as inhibit the JAK2/STAT3 signaling pathway. In conclusion, ISO at all three dosages could efficiently improve the renal injury induced by STZ via ameliorating renal fibrosis, oxidative stress, and inhibiting JAK2/STAT3 signaling pathways in the DN rats.

Developing Type-I photosensitizers is considered as an efficient approach to overcome the deficiency of traditional photodynamic therapy (PDT) for hypoxic tumors. However, it remains a challenge to design photosensitizers for generating reactive oxygen species by the Type-I process. Herein, we report a series of α,β-linked BODIPY dimers and a trimer that exclusively generate superoxide radical (O2-. ) by the Type-I process upon light irradiation. The triplet formation originates from an effective excited-state relaxation from the initially populated singlet (S1 ) to triplet (T1 ) states via an intermediate triplet (T2 ) state. The low reduction potential and ultralong lifetime of the T1 state facilitate the efficient generation of O2-. by inter-molecular charge transfer to molecular oxygen. The energy gap of T1 -S0 is smaller than that between 3 O2 and 1 O2 thereby precluding the generation of singlet oxygen by the Type-II process. The trimer exhibits superior PDT performance under the hypoxic environment.

Cardiac hypertrophy and the resultant heart failure are among the most common causes of morbidity and mortality worldwide; thus, identifying the key factor mediating pathological cardiac hypertrophy is critically important for developing the strategy to protect against heart failure. Runx1 (Runt‐related transcription factor 1) acts as an essential transcription factor that functions in a variety of cellular processes including differentiation, proliferation, tissue growth and DNA damage response. However, relatively little is known about the role of Runx1 in heart, especially cardiac hypertrophy and heart failure. In the present study, we investigated the role of Runx1 in experimentally pathological cardiac hypertrophy. The in vitro model was induced by Ang II exposure to cultured neonatal rat cardiomyocytes, and the in vivo pathological cardiac hypertrophy models were induced by chronic pressure overload in mice. Runx1 expression is increased in heart tissues from mice with pressure overload–induced cardiac hypertrophy and in neonatal rat cardiomyocytes in response to Ang II stimulation. Moreover, knockdown of cardiac Runx1 alleviates the pressure overload–induced cardiac hypertrophy. Mechanistically, Runx1 activates the p53 signalling by binding to the p53 gene and promotes its transcription. Rescue experiments indicate that Runx1 promotes cardiac hypertrophy in a p53‐dependent manner. Remarkably, we demonstrated that Ro5‐3335 (a Runx1 inhibitor) acts as a potential therapeutic drug for treating pathological cardiac hypertrophy. In summary, we conclude that Runx1 is a novel mediator and therapeutic target for pathological cardiac hypertrophy.

An annealed polypyrrole (PPy)/poly(vinyl alcohol) PVA film was successfully applied to the ZnCo2O4 nanorod surface via a liquid-phase synthesis approach and a subsequent annealing process. PVA play...

PM2.5 and its main chemical components have been investigated during six air pollution periods across four seasons from Jun. 16, 2016 to Jun. 15, 2017 at a suburban site in Beijing, China. Daily PM2.5 mass concentrations were measured with associated ions, OC, EC, 16 PAHs and seven heavy metals. Mass closure analyses were conducted using measured and reconstructed chemical components. Chemical ratios were used to identify possible pollution sources, while principal component analysis (PCA) coupled with multiple linear regression (MLR) method was used to estimate the source contribution to PM2.5 mass. The annual mean PM2.5 concentration (96.7 μg m−3) is about 2.8 times the national level-2 standard limit, with apparent seasonal variation of daily exceedances as winter > spring > autumn > summer. Generally, higher levels are observed in winter and autumn than in spring and summer for NO3−, SO42−, NH4+, Cl−, K+, OC, EC, PAHs and metals Zn, As, Cu, Pb, along with higher concentrations of NOx, CO and SO2. Secondary ions and carbon fractions are most abundant over all seasons, except levels of dust related species Ca2+, Mg2+, Ca, Fe and Mn are also high in spring. The reconstructed results show that PM2.5 consists of mostly organic compounds (26–38%) and ammonium salts (NH4NO3 + (NH4)2SO4) (43–53%) in winter and autumn, while summer is dominated mainly by ammonium salts (81%). In spring, very high PM2.5 episodes are occasionally composed of large amount of soil/road dust and gypsum particles (23–55%) due to floating dust events with drier weather conditions and human activities. Fuel combustions and secondary sources are responsible for ~70% of PM2.5 mass while mobile source is mostly a regional origin.

An atom- and step-economic intermolecular multi-component palladium-catalyzed C–H amidation of alkenes with carbon monoxide and organic azides has been developed for the synthesis of alkenyl amides. The reaction proceeds efficiently without an ortho-directing group on the alkene substrates. Nontoxic dinitrogen is generated as the sole by-product. Computational studies and control experiments have revealed that the reaction takes place via an unexpected mechanism by tandem palladium catalysis.

