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Enzyme-polymer conjugates are complex molecules with great practical significance. This work was designed to develop a novel enzyme-polymer conjugate by covalently coupling a zwitterionic polymer with side dimethyl chains (pID) to Candida rugosa lipase (CRL) via the reaction between the anhydrides of polymer chains with the amino groups of the enzyme. The resulting two CRL-pID conjugates with different pID grafting densities were investigated in term of the catalytic activity, stability and structural changes. In comparison with native CRL, both the CRL conjugates displayed 2.2 times higher activity than the native enzyme, and showed an increase in the maximum reaction rate (Vmax) and a decrease in the Michaelis constant (Km), thus resulting in about three-fold increases in the catalytic efficiency (kcat/Km). These are mainly attributed to the activation of lipase by the hydrophobic alky side chains. Moreover, the thermostability and pH tolerance of the lipase conjugates were significantly enhanced due to the stabilizing effect of the zwitterion moieties. For instance, a five-fold increase of the enzyme half-life at 50 oC for the high-pID conjugated CRL was observed. Spectroscopic studies reveal that the pID conjugation protected the enzyme in the changes in its microenvironment and conformation, well correlating with enhanced activity and stability of lipase conjugates. The findings indicate that enzyme conjugation to the zwitterionic polymer is promising for improving enzyme performance and deserves further development.

Inhibition of protein misfolding and aggregation is a great challenge in the field of biochemical and biopharmaceutical engineering. Alzheimer's disease (AD) is a protein-misfolding disease, and the interactions between 40-amino-acid-residue β-amyloid peptide (Aβ40) and its N-terminal truncated peptide Aβ11-40 demonstrate that Aβ11-40 may play an important role in the pathological process of AD. However, the effect of inhibitors on Aβ11-40 aggregation and on the cross-amyloid aggregation (co-assembly) between Aβ40 and Aβ11-40 has never been studied. Herein, coaggregation and seeding interactions between Aβ40 and Aβ11-40 as well as the effect of epigallocatechin gallate (EGCG), a small molecule inhibitor, on the cross-amyloid aggregation have been investigated by extensive analyses. It is found that Aβ11-40 participates in the aggregation of Aβ40 and leads to the formation of coaggregates that contain less β-sheet structures than pure Aβ40 aggregates. The aggregation kinetics along with morphologies and secondary structures of the coaggregates are also significantly affected by the Aβ40/Aβ11-40 ratio. EGCG accelerates the nucleation of Aβ40 but retards that of Aβ11-40 by affecting their elongation and secondary nucleation processes in solution and on solid surfaces. Meanwhile, EGCG makes the conformations of the seeding-induced Aβ aggregates more compact, especially for the homologous seedings. Isothermal titration calorimetry measurement indicates that hydrophobic interactions mainly contribute to the inhibition of the two Aβ isoforms by EGCG. The findings of this research have provided new insights into Aβ aggregation and the effect of an important inhibitor and the results would benefit in the development of potent inhibitors against co-assembly of different amyloid proteins.

With introduction into endodontics, bioceramic-based sealers have gained considerable popularity for excellent properties. The aim of this study was to investigate the physicochemical properties of a novel bioceramic silicone-based sealer, GuttaFlow Bioseal, and measure heat flow of setting reactions.Film thickness, flow, working and setting time of Bioseal were compared with other 4 kinds of sealers: iRoot SP, AH Plus, RoekoSeal and GuttaFlow2. Differential scanning calorimetry test was performed to measure heat flow.Bioseal demonstrated the highest film thickness of 44 μm, double to triple that of the other 4 sealers (P 0.05). The highest flow was detected in iRoot SP and RoekoSeal, with values of 27.35 and 27.20 mm, while GuttaFlow2 and Bioseal had the lowest of 22.31 and 21.43 mm (P 0.05). For each sealer, working time at 37 °C was shorter than that at 23 °C (P 0.05). At 37 °C, Bioseal had the shortest working and setting time of 4.5 and 16.3 min, while iRoot SP showed the longest of 105.0 and 571.7 min (P 0.05). Differential scanning calorimetry test revealed that setting process of all the tested sealers was exothermic. Bioseal reached an exothermic peak at 14 min, with almost 1.5 times peak intensity of GuttaFlow2 and RoekoSeal. Whereas iRoot SP and AH Plus reached an exothermic peak 5 h after mixing, with intensity 1/2 to 2/3 that of Bioseal.The novel bioceramic silicone-based sealer Bioseal showed intense and fast exothermic reactions with characteristic physicochemical properties.

In order to understand the formation mechanism of CH4 during the lignin pyrolysis process, 4-(3-hydroxypropyl)-2-methoxyphenol was selected as the G-type lignin monomer model compound. Theoretical studies on its pyrolysis process were conducted by using the density functional theory (DFT) method. The results show that the key of CH4 formation in the process of lignin pyrolysis is the homolytic cleavage of the O-CH3 bond of the methoxyl functional group to generate methyl radical. Then the methyl radical will abstract H to form CH4 through the unimolecular reaction or bimolecular reaction. The former reaction is difficult to occur due to the limited number of free H radicals in the pyrolysis process of lignin. The latter reaction is more likely to take place because of the lower reaction energy barriers. Both the alkyl side chain and the characteristic functional groups of the benzene ring can undergo bimolecular reactions to donate H for methyl radicals to form CH4.

A novel Gram-negative, rod-shaped, aerobic, oxidase-positive and catalase-negative bacterium, designated strain SM1970T, was isolated from a seawater sample collected from the Mariana Trench. Strain SM1970T grew at 15-37 oC and with 1–5% (w/v) NaCl. It hydrolyzed colloidal chitin, agar and casein but did not reduce nitrate to nitrite. Phylogenetic analysis based on the 16S rRNA gene sequences revealed that strain SM1970T formed a distinct lineage close to the genus Catenovulum within the family Alteromonadaceae, sharing the highest sequence similarity (93.6%) with type strain of Catenovulum maritimum but < 93.0% sequence similarity with those of other known species in the class Gammaproteobacteria. The major fatty acids of strain SM1970T were summed feature 3 (C16: 1 ω7c and/or C16: 1 ω6c), C16: 0 and summed feature 8 (C18: 1 ω7c and/or C18: 1 ω6c). The major polar lipids of the strain included phosphatidylethanolamine and phosphatidylglycerol and its main respiratory quinone was ubiquinone 8. The draft genome of strain SM1970T consisted of 77 scaffolds and was 4,172,146 bp in length, containing a complete set of genes for chitin degradation. The average amino acid identity (AAI) values between SM1970T and type strains of known Catenovulum species were 56.6–57.1% while the percentage of conserved proteins (POCP) values between them were 28.5–31.5%. The genomic DNA G + C content of strain SM1970T was 40.1 mol%. On the basis of the polyphasic analysis, strain SM1970T is considered to represent a novel species in a novel genus of the family Alteromonadaceae, for which the name Marinifaba aquimaris is proposed with the type strain being SM1970T (= MCCC 1K04323T = KCTC 72844T).

