Search

Background Bone tissue engineering (BTE) is considered a promising technology for repairing bone defects. Mg2+ promotes osteogenesis, which makes Mg-based scaffolds popular for research on orthopedic implant materials. Angiogenesis plays an important role in the process of bone tissue repair and regeneration, and it is one of the important problems in BTE urgently needs to be solved. Methods Mg was firstly coated with Ca-deficient hydroxyapatite (CDHA) via hydrothermal treatment, and polydopamine (DOPA) was then used as the connecting medium to immobilize vascular endothelial growth factor (VEGF) on the CDHA coating. The physicochemical properties of the coatings were characterized by SEM, EDS, XPS, FTIR and immersion experiment in SBF. The ahesion, proliferation, and angiogenesis potential of the coatings were determined in vitro. Results The composite coating significantly improved the corrosion resistance of Mg and prohibited excessively high local alkalinity. VEGF could be firmly immobilized on Mg via polydopamine. The CCK-8, live/dead staining and adhesion test results showed that the VEGF-DOPA-CDHA coating exhibited excellent biocompatibility and could significantly improve the adhesion and proliferation of MC3T3-E1 cells on Mg. Microtubule formation, immunofluorescence and Quantitative Real-Time PCR (qRT-PCR) experiments showed that VEGF immobilized on Mg still possessed bioactivity in promoting the differentiation of rat mesenchymal stem cells into endothelial cells. Conclusion In this study, we enabled the angiogenic biological activity of Mg by immobilizing VEGF on Mg. Mg was successfully coated with a functional VEGF-DOPA-CDHA composite coating. The CDHA coating significantly increased the corrosion resistance of Mg and prohibited the negative effect of excessively high local alkalinity on the biological activity of VEGF. As an intermediate layer, the DOPA coating protects Mg, and DOPA provides a binding site for VEGF so that VEGF can be firmly immobilized on Mg and give Mg angiogenic bioactivity during the initial period of implantation. The translational potential of this article The treatment of large bone defect is still one of the orthopedic trauma diseases that are difficult to be completely treated in clinic. The development of tissue engineering technology provides a new option for the treatment of large bone defects. The regeneration of blood vessels is of great significance for the repair of bone defects. In this study, VEGF was connected on the surface of degradable magnesium by covalent bonding. Vascular biofunctionalized magnesium scaffolds are expected to regenerate bone tissue with blood transport and be used in the clinical treatment of large bone defects.

The very slow degradation of biodegradable polymers in the marine environment is due to the lack of dedicated degradation enzymes in open seas. As a result, introducing monomers that have a fast hydrolysis process is required to accelerate seawater degradation. Poly(butylene succinate-co-glycolate) (PBSGA) copolyesters with glycolic acid (GA) units ranging from 5 to 40% were synthesized by our newly developed polymerizing method based on oligo(glycolic acid). The results of ¹H-NMR and GPC revealed that short GA segments were evenly distributed between BS segments, obtaining random copolyesters with a weight-average molecular weight over 6.24 * 10⁴ g/mol. The copolymerized GA units hinder its crystallization capability and increase hydrophilicity of the PBSGAs, which still displayed mechanical properties comparable or even better than most biodegradable polymers. Fast degradation in seawater and enzymatic environments (Candida antarctica lipase B enzymes) is proved experimentally. The quick decomposition in seawater was originated from accelerated hydrolysis. For instance, the weight loss of PBSGA40 (compositions of GA units) exceeded 22% after 49 days. Possible degradation mechanisms were proposed based on Fukui function analysis and frontier molecular orbital calculation. Additionally, the energy barrier for hydrolysis was calculated by the density functional theory method, indicating that the hydrolysis of the polymer chain became more and more easy with the increase in GA units. At last, the addition of GA units only had a mild effect on the shelf life of the PBSGAs.

In this research, we investigated the inhibitory effect of the ethanolic (EtOH) extract of bignay (Antidesma bunius) fruit on the viability of breast cancer cells (MDA-MB-231) by CCK-8 assay. The results showed that the half inhibitory concentration (IC50) was 219 μg/mL after the cells were treated with EtOH extract for 72 hours. The EtOH extract was sequentially extracted by petroleum ether (PET), ethyl acetate (EtOAc), and n-butanol (nBuOH). Among them, the EtOAc fraction showed higher anti-proliferative activity than the other fractions. Wound healing experiment showed the EtOAc fraction inhibited the migration of MDA-MB-231 cells and significantly delayed the transition of the G1 to S phase compared to control. UHPLC-MS/MS analysis showed that in addition to citric acid and phenolic acids (3-Hydroxybenzoic acid, aspirin, fertaric acid), EtOH extract of bignay fruit contains active ingredient like coumarin, genistin, amentoflavone, and luteolin 7-galactoside. The anti-proliferation activity of amentoflavone against MDA-MB-231 cells was also confirmed.

The gradual degradation of polyester in daily use causes unpredictable failure and restricts its reliable applications. The realization of excellent stability in use and controlled degradation in a...

In this study, three series of quinazolinone derivatives containing hydrazone structures were designed and synthesized. Bioactivity assays indicated that these compounds showed good antitumour activities towards human lung cancer cells (A549) and human prostate cancer cells (PC-3) and no apparent toxicity towards those nontumorigenic rat renal tubular epithelial cells (NRK-52E). In particular, compound 7n showed potent inhibitory activity towards A549 and PC-3 with IC50 of 7.36 and 7.73 μmol L−1, respectively. Subsequently, the relationships between the compound structures and numerous biological activities are discussed. A good predictive three-dimensional quantitative structure–activity relationship (3D-QSAR) model was constructed via CoMFA to direct the future structural units. The present results strongly show that 7n with the introduction of 2-fluorobenzoyl should be considered as a lead compound to develop novel antitumour agents.

Polylactic acid (PLA) is a biodegradable thermoplastic polyester produced from natural resources. Because of its brittleness, many tougheners have been developed. However, traditional toughening me...

Chiral molecules have the ability to rotate the polarization plane of polarized light. Polymers that own a chiral segment are called optically active polymers, and a rigid backbone is usually requi...