Clarifying the signaling pathway associated with nitric oxide (NO) and glutathione (GSH) in cardiovascular disease therapy is important for understanding its physiological and pathological processes but is challenging due to the lack of efficient analytical techniques. Herein, we report a BODIPY-based fluorescent probe for recognition of NO and GSH in sequence with high sensitivity and selectivity. The probe exhibits turn-on fluorescence triggered by NO, followed by red-shifted emission in the presence of GSH. The sequentially activated mechanism allows the visualization of NO-induced GSH upregulation in drug-treated endothelial cells and zebrafish for the first time, revealing a signal pathway during the therapy. We hope that it can be used as a convenient and efficient tool for the study of the interplay between NO and GSH and for the screening of effective drugs for cardiovascular disease therapy.

An efficient [3 + 1 + 1] cyclization of vinyl oxiranes for the synthesis of oxazolidinones has been developed via tandem palladium catalysis. This reaction provides an atom- and step-efficient strategy to produce oxazolidinones from readily available azides and carbon monoxide under mild additive- and base-free conditions. The mechanistic studies showed that the reaction occurred through an in situ generated isocyanate intermediate.

TiNb2O7 is considered to be one of the ideal candidate anode materials for lithium-ion batteries (LIBs) because of its safe working potential and high theoretical capacity. However, its low intrinsic conductivity and poor ionic diffusion rate hinder its practical application. In this study, an ultrathin N-doped carbon coating was uniformly deposited onto hierarchical porous TiNb2O7 microspheres by combining a solvothermal route with a carbonization process using ionic liquid. The TiNb2O7@N-doped carbon microspheres exhibited an ultra-high rate performance (208 mA h g−1 at 30 C) and excellent cycling stability (specific capacity retention of 79% after 500 cycles at 10 C), and showed excellent electrochemical performance in a full cell using LiNi0·5Mn0·3Co0·2O2 as a cathode. The superior performance can be attributed to the synergistic effects between the ultrathin N-doped carbon coating and unique microstructure. Therefore, TiNb2O7@N–C is a promising negative electrode for high-power LIBs.

Oxygen (O2) levels provide an important parameter in the early-stage diagnosis of cancers and other diseases. Ratiometric optical O2 sensing has attracted much interest due to its better calibration of oxygen levels at two wavelengths. Oxygen sensing nanoprobes are generally designed by the incorporation of a reference dye and phosphorescent indicator into various matrixes. Silica nanomaterials with intriguing characteristic properties are highly preferable in hypoxia sensing. However, physical entrapment of dyes in silica suffers from leaching and moderate sensitivity. Reported herein is a covalently encapsulated dual-dye silica nanoprobe for ratiometric hypoxia detection and imaging. The nanoprobe prepared in a one-pot approach has a core–shell nanostructure where silanized indicators and reference dyes are covalently grafted within the silica core, while poly(ethylene glycol) chains form an outer shell. To our delight, through the covelent bonding of the dyes for efficient energy transfer between the reference dye and the indicator, high phosphorescence brightness, long lifetime and excellent stability of the nanoprobe were achieved. More importantly, the designed nanoprobe can respond to different oxygen levels in both solution and living cells with impressive sensitivity and stability.

An atom- and step-economic multi-component cobalt-catalyzed synthesis of amidines has been reported by using amines, isocyanides, and diazo compounds as carbene sources. This protocol provides a synthetically simple, highly efficient strategy for the straightforward synthesis of functionalized amidines with a range of substrates.

Two efficient probes were presented for dual channel simultaneous distinguishing detection of ClO− and Cu2+. Strong color changes and fluorescent emissions driven by ClO− induce irreversible oxidat...

The amide linkage is one of the most important structural moieties in both chemistry and biology. Here, we briefly discuss recent advances in catalytic intermolecular C–H carbonylation reactions for the synthesis of amides, with particular attention to our intermolecular C–H amidation of arenes with carbon monoxide and organic azides to produce amides.1 Introduction2 Representative Methods for Amide Synthesis3 C–H Aminocarbonylation with Carbon Monoxide and Amines4 C–H Amidation to Amides with Carbon Monoxide and Azides5 Summary and Outlook

In this paper, a nanosecond pulsed discharge was employed to modify activated carbon (AC) adsorbents for the purpose of detecting gas-phase polycyclic aromatic hydrocarbons (PAHs). The raw and modified AC were characterized by helium ion microscopy, N2 adsorption/desorption, and X-ray photoelectron spectroscopy. The treatment time, gas composition, and pulse peak voltage of discharge were optimized to improve the adsorption capacity of AC. And the adsorption kinetics of AC was investigated. It is found that the pore structure of AC is changed and the oxygen-containing groups on AC surface are increased after plasma treatment. As a result, the roles of physisorption and chemisorption are promoted, and the adsorption rate of naphthalene is improved by about 10%. More importantly, modified AC adsorbing PAHs obeys Pseudo-first-order model and Langmuir isotherm model, and the corresponding adsorption coefficients are fitted, which contributes to detecting PAHs more accurately. After modified AC enriching, the gas-phase PAHs can be detected with the limit of detections in the range of 20–120 μg/m3.

