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Fe-N-C structures have been considered as a candidate to replace noble metal catalysts towards oxygen reduction reaction (ORR) due to their excellent electrocatalytic activity and durability. Herein, a zinc-mediated synthesis strategy is proposed for N-doped graphitic porous carbon encapsulated uniform dispersed Fe3C nanoparticles coupled with atomically dispersed Fe-Nx moieties (NPC/Fe-N-C) derived from biomass coconut shell. The introduction of zinc species could be conductive to the dispersion of iron species and formation of porous structures. Density functional theory calculations demonstrate that the N-doped carbon coating structures can weaken the oxygen intermediates adsorption energy barrier of Fe3C. Besides, the graphitic carbon could promote the electron transfer during the electrochemical reaction. These special structures enable NPC/Fe-N-C to have excellent ORR activity with an Eonset of 1.0 V, which is much better than Pt/C. Furthermore, the zinc-air battery assembled by pairing NPC/Fe-N-C with a high-efficiency oxygen evolution reaction (OER) catalyst can continuously and stably operate a charge-discharge potential gap of 0.8 V at 10 mA/cm2 for more than 600 hours. More importantly, the assembled batteries could drive overall water splitting device, realizing the effective energy conversion.

Study of the segmental mobility of polymer chains is important when the polymer is used as drag reduction agents of crude oil. Electron spin resonance (ESR) spectroscopy can provide important information about segmental dynamics of polymer chains, which is related to their microenvironment. In this article, we employed an amphiphilic polymer to study the effect of hydrophilic/hydrophobic balance of the polymers on the segmental motion of polymer chains. Poly(styrene-co-maleic acid) (PSMA) was spin labeled with 4-amino TEMPO radicals by increasing the concentration of radical moiety on the polymer chains. The PSMA and spin labeled-PSMAs (SL-PSMAs) were characterized by nuclear magnetic resonance (NMR), Fourier transform infrared (FT-IR) spectroscopy, Cyclic voltammetry (CV) and ESR techniques. Inter-polymer complexes (IPCs) of SL-PSMA-2 were prepared by employing polyethylene glycols (PEGs) of varying molecular weights. The results showed that the increased hydrophobic interactions of nitroxide radicals on the SL-PSMAs’ chains reduced the rotational mobility of spin labels and the random coil-to-globular transition of polymer chains occurred at higher pH value for SL-PSMAs, which showed a slow motion component in the ESR spectra of SL-PSMAs. Further, by increasing the molecular weight of PEGs in IPCs the complexation was increased, which also reduced the rotational motion of spin labels due to interpolymer hydrogen bonding causing a slow motion component in the ESR spectra.

Common solvatochromic fluorophores exhibit a bathochromic fluorescence emission wavelength shift accompanied by intensity attenuation due to the presence of nonradiative decay pathways at the excited state. Such intrinsic but inevitable fluorescence quenching of solvatochromism impedes its applications to faithfully quantify local polarity, especially in a polar environment. Herein, we report a new donor-π-acceptor (D-π-A) type solvatochromic fluorophore scaffold containing a perfluorophenyl group that exhibits both a solvatochromic emission wavelength shift and a controllable emission intensity upon polarity fluctuation. The regulation of fluorescence solvatochromism and colors was achieved by tuning the aryl donors. We exploited such desired solvatochromism of these probes to monitor protein misfolding and aggregation via wavelength shift. Finally, the polarity of pathogenic aggregated proteins was quantified by HaloTag bioorthogonal labeling technology in live cells. While much effort has been devoted to resolving the morphology of pathogenic aggregated proteins, this work provides quantitative hints regarding the chemical information at this disease-related protein interphase.

Physicochemical details at the interphase of protein aggregation have been less explored especially in live cells. Herein, we reported a crystallization induced emission fluorophore to quantitatively interrogate the polarity of aggregated proteins. This solvatochromic probe, namely "AggRetina" probe, inherently binds to aggregated proteins and exhibits both polarity-dependent fluorescence emission wavelength shift and viscosity-dependent fluorescence intensity increase. Regulation of its polarity sensitivity was achieved by extending the conjugation length. Empowered by this probe, we observed that different proteins bear diverse polarity upon aggregation, leading to different resistance to proteolysis. We further showed that polarity primarily decreases during protein misfolding but viscosity mainly increases upon the formation of insoluble aggregates. Finally, we quantified the polarity of aggregated protein-of-interest in live cells via HaloTag bioorthogonal labeling, revealing polarity heterogeneity within cellular aggregates. This work highlights the enriched micro-environment details inside misfolded and aggregated proteins that may correlate to their bio-chemical properties and pathogenicity.

Phenol is the toxicant present in cigarette smoke that causes pulmonary diseases, eyes infection, and even various kinds of cancer. So, in this research, an attempt was done to prepare a suitable absorbent to remove phenol from cigarette smoke. A novel bio-based adsorbent succinylated carboxymethyl starch (S-CMS) was prepared by reacting carboxymethyl starch (CMS) with succinic anhydride (SA) in the presenting of N, N-dimethylformamide (DMF) solvent and pyridine. The structure of the S-CMS was confirmed by spectroscopic techniques including proton nuclear magnetic resonance and Fourier transform infrared. The S-CMS crystallinity and thermal properties were checked by x-ray diffraction and thermogravimetric analysis. The results showed a decrease in thermal properties and crystallinity for S-CMS. The S-CMS were tested as adsorbents for the removal of phenol. The adsorption efficiencies of CMS, S-CMS1, S-CMS2, and S-CMS3 towards phenol were shown to be 0.297 g/g, 0.321 g/g, 0.322 g/g, and 0.324 g/g, respectively.