A Gram-stain-negative, aerobic, ovoid-rod-shaped bacterium, designated strain SM1903T, was isolated from surface seawater of the Mariana Trench. The strain grew at 15–37 °C (optimum, 35 °C) and with 1–15 % (optimum, 4 %) NaCl. It hydrolysed aesculin but did not reduce nitrate to nitrite and hydrolyse Tween 80. Phylogenetic analysis based on the 16S rRNA gene sequences revealed that strain SM1903T formed a separate lineage within the family Rhodobacteraceae , sharing the highest 16S rRNA gene sequence similarity with type strains of Pseudooceanicola antarcticus (95.7 %) and Roseisalinus antarcticus (95.7 %). In phylogenetic trees based on single-copy OCs and whole proteins sequences, strain SM1903T fell within a sub-cluster encompassed by Oceanicola granulosus , Roseisalinus antarcticus and Histidinibacterium lentulum and formed a branch adjacent to Oceanicola granulosus . The major cellular fatty acids were summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c), C16 : 0 and 11-methyl-C18 : 1 ω7c. The polar lipids mainly comprised phosphatidylglycerol, phosphatidylcholine, one unidentified lipid, one unidentified aminolipid, and one unidentified glycolipid. The solo respiratory quinone was ubiquinone-10. The genomic DNA G+C content of strain SM1903T was 66.0 mol%. Based on the results of phenotypic, chemotaxonomic, and phylogenetic characterization for strain SM1903T, it is considered to represent a novel species of a novel genus in the family Rhodobacteraceae , for which the name Pelagovum pacificum gen. nov., sp. nov. is proposed. The type strain is SM1903T (=MCCC 1K03608T=KCTC 72046T).

Context The phosphorus (P) sorption capacity of biochar and the effects of biochar amendment on soil P sorption and availability remain uncertain. Aims This study determined the specific contributions of the biochar inorganic component (mineral ash) and its carbon skeleton to the P sorption capacity of biochar. Methods A woody biochar and its acid-washed counterpart were added to two types of paddy soils with two P-retention capacities: high P sorption (HPS) and low P sorption (LPS). Key results Washing biochar with HCl solution drastically decreased the concentrations of calcium, magnesium, iron (Fe), and aluminium (Al) in the biochar. However, Fourier transform infrared and X-ray photoelectron spectroscopy spectra indicated that the washing procedure did not decrease the biochar organic carbon content and its surface functional groups. Acid-washed biochar showed nearly zero P sorption after 24 h of equilibration with P solution, and its incorporation had little effect on P sorption of the two paddy soils. Amendment with original alkaline woody biochar tended to increase P sorption capacity of LPS soils, but decreased that of HPS soils. The variations in Langmuir P sorption maxima, an indicator of soil P sorption capacity, among the soils and biochar treatments could be primarily explained by the amorphous Fe and Al concentrations, which indicates that the effect of biochar addition on soil P sorption was highly dependent on intrinsic soil P-retentive properties. Conclusion These results demonstrate that the biochar carbon skeleton had a very limited contribution to biochar P-retention capacity. Implications Our results suggest that the application of aged biochar with lower mineral contents to humid acidic highly weathered soils will have limited P retention capacity.

We disclose that the carbonates of 4-hydroxy-2-cyclopentenones can form π-allylpalladium-based 1,2-carbodipoles, which isomerize to interesting η2 -Pd0 -cyclopentadienone complexes. Compared with the labile parent cyclopentadienone, the HOMO energy of the related η2 -complex was significantly raised via the back-bonding of Pd0 as a π-Lewis base, rendering the uncoordinated C=C bond an electron-richer dienophile in inverse-electron-demand aza-Diels-Alder-type reactions with diverse 1-azadienes. The vinylogous (aza)Morita-Baylis-Hillman or cross Rauhut-Currier addition to (imine)carbonyls or activated alkenes, respectively, was also realized to afford chiral [4+2] or [2+2] cycloadducts, respectively, after trapping the re-generated π-allylpalladium species. New C1 -symmetric ligands from simple chiral sources were developed, exhibiting high stereoselectivity even with racemic substrates via an unusual dynamic kinetic resolution process. Besides, tropone could be similarly activated by a Pd0 complex.

A cooperative Rh(II)/Pd(0) dual-catalysis strategy that promotes a cyclization/allylic alkylation cascade of stable α-diazo-δ-keto-esters has been developed. Highly substituted 3(2H)-furanones with a C2-quaternary center can be obtained efficiently under mild conditions via one-pot synthesis. Remarkably, this binary catalytic system shows high chemo-, regio-, and stereoselectivity and excellent tolerance to various functionalities.

N-Acyl-N,O-acetals are key components in a variety of bioactive natural products. Furthermore, they are synthetic equivalents of unstable N-acylimines and building blocks in organic synthesis. Tremendous efforts have been made in the synthesis of such acetals, these methods can be broadly classified into two categories: electrochemical oxidation and chemical methods. Herein, we will summarize progress in the preparation of these subunits, which may aid the development of new synthetic methods for N-acyl-N,O-acetals.1 Introduction2 Synthetic Methods for Preparing N-Acyl-N,O-acetals2.1 Electrochemical Oxidation2.2 Chemical Methods2.3 Other Methods3 Summary and Outlook

Developing a coreactant-free ratiometric electrochemiluminescence (ECL) strategy based on a single luminophore to achieve more accurate and sensitive microRNA (miRNA) detection is highly desired. Herein, utilizing zinc-metal organic frameworks (Zn-MOFs) as the single luminophore, a novel dual-potential ratiometric ECL biosensor was constructed for ultrasensitive detection of miRNA-133a. The as-prepared Zn-MOFs exhibited simultaneous cathode and anode ECL emission. Furthermore, the Zn-MOFs were confirmed to be a multichannel ECL sensing platform with excellent annihilation and coreactant ECL emission. The corresponding ECL behaviors were investigated in detail. Benefiting from the hybridization chain reaction (HCR) amplification technology, N,N-diethylethylenediamine (DEAEA) was modified on hairpin DNA, and the gained products loaded with quantities of DEAEA enhanced the anodic ECL intensity of Zn-MOFs. In the presence of miRNA-133a, the ECL intensity ratio of anode to cathode (Ia/Ic) was significantly increased, which realized the ultrasensitive ratiometric detection of miRNA-133a. In addition, without an exogenous coreactant, the biosensor revealed superb accuracy and stability. Under optimal conditions, the detection linearity of miRNA-133a was from 50 aM to 50 fM with a low detection limit of 35.8 aM (S/N = 3). This is the first work to use Zn-MOFs as a single emitter for reliable ratiometric ECL bioanalysis, which provides a new perspective for fabricating a ratiometric ECL biosensor platform.