Xanthomonas oryzae pv. oryzae (Xoo) is an offensive phytopathogen that can invade a wide range of plant hosts to develop bacterial diseases, including the well-known rice bacterial leaf blight. However, few agrochemicals have been identified to effectively prevent and eliminate Xoo-induced diseases. Thus, designing novel antibacterial compounds on the basis of the potential targets from Xoo may lead to the discovery of highly efficient and innovative anti-Xoo agents. Filamentous temperature-sensitive protein Z (FtsZ), an important functional protein in the progression of cell division, has been widely reported and exploited as a target for creating antibacterial drugs in the field of medicine. Therefore, the fabrication of innovative frameworks targeting XooFtsZ may be an effective method for managing bacterial leaf blight diseases via blocking the binary division and reproduction of Xoo. As such, a series of novel N-(cinnamoyl)-N'-(substituted)acryloyl hydrazide derivatives containing pyridinium moieties were designed, and the anti-Xoo activity was determined. The bioassay results showed that compound A7 had excellent anti-Xoo activity (EC50 = 0.99 mg L-1) in vitro and distinct curative activity (63.2% at 200 mg L-1) in vivo. Further studies revealed that these designed compounds were XooFtsZ inhibitors, validating by the reduced GTPase activity of recombinant XooFtsZ, the nonfilamentous XooFtsZ assembly observed in the TEM images, and the prolonged Xoo cells from the fluorescence patterns. Computational docking studies showed that compound A7 had strong interactions with ASN34, GLN193, and GLN197 residues located in the α helix regions of XooFtsZ. The present study demonstrates the developed FtsZ inhibitors can serve as agents to control Xoo-induced infections.

Developing robust nonprecious electrocatalysts towards hydrogen/oxygen evolution reactions is crucial for widespread use of electrochemical water splitting in hydrogen production. Here, we report that intermetallic Co3Mo spontaneously separated from hierarchical nanoporous copper skeleton shows genuine potential as highly efficient electrocatalysts for alkaline hydrogen/oxygen evolution reactions in virtue of in-situ hydroxylation and electro-oxidation, respectively. The hydroxylated intermetallic Co3Mo has an optimal hydrogen-binding energy to facilitate adsorption/desorption of hydrogen intermediates for hydrogen molecules. Associated with high electron/ion transport of bicontinuous nanoporous skeleton, nanoporous copper supported Co3Mo electrodes exhibit impressive hydrogen evolution reaction catalysis, with negligible onset overpotential and low Tafel slope (~40 mV dec−1) in 1 M KOH, realizing current density of −400 mA cm−2 at overpotential of as low as 96 mV. When coupled to its electro-oxidized derivative that mediates efficiently oxygen evolution reaction, their alkaline electrolyzer operates with a superior overall water-splitting output, outperforming the one assembled with noble-metal-based catalysts. Electrochemical water splitting is an attractive energy conversion technology, but it usually suffers from low efficiency. Here, the authors report intermetallic Co3Mo integrated on porous Cu as highly efficient electrocatalysts for alkaline HER/OER due to in-situ hydroxylation and electro-oxidation.

Developing multipurpose agricultural chemicals is appealing in crop protection, thus eventually realizing the reduction and efficient usage of pesticides. Herein, an array of versatile pyrazole hydrazide derivatives bearing a 1,3,4-oxadiazole core were initially synthesized and biologically evaluated the antifungal, antioomycetes, and antibacterial activities. In addition, the pyrazole ring was replaced by the correlative pyrrole, thiazole, and indole scaffolds to extend the molecular diversity. The results showed that most of these hybrid compounds were empowered with multifunctional bioactivities, which are exemplified by compounds a1-a6, b1-b3, b7, b10, b13, and b18. For the antifungal activity, the minimal EC50 values could afford 0.47 (a2), 1.05 (a2), 0.65 (a1), and 1.32 μg/mL (b3) against the corresponding fungi Gibberella zeae (G. z.), Fusarium oxysporum, Botryosphaeria dothidea, and Rhizoctonia solani. In vivo pot experiments against corn scab (caused by G. z.) revealed that the compound a2 was effective with protective and curative activities of 90.2 and 86.3% at 200 μg/mL, which was comparable to those of fungicides boscalid and fluopyram. Further molecular docking study and enzymatic activity analysis (IC50 = 3.21 μM, a2) indicated that target compounds were promising succinate dehydrogenase inhibitors. Additionally, compounds b2 and a4 yielded superior anti-oomycete and antibacterial activities toward Phytophora infestins and Xanthomonas oryzae pv. oryzae with EC50 values of 2.92 and 8.43 μg/mL, respectively. In vivo trials against rice bacterial blight provided the control efficiency within 51.2-55.3% (a4) at 200 μg/mL, which were better than that of bismerthiazol. Given their multipurpose characteristics, these structures should be positively explored as agricultural chemicals.

Polymer-based catalysts have been of special interest because of their several advantages such as easy processibility. Inorganic catalyst generally have been introduced into polymer-based media to endow catalytic activity. Surface decoration or sol–gel reaction have been performed so far, but inherent low affinity between organic/inorganic causes low efficiency in loading amount, resulting in low catalytic activity. Herein, we synthesized easily processible and highly functionalizable polyoxazoline as polymer nonwoven fiber-based catalytic supporter. Zr(OH)4 was grown on surface of fiber-web via sol–gel reaction. The Zr(OH)4 grown fiber exhibited not only excellent mechanical properties but also effective decontamination efficiency against organophosphate-based toxic agents.

Most biodegradable thermoplastic materials cannot be used as elastomers due to their relatively poor elasticity. Poly(butylene furandicarboxylate-co-e-caprolactone) (PBFCL) copolyesters were synthe...