Background: Triclopyr(Dow-503), whose commercial name was green grass, was an internal absorption and selective novel herbicide, developed by Dow agricultural sciences using the basic structure of 2,4-D. Triclopyr was suitable for preventing broadleaf weeds for removing shrubs, maintaining fireproof lines, raising pine trees and forest areas. Moreover, it could be used in paddy fields to prevent some broad-leaved weeds at the dose of 150-500g/hm. Methods: Two novel Triclopyr derivatives were synthesized based on the structure of commerical herbicide Triclopyr. Their structures were confirmed by 1H NMR melting point and elemental analysis. The preliminary bioassay were also evaluated. Results: The preliminary bioassay results showed that the title compounds had some herbicidal activities at the dosage of 150 g/hm2.The compound 1 and 2 show the 100% inhibition against three kinds of test weeds. Further test revealed that compound 2 showed the 100% inhibition against the Amaranthus. The safety test for crop revealed that the compound 2 was safe for paddy at the dosage of 150 g/hm2. Conclusion: The two compounds can be used as the leading compounds with certain optimized value.

Thermal rectification is an attractive phenomenon for thermal management, which refers to a specific behavior in a heat transfer system where heat flow in one direction is stronger than that in the opposite direction under the same conditions. Two-dimensional monolayer molybdenum disulfide (MoS2) synthesized by chemical vapor deposition (CVD) has exhibited exceptional thermal, optical, and electrical properties due to its special structure; however, the thermal rectification in monolayer MoS2 is still not achieved by experimental measurement. Here, we successfully transferred monolayer MoS2 samples with three geometrical morphologies to the suspended microelectrodes by the PMMA approach. Through further heating the suspended microelectrodes with AC power in the opposite directions of these three monolayer MoS2 samples, we experimentally measured the thermal conductivity and first obtained the thermal rectification of monolayer MoS2. The rectification coefficients of monolayer MoS2 with three different geometrical morphologies are 10-13, 11-4, and 69-70%. Moreover, a theoretical model was also applied to discuss the dependence of thermal rectification on the geometrical asymmetry (angle and spacing). The results demonstrate that the monolayer MoS2 has an obvious thermal rectification phenomenon owing to the asymmetric structure, and it would have great potentials in the application of thermal energy control and management.

We report a novel strategy of integrating microbial fuel cell (MFC) with microbial immobilization technology (MIT) in a sequencing batch reactor (SBR) to test the performance of nitrate removal for the first time. Results showed that MFC could enhance nitrate removal in the novel integrated system, especially for wastewater with low carbon-to-nitrogen ratios, and the nitrate removal efficiency reached 91.35% in the lab-scale integrated system, including 12.25% nitrate consumption by MFC in one typical cycle. The anode of MFC recovered energy in the form of electricity, floating cathode of MFC prevented the loss of immobilized denitrifying bacteria particles and degraded a portion of nitrate, and the maximum voltage production of MFC was 0.246 V. The novel integrated system in this paper showed excellent nitrate removal performance and it will be a highly potential novel setup for efficient nitrate removal of wastewater treatment.

Low-temperature coal tar (LTCT) is a sticky liquid mixture produced mainly from coal pyrolysis, which contains various value-added chemicals (VACs). Liquid-liquid extraction is considered as one of the green and effective ways to explore the organic composition and separate the VACs from LTCT. Herein, petroleum ether, methanol, and carbon disulfide were used to extract arenols from a LTCT. As a result, the relative content and absolute content of arenols extracted from the LTCT are ca. 96.3% and 85.9%, respectively. Among them, p-cresol is predominant, accounting for 22.2%. The isolated contents of arenols are up to 84.6%. Moreover, a kilogram-scale operation was carried out under the same conditions, which offers a potential application in industrial production.

We investigate the development of gate-modulated tungsten diselenide (WSe2)-based lateral pn-homojunctions for visible and near-infrared photodetector applications via an effective oxygen (O2) plasma treatment. O2 plasma acts to induce the p-type WSe2 for the otherwise n-type WSe2 by forming a tungsten oxide (WOx) layer upon O2 plasma treatment. The WSe2 lateral pn-homojunctions displayed an enhanced photoresponse and resulted in open-circuit voltage (VOC) and short-circuit current (ISC) originating from the pn-junction formed after O2 plasma treatment. We further notice that the amplitude of the photocurrent can be modulated by different gate biases. The fabricated WSe2 pn-homojunctions exhibit greater photoresponse with photoresponsivities (ratio of the photocurrent and incident laser power) of 250 and 2000 mA/W, high external quantum efficiency values (%, total number of charge carriers generated for the number of incident photons on photodetectors) of 97 and 420%, and superior detectivity values (magnitude of detector sensitivity) of 7.7 × 109 and 7.2 × 1010 Jones upon illumination with visible (520 nm) and near-infrared lasers (852 nm), respectively, at low bias (Vg = 0 V and Vd = 1 V) at room temperature, demonstrating very high-performance in the IR region superior to the contending two-dimensional material-based photonic devices. These superior optoelectronic properties are attributed to the junctions induced by O2 plasma doping, which facilitate the effective carrier generation and separation of photocarriers with applied external drain bias upon strong light absorption.