Purple-fleshed sweetpotato (Ipomoea batatas（L.）Lam.) is rich in anthocyanins. R2R3-type MYB transcription factors（TFs）with EAR motifs inhibiting anthocyanin biosynthesis have been reported, and there is still a lack of information on how mutations in the EAR motifs of MYBs affect anthocyanin accumulation. In this study, we obtained three IbMYB44 TFs by bioinformatics. Among these TFs, IbMYB44.1, IbMYB44.3 with a complete EAR motif and IbMYB44.2 with a single amino acid mutant in the EAR motif caused an amino acid substitution from leucine to valine. RT-qPCR analysis showed that IbMYB44s was expressed at lower levels in the purple-fleshed sweetpotato than in nonpurple-fleshed sweetpotato (P 0.01). Transient expression assays showed that the inhibitory effect of IbMYB44.1/3 was stronger than IbMYB44.2 in tobacco leaves and red-skinned pears. RT-qPCR analysis further proved that IbMYB44.1/3 significantly inhibited the expression of anthocyanin biosynthesis-related genes compared with IbMYB44.2 in tobacco leaves and red-skinned pears. A dual luciferase reporter assay showed that IbMYB44s cannot directly activate the IbANS promoter, and the result was also verified by yeast one-hybrid (Y1H) experiments. Moreover, we identified the interaction of IbMYB340 with IbMYB44.1, IbMYB44.2 and IbMYB44.3 via yeast two-hybrid (Y2H) assays. Thus, IbMYB44.1/3 could interact with IbMYB340 to negatively regulate anthocyanin biosynthesis. This study enriched the regulatory network of anthocyanins and also provided a theoretical basis for a single amino acid mutant from leucine to valine in the EAR motif of IbMYB44.2 affecting anthocyanin biosynthesis in the purple-fleshed sweetpotato.

Background/purpose: There is limited literature on the polishability of new launched nanofilled and nanohybrid. The aim of this study is to evaluate the polishability of nanofilled and nanohybrid composites by measuring surface roughness and gloss values and explore the surface qualities of composite before and after polishing in vitro. Materials and methods: One nanofilled resin composite, two nanohybrid resin composites and one microhybrid resin composite were selected. All specimens were light cured against celluloid matrix strips. Then surface roughness(Ra) and gloss(GU) values were tested as negative control. Specimens were roughened with a 600-grit silicon carbide paper for 30 s to serve as positive control and then polished with Sof-Lex polishing disk system. Mean Ra and GU values of each step were measured with a profilometer and a small-area glossmeter. The surface qualities were observed by scanning electron microscope. Results: Ra values of polished surfaces were significantly higher than negative control and lower than positive control(P 0.05). GU values of polished surfaces were significantly lower than negative control and higher than positive control(P

Silver nanoparticle (AgNP) aqueous colloids with different surface plasmon resonance (SPR) frequencies were controllably synthesized by a facile and green chemical synthesis method. The obtained AgNPs with an average diameter of ~ 15 nm show a symmetrical SPR peak at ~ 400 nm. Another longitudinal SPR mode at ~ 520 nm occurs when increasing the amount of ethanol according to the ultraviolet–visible light spectra. The third-order nonlinear optical (NLO) absorption properties of the AgNP colloids were found to switch from two-photon absorption (TPA) to saturable absorption (SA) by tuning the SPR frequency using Z-scan technique with 340 fs pulses at 515 nm. When combined with two-dimensional (2D) MoS2, an enhanced SA response is observed for Ag/MoS2 nanocomposites compared with the counterparts. The nonlinear absorption coefficient of Ag/MoS2 nanocomposites is about − (10.93 ± 0.6) × 10–2 cm·GW−1, which is almost three times higher than that of MoS2. Our work has an instructive value in promoting the potential application of AgNPs and its nanocomposites in optoelectronic and photonic devices, such as optical limiting and ultrafast laser pulse generation.

Synthesis methods of composites materials can tailor individual materials properties and make the composite possess more superior performance than individual materials. Herein, by combining –NH2 group in graphitic carbon nitride (g-C3N4) and a facile electrolytic route, g-C3N4-bridging reduced graphene oxide nanocomposite (g-C3N4/r-GO) was successfully prepared to construct chemical sensor for detection of Pb2+. Because g-C3N4 contains a large amount of –NH2 group, covalent bonds as bridges between GO and g-C3N4 could be successfully formed by successively electrolyzing, which simultaneously induced removal of electron withdrawing group in r-GO. Such bridges could shorten the planar distance between GO and g-C3N4 in comparison with the conventional π-π stacking, improving the electrochemical performance of r-GO and g-C3N4. Moreover, the above unique chemical structure of g-C3N4/r-GO not only exhibited excellent electrical conductivity but also provided plenty active sites to chelate Pb2+ from solution. Therefore, the prepared g-C3N4/r-GO ensured chemical sensor for Pb2+detection with wide linear range (1.0–300 μg/L) and low detection limit (0.15 μg/L at S/N = 3). This simple method could also be extended to preparation of other elements-contained nanomaterials functionalized oxide graphene for improve its properties and widen its potential applications.

A Gram-negative, aerobic, non-flagellated and ovoid- or rod-shaped bacterium, designated strain SM1902T, was isolated from the sediment sampled at the Jia River estuary, Yantai, PR China. The strain grew at 10–37 °C (optimum, 25–30 °C), pH 6.0–10.0 (pH 7.0) and with 0.5–13.0 % (w/v) NaCl (2.5%). It reduced nitrate to nitrite, but did not produce bacteriochlorophyll a. The results of phylogenetic analysis based on 16S rRNA gene sequences revealed that strain SM1902T constituted a separated lineage within the family Rhodobacteraceae and was closely related to Meridianimarinicoccus roseus TG-679T and Phycocomes zhengii LMIT002T with 96.1 and 94.3 % 16S rRNA gene sequence similarities, respectively. The predominant cellular fatty acid was summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c). The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, an unidentified aminolipid and an unidentified lipid. The sole respiratory quinone was ubiquinone-10. The in silico DNA–DNA hybridization values between strain SM1902T and Meridianimarinicoccus roseus TG-679T and Phycocomes zhengii LMIT002T were 19.6 and 19.5 %, respectively; and the average nucleotide identity values between them were 76.1 and 74.2 %, respectively. The genomic DNA G+C content of strain SM1902T was 58.2 mol%. Based on the phylogenetic, chemotaxonomic and phenotypic data obtained in this study, strain SM1902T is considered to represent a novel species in a new genus within the family Rhodobacteraceae , for which the name Fluviibacterium aquatile gen. nov., sp. nov. is proposed. The type strain is SM1902T (=KCTC 72045T=MCCC 1K03596T=CCTCC AB 2018346T).