Poly (butylene furandicarboxylate) based poly (ether ester), with poly (ethylene glycol) (PEG) molecular weight from 600 to 20 K g mol−1 and mass fraction of hard segments fixed at 50%, are synthesized through transesterification and melt polycondensation. When Mn (PEG) is less than 1500 g mol−1, the copolymers tend to be homogeneous. The tendency of microphase separation is facilitated by the increasing Mn (PEG). The mechanical properties and water swelling are influenced by Mn (PEG), equilibrium water-uptake and PEG crystals. Elastic modulus of samples with no PEG crystals vary from 34 to 64 MPa, with elongation at break exceeding 1000%. The hydrolytic degradation is strongly affected by Mn (PEG), degradation medium and alkalinity. The degradation of copolymers with short PEG (

Background: Mucosal epithelial apoptosis with non-specific inflammation is an essential pathological characteristic in portal hypertensive gastropathy (PHG). However, whether a coordinated crosstalk between myeloid cells and epithelial cells involved in PHG remains unclear. Methods: Gastric injury and mucosal apoptosis were examined in patients with PHG and the PHG model of p65ΔM/ΔM (myeloid cells specific NF-κBp65 deletion) and p65f/f (floxed p65) mice, PUMA-WT (PUMA wild-type) and PUMA-KO (PUMA knockout) mice. The interaction of IL-6, Fas, FasL, NF-κBp65 and PUMA expression was investigated, and the mechanisms underlying IL-6-regulated gastric epithelial apoptosis were analysed. Findings: IL-6, which is induced in the mucosa of PHG patients and mice, promotes FasL production via enhancing NF-κBp65 activation in myeloid cells, while blockage of IL-6 signaling by Tocilizumab or deletion of NF-κBp65 in myeloid cells attenuates the inflammatory response and Fas/FasL-mediated epithelial apoptosis in PHG. IL-6-driven FasL from myeloid cells combines with epithelial Fas receptor to encourage NF-κBp65/PUMA-mediated epithelial apoptosis in PHG, and inhibition of NF-κBp65 or knockout of PUMA dramatically alleviates Fas/FasL network-mediated epithelial apoptosis in PHG. Interpretation: These results indicate that IL-6 drives FasL generation via NF-κBp65 in myeloid cells to promote Fas/NF-κBp65/PUMA-mediated epithelial apoptosis in PHG. Funding: This work was supported by grants from the National Natural Science Foundation of China (U1501224, 81700536), the Natural Science Foundation Team Project of Guangdong Province (2018B03031200), the Science and Technology Developmental Special Foundation of Guangdong Province (2017B020226003), the Basic Research Programme of Young Teachers' Training Project of Sun Yat-sen University (17ykpy51), the Science and Technology Planning Projects of Guangzhou City (201604020118, 201604020002). Declaration of Interest: The authors declare that there are no conflicts of interest. Ethical Approval: The study protocol and the acquisition of the tissue samples were approved by the Institutional Review Board of The Third Affiliated Hospital of Sun Yat-Sen University.

A series of hybrid antifouling coatings consisting of silicone elastomer and nanocomposite hydrogel were successfully prepared. The morphology of the hybrid coatings and the silver nanoparticles (AgNPs) embedded into the coatings were studied by SEM and TEM. The pure silicone coating showed a relatively flat morphology. Smooth spheroidal aggregates self-assembled by hydrophilic polymer with a diameter of 4–14 μm appeared when the polymer chains were introduced. However, with increasing of AgNPs the spheroidal aggregates were gradually covered with a thin silicone film and were firmly embedded into the coatings. The glass transition temperature of the hybrid coatings measured by DSC technique showed that the silicone elastomer and the hydrogel matrix formed interpenetrating polymer networks (IPN). The static water contact angle of the hybrid coatings with different amount of the hydrophilic polymer chains before and after being immersed into water was also measured. Furthermore, these hybrid coatings showed good antimicrobial performance for Escherichia coli and anti-algae property. The result showed that the SH-0.25-1.5 sample could almost kill 100% E. coli. Compared with the control sample, the settlement of the Phaeodactylum tricornutum, Navicula torguatum and Chlorella on the surface of SH-0.25-1.5 sample decreased approximately 37%, 37% and 52%, respectively. The antifouling performances of the hybrid coatings were examined by field tests in South China Sea and the result showed the hybrid coatings with nanocomposite hydrogel exhibited good antifouling property. These hybrid coatings have promising applications in marine antifouling coating and interfaces of biomaterials.

A novel convenient dual-side initiator of lutidine dianion for anionic polymerization has been investigated in terms of their initiation and propagation kinetics. This lutidine dianion could be synthesized in quantitative yields reacting commercial products of 2,6-lutidine with sec-butyl lithium without any complex organic synthesis, and could be used effectively as the dual-side initiator to synthesize polyisoprene with various molecular weights via living anionic polymerization. In addition, this lutidine dianion can produce 50% of 1.4-microstructure contents in polyisoprene which is very important for elastomeric property of polydienes. All experimental evidences showed the living property and were consistent with quantitative yields without any side reactions when the anionic living polymerization proceeded using lutidine dianion as the initiator.

To improve the toughness of the epoxy resin while maintaining their transparency, a novel polymer, which has an aliphatic structure, is synthesized via in-situ azide-alkyne polymerization as a toughening agent. Because of the dissimilar kinetics of the epoxy system and click reaction, sequential curing process was designed. There in-situ toughened epoxy with about 10wt% content of in-situ toughener of poly(BAC/PCLDA) showed excellent increase of fracture toughness while the transmittance of epoxy system was maintained. The homogeneous phase for the fracture surface of in-situ toughened epoxies in SEM micrographs was quite different from the two-phase morphology for the conventional preformed polymer-toughened epoxy systems.

The PAX3 (paired box 3) gene plays an important role in embryonic development, diseases, and cancer formation. Our preliminary studies have shown that PAX3 gene is upregulated in glioma cells, which is associated with a worse prognosis. Moreover, PAX3, by facilitating cell proliferation and invasion and inhibiting cell apoptosis, plays an oncogenic role in glioma. However, the specific molecular mechanism of PAX3 acting as an oncogene in glioma remains unclarified. In the present study, we have found that PAX3 overexpression was observed in high grade glioma and predicted a worse prognosis. PAX3 overexpression did not correlate significantly to IDH1 mutation and MGMT methylation. Moreover, the expression of PAX3 was positively correlated with that of β-catenin. In U87 glioma cells, PAX3 interacted with β-catenin, as was confirmed by CO-IP. Besides, PAX3 overexpression promoted cell proliferation and cell cycle progression, while it inhibited cell apoptosis by altering the expressions of important molecules associated with the Wnt signaling pathway, including β-catenin, Myc, VEGF, cyclinD1, MMP7, and Wnt1. In the meantime, it was also proved that PAX3 correlated to β-catenin through a negative regulatory mechanism with respect to the promotion of U87 glioma cell proliferation and cell cycle progression and inhibition of the cell apoptosis. Our experiment demonstrated the role of PAX3 in promoting glioma growth and development, possibly by interacting directly with β-catenin and regulating the Wnt signaling pathway.