Carbon quantum dots (CQDs) are extensively applied for bioimaging due to their unique photoluminescence properties, while less attention has been paid to their inherent bio-functions as targeted drug delivery vehicles. To address this limitation, a novel CQDs-based drug delivery system (Arg-Ag@Cu) was constructed using l -arginine as precursor with duplex metal co-doping (Ag&Cu) for further DOX-loading/releasing and synergistic tumor theranostics. Specifically, the functional residues retention ability of CQDs guaranteed the reactive nitrogen species (RNS) replenishment, Ag-doping enhanced the photoluminescence intensity, and Cu2+-functionalizing could act as the anchor for further interparticle self-assembly, resulting in intelligent adjustable CQDs size for increasing the drug-loading capacity. After reaching targeted sites, CQDs could act as NO/ONOO− donors for gas-involving therapy, and Cu2+ could not only generate ROS through chemodynamic therapy (CDT), but also modulate the band structure of as-prepared CQDs for laser-induced photodynamic therapy (PDT) to further replenishing ROS. Simultaneously, with Cu2+ depletion, the structure of Arg-Ag@Cu was disrupted, which guaranteed in situ DOX-releasing. As such, these orchestrated procedures fully exerted the intrinsic bio-functions of CQDs then act as adjuvants in drug delivery systems, thus representing synergistic effects in suppressing tumor progression and migration with minimal side effects, and provides a paradigm of potent CQDs-based nanotheranostics.

Rapid and sensitive pathogenic bacterial identification and isolation from complicated clinical specimens are of great importance for the early diagnosis and prevention of osteomyelitis. Herein, we proposed a novel methicillin-resistant Staphylococcus aureus (MRSA) detection strategy through two specially designed streptavidin magnetic bead-based probes, including a capture probe and a report probe. In detail, the capture probe takes the responsibility to specially bind with the surface protein of MRSA and leads to the liberation of the promoter which could subsequently initiate report probe-based signal amplification. Afterward, the hybridization of the promoter probe with the report probe could then transform the protruding 3' terminus of template DNA in the report probe into a blunt end. With the assistance of Exo III, the template could be digested to liberate the promoter to form a recycle and to liberate the biprobe to induce the following rolling circle amplification (RCA)-based signal amplification. Through the integration of the Exo III-assisted recycle and RCA-based signal amplification, the proposed method exhibited a favorable detection performance.

Pleiotrophin (PTN) is a potent mitogenic cytokine whose activities are controlled by its interactions with glycosaminoglycan (GAG). We examined the specificity of PTN for several types of GAG oligosaccharides. Our data indicate that the interaction of PTN with GAGs is dependent on the sulfation density of GAGs. Surprisingly, an acidic peptide also had similar interactions with PTN as GAGs. This shows that the interaction of PTN with anionic polymers is flexible and adaptable and that the charge density is the main determinant of the interaction. In addition, we show that PTN can compensate for the loss of its termini in interactions with heparin oligosaccharides, allowing it to maintain its affinity for GAGs in the absence of the termini. Taken together, these data provide valuable insight into the interactions of PTN with its proteoglycan receptors.

Succinylated starches (SS) were prepared by the reaction of normal starch (NS) and porous starch (PS) with succinic anhydride (SA) in the presence of DMF solvent and base pyridine, respectively. The proton nuclear magnetic resonance and Fourier transform infrared were used to confirm the successful synthesis of the SS (SS1, SS2, SS3 and SS4, respectively). The X-ray diffractometer XPert PRO (Cu Kα, λ = 1.54 A) was used to study the crystallinity of NS, PS and SS. The XRD analysis showed that the SS exhibited amorphous nature after succinylation. Thermogravimetric analysis and differential thermal analysis of NS, PS and SS showed that succinylation decreased the thermal stability. The morphology of the NS, PS and SS was studied by SEM. These SS were used as adsorbents for phenol removal. The adsorption efficiencies for phenol by NS, SS1, SS2, SS3 and SS4 were found to be 0.084 g/g, 0.165 g/g, 0.173 g/g, 0.183 g/g and 0.189 g/g, respectively.

Integrin Mac-1 (αMβ2) is an adhesion receptor vital to many functions of myeloid leukocytes. It is also the most promiscuous member of the integrin family capable of recognizing a broad range of ligands. In particular, its ligand-binding αMI-domain is known to bind cationic proteins/peptides depleted in acidic residues. This contradicts the canonical ligand-binding mechanism of αI-domains, which requires an acidic amino acid in the ligand to coordinate the divalent cation within the metal ion-dependent adhesion site (MIDAS) of αI-domains. The lack of acidic amino acids in the αMI-domain-binding sequences suggests the existence of an as-yet uncharacterized interaction mechanism. In the present study, we analyzed interactions of the αMI-domain with a representative Mac-1 ligand, the cationic cytokine pleiotrophin (PTN). Through NMR chemical shift perturbation analysis, cross saturation, NOESY, and mutagenesis studies, we found the interaction between the αMI-domain and PTN is divalent cation-independent and mediated mostly by hydrophobic contacts between the N-terminal domain of PTN and residues in the α5-β5 loop of αMI-domain. The observation that increased ionic strength weakens the interaction between the proteins indicates electrostatic forces may also play a significant role in the binding. On the basis of the results from these experiments, we formulated a model of the interaction between the αMI-domain and PTN.