Petroselinic acid (18:1Δ6), a monounsaturated cis Δ-6 fatty acid, has many prospective applications in functional foods and for the nutraceutical and pharmaceutical industries. Up to 80% of petrose...

N-doped graphene (NG)/TiO2composites were prepared by a two-step hydrothermal method using HF as the surface etchant and urea as the nitrogen source. The morphology, structure, and bonding conditions of the NG/TiO2composites were characterized by X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, UV-visible diffuse reflectance spectroscopy (UV-Vis DRS), and photoluminescence (PL) spectroscopy. The effects of NG on the lifetime of photogenerated electron-hole pairs, adsorption capacity, and photocatalytic activity of the composite photocatalysts were also investigated. The photocatalytic activity was evaluated under ultraviolet light and sunlight irradiation. The recovery testing was completed under ultraviolet light irradiation. The results show that TiO2was uniformly loaded on the NG surface by chemical bonding. The introduction of NG effectively inhibited the recombination of photogenerated electron-hole pairs and improved both the adsorption capacity and photocatalytic activity of the composites. The 7 wt % NG/TiO2showed the best adsorption capacity of methyl orange (MO). The best photocatalytic activity occurred for 5 wt % NG/TiO2composites, and after four recovery tests, the photocatalytic degradation of MO under 60 min ultraviolet light irradiation exceeded 90%.

An organic crystal of 4,4'-bis(N-carbazolyl)-1,1'-biphenyl (pCBP) exhibits time-dependent afterglow color from blue to orange over 1 s. Both experimental and computational data confirm that the color evolution results from well-separated, long-persistent thermally activated delayed fluorescence (TADF) and room-temperature phosphorescence (RTP) with different but comparable decay rates. TADF is enabled by a small S1 -T1 energy gap of 0.7 kcal mol-1 . The good separation of TADF and RTP is due to a 11.8 kcal mol-1 difference in the S0 energies of the S1 and T1 structures, indicating that apart from the excited-state properties, tuning the ground state is also important for luminescence properties. This afterglow color evolution of pCBP allows its applications in anticounterfeiting and data encryption with high security levels.

Current lithium metal batteries are haunted by stability issues and safety concerns that are critically linked to the growth of dendritic lithium. A quasi-solid electrolyte is designed that is non-flammable and is capable of suppressing dendrites by in-situ polymerizing a poly (methyl methacrylate) skeleton to support phosphate-based electrolytes with high salt concentrations. By varying the polymer-to-electrolyte ratio, we reveal that there is a strong interplay between the mechanical strength, the ionic conductivity, and the ability to suppress dendrites. A carefully chosen composition leads to a quasi-solid electrolyte with a high ionic conductivity of 0.11 mS cm−1, a wide electrochemical window up to 4.8 V vs. Li/Li+, and the ability to suppress lithium dendrites at high current densities. Stable lithium plating and stripping is achieved using such electrolyte at a current density of 1.2 mA cm−2, a two-fold increase compared with its liquid counterpart. A lithium-metal battery using a LiFePO4 cathode with a high active material loading of ~15 mg cm−2 based on the quasi-solid electrolyte is demonstrated which exhibits high specific capacity of over 100 mAh g−1 and is able to be cycled 150 times without obvious capacity decay. The current work offers a practical solution to the safety concerns as well as the stability issues of lithium metal batteries.

A variety of controlled release carriers for bone morphogenetic protein 2 (BMP-2) delivery have been developed and tested in animal models. An alginate-based polyelectrolyte complex (PEC) for controlled release of low-dose BMP-2 has shown promising results in preclinical research. However, the poor handling properties and long-term stability of PEC need to be improved for translational applications. This study aimed to address these limitations of alginate-based PEC by employing a freeze-drying technique. The size and structure of freeze-dried PEC (FD-PEC) were maintained with the addition of a cryoprotectant, trehalose. The release profile of BMP-2 from FD-PEC was similar to that of freshly prepared PEC. In vitro bioactivity analysis of the released BMP-2 showed that the carrier performance of PEC was not compromised by freeze-drying up to three-month storage at room temperature. BMP-2-bound FD-PEC induced comparable bone formation to that using freshly prepared regular PEC in a rat posterolateral spinal fusion model. These results suggest that FD-PEC is capable of delivering low-dose BMP-2 and could be developed as an off-the-shelf product for translational applications. The simplicity of this preservation method provides promise for the translational application of PEC.

C7H6F3NO2, monoclinic, P21/c (no. 14), a = 11.3688(4) Å, b = 10.6836(3) Å, c = 14.4518(5) Å, β = 112.5320(10)°, V = 1621.32(9) Å3, Z = 8, R gt (F) = 0.0554, wR ref (F 2) = 0.1647, T = 170 K.