Patients with Parkinson's disease (PD) have a higher incidence rate of duodenal ulcers. The mucus barrier provides the first line of defense for duodenal mucosal protection. However, it is unknown whether duodenal mucus secretion is affected in PD. In the present study, we used the rats microinjected 6-hydroxydopamine (6-OHDA) into the bilateral substantia nigra to investigate duodenal mucus secretion and potential therapeutic targets in duodenal ulcer in PD. Alcian blue-periodic acid-Schiff, transmission electron microscopy, immunofluorescence, duodenal mucosal incubation, and enzyme-linked immunosorbent assays were used. The 6-OHDA rats exhibited mucin accumulation and retention in duodenal goblet cells. Mucin granules were unable to fuse with the apical membranes of goblet cells, and the exocytosis ratio of goblet cells was significantly reduced. Moreover, decreased acetylcholine and increased muscarinic receptor 2 (M2R) levels were detected in the duodenal mucosa of 6-OHDA rats. Bilateral vagotomy rats were also characterized by defective duodenal mucus secretion and decreased acetylcholine with increased M2R levels in the duodenal mucosa. Application of the cholinomimetic drug carbachol or blocking M2R with methoctramine significantly promoted mucus secretion by goblet cells and increased MUC2 content in duodenal mucosa-incubated solutions from 6-OHDA and vagotomy rats. We conclude that the reduced acetylcholine and increased M2R contribute to the impaired duodenal mucus secretion of 6-OHDA rats. The study provides new insights into the mechanism of duodenal mucus secretion and potential therapeutic targets for the treatment of duodenal ulcers in PD patients.

Reactions of (NH4 )2 WS4 with CuCN, CuCN/1,2-bis(4-pyridyl)propane (bppa) or [Cu(MeCN)4 ]PF6 /bppa under different reaction conditions afforded a set of two- or three-dimensional W/Cu/S cluster-based coordination polymers including {[Et4 N]2 [WS4 Cu4 (μ-CN)2 (μ-I)2 ]}n (1), [WS4 Cu4 (μ-CN)2 (bppa)2 ]n (2) and {[WS4 Cu4 (bppa)4 ](PF6 )2 }n (3), respectively. Compound 2 can be readily formed from reaction of 1 with bppa under solvothermal conditions. Compounds 1 and 2 feature two-dimensional networks with a "sql" topology, while 3 possesses a two-fold interpenetrated three-dimensional net with a rare "reo" topology. Compounds 1-3 in DMF exhibited different third-order nonlinear optical responses, and they all showed a reverse saturable absorption while 2 held a strong self-focusing effect.

Improving proton conduction in cathodes is regarded as one of the most effective methods to accelerate the sluggish proton-involved oxygen reduction reaction (P-ORR) for proton-conducting solid oxide fuel cells (P-SOFCs). In this work, K+ dopant was used to improve the proton uptake and migration ability of SrCo0.9 Nb0.1 O3-δ (SCN). K+ -doped SCN (KSCN) demonstrated great potential to be a promising cathode for P-SOFCs. Density functional theory calculations suggested that doping with K+ led to more oxygen vacancies and more negative values of hydration enthalpy, which was helpful for the improvement of proton concentration. Importantly, the proton migration barriers could be depressed, benefiting proton conduction. Electrochemical investigations signified that the cell using KSCN cathode had a peak power density of 967 mW cm-2 at 700 °C, about 54.1 % higher than that using a SCN cathode. This research highlights the K+ -doping strategy to improve electrochemical performance of cathodes for P-SOFCs.

Endometrial cancer is generally one of the most evident malignant tumours of the female reproductive system, and the mechanisms underlying its cell proliferation and apoptosis are key to research in gynaecological oncology. In the paper, the in-depth molecular mechanism by which DJ-1 protein regulates the proliferation and apoptosis of Ishikawa cells was investigated. DJ-1 knockdown and overexpressing Ishikawa stable cell lines were established by lentiviral transduction. The levels of DJ-1 and noncanonical NF-κB signaling proteins were evaluated by Western blotting. Cell counting kit-8 (CCK-8) and flow cytometry were applied to analyze the cell viability and apoptosis. Co-immunoprecipitation experiment was utilized to assess the DJ-1-Cezanne interaction. The results showed that DJ-1 overexpression conferred apoptosis resistance and high proliferation on Ishikawa cells, while DJ-1 knockdown in Ishikawa cells produced the opposite results. These findings again suggested that DJ-1 inhibits the apoptosis and promotes the proliferation of Ishikawa cells. More crucially, further data showed that the noncanonical NF-κB activation was required for the regulation of Ishikawa cell proliferation and apoptosis by DJ-1. Meanwhile, it was found that noncanonical NF-κB pathway may be activated by DJ-1 interacting with and negatively regulating Cezanne in Ishikawa cells. Overall, this work revealed that DJ-1 associates with and negatively regulates Cezanne and consequently triggers the noncanonical NF-κB activation, thereby regulating Ishikawa cell proliferation and apoptosis.

Metabolite lactic acid has always been regarded as a metabolic by-product rather than a bioactive molecule. Recently, this view has changed since it was discovered that lactic acid can be used as a signal molecule and has novel signal transduction functions both intracellular and extracellular, which can regulate key functions in the immune system. In recent years, more and more evidence has shown that lactic acid is closely related to the metabolism and polarization of macrophages. During inflammation, lactic acid is a regulator of macrophage metabolism, and it can prevent excessive inflammatory responses; In malignant tumors, lactic acid produced by tumor tissues promotes the polarization of tumor-associated macrophages, which in turn promotes tumor progression. In this review, we examined the relationship between lactic acid and macrophage metabolism. We further discussed how lactic acid plays a role in maintaining the homeostasis of macrophages, as well as the biology of macrophage polarization and the M1/M2 imbalance in human diseases. Potential methods to target lactic acid in the treatment of inflammation and cancer will also be discussed so as to provide new strategies for the treatment of diseases.

Hawthorn (Crataegus pinnatifida Bunge. var. major) is an edible and medicinal fruit that is very common in food and traditional Chinese medicine. Corosolic acid (CA), a pentacyclic triterpenoid, which is an active component of hawthorn (Crataegus pinnatifida Bunge. var. major), has been exhibiting various pharmacological activities such as antidiabetic, antibacterial, anticancer, antiinflammatory, and antioxidant effects. The study aimed to evaluate the effect of CA on non-alcoholic steatohepatitis (NASH) in mice induced by 60 kcal% high-fat diet (HFD) and carbon tetrachloride (CCl4 ). CA lowered liver index and serum AST, ALT, TG, and TC levels compared to those in the model group. Histological analyses of the liver tissues of mice treated with CA revealed significantly decreased number of lipid droplets and alleviated inflammation and fibrosis. CA inhibited the transcripts of pro-fibrogenic markers (including α-SMA, collagen I, and TIMP-1) and the levels of pro-inflammatory cytokines (including TNF-α, IL-1β, caspase-1, and IL-6) associated with hepatic fibrosis, and NF-κB translocation and TGF-β1/Smad2 and AMPK pathways. In addition, CA reduced lipid accumulation via the regulation of AMPK and NF-κB activation in FFA-induced steatotic HepG2 cells. CA also decreased α-SMA, collagen I expressions, and Smad2 phosphorylation, which were reduced by TGF-β1 treatment in LX2 cells. Our results suggested that CA ameliorated NASH through regulating TGF-β1/Smad2, NF-κB, and AMPK signaling pathways, and CA could be developed as a potential health functional food or therapeutic agent for NASH patients.