Microneedles with insulin-loaded glucose-responsive particles are promising to control the blood glucose levels of diabetic patients. In particular, the long-term usage of these microneedles calls for biodegradable and cost-effective particles, which are still large challenges. In this paper, glucose-responsive 4-carboxy-3-fluorophenylboronic acid-grafted e-polylysine (CFPBA-g-PL) was synthesized to meet these requirements. CFPBA-g-PL had low cytotoxicity, good hemocompatibility and no tissue reaction. The pharmacokinetics of CFPBA-g-PL were also studied. The self-assembled particles of CFPBA-g-PL were prepared via simple ultrasonic treatment. The insulin-loaded particles of CFPBA-g-PL (named INS/GRP-12.8) presented a glucose-responsive insulin delivery performance based on the disassembly-related mechanism in vitro. The INS/GRP-12.8-encapsulated microneedle patch with a uniform morphology and moderate skin penetration performance was prepared via a molding strategy. INS/GRP-12.8 lasted for more than 8 hours of normoglycemia on STZ-induced diabetic SD rats via subcutaneous injection and the INS/GRP-12.8-encapsulated microneedle patch also showed a blood-glucose-level-lowering performance in vivo via transdermal administration.

To overcome the migration problems of burning rate catalysts (BRCs), ferrocene-based amide compounds (AM-Fcs) were synthesized. The successful synthesis of AM-Fcs were confirmed by proton nuclear magnetic resonance, and Fourier transform infrared spectroscopy. The electrochemistry behaviors of AM-Fcs were examined by cyclic voltammetry (CV). The CV experimental results indicated that these AM-Fcs showed good electrochemical performances, which were contributable to their burning rate (BR) catalytic activity in composite solid propellants. The anti-migration test of AM-Fcs verified significantly slower migration than ferrocene and the most commonly used BRCs catocene. Thermal stability and BR catalytic impact of AM-Fcs on the thermal decomposition of ammonium perchlorate (AP) were studied by thermogravimetry and differential thermogravimetry. These AM-Fcs revealed good catalytic behaviors on the thermal degradation of AP.

Polyisoprene (PI) has been widely used in many industries for decades. Many researches have reported that most significant weaknesses of polyisoprene are caused by unsaturated double bond C=C. The aim of this research was to synthesis and characterize a new copolymer utilizing the unsaturated double bond C=C of polyisoprene. PI is first modified to form hydroxylated polyisoprene (PIOH). The absence of alkene proton peak in NMR spectrum of PIOH is a strong evidence that the unsaturation of PI has been reduced. After that, PIOH is subjected as an initiator for the ringopening polymerization of D,L-lactide in bulk condition to form hydroxylated polyisoprene-graft-polylactide copolymer (PI-g-PLA). The NMR spectrum of the new copolymer structure showed an unique peak at 4.09 ppm corresponding to methine proton of polyisoprene backbone adjacent to the PLA chains, indicating the grafting of D,L-lactide is successful to form PIOH-g-PLA. The average molecular weight, Mw of PIOH-g-PLA was significantly increased compared to PIOH, from 38260 to 56870 according to GPC. The surface of PIOH-g-PLA displayed significantly higher wettability and hidrophilicity than polyisoprene with water contact angle of below 30°. This owes to the terminal hydroxyl groups of PLA chains that lead to the formation of hydrogen bonds. Thermal stability studies by TGA and DTG of PIOH-g-PLA indicated two thermal degradations at Tmax 260 and 392 ℃ corresponding to PLA side chains and PIOH backbone, respectively, with PIOH exhibiting highest thermal stability compared to PI and the graft copolymer.

Ethylene response factors (ERFs) widely exist in plants and have been reported to be an important regulator of plant abiotic stress. Celery, a common economic vegetable of Apiaceae, contains lots of ERF transcription factors (TFs) with various functions. AP2/ERF TFs play positive or negative roles in plant growth and stress response. Here, AgERF8, a gene encoding EAR-type AP2/ERF TF, was identified. The AgERF8 mRNA accumulated in response to both abscisic acid (ABA) signaling and salt treatment. AgERF8 was proving to be a nucleus-located protein and could bind to GCC-box. The overexpression of AgERF8 in Arabidopsis repressed the transcription of downstream genes, AtBGL and AtBCH. Arabidopsis overexpressing AgERF8 gene showed inhibited root growth under ABA and NaCl treatments. AgERF8 transgenic lines showed low tolerance to ABA and salt stress than wild-type plants. Low increment in SOD and POD activities, increased accumulation of MDA, and significantly decreased plant fresh weights and chlorophyll levels were detected in AgERF8 hosting lines after treated with ABA and NaCl. Furthermore, the overexpression of AgERF8 also inhibited the levels of ascorbic acid and antioxidant-related genes (AtCAT1, AtSOD1, AtPOD, AtSOS1, AtAPX1, and AtP5CS1) expression in transgenic Arabidopsis. This finding indicated that AgERF8 negatively affected the resistance of transgenic Arabidopsis to ABA and salt stress through regulating downstream genes expression and relevant physiological changes. It will provide a potential sight to further understand the functions of ERF TFs in celery.

In this study, poly(cyclotriphosphazene-co-piperazine) p(HCCP-co-PIP) nanospheres were prepared. The successful preparation of the p(HCCP-co-PIP) nanospheres was confirmed by FT-IR, SEM, TEM, XRD, ...