A series of biobased poly(neopentyl glycol succinate/furandicarboxylate) (PNSF) copolyesters were synthesized via a transesterification and melt polycondensation process. The 1H NMR and analysis using the Fox equation suggested the formation of random microstructures. PNSFs displayed poor crystallization capability with a slow crystallization rate. The copolymerization destroyed the spherulite morphology of the homopolyester PNF, and the melting temperature (Tm) also decreased with decreasing neopentyl glycol furandicarboxylate content (mNF). Rheological tests revealed the slight increase in the free volume with the addition of succinic acid. The crystallization induced by thermal annealing enhanced the elastic modulus and tensile strength. PNSF50–PNSF70 possessed modulus and strength greater than 1000 and 27 MPa, respectively, exceeding those of most biodegradable packaging materials. On the other hand, PNSF80 and PNSF90 possessed high modulus of 3.0 GPa and strength of 100 MPa, which were comparable to ...

The hydrogen evolution reaction (HER) is a crucial step in alkaline water electrolysis, but suffers from sluggish reaction kinetics, which calls for the development of active and robust catalysts for the highly efficient production of high-purity hydrogen. Here, we report hierarchical nanoporous (NP) transition-metal (TM = Fe, Co)-doped Pt3Al intermetallic compounds, which are composed of surface alloys of Pt and TMs with in situ self-grown TM hydroxides in an alkaline environment, NP (Pt1−xTMx)3Al/Pt-TM(OH), as highly efficient bifunctional catalysts for the HER. By virtue of the constituent Co(OH)2 having moderate hydroxyl adsorption to accelerate water dissociation and the Pt atoms facilitating the adsorption/desorption of reactive hydrogen intermediates, the NP (Pt1−xCox)3Al/Pt-Co(OH)2 exhibits superior HER activity in 0.1 M KOH, with a low Tafel slope of 48 mV dec−1 and an overpotential of ∼43 mV at 10 mA cm−2, as well as exceptional durability due to its unique nanoporous structure with stable intermetallic bonds. These electrocatalytic properties outperform state-of-the-art Pt-based catalysts, suggesting that multi-site design is suitable for producing highly efficient catalysts towards the HER in alkaline environments.

Aliphatic polycarbonates are an attractive research subject in the field of degradable materials. However, their relatively poor thermal properties limit their application. Here, poly(butylene carbonate) (PBC) was modified with 1,4-cyclohexanedicarboxylic acid (CHDA), a biomass-derived aliphatic ring monomer. Thermal degradation of short butylene carbonate segments was effectively avoided by one-step melt polycondensation of the oligomers. All the PBCCEs were random copolymers, and the trans content of CHDA in all cases was no less than 90%; this ensured the crystallizability of the butylene cyclohexanedicarboxylate (BCE) units. The glass transition temperature, melting temperature and thermal stability increased with the number of BCE units. The PBCCEs were semi-crystalline after thermal equilibrium was reached, and PBCCE50 to PBCCE90 contained PBCE crystals while PBCCE20 possessed XRD diffraction peaks similar to those of PBC. Small-angle X-ray scattering suggested that the randomly oriented lamellar structure of the PBCCEs became more ordered as the number of BCE units increased. PBCCE70-PBCE revealed a t1/2 of less than 30 s, indicating the rapid crystallization rate of the BCE units. The mechanical properties were closely related to the crystallization ability, and PBCCE50 to PBCCE90 showed good elastic moduli (87 to 520 MPa), high tensile strengths (22.8 to 39.5 MPa) and large elongations at break (930% to 413%). The gas barrier properties gradually increased with the number of BCE units, showing results several times higher than those of commercial poly(butylene adipate-co-terephthalate) (PBAT). Moreover, the addition of aliphatic rings slightly weakened the biodegradability, and obvious weight loss could be observed for PBCCE70. This result was higher than those of most aliphatic-aromatic copolyesters, which are degradable when their aromatic diacid content is less than 60%. PBCCE50 displayed a weight loss greater than 90% after 30 days, which is much faster than that of PBC. The results of this study indicate that PBCCE copolyesters exhibit great potential for applications in the plastics industry, such as green packaging and tissue engineering.

The melt polycondensation of glycolic acid based copolymers with high molecular weights remains a big challenge. In this work, poly(butylene furandicarboxylate-co-glycolate) (PBFGA) and poly(butylene furandicarboxylate)-b-poly(glycolic acid) (PBF-b-GA) copolyesters were synthesized via melt oligomer polycondensation and melt bulk transesterification, respectively. Herein, melt oligomer polycondensation is a better method with mild preparation conditions and products with higher molecular weights (Mw). The analysis of GPC demonstrated that PBFGAs possessed a Mw of up to 8.95 × 104 g mol−1. The PBFGAs also possessed excellent thermal stability (>320 °C), which endowed the copolymers with a wider processing window than thermolabile PGA. DSC analyses displayed that PBFGA40–PBFGA10 were semi-crystalline materials that melted between 84.5 and 156 °C, while PBFGA50–60 were amorphous. Tensile tests indicated a high elastic modulus of 524–1262 MPa, tensile strength of 16–44 MPa and good elongation at break over 220% of PBFGAs, exceeding most biodegradable packaging materials. The increase of GA units slightly impacted the barrier properties, with reduced CO2 (53×) and O2 (15×) permeability coefficients than those of commercial PBAT films, and also better than those of PET. The hydrolysis of the glycolate was restrained by steric hindrance of furan rings, while in enzymatic degradation PBFGAs displayed obvious weight loss with GA units >20 mol%. With superior thermal, tensile, barrier and degradable properties, PBFGAs have the potential to serve as promising and innovative bio-based polymers for eco-friendly and sustainable plastic packaging.