After paraquat (PQ) poisoning, it is difficult to accurately diagnose patients' condition by only measuring their blood PQ concentration. Therefore, it is important to establish an accurate method to assist in the diagnosis of PQ poisoning, especially in the early stages. In this study, a gas chromatography-mass spectrometry (GC-MS) metabonomics strategy was established to obtain metabolite information. A random forest algorithm was used to search for potential biomarkers of PQ poisoning, and data mining and network pharmacological analysis were used to evaluate the active components, drug-disease targets, and key pathways of Xuebijing (XBJ) injection in the treatment of PQ-induced pulmonary fibrosis. Targets from the network pharmacology analysis and metabolites from plasma metabolomics were jointly analyzed to select crucial metabolic pathways. Finally, molecular docking technology and in vitro experiments were used to verify the pathway targets to further reveal the potential mechanisms underlying the antipulmonary fibrosis effect of XBJ. Metabonomics studies showed that l-valine, glycine, citric acid, d-mannose, d-galactose, maltose, l-tryptophan, and arachidonic acid contributed more to the differentiation of different groups than other metabolites. Compared with the control group, the PQ poisoning group had higher levels of l-valine, glycine, citric acid, l-tryptophan, and arachidonic acid, and lower levels of d-mannose, d-galactose, and maltose. After treatment with XBJ injection, the relative levels of these metabolites were reversed. The network pharmacological analysis screened a total of 180 targets, mainly involving multiple signaling pathways and metabolic pathways, which jointly played an antipulmonary fibrosis effect. Based on the combined analysis of 180 targets and 8 different metabolites, arachidonic acid metabolism was selected as the key metabolic pathway. Molecular docking analysis showed that the XBJ compound had strong binding activity with the target protein. Western blot results showed that XBJ injection could reduce the inflammatory response by downregulating the expressions of p-p65, p-IKBα, and p-IKKβ, thus inhibiting the development of PQ-induced pulmonary fibrosis. In summary, the combined results from metabolomics and network pharmacology studies showed that Xuebijing has the characteristics of multitarget, multichannel, and multicomponent action in the treatment of pulmonary fibrosis caused by PQ.

Edaravone (Eda) is a free radical scavenger used in clinical trials for the treatment of ischemic stroke and amyotrophic lateral sclerosis. However, how Eda exerts its neuroprotective effects remains to be elucidated. We investigated the neuroprotective effects of Eda in cultured hippocampal neurons and in a mouse model of AlCl3/D-galactose-induced cognitive impairment. Eda protected hippocampal neurons by eliminating H2O2 or glutamate-induced toxicity, leading to decreased cell viability and neurite shortening. Consistently, Eda restored impaired levels of BDNF, FGF2 and their associated signaling axes (including TrkB, p-Akt and Bcl-2) to attenuate neuronal death. In a mouse model of chemically-induced cognitive impairment, Eda restored the levels of BDNF, FGF2 and TrkB/Akt signaling axis to attenuate neuronal apoptosis, thereby ameliorating cognitive impairment. Meanwhile, the pro-inflammation was eliminated due to the restoration of pro-inflammatory factors such as TNF-α, IL-6, IL-1β, and NOS2. In summary, Eda is an effective drug for protecting neurons from neurotoxic injury. BDNF, FGF2, and their regulated pathways may be potential therapeutic targets for neuroprotection.

Non-small cell lung cancer (NSCLC) accounts for 85% of lung cancer cases, and is characterized by more insensitivity to chemotherapy and poor prognosis. Epidermal growth factor receptor (EGFR) has been confirmed as a tumorigenic driving factor of NSCLC. Taspine has been proved effective in the inhibition of malignant tumours. Here, we found TPD7, a novel taspine derivative, exerted most inhibitory effect on EGFR-dependent HCC827 cells and investigated the underling mechanism. In addition, TPD7 could block cell cycle at G0/G1 phase of HCC827 cells by regulating the expression of cyclin D1 and cyclin E. Furthermore, TPD7 induced HCC827 cell apoptosis by regulating the expression of BCL-2 family proteins. Further study revealed that TPD7 could down-regulate the phosphorylation of EGFR and downstream members. TPD7 might present a potential EGFR inhibitor in the treatment of NSCLC.

Transition metal chalcogenide quantum dots (TMCs QDs) constitute a crucial sector of semiconductors on account of large absorption coefficient for light harvesting, peculiar quantum confinement effect, and abundant active sites stemming from ultra-small size. However, elaborate and tunable modulation of anisotropic photoinduced charge carriers over TMCs QDs represents an enduring challenge in terms of sluggish charge transfer kinetic and ultra-short charge lifetime compared with nanoparticulate counterparts, thereby rendering maneuvering charge transfer of TMCs QDs a tough issue. We herein conceptually unlock the unanticipated charge transport capability of solid-state non-conductive poly(diallyl dimethylammonium chloride) (PDDA) for constructing cascade charge transfer pathway over self-assembled wide bandgap semiconductors (WBS)/PDDA/TMCs QDs multilayered heterostructures, by which unidirectional and accelerated electron transfer from TMCs QDs to WBS support mediums was spontaneously activated, markedly boosting the charge separation/migration efficiency. The integrated roles of such ultrathin insulating PDDA intermediate layer as simultaneous surface charge modifying agent and interfacial charge transfer mediator have been evidenced to be universal. The unexpected electron-withdrawing capability of ultrathin PDDA layer endows WBS (SnO 2, TiO2)@PDDA@TMCs (CdSe, CdS) QDs heterostructures with significantly enhanced net efficiency of photoactivities toward selective anaerobic reduction of nitroaromatics to amino derivatives under visible light irradiation. Our work would feature a promising scope for rational design of multifarious novel insulating polymers-based photosystems for solar energy conversion.

Waste sugar solution (WSS), a waste by-product of manufacturing vitamin C, contains abundant waste acids and organics. In this work, a N/O-enriched copolymer was synthesized via a facile polymerization via the hydrogen bonding of O-containing functional groups and melamine and the crosslinking of aldehyde groups. Subsequently, N-doped carbon spheres were prepared by a typical carbonation/activation method. Remarkably, benefiting from an ultrahigh specific surface area (3612 m2/g) and rich heteroatom content (4.3% for N, 8.8% for O), the carbon spheres deliver a high specific capacitance of 387 F/g at 50 mA/g and 283 F/g at 5 A/g with 6 M KOH in two-electrode system. The assembled symmetric electric double-layer capacitor exhibits high energy density of 10.83 Wh/kg at 11.10 W/kg. This research provides a facile method for preparing N/O-doped carbon spheres by WSS, and confirms the excellent electrochemical performance of WSS-derived carbons in energy storage applications.