Background Hepatocellular carcinoma (HCC) caused by hepatitis C virus (HCV) infection has become less and less due to the use of direct-acting antiviral agents (DAAs). Although it may be common to assume that eradication of the virus should improve the survival of HCC patients, large-scale randomized clinical data to support the correlation between viral load and prognosis are still lacking in China. The aim of the study was to evaluate the efficacy of antiviral therapy for HCC patients with active HCV infection. Patients and methods We retrospectively enrolled 80 HCC patients with active HCV infection. Active HCV infection was defined as positive for HCV antibody with detectable HCV RNA by polymerase chain reaction. Results Forty-four patients (55.0%) received interferon combined with ribavirin treatment and 23 patients achieved sustained virological response (SVR). The 1-year survival rate in patients who achieved SVR was the highest, followed by those with non-SVR after antiviral treatment, and those without antiviral therapy (1-year survival rate were 91.3%, 88.4%, and 73.1%, respectively, P = 0.012). In the univariate analysis, alcohol intake and alpha-fetoprotein >20 ng/mL were associated with lower overall survival (OS) (P = 0.025 and P = 0.044, respectively), while SVR after antiviral treatment was associated with longer OS (P = 0.016). In the multivariate analysis, only SVR after antiviral treatment was significantly associated with OS (P = 0.014). Conclusion Our results ensured that the elimination of HCV substantially improved OS in HCC patients with active HCV infection, and the prognosis of those patients without antiviral therapy was poor.

Increasing the level of AsA and maintaining proper lignin content will improve the quality of celery (Apium graveolens L.). However, the study on the regulation mechanism of genes related to AsA an...

Lipid overload results in lipid redistribution among metabolic organs such as liver, adipose, and muscle; therefore, the interplay between liver and other organs is important to maintain lipid homeostasis. Here, we show that liver responds to lipid overload first and sends hepatocyte-derived extracellular vesicles (EVs) targeting adipocytes to regulate adipogenesis and lipogenesis. Geranylgeranyl diphosphate synthase (Ggpps) expression in liver is enhanced by lipid overload and regulates EV secretion through Rab27A geranylgeranylation. Consistently, liver-specific Ggpps deficient mice have reduced fat adipose deposition. The levels of several EV-derived miRNAs in the plasma of non-alcoholic fatty liver disease (NAFLD) patients are positively correlated with body mass index (BMI), and these miRNAs enhance adipocyte lipid accumulation. Thus, we highlight an inter-organ mechanism whereby the liver senses different metabolic states and sends corresponding signals to remodel adipose tissue to adapt to metabolic changes in response to lipid overload., Extracellular vesicles (EVs) containing miRNAs or proteins can coordinate metabolic responses between tissues. Here the authors demonstrate that during lipid overload, the liver secretes miRNA-containing EVs through a Ggpps-Rab27 dependent mechanism, which controls adipose tissue lipid storage capacity.

White celery (Apium graveolens L.), a variety of common celery, is an important leafy vegetable in the Apiaceae family and is famous for its nutritional value. However, limited work has been devoted to quality formation and regulation in white celery. In this study, four white celery varieties, ‘Xuebaiqincai’, ‘Saixue’, ‘Baiganshiqin’ and ‘Ruixue’, were selected and analyzed for the comparison of ascorbic acid (AsA) and lignin levels, which are two important quality evaluation indicators in celery. The expression levels of the genes involved in AsA and lignin metabolic pathways were also detected. In the leaf blades, the AsA content was highest in ‘Xuebaiqincai’ compared with other varieties, whereas the most abundant AsA levels in the petioles were observed in ‘Baiganshiqin’ and ‘Ruixue’. The expression levels of AsA-related genes varied among the studied varieties. The highest level was detected in ‘Xuebaiqincai’, whereas other varieties exhibited relatively lower levels. The lignin content in the leaf blades was lower than that in the petioles. Correspondingly, the transcript profiles of genes involved in lignin biosynthesis were in accordance with the different levels in the petioles and blades. The results of this study provide potentially useful information for white celery breeding aimed at quality improvement and regulation.

To simplify the preparation process of a glucose-responsive microneedle patch, a cross-linking-density changeable microneedle patch was designed. The microneedle patch was made up of a hydrogel formed by phenylboronic acid-grafted polyallylamine and poly(vinyl alcohol) (PVA). The gel was cross-linked by boronate ester bonds between phenylboronic acid groups and PVA. It still had fluidity and could be filled into a mold to prepare microneedle patches. Moreover, insulin could be directly loaded into the microneedle patch by mixing with the gel. The boronate ester bond would be broken in the presence of glucose, resulting in a decrease in the cross-linking density. Therefore, the gel could achieve a greater swelling degree and insulin could be released faster. In addition, PVA chains were crystallized by repeatedly freezing and thawing to improve the mechanical strength of the microneedle patch. In terms of glucose-dependent insulin release, the gel showed good glucose-responsive insulin-release ability. Through additional ion cross-linking, the microneedle patch could also control the insulin release according to glucose concentration. In the hypoglycemic experiment of diabetic rats, the microneedle patch effectively pierced the skin and slowly released insulin.

Ascorbate is an antioxidant in plants. Its content is an important index to evaluate the nutritional quality of celery. In higher plant, ascorbate accumulation is effected by CO2 concentration. To study the effects of elevated CO2 (1000 µmol mol−1) on ascorbate accumulation in celery, ascorbate contents and the transcript levels of genes related to ascorbate metabolism in the leaves (leaf blade and petiole) were detected. The results of current study showed that the ascorbate and total ascorbate levels increased during all the treated stages in celery petioles, and they were 1.09–3.91 fold of the control. In leaf blades, the ascorbate contents exhibited a lower level (96.12% and 90.46% of the control) in treatments at 2 and 4 days, and then increased to 1.04 and 1.27 fold of the control in treatments at 6 and 8 days, respectively. Elevated CO2 altered the expression profiles of ascorbate-related genes and the activities of corresponding enzymes. Expression levels of the genes, AgPGI2, AgGMP, AgPMI, AgGalDH, AgGalLDH, GalUR, AgDHAR1, AgAPX1, and AgAO, in the leaf blades corresponded well to the change in ascorbate contents. At 6 days of treatment, the relative expression levels of AgPGI2, AgPMI, AgGGP1, AgGGP2, AgGalUR, AgMDHAR, AgDHAR1, and AgAPX1 in leaf blades increased, and were 4.41, 2.39, 4.65, 3.64, 3.11, 4.53, 4.59, and 3.86 times higher than that of the control. Increased ascorbate accumulation in celery leaves under elevated CO2 treatments might be also related to the change in SOD, POD, and CAT activities, as well as GSH content. These results will enhance our understanding on the effects of elevated CO2 on ascorbate accumulation and potential molecular mechanism regulating ascorbate metabolism in celery.