BACKGROUND & AIM: Coexisting alcoholic liver disease and virus-induced liver cirrhosis (ALD+HBV and ALD+HCV) has not been thoroughly studied. This cross-sectional study aims to showcase the influence of alcohol on the laboratory values and on the clinical outcomes of patients with hepatitis B and C virus-induced liver cirrhosis.METHOD: Patients diagnosed with liver cirrhosis (n=22287) from January 2010 to December 2019 were collected from our hospital electronic database, and divided into five groups according to the etiology: ALD (1652 cases, 7.4%), HBV (18079 cases, 81.1%), HCV (682 cases, 3.1%), ALD+HBV (1594 cases, 7.2%) and ALD+HCV (280 cases, 1.3%). Laboratory results and proportion of different liver cirrhosis complications were contrasted between groups.RESULTS: ALD+HBV and ALD+HCV presented with higher proportions of poor prognosis patients and cirrhosis complications compared to HBV and HCV respectively. Multivariate logistic regression revealed that the risk of HCC and that of EGVB in the ALD+HBV group was respectively 2.14-fold and 1.47-fold that in the HBV group (HCC: OR=2.14, 95%CI: [1.71-2.69]; EGVB: OR=1.47, 95%CI: [1.17-1.84]) after adjusting for potential confounders. Furthermore, a decrease in the risk of HCC and EGVB with the duration of alcohol abstinence was observed. Similar pattern was noticed while comparing ALD+HCV group to HCV group.CONCLUSION: Alcohol significantly increased the severity of liver function impairment and the prevalence of liver cirrhosis complications such as HCC and EGVB in hepatitis virus-induced liver cirrhosis patients. Remarkably, long period of alcohol abstinence significantly decreased the prevalence of HCC and EGVB in these populations.

Background Regnase-1 (MCPIP) has been identified as an anti-inflammatory agent, but little is known about its influence on liver ischemia/reperfusion (I/R) injury. Macrophages can evolve biphasic responses and differentiate into remarkable polarizations, contributing greatly to the uncontrolled inflammatory cascades during liver I/R injury. Therefore, the aim of this study was to explore whether regnase-1 participated in liver I/R via manipulating macrophage polarization. Materials and methods C57BL/6 mice were randomly divided into five groups: Sham, I/R, Clodronate, Clo + BMDM, and Clo + LV MCPIP BMDM. A liver I/R model was established, and histopathological and immunostaining examinations were performed for the liver specimens; double immunofluorescence staining was used to localize MCPIP in the liver. Primary hepatocytes were isolated to simulate a hypoxia and reoxygenation (H/R) model in vitro. Bone marrow-derived macrophages (BMDM) were extracted and subjected to lentiviral transduction to knockdown MCPIP expression. BMDM with or without MCPIP deletion were exposed to H/R supernatants, and the polarized states were measured by flow cytometry. RT-PCR analysis and Western blot were also conducted. Results Compared to those in the Sham group, liver functions and Suzuki's scores were deteriorated in the I/R group, which were reversed in the Clodronate group. The increased expression of regnase-1 in the I/R group diminished with pretreatment of clodronate liposomes. Subsequent double immunofluorescence staining established the localization of regnase-1 in macrophages in the liver. The insulted lesions in the Clodronate group became progressively aggravated with adoptive transfer of BMDM in the Clo + BMDM group, and they were further exacerbated with the transfusion of BMDM with MCPIP knockdown in the Clo + LV MCPIP BMDM group. Gene expressions of M1 and M2 markers were detected by RT-PCR, suggesting that MCPIP knockdown tended to favor the M1 transformation. Subsequently, ex vivo flow cytometrical detection showed that, upon stimulation by H/R supernatants, LV-MCPIP BMDM posed a higher ratio of M1/M2 than BMDM. Finally, we found that MCPIP participated in macrophage M1/M2 polarization through the NF-κB, C/EBPβ, and PPARγ signaling pathways during liver I/R. Conclusion Our study confirms that regnase-1 plays a critical role in liver I/R via regulation of macrophage polarization and, thus, might offer a potential therapeutic target.

A series of new 1-tert-butyl-5-amino-4-pyrazole bioxadiazole sulfide derivatives containing a 1,3,4-oxadiazole moiety were designed and synthesized. The bioactivity results showed that some title compounds exhibited excellent protective activity against TMV and certain insecticidal activity. Among the tested compounds, the EC50 values of 5d, 5j, 5k and 5l were 165.8, 163.2, 159.7 and 193.1 mg/L, respectively, which are better than the EC50 value of ningnanmycin (271.3 mg/L). The chlorophyll contents and the defense enzyme activities of the tobacco leaves after treatment with 5j were significantly increased, which indicated that this series of title compounds may induce the systemic acquired resistance of host to defend against diseases. Further in vivo protective activity research on 5j using TMV with a GFP gene tag found that it can effectively inhibit the spread of TMV in inoculated tobacco. A morphological study with TEM revealed that title compound 5h can cause a distinct break of the rod-shaped TMV. Moreover, the insecticidal activity revealed that the fatality rates of 5a, 5b and 5m against aphidoidea were 85%, 83% and 87%, respectively, which indicated that the title compounds can effectively block the common carrier of plant viruses, thereby effectively reducing the TMV infection risk of tobacco. This series of synergistic effects provide key information for the research and development of antiviral agents.

A stretchable electronic skin (e-skin) requires a durable elastomeric matrix to serve in various conditions. Therefore, excellent and balanced properties such as elasticity, water proof capability, toughness, and self-healing are demanded. However, it is very difficult and often contradictory to optimize them at one time. Here, a polyurethane (BS-PU-3) containing a polydisperse hard segment, hydrophobic soft segment, and a dynamic disulfide bond was prepared by one-pot synthesis. Unlike the normal two-pot reaction, BS-PU-3 obtained through the one-pot method owned a higher density of self-healing points along the main chain and a faster self-healing speed, which reached 1.11 μm/min in a cut-through sample and recovered more than 93% of virgin mechanical properties in 6 h at room temperature. Moreover, a remarkable toughness of 27.5 MJ/m3 assures its durability as an e-skin matrix. Even with a 1 mm notch (half of the total width) on a standard dumbbell specimen, it could still bear the tensile strain up to 324% without any crack propagation. With polybutadiene as the soft segment, the shape, microstructure, and conductivity in BS-PU-3 and BS-PU-3-based stretchable electronics kept very stable after soaking in water for 3 days, proving the super waterproof property. An e-skin demo was constructed, and self-healing in pressure sensitivity, mechanical, and electrical properties were verified.