Leading by cytotoxicity against HepG2 cells, bioactivity-guided fractionation of the EtOAc fraction from Artemisia atrovirens led to the isolation of 18 new guaianolide dimers, artematrolides A–R and lavandiolides A, B, C, H, and J. Eight compounds (1, 4, 10, 12, 13, and 19–21) were unambiguously confirmed by the single-crystal X-ray diffraction analyses, and the others were elucidated based on IR, UV, HRESIMS, 1D and 2D NMR experiments, and comparison of the experimental and calculated ECD data. Structurally, all of them were [4 + 2] Diels–Alder adducts of two monomeric guaianolides. The isolates were evaluated for their cytotoxicity against three human hepatoma cell lines, and 19 compounds demonstrated cytotoxicity against HepG2, SMMC-7721, and Huh7 cell lines. Especially, compounds 1, 12, 14, and 15 exhibited cytotoxicity with IC50 values of 4.4, 3.8, 7.6, and 6.7 μmol/L (HepG2), 9.6, 4.6, 6.6, and 6.0 μmol/L (SMMC-7721), and 7.6, 4.5, 6.9, and 5.6 μmol/L (Huh7), respectively. Notably, compound 12 showed the most promising activity against three human hepatoma cell lines and dose-dependently inhibited cell migration and invasion, induced G2/M cell cycle arrest and cell apoptosis in HepG2 cells, down-regulated the expression of BCL-2 and PARP-1, and activated PARP-1 to up-regulate the expression of cleaved-PARP-1.

As a signaling molecule, hydrogen sulfide (H2S) plays an indispensable role in the modulation of ripening and senescence in fruits and vegetables. To explore the role of H2S in regulating metabolism of postharvest tomato, ripening-related physiological parameters, activities of antioxidant enzymes and gene expression were analyzed in H2S-fumigated tomato fruits. These results show that H2S significantly delayed the color transition and softening of tomato fruit, and maintained higher level of flavonoids and lower level of anthocyanin during storage. Besides, H2S could maintain higher level of nutritional-related metabolites, such as reducing sugar, ascorbic acid during postharvest storage. Moreover, H2S decreased the rate of O2− production, inhibited the production of H2O2 and malondialdehyde (MDA), enhanced the activities of antioxidant enzymes including ascorbate peroxidase (APX), superoxide dismutase (SOD), catalase (CAT) and guaiacol peroxidase (POD) in tomato fruits, while reduced the activities of phenylalanine ammonia lyase (PAL), polyphenol oxidase (PPO) and lipoxygenase (LOX). Besides, the expression of the antioxidant-encoding genes SlCAT2, SlPOD12 was generally upregulated with H2S fumigation. Principal component analysis (PCA) suggests that H2S induced significant discrepancy mainly to the differences in firmness, anthocyanin, flavonoid and the activity of guaiacol peroxidase (POD), and the correlation analysis further shows that H2S affected pigment metabolism and nutritional quality. In conclusion, H2S could maintain better appearance and nutritional quality, and prolong the storage period of postharvest tomato fruits through activating the antioxidative system.

This study aimed to investigate the effects of arachidonic acid metabolite epoxyeicosatrienoic acid (EETs) in the apoptosis of endothelial cells induced by tumor necrosis factor-alpha (TNF-α). After human umbilical vein endothelial cells were cultured, TNF-α/ActD, 14, 15-EET, and HMR-1098 were added, respectively, into the culture medium. The apoptosis level of endothelial cells was detected by flow cytometry. After TNF-α/ActD induced endothelial cell apoptosis, flow cytometry staining showed that endothelial cell apoptosis increased significantly, and the apoptotic cells were significantly reduced after the addition of 14, 15-EET. However, the apoptotic cells significantly increased after the addition of HMR-1098. Western Blot results showed that the phosphorylation levels of LC3-II and AMPK were increased after TNF-α/ActD induction, and the increase was noticeable after the addition of 14, 15-EET. However, the phosphorylation levels of LC3-II and AMPK significantly decreased after the addition of HMR-1098. The activity of Caspase-8 and -9 decreased significantly after the addition of 14, 15-EET but increased after the addition of HMR-1098. Arachidonic acid can inhibit TNF-α induced endothelial cell apoptosis by upregulating autophagy.

Sensory materials that show color and/or fluorescence changes in response to specific gases or vapors have important applications in many fields. Here, we report the postsynthetic preparation of novel sensory metal-organic frameworks (MOFs) and their multiple responsive properties. Through postsynthetic N-amination, the 2,2'-bipyridyl spacers in a Zr(IV) MOF are partially transformed into N-aminobipyridinium. The new MOF (Zr-bpy-A) shows chromic behavior toward ammonia and amines because the electron-deficient pyridinium groups form charge-transfer complexes with amino moieties. It also shows a unique chromic response to formaldehyde owing to the Schiff-base condensation with the N-amino groups. Furthermore, the N-amino group can be used to graft different polycyclic aromatic hydrocarbons, which endow the MOF with strong fluorescence of variable colors and afford a high-contrast fluorescence response to ammonia/amines and formaldehyde associated with the chromic response. The presence of the unquaternized bipyridyl group also leads to a fluorescence response to HCl. The multiple responsive behaviors hold appeal for applications in sensing, switching, and antifake marking, which are illustrated with a test paper and writing ink.

Because of considerable adsorption capacities of competitive gases N₂ and CO₂, many kinds of porous materials suffer from unsatisfied SO₂/CO₂ and SO₂/N₂ selectivities and thus hardly achieve deep removal of SO₂ from flue gas. Herein, a novel type of guanidinium-based poly(ionic liquid) with the feature of nonporosity was designed and prepared through a facile copolymerization procedure. It is very attractive that nonporous guanidinium-based poly(ionic liquids) P([allyl-TMG]Br-DVB) by polymerization of (allyl-tetramethylguanidine)bromide with divinylbenzene had almost excluded the adsorption of N₂ (0.01 mmol g–¹) and CO₂ (0.07 mmol g–¹) but showed very high SO₂ capacity (9.79 mmol g–¹) at 25 °C and 1 bar. The high selectivities of SO₂/CO₂ (452) and SO₂/N₂ (2294) were accordingly obtained. Furthermore, column breakthrough experiments confirmed the excellent separation performance of P([allyl-TMG]Br-DVB) in deeply eliminating 2000 ppm SO₂ in the mixture of SO₂/N₂/CO₂. The employment of nonporous poly(ionic liquids) as efficient adsorbents is an effective strategy for the deep removal of SO₂ from flue gas.

Cerebral ischemia-reperfusion (CI/R) injury is a serious complication when treating patients experiencing ischemic stroke. Although the microRNA miR-27a-3p reportedly participates in ischemia/reperfusion (I/R) injury, its actions in CI/R remain unclear. To mimic CI/R in vitro, HT22 cells were subjected to oxygen glucose deprivation/reoxygenation (OGD/R). The results indicate that OGD inhibited growth and induced apoptosis among HT22 cells. The apoptosis was accompanied by increases in activated caspases 3 and 9 and decreases in Bcl-2. Oxidative stress was also increased, as indicated by increases in ROS and malondialdehyde and decreases in glutathione and superoxide dismutase. In addition, OGD induced G1 arrest in HT22 cells with corresponding upregulation of FOXO1 and p27 Kip1, suggesting the cell cycle arrest was mediated by FOXO1/p27 Kip1 signaling. Notably, FOXO1 was found to be the direct target of miR-27a-3p in HT22 cells. MiR-27a-3p was downregulated in OGD/R-treated HT22 cells, and miR-27a-3p mimics partially or entirely reversed all of the in vitro effects of OGD. Moreover, miR-27a-3p agomir significantly alleviated the symptoms of CI/R in vivo in a rat model of CI/R. Thus, MiR-27a-3p appears to suppress CI/R injury by targeting FOXO1.