Semi-solid squeeze casting (SS-SC) is a new processing technology which combines semi-solid processing (SSP) and squeeze casting (SC). In this process, semi-solid slurry fills mold by using its rheological property and solidifies under high pressure. It has several advantages, such as stable filling, small heat impact to the mold, low cost, high density and excellent mechanical properties of castings, which receives more and more attention. The microstructure of castings provided by SS-SC is quite different from that of casting provided by conventional SC in as-cast condition, which leads to differences in the evolution of microstructure and mechanical properties in heat treatment process. In this study, A356.2 aluminum alloys castings were provided by both SS-SC and conventional SC respectively. The evolution of microstructure and mechanical properties of castings during heat treatment was investigated to obtain the best mechanical properties of semi-solid squeeze castings. Keywords:Microstructure, Mechanical properties, Heat treatment, A356 alloy, Semi-Solid Squeeze Casting

An unprecedented base-catalysed reductive relay hydroboration of allylic alcohols is described. Commercially available nBuLi was found to be a robust transition metal-free initiator for this protocol, affording various boronic esters in high yield and selectivity. Mechanistically, this methodology involves a one-pot three-step successive process (dehydrocoupling/allylic hydride substitution/anti-Markovnikov hydroboration).

The formation of macrophage foam cells by ingesting ox-LDL and focal retention in the subendothelial space are the hallmarks of the early atherosclerotic lesion. The C-C chemokine receptor type 7 (CCR7) is positively correlated with the macrophage migration. But the mechanism of CCR7 regulation is not fully clearness. In the present study, we demonstrates that expression in UNC5b and netrin-1 was enhanced in respond to ox-LDL in Raw264.7 macrophage and associated with decreasing cell migration. Interestingly, it was found that ox-LDL significantly downregulate CCR7 gene expression. The expression of CCR7 in mRNA and protein levels were decreased in ox-LDL treated Raw264.7 macrophage when we over expression of UNC5b with pcDNA3.1-UNC5b plasmid. We got the inverse results after silence UNC5b gene with siUNC5b. Meanwhile, the data show that in ox-LDL inducement, UNC5b down-regulated CCR7, and then inhibited macrophage migration. This novel phenomenon is of a crucial highlights to understand deeply the pathogenesis of atherosclerosis. The molecular mechanism of CCR7 regulation deserves intensive study.

Unlike amyloid aggregates, amorphous protein aggregates with no defined structures have been challenging to target and detect in a complex cellular milieu. In this study, we rationally designed sensors of amorphous protein aggregation from aggregation-induced-emission probes (AIEgens). Utilizing dicyanoisophorone as a model AIEgen scaffold, we first sensitized the fluorescence of AIEgens to a nonpolar and viscous environment mimicking the interior of amorphous aggregated proteins. We identified a generally applicable moiety (dimethylaminophenylene) for selective binding and fluorescence enhancement. Regulation of the electron-withdrawing groups tuned the emission wavelength while retaining selective detection. Finally, we utilized the optimized probe to systematically image aggregated proteome upon proteostasis network regulation. Overall, we present a rational approach to develop amorphous protein aggregation sensors from AIEgens with controllable sensitivity, spectral coverage, and cellular performance.

Covalent chemical reactions to modify aggregated proteins are rare. Here, we reported covalent Michael addition can generally occur upon protein aggregation. Such reactivity was initially discovered by a bioinspired fluorescent color-switch probe mimicking the photo-conversion mechanism of Kaede fluorescent protein. This probe was dark with folded proteins but turned on red fluorescence (620 nm) when it non-covalently bound to misfolded proteins. Supported by the biochemical and mass spectrometry results, the probe chemoselectively reacted with the reactive cysteines of aggregated proteins via covalent Michael addition and gradually switched to green fluorescence (515 nm) upon protein aggregation. Exploiting this Michael addition chemistry in the malachite green dye derivatives demonstrated its general applicability and chemical tunability, resulting in different fluorescence color-switch responses. Our work may offer a new avenue to explore other chemical reactions upon protein aggregation and design covalent probes for imaging, chemical proteomics, and therapeutic purposes.

Ferrocene-based polypyrrole (PPyFc) composites containing multi-walled carbon nanotube (MWCNT), reduced graphene oxide (RGO) and carbon black (CB) have been prepared by chemical oxidative polymerization. The prepared PPyFc/MWCNT, PPyFc/RGO and PPyFc/CB composites have been characterized by SEM, TEM, FTIR, XRD, XPS and TGA. Electrical conductivity of the PPyFc/MWCNT, PPyFc/RGO and PPyFc/CB composites has been tested by a typical four-probe method. Furthermore, the electromagnetic interference shielding effectiveness (EMI SE) of the PPyFc/CB, PPyFc/RGO and PPyFc/MWCNT composites has been measured through a coaxial method in the S-band frequency range. The EMI SE achieved for PPyFc/CB, PPyFc/RGO and PPyFc/MWCNT composites was − 11.08 dB, − 11.44 dB and − 23.74 dB, respectively.