Designing highly active and robust platinum-free electrocatalysts for hydrogen evolution reaction is vital for large-scale and efficient production of hydrogen through electrochemical water splitting. Here, we report nonprecious intermetallic Cu 5 Zr clusters that are in situ anchored on hierarchical nanoporous copper (NP Cu/Cu 5 Zr) for efficient hydrogen evolution in alkaline medium. By virtue of hydroxygenated zirconium atoms activating their nearby Cu-Cu bridge sites with appropriate hydrogen-binding energy, the Cu 5 Zr clusters have a high electrocatalytic activity toward the hydrogen evolution reaction. Associated with unique architecture featured with steady and bicontinuous nanoporous copper skeleton that facilitates electron transfer and electrolyte accessibility, the self-supported monolithic NP Cu/Cu 5 Zr electrodes boost violent hydrogen gas release, realizing ultrahigh current density of 500 mA cm -2 at a low potential of -280 mV versus reversible hydrogen electrode, with exceptional stability in 1 M KOH solution. The electrochemical properties outperform those of state-of-the-art nonprecious metal electrocatalysts and make them promising candidates as electrodes in water splitting devices.

The mixing-frequency method is an effective technique to measure the magnetic nonlinearity of medium carbon steel. In this paper, the magnetic mixing-frequency method was investigated to evaluate the hardness of medium carbon steels. The magnetic nonlinear factors related to the bispectral amplitudes at sum frequency, different frequencies, and fundamental frequencies in the measured signal are proposed for hardness evaluation. Nonlinear magnetic mixing-frequency measurements were conducted on samples of medium carbon steel tempered at different temperatures. The experimental results showed that the magnetic mixing-frequency technique is an effective way to measure the hardness of medium carbon steels and the magnetic nonlinearity is more sensitive to the change of hardness than magnetic Barkhausen noise measurements. The proposed method has a potential for use in the mechanical properties measurement of ferromagnetic steel.

Summary About 10% of gastric carcinomas are associated with Epstein–Barr virus (EBV), which are defined as EBV-associated gastric carcinomas (EBVaGCs). EBVaGCs are usually accompanied by massive lymphocytes infiltration, among which CD8+ T cells are predominant. To date, the apoptosis of the infiltrating CD8+ T cells in EBVaGC has not been investigated. In the present study, we assessed the immunophenotype and apoptosis of tumour infiltrating lymphocytes (TILs) in both EBVaGC and EBV-negative gastric carcinoma (EBVnGC). We found that CD8+CCR7+ T lymphocytes were increased in EBVaGC compared to EBVnGC [60.53 ± 28.41/high power fields (HPF) vs 19.63 ± 15.97/HPF; p

This paper presents the design, fabrication, and characterization of a novel inclination-angle sensor (inclinometer) using heating and sensing elements based on conductive polydimethylsiloxane (PDMS) composited with carbon nanotubes (CNTs). The inclinometer consists of a PDMS cube-shaped chamber, a CNTs/PDMS composite-based heater, and four CNTs/PDMS composite-based temperature sensors. The working mechanism of this sensor is based on thermal convective sensing theory on the basis of the detection of thermal disturbance caused by inclination-induced convection in a sealed chamber. In order to prepare the conductive CNTs/PDMS composite, toluene was applied as a solvent to facilitate CNT dispersion in PDMS matrix and then was removed by evaporation. The resistive heating and thermal sensing properties of CNT/PDMS composite-based elements were tested and analyzed first. Then, the responses to inclination-angle were monitored and reported. Experimental results demonstrate that the inclinometer can measure dual-axis angular position in the range of 360° with high stability and repeatability.

Fully biobased poly(butylene 2,5-furandicarboxylate)-co-poly(lactic acid)s (PBFLAs) of lactic acid composition from 10% to 40% are synthesized. They are subjected to molecular, thermal, diffractometric, degradable and mechanical characterizations. Thermogravimetric analysis shows that PBFLA are thermally stable at least 350 °C, much higher than PLA. After the incorporation of lactic acid units, both Tm and crystallization rate decrease with respect to homopolymers. X-ray diffraction measurements indicate that no PLA crystal is present during crystallization. All samples perform better barrier properties with respect to PLA, implying potential application in packaging. These samples behave like semicrystalline plastic in the tensile tests. PBFLA copolyesters show Young’s modulus, maximum tensile strength and breakage elongation higher than 1000 MPa, 38 MPa, and 230%, respectively. Such comprehensive mechanical behaviors exceed most biodegradable materials. Lastly, biodegradability could be significantly im...

A type of pyridinium-decorated 1,4-pentadien-3-one derivatives possessing flexible alkyls were designed and synthesized by integrating the key scaffolds of pyridinium cations and 1,4-pentadien-3-one skeleton in a single molecular architecture. Antimicrobial bioassays indicated that some of the target molecules exerted considerable bioactivities against six phytopathogenic strains, especially for Xanthomonas oryzae pv. oryzae, the minimal EC50 value can reach to 0.504 µg/mL. A plausible action mechanism for this kind of compounds was proposed and confirmed by employing fluorescent spectroscopy, fluorescence microscopy, and scanning electron microscopy. We anticipated that this finding can promote high-efficient lead compounds discovery in the research of antimicrobial chemotherapy.

A series of biobased poly(butylene carbonate-co-furandicarboxylate) (PBCF), are synthesized through a two-step polycondensation reaction. Chemical structures, thermal properties, crystallization behaviors, mechanical properties, barrier properties, and enzymatic degradation of PBCFs are investigated. The linear variation of the glass transition temperatures with the content ratio confirms the good miscibility between butylene carbonate (BC) and butylene furandicarboxylate (BF) units. BF segments could crystallize in most contents under different temperatures. Consequently, mechanical properties of these copolymers depend not only on the composition but also on the annealing conditions. Long-time annealing at room temperature or short-time annealing under high temperature could tremendously increase the tensile modulus. For room-temperature annealing, the formation of less perfect crystals of the poly(butylene furandicarboxylate) (PBF) could interpret the enhancement of modulus. On the other hand, the high...