Neonatal jaundice is a common symptom that occurs in neonates during the first month of their life and is generally divided into physiological and pathological subtypes. In serious cases, pathological neonatal jaundice frequently shows complications including seizures, cerebral palsy, and kernicterus. However, due to the unclear pathogenesis of pathological neonatal jaundice, effective drugs for this disease remain unsatisfied. In the present study, we first estimated the protective effects of folic acid (FA) on phenylhydrazine (PHA) or homocysteine (Hcy)-injected neonatal rats (2-3 days aged). Intriguingly, we found that FA significantly decreased the elevated total bilirubin (TBIL) and direct bilirubin (DBIL) concentration, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) activity in PHA- or Hcy-injected rats, indicating that FA improves liver functions. Meanwhile, our results also showed that the plasma Hcy level and N-homocysteinylation (N-Hcy) modification of albumin were significantly elevated in the jaundice rats, which were obviously reversed after FA administration. Furthermore, we identified a novel N-Hcy modification site K545 of human serum albumin (HSA) using LC-MS/MS, and the mutagenesis assay in HEK293 further validated these observations. Besides, we demonstrated that the N-Hcy modification of albumin functionally inhibits the bilirubin-binding ability of albumin without altering its protein level both in vitro and in vivo. Altogether, we highlight a mechanism that FA reduces the plasma Hcy level and thereby enhance the bilirubin-binding ability of albumin, which may provide a novel therapeutic strategy for the treatment of pathological neonatal jaundice.

Due to their unique properties, paper-based biosensors have attracted attention as inexpensive devices for on-site analysis. To achieve fast and sensitive detection of analytes, immobilization of enzymes with high apparent activities on paper is highly desirable; however, this is challenging. Herein, we report an improved approach to attach a malathion degrading enzyme, PoOPHM9, on paper via an interlocking network of Pluronic F127 (PF127)–poly(acrylic acid)–enzyme conjugates. The addition of PF127 improved retention of enzymatic activity as the apparent kinetic constant Vmax of the immobilized enzyme increased two-fold compared with the paper prepared without PF127. The PF127–poly(acrylic acid)–PoOPHM9 papers provided rapid colorimetric detection of malathion at 0.1–50 mM. The detection was completed within 5 min using a smartphone and image analysis software. As a proof-of-concept, malathion-contaminated water, plant, and apple samples were analyzed with the papers successfully. This material is promising for on-site rapid analysis of malathion-contaminated samples.

Rationale: The mechanisms underlying atrial fibrillation (AF), the most common clinical arrhythmia, are poorly understood. Nucleoplasmic Ca 2+ regulates gene expression, but the nature and significance of nuclear Ca 2+ -changes in AF are largely unknown. Objective: To elucidate mechanisms by which AF alters atrial-cardiomyocyte nuclear Ca 2+ ([Ca 2+ ] Nuc ) and CaMKII (Ca 2+ /calmodulin-dependent protein kinase-II)-related signaling. Methods and Results: Atrial cardiomyocytes were isolated from control and AF dogs (kept in AF by atrial tachypacing [600 bpm × 1 week]). [Ca 2+ ] Nuc and cytosolic [Ca 2+ ] ([Ca 2+ ] Cyto ) were recorded via confocal microscopy. Diastolic [Ca 2+ ] Nuc was greater than [Ca 2+ ] Cyto under control conditions, while resting [Ca 2+ ] Nuc was similar to [Ca 2+ ] Cyto ; both diastolic and resting [Ca 2+ ] Nuc increased with AF. IP 3 R (Inositol-trisphosphate receptor) stimulation produced larger [Ca 2+ ] Nuc increases in AF versus control cardiomyocytes, and IP 3 R-blockade suppressed the AF-related [Ca 2+ ] Nuc differences. AF upregulated nuclear protein expression of IP 3 R1 (IP 3 R-type 1) and of phosphorylated CaMKII (immunohistochemistry and immunoblot) while decreasing the nuclear/cytosolic expression ratio for HDAC4 (histone deacetylase type-4). Isolated atrial cardiomyocytes tachypaced at 3 Hz for 24 hours mimicked AF-type [Ca 2+ ] Nuc changes and L-type calcium current decreases versus 1-Hz-paced cardiomyocytes; these changes were prevented by IP 3 R knockdown with short-interfering RNA directed against IP 3 R1. Nuclear/cytosolic HDAC4 expression ratio was decreased by 3-Hz pacing, while nuclear CaMKII phosphorylation was increased. Either CaMKII-inhibition (by autocamtide-2-related peptide) or IP 3 R-knockdown prevented the CaMKII-hyperphosphorylation and nuclear-to-cytosolic HDAC4 shift caused by 3-Hz pacing. In human atrial cardiomyocytes from AF patients, nuclear IP 3 R1-expression was significantly increased, with decreased nuclear/nonnuclear HDAC4 ratio. MicroRNA-26a was predicted to target ITPR1 (confirmed by luciferase assay) and was downregulated in AF atrial cardiomyocytes; microRNA-26a silencing reproduced AF-induced IP 3 R1 upregulation and nuclear diastolic Ca 2+ -loading. Conclusions: AF increases atrial-cardiomyocyte nucleoplasmic [Ca 2+ ] by IP 3 R1-upregulation involving miR-26a, leading to enhanced IP 3 R1-CaMKII-HDAC4 signaling and L-type calcium current downregulation. Graphic Abstract: A graphic abstract is available for this article.

To explore candidate fungicides from plant secondary metabolites, 16 novel obovatol-type phenazine derivatives were semi-synthesized from obovatol isolated from the leaves of Magnolia obovata Thunb. The antifungal activity of synthesized compounds was investigated in vitro against four phytopathogenic fungi using the spore germination method. The bioassay results showed that eight derivatives (8b, 8g, 8h–k, 8i′, and 8k′) exhibited better antifungal activity against Fusarium solani than two positive controls, especially compounds 8b (IC50 = 64.61 μg mL−1) and 8i′ (IC50 = 79.97 μg mL−1) showed pronounced inhibition of spore germination activity against F. solani. They could be used as lead compounds for further structural optimization. Additionally, the preliminary structure-activity relationships (SARs) illustrated that the introduction of a benzene ring monosubstituted with electron-withdrawing groups into the obovatol scaffold could lead to potentially antifungal compounds.