Patients with obesity have a high prevalence of non-alcoholic fatty liver disease (NAFLD) and, in parallel, increased susceptibility to fibrosis/cirrhosis/hepatocellular carcinoma (HCC). Herein, we report that a high-fat diet (HFD) can augment glycolysis and then accelerate NAFLD-fibrosis progression by downregulating the expression of geranylgeranyl diphosphate synthase (GGPPS), which is a critical enzyme in the mevalonate pathway. Long-term HFD overloading decreases GGPPS expression in mice, which shifts the fuel preference from fatty acids towards glucose. Liver-specific Ggpps deficiency drives the Warburg effect by impairing mitochondrial function, and then induces hepatic inflammation, thus exacerbating fibrosis. Ggpps deficiency also enhances the hyperfarnesylation of liver kinase B1, and promotes metabolic reprogramming by regulating 5'-AMP-activated protein kinase activity. Clinical data further imply that GGPPS expression can predict the stage of NAFLD and recurrence of NAFLD-associated HCC. We conclude that the level of GGPPS is a susceptibility factor for NAFLD-fibrosis progression, and requires more stringent surveillance to ensure early prediction and precision of treatment of NAFLD-related HCC. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Given the sub-lethal risks of synthetic surfactants, rhamnolipid is a promising class of biosurfactants with the potential to promote the bioavailability of polycyclic aromatic hydrocarbons (PAHs), to provide a favorable substitute for synthetic surfactants. However, few previous studies have integrated the behavior and mechanism behind rhamnolipid-influenced PAH biosorption and biodegradation. This is, to our knowledge, the first report of a bacterial envelope regulated link between phenanthrene (PHE) biosorption and biodegradation by rhamnolipid-induced PHE-degrading strain Pseudomonas sp. Ph6. Rhamnolipid (0─400 mg L−1) can change the cell-surface zeta potential, cell surface hydrophobicity (CSH), cell ultra-microstructure and functional groups, and then alter PHE biosorption and biodegradation of Ph6. Greater amounts of PHE sorbed on cell envelopes results in more PHE diffusing into cytochylema, thus favoring PHE intracellular biodegradation of Ph6. Rhamnolipid (≤100 mg L−1) could change the microstructures and functional groups of cell envelopes of Ph6, enhance the cell-surface zeta potential and CSH, thus consequently favor PHE biosorption and biodegradation by strain Ph6. By contrast, rhamnolipid at higher concentrations (≥200 mg L−1) hindered PHE biosorption and biodegradation. Rhamnolipid, as a biosurfactant, can be successfully utilized as an additive to improve the microbial biodegradation of PAHs in the environments.

In this study, whey protein isolate (WPI)-quercetin (Que)-lotus root amylopectin (LRA) hydrogels (WPI-QUE-LRA) was developed to improve the solubility, stability and bioavailability of quercetin. Results showed that the favorable WPI-QUE-LRA was formed using WPI and LRA in the ratio of 1:2 at pH 7.0. Under this condition, the average size, polydispersity index, zeta potential of the WPI-QUE-LRA was 179.5 nm, 0.271, -18.6 mV, respectively. The analysis of transmission electron microscopy, fourier transform infrared spectroscopy and X-ray diffractometer revealed that the quercetin was successfully encapsulated in WPI-LRA, giving a high encapsulation efficiency of 92.4 %. Moreover, the WPI-LRA could significantly improve the storage stability and photochemical stability of quercetin. The in vitro and in vivo experiments showed that LRA-coated WPI hydrogel can enable quercetin to be stable in stomach and be effectively released in small intestine, leading to the enhancement of the bioavailability of quercetin.

Gestational diabetes mellitus (GDM) is a metabolic syndrome occurring in pregnant women and increases the risk of placental dysplasia. Neutrophil extracellular traps (NETs) may play a critical role in placental dysplasia. NETosis (neutrophil cell death by NET release) depends on NADPH/ROS pathway. In view of the adiponectin which is widely believed to be reduced in GDM patients suppresses NADPH oxidase and ROS generation of neutrophil. We speculate that increased NET release is associated with hypoadiponectinemia. Trophoblast apoptosis is significantly increased in GDM patients, but it is not clear whether NETs promotes cell apoptosis. This study aims to reveal the mechanism of Neutrophil Extracellular Traps generation and their role in trophoblast apoptosis in Gestational Diabetes Mellitus. We investigated the generation of NETs by cell-free DNA (cf-DNA) quantification, live-cell imaging, and reactive oxygen species (ROS) measurement. ERK1/2 and p38 MAPK signalling pathway proteins were detected by western blotting. The Cell Counting Kit-8 (CCK-8) assay, flow cytometry, and western blotting were performed to explore the effects of NETs on trophoblast apoptosis. We found that adiponectin inhibited NET release by suppressing ROS production, and p38 MAPK and ERK1/2 proteins were involved in the process. Further, NETs promoted trophoblast apoptosis by activating the ROS-dependent mitochondrial pathway, which is mediated by ERK1/2 signalling. The current study demonstrated that hypoadiponectinemia is the cause of NETs formation and NETs promoting trophoblast apoptosis.

Wound dressings with excellent adhesiveness, antibacterial, self-healing, hemostasis properties and therapeutic effects have great significance for the treatment of acute trauma. So far, numerous mussel-inspired catechol-based wet adhesives have been reported, opening a pathway for the treatment of acute trauma. However, catechol-based hydrogels are easily oxidized, which limits their applications. Here, the design of a polyphosphazene and non-catechol based antibacterial injectable hydrogel is reported as a multifunctional first aid bandage. Inspired by barnacle cement proteins (CPs), a series of dynamic phenylborate ester based adhesive hydrogels were prepared by combining the cation-π structure modified polyphosphazene with polyvinyl alcohol (PVA). The inherent antibacterial property (4 hours' antibacterial rate 99.6±0.2%), anti-mechanical damage, hemostatic behavior were investigated to confirm multi-functions of wound dressings. In water, the hydrogels firmly adhere to tissue surfaces through cation-π and π-π interactions as well as hydrogen bonding (adhesion strength = 45 kPa). Moreover, in vivo experiments indicated the hydrogels could shorten the bleeding time and reduce the amount of bleeding by 88%, and significantly accelerated the wound healing rate. These hydrogels have a promising application in the treatment of acute trauma, which is in urgent need of anti-infection and hemostasis. This article is protected by copyright. All rights reserved.