Deoxynivalenol (DON) is one of the most widespread trichothecene mycotoxins in contaminated cereal products. DON plays a vital role in the pathogenesis of Fusarium graminearum, but the molecular mechanisms of DON underlying Fusarium–wheat interactions are not yet well understood. In this study, a novel wheat ADP-ribosylation factor-like protein 6-interacting protein 4 gene, TaArl6ip4, was identified from DON-treated wheat suspension cells by suppression subtractive hybridization (SSH). The qRT-PCR result suggested that TaArl6ip4 expression is specifically activated by DON in both the Fusarium intermediate susceptible wheat cultivar Zhengmai9023 and the Fusarium resistant cultivar Sumai3. The transient expression results of the TaARL6IP4::GFP fusion protein indicate that TaArl6ip4 encodes a plasma membrane and nucleus-localized protein. Multiple sequence alignment using microscale thermophoresis showed that TaARL6IP4 comprises a conserved DON binding motif, 67HXXXG71, and exhibits DON affinity with a dissociation constant (KD) of 91 ± 2.6 µM. Moreover, TaARL6IP4 exhibited antifungal activity with IC50 values of 22 ± 1.5 µM and 25 ± 2.6 µM against Fusarium graminearum and Alternaria alternata, respectively. Furthermore, TaArl6ip4 interacted with the plasma membrane of Fusarium graminearum spores, resulting in membrane disruption and the leakage of cytoplasmic materials. The heterologous over-expression of TaArl6ip4 conferred greater DON tolerance and Fusarium resistance in Arabidopsis. Finally, we describe a novel DON-induced wheat gene, TaArl6ip4, exhibiting antifungal function and DON affinity that may play a key role in Fusarium–wheat interactions.

An efficient Pd-catalyzed amidation of 1,3-diketones has been developed using carbon monoxide and organic azides. This reaction provides a step-economic approach to produce β-ketoamides from readily available compounds under mild ligand-, oxidant-, and base-free conditions. The mechanistic studies showed that the reaction occurred through an in situ generated isocyanate intermediate.

We demonstrate a solid luminescent material based on difluoroboron β-diketonate containing a triphenylamine moiety manifesting tunable solid-state luminescence and thermally activated delayed fluorescence (TADF). The compound shows strong fluorescence in both organic solutions and solid states. It exhibits significantly different emission colours in different aggregation states: bright orange emission in its crystalline solid state and red emission in the amorphous state. The orange and red emissive states are able to be reversibly switched by repetitive grinding–fuming processes with little fatigue. More importantly, the aggregation state plays a key role in the TADF properties. Its solid exhibits TADF properties in the amorphous state but not in the crystalline solid state due to the different ΔEST values in the relative morphologies.

A bright difluoroboron β-diketonate derivative 1 showing four emission colors (green, yellow, orange and red) with high quantum yields (41–74%) in four polymorphs and one amorphous state is reported. Green-emissive crystals (1-G and 1-G′) exhibit dimeric aggregation structures due to the strong molecular π–π interaction but exhibit hypsochromic emission compared to yellow-emissive crystals (1-Y) with monomeric aggregation because of lacking such π–π interactions. These novel emission phenomena are rationalized by theoretical calculations. High fluorescence sensitivity of compound 1 to its molecular packing modes results in excellent responsive behavior to multiple external stimuli thereby showing reversible change of emission colors under mechanical grinding, heating, solvent fuming and hydrostatic pressure.

Oxidation of cysteine residues constitutes an important regulatory mechanism in the function of biological systems. Much of this behavior is controlled by the specific chemical properties of the thiol side-chain group, where reactions with reactive oxygen species take place. Herein, we investigated the entire cysteine oxidation cycle Cys-SH → Cys-SOnH (n = 1, 2, and 3) using cryogenic negative ion photoelectron spectroscopy and quantum-chemical calculations. The conventional view of the first reversible oxidation step (n = 1) is associated with sulfenate species. Yet our results indicate that an alternative option exists in the form of a novel distonic radical anion, ˙OS–CH2CH(NH2)–COO−, with an unpaired electron on the thiol group and excess negative charge on the carboxylate group. Higher order oxidation states (n = 2 and 3) are thought to be associated with irreversible oxidative damage, and our results show that excess negative charge in those cases migrates to the –SOn− group. Furthermore, these species are stable towards 1e oxidation, as opposed to the n = 1 case that undergoes intra-molecular proton transfer. The molecular level insights reported in this work provide direct spectroscopic evidence of the unique chemical versatility of Cys-sulfenic acid (Cys-SOH) in post-translational modifications of protein systems.