Comparing to classical Grignard-type carbonyl additions, transfer hydrogenative C–C bond-forming reactions using alcohols as carbonyl precursors have shown remarkable advantages from the perspective of atom economy, step economy and redox economy. The significant drawbacks of conventional method, such as the use of multi-step reactions, the premetalated reagents, and stoichiometric oxidants and reductants, can be avoided by using hydrogen transfer processes. Moreover, the development of reactions employing earth-abundant and eco-friendly base metal as catalysts is an important objective in modern sustainable chemistry. In this review, we summarized recent advances in base metal-catalyzed C–C coupling of alcohols under hydrogen transfer conditions.

Polyurethane nanofibers functionalized by high amount of N-chloro hydantoin were prepared for the decontamination of chemical warfare agents. Azido-polyurethane was firstly synthesized using azido-polydiol with 4,4′-methylenebis(phenylisocyanate) and 1,4-butanediol via step-addition polymerization. Hydantoin was introduced into the polyurethane via click reaction, followed by electrospinning and chlorination to obtain the decontaminable fibers. This N-chlorinated hydantoin-polyurethane fiber is an active decontaminable species for 2-chloroethyl ethyl sulfide and demeton-S-methyl, the simulant of chemical warfare agent. The decontamination efficiency of each exhibits 69% and 16% for 2-chloroethyl ethyl sulfide and demeton-S-methyl, respectively, with molar ratio of 1/1 for 2 h at ambient condition. This N-chlorinated hydantoin-polyurethane fiber exhibited considerable potential as the decontaminable material against toxic chemical warfare agents.

The threat of antibiotic resistant bacteria has called for alternative antimicrobial strategies that would mitigate the increase of classical resistance mechanism. Many bacteria employ quorum sensing (QS) to govern the production of virulence factors and formation of drug-resistant biofilms. Targeting the mechanism of QS has proven to be a functional alternative to conventional antibiotic control of infections. However, the presence of multiple QS systems in individual bacterial species poses a challenge to this approach. Quorum sensing inhibitors (QSI) and quorum quenching enzymes (QQE) have been both investigated for their QS interfering capabilities. Here, we first simulated the combination effect of QQE and QSI in blocking bacterial QS. The effect was next validated by experiments using AiiA as QQE and G1 as QSI on Pseudomonas aeruginosa LasR/I and RhlR/I QS circuits. Combination of QQE and QSI almost completely blocked the P. aeruginosa las and rhl QS systems. Our findings provide a potential chemical biology application strategy for bacterial QS disruption.

Carbonatites are the most important sources of global niobium (Nb) and rare earth element (REE) resources, particularly the light REEs. The Huanglongpu carbonatite in central China is unique for the enrichment of molybdenum (Mo) and heavy REEs. Till now, the source nature of the Huanglongpu carbonatites is still poorly understood. In this contribution, we present elemental and C-O-Sr-Nd-Pb isotopic data of calcite to constrain the source signatures of the Huanglongpu carbonatite. Elemental geochemistry and C-O isotopes of the calcite vein-networks in the carbonatite reveal that the Huanglongpu carbonatites is of igneous genesis and originated from mantle-derived carbonatitic melts. The negative eNd(t) values (−8.03–−5.05) and elevated initial 87Sr/86Sr ratios (0.7049–0.7056) indicate considerable contribution of recycled crustal components in the mantle source. Combination of O-Sr-Nd-Pb isotopes suggests that over 10 wt% of recycled sediments might have been involved into the depleted mantle, accounting for the source of the Huanglongpu carbonatite. Considering the enrichment of heavy REE, REE distribution simulation indicates that the Huanglongpu carbonatite might be from the 30% partial melting of eclogite facies sediments. Accordingly, we infer that the Huanglongpu carbonatite might have been derived from the partial melting of a hybridized mantle source modified by recycled sediments of eclogite facies. The enrichment of Mo and heavy REEs plausibly resulted from the contribution of garnet/pyroxene from the eclogitic sediments within the subducted slab.

Natural products (NPs) are inexhaustible wellsprings for new agrochemicals discovery. To excavate novel natural products-based antibacterial leads or candidates potentially targeting FtsZ (filamentous temperature-sensitive protein Z) which is widely regarded as a promising antibacterial target for novel drug discovery, herein, a rapid and efficient screening platform was initially established to disclose the potential FtsZ inhibitors from a variety of commercial natural products. Screening results revealed that 4'-demethylepipodophyllotoxin (DMEP) from renewable Dysosma versipellis (D. versipellis) species could distinctly decrease the XooFtsZ’ GTPase activity and afforded a ponderable bacteriostatic effect (EC50 = 38.7 mg L-1) against Xanthomonas oryzae pv. oryzae (Xoo). Further explorations found that DMEP could disorganize the assembly dynamics of XooFtsZ, and thereby yielding long and filamentous Xoo cells from the transmission electron microscopic and fluorescence microscopic imaging. Molecular docking study showed that DMEP displayed strong interactions with Asp38 and Arg205 residues of XooFtsZ, indicating that a natural potential FtsZ inhibitor was discovered gradually. The following bioassay result against rice bacterial blight in vivo presented good curative activity (50.0% at 200 mg L−1) and protective activity (46.8% at 200 mg L−1). Given that natural DMEP has many sites for structural modification, therefore, it can concurrently serve as a novel lead compound for exploring highly bioactive FtsZ inhibitors based on the molecular skeleton of DMEP.

Here we report a chemical strategy that uses rigid molecules to straightforwardly construct amphiphilic carbon dots (ACDs) with high luminescence quantum yields (QYs)., In nanoscience, amphiphilic carbon dots (ACDs) are of great importance due to their excellent transferability for application in biological sensing, imaging and labelling. However, facile synthetic strategies are still limited, especially for obtaining high-emissive ACDs. Since the development of a high-emissive feature is strongly desired for improving the practical resolution in vivo, here we report a chemical strategy that uses rigid molecules to straightforwardly construct amphiphilic carbon dots (ACDs) with high luminescence quantum yields (QYs). By using 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (HATU), a typical coplanar compound, as the only precursor, well-defined ACDs were prepared via a one-step solvothermal process which exhibited a superior QY of up to 29%, largely superior to those prepared from precursors with less rigid structures. The effect can be mainly attributed to a significant suppression of the competition of non-radiative decay through rigidity derivation. Metal ionic doping during the synthesis resulted in a further improvement of the crystallinity and monodispersity of the materials, with retention of the high-emissive ability. This high-emissive photoluminescence behavior of the ACDs is accompanied with an excitation-wavelength dependence, a high biocompatibility and a low toxicity, which together make the ACDs advantageous for application in multi-channel bioimaging.