Currently, there is no standard therapy for non-alcoholic fatty liver disease (NAFLD), and statins have been developed as a first-line pharmaceutical therapeutic option for NAFLD-associated dyslipidemia. However, prolonged statins therapy has side effects, as statins inhibit HMG-CoA reductase, an enzyme at the very beginning of the mevalonate pathway. Here, we found that zoledronic acid (ZA), an inhibitor of farnesyl diphosphate synthase in the downstream mevalonate pathway, could attenuate hepatic lipid accumulation and improve liver injury in both high-fat diet-induced C57BL/6J mice and ob/ob mice. Moreover, the hepatic lipid metabolism was largely inhibited after ZA administration in high-fat diet-induced obese mice. Mechanically, ZA inhibited SREBP-1c-mediated de novo lipogenesis through suppressing RhoA activation via decreasing farnesyl diphosphate and geranylgeranyl diphosphate levels. In conclusion, our data provide a novel application of ZA in improving hepatic steatosis.

Pleiotrophin (PTN) is a multifunctional, cationic, glycosaminoglycan-binding cytokine and growth factor involved in numerous physiological and pathological processes, including tissue repair and inflammation-related diseases. PTN has been shown to promote leukocyte responses by inducing their migration and expression of inflammatory cytokines. However, the mechanisms through which PTN mediates these responses remain unclear. Here, we identified the integrin Mac-1 (αMβ2, CD11b/CD18) as the receptor mediating macrophage adhesion and migration to PTN. We also found that expression of Mac-1 on the surface of human embryonic kidney (HEK) 293 cells induced their adhesion and migration to PTN. Accordingly, PTN promoted Mac-1–dependent cell spreading and initiated intracellular signaling manifested in phosphorylation of Erk1/2. While binding to PTN, Mac-1 on Mac-1–expressing HEK293 cells appears to cooperate with cell-surface proteoglycans because both anti-Mac-1 function-blocking mAb and heparin were required to block adhesion. Moreover, biolayer interferometry and NMR indicated a direct interaction between the αMI domain, the major ligand-binding region of Mac-1, and PTN. Using peptide libraries, we found that in PTN the αMI domain bound sequences enriched in basic and hydrophobic residues, indicating that PTN conforms to the general principle of ligand-recognition specificity of the αMI domain toward cationic proteins/peptides. Finally, using recombinant PTN-derived fragments, we show that PTN contains two distinct Mac-1–binding sites in each of its constitutive domains. Collectively, these results identify PTN as a ligand for the integrin Mac-1 on the surface of leukocytes and suggest that this interaction may play a role in inflammatory responses.

Stimuli-responsive materials based on mesoporous silica have been widely studied for the controlled release of drugs. Glucose-responsive systems play a vital role in the controlled release of insulin because they can smartly adjust the amount of released insulin in response to the fluctuational blood glucose concentration. Here, the mesoporous silica (MS) was modified with 3-fluoro-4-carboxyphenylboronic acid (FCPBA) to prepare phenylboronic acid-modified mesoporous silica (MS-FCPBA). N-acryloyl glucosamine (AGA) was copolymerized with N-isopropyl acrylamide (NIPAM) and acrylic acid (AAc) respectively to synthesize two polymers with diol groups, noted as P(NIPAM-co-AGA) and P(AAc-co-AGA) respectively. Since the phenylboronic acid group can form a borate ester bond with the diol group, the polymers were coated on the surface of insulin-loaded MS-FCPBA to obtain the insulin release systems. The results showed that the loading capacity and encapsulation efficiency of insulin could reach 14.7% and 85.9%, respectively. The two systems exhibited different glucose-responsive performance.

Herein, a facile strategy for the synthesis of sandwich pyrolyzed bacterial cellulose (PBC)/graphene oxide (GO) composite was reported simply by utilizing the large-scale regenerated biomass bacterial cellulose as precursor. The unique and delicate structure where three-dimensional interconnected bacterial cellulose (BC) network embedded in two-dimensional GO skeleton could not only work as an effective barrier to retard polysulfide diffusion during the charge/discharge process to enhance the cyclic stability of the Li–S battery, but also offer a continuous electron transport pathway for the improved rate capability. As a result, by utilizing pure sulfur as cathodes, the Li–S batteries assembled with PBC/GO interlayer can still exhibit a capacity of nearly 600 mAh·g−1 at 3C and only 0.055% capacity decay per cycle can be observed over 200 cycles. Additionally, the cost-efficient and environment-friendly raw materials may enable the PBC/GO sandwich interlayer to be an advanced configuration for Li–S batteries.