Immunosenescence comprises a set of dynamic changes occurring in innate and adaptive immune systems, and macrophage aging plays an important role in innate and adaptive immunosenescence. However, function and polarization changes in aging macrophages have not been fully evaluated, and no effective method for delaying macrophage senescence is currently available. The results of this study reveal that D-galactose (D-gal) can promote J774A.1 macrophage senescence and induce macrophage M1 polarization differentiation. Bifidobacterium lactis BB-12 can significantly inhibit J774A.1 macrophage senescence induced by D-gal. IL-6 and IL-12 levels in the BB-12 groups remarkably decreased compared with that in the D-gal group, and the M2 marker, IL-10, and Arg-1 mRNA levels increased in the BB-12 group. BB-12 inhibited the expression of p-signal transducer and activator of transcription 1 (STAT1) and promoted p-STAT6 expression. In summary, the present study indicates that BB-12 can attenuate the J774A.1 macrophage senescence and induce M2 macrophage polarization, thereby indicating the potential of BB-12 to slow down immunosenescence and inflamm-aging.

The homogenous dispersion of graphene in Al powders is a key challenge that limits the development of graphene-reinforced metal matrix composites with high performance. Here, uniform distribution of graphene oxide (GO) coated on flake Al powders were obtained by a simply stirring and ultrasonic treatment in the water/alcohol solution. The effect of water volume content on the formation of GO/Al composite powders was investigated. The results showed that GO adsorbed with synchronous reduction on the surface of Al powders, but when the water content was higher than 80% in the solution, Al powders were totally changed into Al(OH)3. With optimizing the water content of 60% in the solution, reduced GO was homogenously coated onto the surface of flake Al powders. The formation mechanism can be ascribed to the balance control between the liquid/solid interaction and the hydrolysis reaction.

Electrochemical sensors are essential for point-of-care testing (POCT) and wearable sensing devices. Establishing an efficient electron transfer route between redox enzymes and electrodes is key for converting enzyme-catalyzed reactions into electrochemical signals, and for the development of robust, sensitive, and selective biosensors. We demonstrate that the site-specific incorporation of a novel synthetic amino acid (2-amino-3-(4-mercaptophenyl)propanoic acid) into redox enzymes, followed by an S-click reaction to wire the enzyme to the electrode, facilitates electron transfer. The fabricated biosensor demonstrated real-time and selective monitoring of tryptophan (Trp) in blood and sweat samples, with a linear range of 0.02-0.8 mm. Further developments along this route may result in dramatic expansion of portable electrochemical sensors for diverse health-determination molecules.

Biothiols, including cysteine (Cys), homocysteine (Hcy), and glutathione (GSH) play important roles in physiological processes, and the detection of thiol using fluorescent probes has attracted attention due to their high sensitivity and selectively and invasive on-time imaging. However, the similar structures and reactivity of these biothiols present great challenges for selective detection. This review focused on the the “aromatic nucleophilic substitution-rearrangement (SNAr-rearrangement) mechanism”, which provided a powerful tool to design fluorescent probes for the discrimination between biothiols. We classify the fluorescent probes according to types of fluorophores, such as difluoroboron dipyrromethene (BODIPY), nitrobenzoxadiazole (NBD), cyanine, pyronin, naphthalimide, coumarin, and so on. We hope this review will inspire exploration of new fluorescent probes for biothiols and other relevant analytes.

A common challenge in the assembly and optimization of plant natural product biosynthetic pathways in recombinant hosts is the identification of gene orthologues that will result in best production titers. Here, we describe the modular assembly of a naringenin biosynthetic pathway in Saccharomyces cerevisiae that was facilitated by optimized naringenin-inducible prokaryotic transcription activators used as biosensors. The biosensors were designed and developed in S. cerevisiae by a multiparametric engineering strategy, which further was applied for the in vivo, high-throughput screening of the established yeast library. The workflow for assembling naringenin biosynthetic pathways involved Golden gate-directed combinatorial assembly of genes and promoters, resulting in a strain library ideally covering 972 combinations in S. cerevisiae. For improving the performance of our screening biosensor, a series of fundamental components was optimized, affecting the efficiency of the biosensor such as nuclear localization signal (NLS), the detector module and the effector module. One biosensor (pTDH3_NLS_FdeR-N_tPGK1-pGPM1-fdeO_mcherry_tTDH1-MV2) showed better performance, defined as better dynamic range and sensitivity than others established in this study as well as other previously reported naringenin biosensors. Using this biosensor, we were able to identify a recombinant S. cerevisiae strain as the most efficient candidate for the production of naringenin from the established naringenin biosynthetic library. This approach can be exploited for the optimization of other metabolites derived from the flavonoid biosynthetic pathways and more importantly employed in the characterization of putative flavonoid biosynthetic genes.

Highly selective hydrogenation of furfural to furan-2-ylmethanol (FM) in isopropanol was achieved over a novel magnetic Cu–Co/C derived from zeolitic imidazolate frameworks prepared by galvanic replacement reaction. Furfural conversion and FM selectivity (FMS) are 100% and 97.2%, respectively, at 200 °C. FMS was held around 95% after 5-times recycle of the Cu–Co/C. In addition, cinnamaldehyde was completely converted with 96.8% of phenylpropanol selectivity over the Cu–Co/C at 150 °C.