Herein, a series of pyridinium-tailored 5-trifluoromethylpyrazoles containing 1,3,4-oxadiazole moieties were constructed through coupling key pharmaceutical fragments of pyridinium, pyrazole, and 1,3,4-oxadiazole scaffolds in single molecular architecture. Antimicrobial results suggested that this kind of compounds exhibited significant activities against three types of pathogenic bacteria and six fungal strains in vitro . The minimal EC 50 values of designed compounds against Xanthomonas oryzae pv . oryzae , Ralstonia solanacearum , and Xanthomonas axonopodis pv . citri could reach to 0.467, 1.04, and 0.600 μg/mL, respectively, through tuning and optimizing N -substituents, bridging atom, and alkyl length of the tailor. Antifungal assays revealed that all title molecules possessed considerable activity against Botrytis cinerea with the minimal EC 50 value up to 2.71 μg/mL; and compounds I-8 , I-10 , I-12 , II-12 , and IV-12 showed the strongest growth suppression toward Rhizoctonia solani with EC 50 values ranging from 10.2 to 24.0 μg/mL. Given the above results, this kind of compounds could serve as new lead compounds in the research of antimicrobial chemotherapy.

A series of novel nucleobase derivatives and their analogues possessing diethoxyphosphoryl scaffolds were synthesized through four-step reactions and screened for their antiviral activity toward tobacco mosaic virus (TMV). Preliminary bioassays suggested that some of these simple structures displayed appreciable anti-TMV activity in vivo. Among them, compound (diethoxyphosphoryl)methyl 4-[2-(1H-benzo[d][1,2,3]triazol-1-yl)acetamido]-benzoate (a-3) exerted the strongest chemotherapeutic and protective effects against TMV with the rates of 52.8 and 72.2% at the dosage of 500 µg/mL, respectively, which were comparable with those of the commercial agricultural antiviral agent ningnanmycin (54.2 and 70.2%). Molecular docking with TMV helicases revealed that compound a-3 had strong interactions with receptor amino acid residues. Given the facile synthetic route and significant chemotherapeutic and protective potentials, compound a-3 could be further studied and exploited as a promising antiviral candidate.

In this paper, a variety of novel 1,3,4-oxadiazole derivatives possessing diamides were synthesized and tested for their antibacterial and antiviral activity. Preliminary antibacterial assays indicated that some intermediates and title compounds displayed excellent inhibition effects against plant pathogens Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas axonopodis pv. citri (Xac). Further studies revealed that compound H15 exhibited the strongest activities against Xoo and Xac with minimal EC50 values of 0.7 and 5.9 μg/mL, respectively. Antiviral bioassays suggested that some of these structures displayed appreciable curative activities and moderate protective effects against tobacco mosaic virus (TMV) in vivo. Among them, compound H8 exerted the best chemotherapeutic effect against TMV with the curative rate of 60.0% at 500 µg/mL, which was comparable with those of commercial agricultural antiviral agent ningnanmycin (54.2%). Given their significant biological activities, this kind of compound could serve as new leading compounds in the study of antibacterial and antiviral chemotherapy.

In general, thermoplastic polyurethane (TPU) is one of the polymers that have great flexibility and processibility. Along with these advantages, when the TPU contains specific functional groups for further reactions, the scope of application will be greatly extended. Here, we attempted to synthesize a highly functional TPU with a reactive group from the synthesized azido diol. Azido-thermoplastic polyurethanes (azido-TPUs), which could be introduced with other groups easily via azido-alkyne “click” reactions, have been studied. Because of their great processibility (even after functionalization), we can prepare azido-TPU films and fibers by spin coating and electrospinning, respectively. To prove the potential applications of azido-TPU, we investigated the mechanical properties of functionalized TPU and application via click reaction on TPU fibers and films.

COX-1/PGE2 is an important protective mediator in ulcerative colitis (UC). β-arrestin1 (β-arr1), which acts as a scaffold protein, is involved in PGE2-mediated signaling pathways. However, the interaction between PGE2 and β-arr1 in maintaining mucosal barrier integrity remains unexplored. In this study, we demonstrated that COX-1 and PGE2 were significantly decreased, and EP4 mRNA was downregulated in both UC patients and mice during the injury phase. PGE2 treatment was found to alleviate mucosal injury and induce EP4 expression during dextran sulfate sodium (DSS)-induced colitis in wild-type (WT) mice. Following DSS-induced injury, β-arr1 deficient mice showed increased signs of colitis compared to β-arr1 WT mice, and the expression of PI3K and p-Akt were remarkably downregulated in β-arr1 deficient mice. In parallel, HCT116 cells transfected with β-arr1 siRNA were examined in the presence or absence of PGE2in vitro. PGE2 treatment in the β-arr1 WT/KO DSS model and β-arr1 siRNA transfection of HCT116 cells confirmed that PGE2 upregulated β-arr1 in vivo and in vitro. Collectively, our results indicate that COX-1/PGE2/EP4 upregulates the β-arr1 mediated Akt signaling pathway to provide mucosal protection in colitis. Thus, these findings provide support for the future development and clinical application of COX-1/PGE2 in UC.

The sulfonated phenyl functionalized polystyrene-butadiene random copolymer was synthesized for application as flexible ion-exchange material. The polymer was prepared through phenyl functionalization via thiol-ene reaction and sulfonation of the base polystyrene-butadiene copolymer with different vinyl contents and phenyl contents. Sulfonation on phenyl functionalized polystyrene-butadiene copolymer was carried out in 1,2-dichloroethane at room temperature using the acetyl sulfonate as the sulfonation agent which was prepared from the reaction of acetyl acetate with sulfuric acid. The sulfonation degrees were adjusted from 7.3 mol% to 24.3 mol% determined by elemental analysis (EA) with great ion exchange capacity (0.60–2.26 meq/g), conductivity (0.47–6.1 mS/cm) and lower water uptake (5.1–12.8 wt.%). These excellent characteristics lead to great potential using as the flexible ion-exchange material.