Geniposide, the main medicinal ingredient of Gardenia jasminoides Ellis, is known to be a resistant agent to atherosclerosis. Some reports its mechanism against atherosclerosis remains completely unclear. Herein, we have investigated the protective effect of geniposide against atherosclerosis as well as clarified the mechanisms related with inhibiting the formation of foam cells and lowering reverse lipid transport via p38/MAPK signaling pathways. Macrophage Raw264.7 was induced by lysophosphatidic acid (LPA) to form foam cell as a cell model. ApoE-/- mice were fed with a high-fat diet for 16 weeks to cause atherosclerosis in carotid artery. After treatment with geniposide, CCK-8, oil red O stain, qRT-PCR and western blot were carried out to explore the effect of geniposide. Morphological changes, histological analyses were used to evaluate atherosclerosis in ApoE-/- mice. Geniposide significantly reduced serum total cholesterol (TC), triglyceride (TG) and LDL cholesterol levels in ApoE-/- mice compared with vehicle control. Meanwhile, geniposide dose dependently inhibited the development of atherosclerosis in ApoE-/- mice. Furthermore, geniposide observably inhibited the formation of foam cells induced by LPA, down-regulated the mRNA and protein levels of SR-A and up-regulated the mRNA and protein levels of ABCA1 or SR-B1 in vitro via inhibition of the p38MAPK and AKT signaling pathways. Our study shows that geniposide protected against atherosclerosis and inhibited the formation of foam cells by regulating the equilibrium on expression of diverse lipid transporters in cytomembrane which related with p38MAPK and AKT signaling pathways. Geniposide is a potential therapeutic drug for atherosclerosis.

Axially chiral biaryl scaffolds are essential structural units in chemistry. The asymmetric Pd-catalyzed Suzuki–Miyaura cross-coupling reaction has been widely recognized as one of the most practical methods for constructing atropisomers of biaryls. However, longstanding challenges remain in this field. For example, substrate scope is often narrow and specialized, functional groups and heterocycles can lead to reduced reactivity and selectivity, bulky ortho-substituents are usually needed, and reported methods are generally inapplicable to tetra-ortho-substituted biaryls. We have developed an unprecedented highly enantioselective N-heterocyclic carbene (NHC)-Pd catalyzed Suzuki–Miyaura cross-coupling reaction for the synthesis of atropisomeric biaryls. These reactions enable efficient coupling of aryl halides (Br, Cl) or aryl triflates with various types of aryl boron compounds (B(OH)2, Bpin, Bneo, BF3K), tolerate a remarkably broad scope of functional groups and heterocycles (>41 examples), employ low lo...

To investigate the effectiveness of adipose tissue-derived stem cells sheet combined with atelocollagen matrix on a mouse model of radiation-induced skin injury, adipose tissue-derived stem cells w...

Observational studies have demonstrated that cardiovascular risk factors are associated with chronic kidney disease (CKD). However, these observational associations are potentially influenced by the residual confounding, including some unmeasured lifestyle factors and interaction risk factors. Two-sample mendelian randomization analysis was conducted in this study to evaluate whether genetically predicted cardiovascular risk factors have a causal effect on the risk of CKD. We selected genetic variants associated with cardiovascular risk factors and extracted the corresponding effect sizes from the largest GWAS summary-level dataset of CKD. Cardiovascular risk factors contain high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, total cholesterol (TC), triglyceride (TG), glycated hemoglobin (HbA1c), fasting glucose, systolic blood pressure (SBP) and diastolic blood pressure (DBP). A Bonferroni corrected threshold of P = 0.006 was considered as significant, and 0.006 < P < 0.05 was considered suggestive of evidence for a potential association. Genetically predicted DBP was significantly associated with CKD [odds ratio (OR) was 1.35 (95% confidence interval (CI) (1.10, 1.65); P = 0.004)]. There was suggestive evidence for potential associations between genetically predicted higher HDL cholesterol [OR: 0.88, 95%CI (0.80, 0.98), P = 0.025] and lower adds of CKD, and between higher SBP [OR: 1.36, 95%CI (1.07, 1.73), P = 0.013] and higher adds of CKD. However, genetically predicted LDL cholesterol, TC, TG, HbA1c, and fasting glucose did not show any causal association with CKD.

Microneedles with self-regulated drug releasing behaviors are desirable and promising to improve the treatment quality of diabetics. Here, we fabricate a phenylboronic acid-based hydrogel microneedle patch (MNP) with glucose responsiveness and excellent biocompatibility for drug delivery at 37 °C. In this hydrogel-based MNP, the glucose-responsive properties are realized by introducing reversible phenylborate ester crosslinking points based on phenylboronic acid units and diol-containing units. The reversible crosslinking points also improve the mechanical strength for skin insertion. This novel phenylboronic acid-based hydrogel MNP lays the foundation for fabrication of a sensitive, safe and stable transdermal drug delivery system.

Cigarette industry plays an important role in the economy of the advanced countries. But the cigarette smoke contains toxic chemicals such as phenol which causes various kind of diseases and affect human life. In this paper, we synthesized carboxymethyl starch grafted poly vinyl imidazole (CMS-g-PVIs) by reacting carboxymehtyl starch (CMS) with vinyl imidazole (VI). The structures of the CMS-g-PVIs were investigated by 1H NMR and FT-IR. The crystalline properties of the CMS and CMS-g-PVIs were checked by XRD. The thermal properties of the original CMS and CMS-g-PVIs were investigated by TGA analysis. It was found that the modified starches had high thermal stability due to aromatic imidazole ring. The modified starches also showed more rough and distorted morphology as compared to native CMS. The CMS-g-PVIs were subjected for phenol adsorption and showed adsorption efficiencies of 0.170 g/g, 0.190 g/g, 0.192 g/g and 0.199 g/g for CMS, CMS-g-PVI 1, CMS-g-PVI 2 and CMS-g-PVI 3, respectively. Due to higher grafting ratio, CMS-g-PVI 3 showed good adsorption efficiency of 0.199 g/g for phenol. The obtained results showed that the grafting of vinyl imidazole on CMS can increase the adsorption efficiency of native CMS towards phenol.