The shuttle effect of lithium polysulfides (LiPSs) is a fundamental problem restricting the commercialization of lithium–sulfur batteries. A polar conductive substrate serving as the sulfur positiv...

MnC2O4 was prepared via precipitation in N, N-dimethylacetamide –H2O mixed solvents followed by vacuum dehydration process. The structure and morphology can be adjusted by the reaction temperature of the precipitation processes. The precursor MnC2O4·2H2O evolves from the rod-shaped particle with an orthorhombic structure to the plate-like particle with a monoclinic structure when the reaction temperature increases from 60 to 170 °C. After dehydration, the two structures are transformed into orthorhombic β-phase MnC2O4 with similar morphologies to their precursors. Mesoporous MnC2O4 rod can be obtained from the precursor prepared at 100 °C. When used as an anode material for LIBs, this mesoporous MnC2O4 rod delivers a high reversible capacity of 905 and 822 mAh·g−1 after 150 cycles at 2 and 4 A·g−1, respectively, exhibiting good cycle stability and rate performance. The enhanced performance can be attributed to the mesoporous rod-like structure that can improve the structural stability and accelerate the electrode kinetics.

Transition-metal-catalyzed asymmetric hydroalkenylation of alkenes provides an atom-economical method to build molecular complexity from easily available materials. Herein we report an iridium-cata...

Immune response plays a vital role in the pathogenesis of neuropathic pain. Immune response-targeted therapy becomes an effective strategy for treating neuropathic pain. Licochalcone A (Lic-A) possesses anti-inflammatory and neuroprotective effects. However, the potential of Lic-A to attenuate neuropathic pain has not been well explored. To investigate the protective effect and evaluate the underlying mechanism of Lic-A against neuropathic pain in a rat model. Chronic constriction injury (CCI) surgery was employed in rats to establish neuropathic pain model. Rats were intraperitoneally administrated with Lic-A (1.25, 2.50 and 5.00 mg/kg) twice daily. Mechanical withdrawal threshold and thermal withdrawal latency were used to evaluate neuropathic pain. After administration, the lumbar spinal cord enlargement of rats was collected for ELISA, Western blot and immunofluorescence analysis. Mechanical withdrawal threshold and thermal withdrawal latency results showed that Lic-A significantly attenuated CCI-evoked neuropathic pain in dose-dependent manner. Lic-A administration also effectively blocked microglia activation. Moreover, Lic-A suppressed p38 phosphorylation and the release of inflammatory factors such as tumor necrosis factor-α, interleukin-1 and interleukin-6. Our findings provide evidence that Lic-A may have the potential to attenuate CCI-evoked neuropathic pain in rats by inhibiting microglia activation and inflammatory response.

Background Cholestatic diseases are often accompanied by elevated plasma levels of endogenous opioid peptides, but it is still unclear whether central or peripheral mechanisms are involved in this process, and little is known about the change of pain threshold in these patients. The purpose of this study was to determine the preoperative pain threshold, postoperative morphine consumption, and central and peripheral β-endorphin levels in patients with obstructive jaundice. This study also tests the hypothesis that activation of the cannabinoid receptor-2 (CB2R) in skin keratinocytes by endocannabinoids is the mechanism underlying circulating β-endorphin elevation in patients with obstructive jaundice. Methods The electrical pain thresholds, 48-hour postoperative morphine consumption, concentrations of β-endorphin in plasma and cerebrospinal fluid, skin and liver β-endorphin expression, and plasma levels of endocannabinoids were measured in jaundiced (n = 32) and control (n = 32) patients. Male Sprague-Dawley rats and human keratinocytes (human immortalized keratinocyte cell line [HaCaT]) were used for the in vivo and in vitro experiments, respectively. Mechanical and thermal withdrawal latency, plasma level, and skin expression of β-endorphin were measured in CB2R-antagonist-treated and control bile duct-ligated (BDL) rats. In cultured keratinocytes, the effect of CB2R agonist AM1241-induced β-endorphin expression was observed and the phosphorylation of extracellular-regulated protein kinases 1/2, p38, and signal transducer and activator of transcription (STAT) pathways were investigated. Results This study found (1) the plasma level of β-endorphin (mean ± standard error of the mean [SEM]) was 193.9 ± 9.6 pg/mL in control patients, while it was significantly increased in jaundiced patients (286.6 ± 14.5 pg/mL); (2) the electrical pain perception threshold and the electrical pain tolerance threshold were higher in patients with obstructive jaundice compared with controls, while the 48-hour postoperative morphine consumption was lower in the jaundiced patients; (3) there was no correlation between plasma β-endorphin levels, electrical pain thresholds, and 48-hour postoperative morphine consumption in patients with obstructive jaundice; (4) the plasma level of the endogenous cannabinoid anandamide was increased in the jaundiced patients; (5) CB2R antagonist treatment of the BDL rats reduced β-endorphin levels in plasma and skin keratinocytes, while it did not alter the nociceptive thresholds in BDL and control rats; (6) the endocannabinoid anandamide-induced β-endorphin synthesis and release via CB2R in cultured keratinocytes; and (7) phosphorylation of extracellular-regulated protein kinases 1/2 is involved in the CB2R-agonist-induced β-endorphin expression in keratinocytes. Conclusions CB2R activation in keratinocytes by the endocannabinoid anandamide may play an important role in the peripheral elevation of β-endorphin during obstructive jaundice.

To analyze various compositions of urinary stones using revolution spectral CT (rapid kV switching dual-energy CT) in vivo. 202 patients with urinary stones underwent spectral CT before surgery. Zeff peak, overall scope and CT values were detected. Moreover, water/iodine attenuating material images were obtained. Removed stones were subjected to infrared spectroscopy after surgery. The results of infrared spectroscopy were compared with CT. 28 stones (14.08%) with single composition, 165 stones with two mixed compositions (81.68%), and 9 stones with three mixed compositions (4.46%) were observed. When Zeff peaks of stones with single/mixed compositions were summarized together, 146 peaks of calcium oxalate monohydrate, 119 peaks of calcium oxalate dihydrate, 55 peaks of carbapatite, 38 peaks of urate, 16 peaks of struvite, and 11 peaks of brushite were totally observed. 93.8% of calcium oxalate monohydrate had Zeff peaks between 13.3 and 14.0. 91.6% of calcium oxalate dihydrate had peaks between 12.0 and 13.3. For carbapatite, 90.9% of stones had peaks from 14.0 to 15.0. A total of 94.8% of urate had peaks between 7.0 and 11.0. 93.8% of struvite had peaks between 11.0 and 13.0, and 90.9% of brushite had peaks between 12.0 and 14.0. Moreover, densities of urate, struvite and brushite were low density in iodine-based images and high-density in water-based images. The in-vivo analysis of spectral CT in urinary stone revealed characteristics of different compositions, especially mixed compositions. An in-vivo predictive model may be constructed to distinguish stone compositions.

In nature, permafrost regions and deep ocean sediments contain a large amount of gas hydrate. As a basic property of the sediments, the particle size of the porous media is a critical factor affect...