A highly active difunctional Ni-Mg2Si/γ-Al2O3 was prepared by thermally decomposing nickel tetracarbonyl onto γ-Al2O3 impregnated with Mg2Si. The non-catalytic hydroconversion (NCHC) and catalytic hydroconversion (CHC) of the extract (E) and extraction residue (ER) from Yinggemajianfeng lignite were investigated over Ni-Mg2Si/γ-Al2O3 at 240 °C in n-hexane. Benzyloxybenzene and oxybis(methylene)dibenzene were used as lignite-related model compounds to speculate the possible mechanisms for the catalytic hydrocracking and hydrogenation over Ni-Mg2Si/γ-Al2O3. As a result, more organic matter in ER was converted to soluble portion (SP) by the CHC than by the NCHC. The main SP from the CHC are chain alkanes and cyclanes, while that from the NCHC is rich in arenes and oxygen-containing organic compounds. The results indicate that Ni-Mg2Si/γ-Al2O3 effectively catalyze the hydrocracking of >Calk–O– linkages and the hydrogenation of aromatic rings in E and ER.

Considering the importance of removing toxic Cr(VI) from practical wastewater containing complex pollutants, this study presented for the first time the utilization of the live heterotrophic microalgae (Botryocossuss sp. NJD-1) to achieve a concurrent abatement of Cr(VI), TOC, NO3-N and PO4-P, through a comprehensive biochemical process. The experimental results showed that the Cr(VI) removal efficiencies in the culture with different types of organic descended in the order of sodium acetate, ethanol and methanol. The highest removal efficiencies were achieved as 94.2%, 98.2%, 66.9% and 99.2% for Cr(VI), TOC, NO3-N and PO4-P, respectively, in the culture with 5 mg L−1 Cr(VI) and sodium acetate of equivalent to 2.92 g C L−1. Through mass balance calculation and characterization, the fate of Cr(VI) and Cr(III) was tracked and quantified in the culture system, which indicates that 87.17% of initial Cr(VI) were reduced to Cr(III) and then adsorbed in algal biomass for the optimal removal case. Consequently, the mechanism demonstrating the correlation among the removal process of Cr(VI), the biological activity of microalgae and the effect of organic compounds was proposed.

Amide bond formation is one of the most important reactions in organic chemistry because of the widespread presence of amides in pharmaceuticals and biologically active compounds. Existing methods for amides synthesis are reaching their inherent limits. Described herein is a novel rhodium-catalyzed three-component reaction to synthesize amides from organic azides, carbon monoxide, and (hetero)arenes via nitrene-intermediates and direct C-H functionalization. Notably, the reaction proceeds in an intermolecular fashion with N2 as the only by-product, and either directing groups nor additives are required. The computational and mechanistic studies show that the amides are formed via a key Rh-nitrene intermediate.

A novel multi-functional yolk-shell SiO2@TiO2/CDs(y-STCs) nanocomposite with interesting structure of SiO2 cores, porous TiO2 shell, and cavities was synthesized by using a simple method. The experimental results indicate that the yolk-shell structure and modification of carbon dots (CDs) play important roles in the enhancement of SERS signals and photocatalytic performance. The y-STCs nanocomposite used as the SERS substrate showed excellent efficiency and reproducibility for the detection of rhodamine 6G (R6G). The detection limit of R6G was shown to be as low as 6 × 10−8 M. Furthermore, the fabricated y-STCs nanocomposite utilized as the photocatalytst for the degradation of dinitraphenols (DNP) can greatly shorten reaction time to 120 min compared with previous studies, and the DNP degradation rate could reach 96% under simulated sunlight irradiation. The y-STCs nanospheres also possessed excellent cycle stability for the photocatalytic degradation of DNP. Thus, the bi-functional y-STCs nanocomposite may have potential applications in the detection and photocatalytic degradation of organic pollutants.

Due to the traditional therapies of cancer inducing huge pains to patients, the non-invasive photo-guided therapies are attracting massive attentions of researchers. Herein, the intelligent-designed carbon-dots/hemin nanoplatforms (HCDs NPs) were developed, owning high-authority photo-therapy for cancer. The fluorescence resonance energy transfer (FRET) effect enhanced the photo-thermal ability of HCDs NPs, endowing the synthesized nanoplatforms with photo-dynamic property simultaneously. Therefore, the obtained HCDs NPs could achieve synergetic photo-thermal and photo-dynamic therapies for cancer. Basing on the experimental results, the prepared HCDs NPs could induce the temperature enhancement high to ca 26 °C under laser irradiation, also with the outstanding photo-dynamic efficacy. More than 90% of cancer cells die after 10 min laser treatment. Thus, the dual-modal photo-therapeutic HCDs NPs are promising and excellent nanomaterials for potential application in synergistic cancer therapy.

Heishan lignite (HL) was extracted with isometric acetone/carbon disulfide mixed solvent under ultrasonic irradiation. The extraction residue (ER) was subjected to thermal dissolution/methanolysis (TD/M) in methanol and catalytic hydroconversion (CHC) in cyclohexane (CH) at 300 °C under 1 MPa of N2 over a supported acid (SA). The methanol-soluble portion (MSP) from the TD/M and CH-soluble portion (CHSP) from the CHC were analyzed with a gas chromatograph/mass spectrometer (GC/MS) and Fourier transform infrared (FTIR) spectrometer, while ER and the residues from the TD/M (RTD/M) and CHC (RCHC) were characterized with the FTIR spectrometer and an X-ray photoelectron spectrometer (XRPES). The results show that the yields of MSP and CHSP are ca. 22.6% and 16.1%, respectively. According to the analysis with GC/MS, CHSP is rich in tetramethylbenzenes and dimethylnaphthalenes, while most of the GC/MS-detectable compounds in MSP are xylenols, trimethylphenols, and methyl normal alkanoates. During the TD/M, the cleavage of some C O bonds could be the main reaction, whereas the SA effectively catalyzed the cleavage of Car Calk bonds connecting some aromatic rings (ARs) and side chains on the ARs in ER. No significant difference in the distribution of functional groups was observed in FTIR spectra between HL and ER, while the distribution of functional groups in MSP is extraordinarily different from that in CHSP. According to the analysis with XRPES, RTD/M has higher carbon content but lower oxygen content.

Raised triglycerides (TG) and reduced high density lipoprotein cholesterol (HDL-c) are components of metabolic syndrome. Both high TG and metabolic syndrome have been reported to be risk factors of endometrial cancer. Therefore, triglycerides-to-high density lipoprotein cholesterol ratio (TG/HDL-c ratio) may be a useful biological indicator in managing endometrial cancer. We aimed to explore the association between pretreatment TG/HDL-c ratio and endometrial cancer in postmenopausal women, and to evaluate its potential role in the disease. Pretreatment serum lipid profile and TG/HDL-c ratio were retrospectively analyzed for 167 postmenopausal women with endometrial cancer and 464 matched noncancer controls. Compared with controls, pretreatment TG/HDL-c ratio in endometrial cancer patients significantly elevated regardless of whether patients had diabetes or overweight/obesity (P < 0.05). Further analyses showed that pretreatment TG/HDL-c ratio increased significantly with advanced tumor stage. Interestingly, TG/HDL-c ratio of type I endometrial cancer patients was higher than those with type II endometrial cancer. A positive association was found between pretreatment TG/HDL-c ratio and tumor stage (adjusted r = 0.176, P = 0.027) in endometrial cancer group. Receiver operating characteristic curve analysis yielded the cut-off value of 1.52 for TG/HDL-c ratio to discriminate patients with cancer from controls (area under the curve, 0.689; sensitivity, 51.5%; specificity, 84.1%). Multivariate logistic regression model identified TG/HDL-c ratio ≥ 1.52 (odds ratio = 4.123; P < 0.001) as an independent predictor of endometrial cancer. TG/HDL-c ratio was positively associated with endometrial cancer clinical features, such as tumor stage and pathogenetic type. Accordingly, pretreatment TG/HDL-c ratio might be a potential marker for endometrial cancer.

Nitric oxide (NO) and glutathione (GSH) have interplaying roles in oxidant-antioxidant balance. In this work, we developed the first example of a single fluorescent probe that displayed a turn-on fluorescence response toward NO and GSH from dual emission channels. The probe was synthesized by introducing 4-amino-3-(methylamino)-phenol to a BODIPY scaffold. Specifically, the NO-mediated transformation of diamine into a triazole triggered the fluorescence in the green channel, and the GSH-induced SNAr substitution reaction led to the red-shifted emission in the red channel. The probe was successfully applied to detect the exogenous and endogenous NO and GSH in macrophage cells. More importantly, the probe revealed that NO induced by interferon-γ (IFN-γ), lipopolysaccharide (LPS), and l-arginine (l-Arg) could also elicit the augmentation of intracellular GSH. We anticipate the probe would hold great potential for investigating the redox balance in biological processes.

Recently, our research group reported the identification of BMS-986104 (2) as a differentiated S1P1 receptor modulator. In comparison to fingolimod (1), a full agonist of S1P1 currently marketed for the treatment of relapse remitting multiple sclerosis (RRMS), 2 offers several potential advantages having demonstrated improved safety multiples in preclinical evaluations against undesired pulmonary and cardiovascular effects. In clinical trials, 2 was found to exhibit a pharmacokinetic half-life (T1/2) longer than that of 1, as well as a reduced formation of the phosphate metabolite that is required for activity against S1P1. Herein, we describe our efforts to discover highly potent, partial agonists of S1P1 with a shorter T1/2 and increased in vivo phosphate metabolite formation. These efforts culminated in the discovery of BMS-986166 (14a), which was advanced to human clinical evaluation. The pharmacokinetic/pharmacodynamic (PK/PD) relationship as well as pulmonary and cardiovascular safety assessments ar...