Ultrasensitive, Label-Free Voltammetric Detection of Dibutyl Phthalate Based on Poly-l-lysine/poly(3,4-ethylenedioxythiophene)-porous Graphene Nanocomposite and Molecularly Imprinted Polymers.

Development of an efficient technique for accurate and sensitive dibutyl phthalate (DBP) determination is crucial for food safety and environment protection. An ultrasensitive molecularly imprinted polymers (MIP) voltammetric sensor was herein engineered for the specific determination of DBP using poly-l-lysine/poly(3,4-ethylenedioxythiophene)/porous graphene nanocomposite (PLL/PEDOT-PG) and poly(o-phenylenediamine)-imprinted film as a label-free and sensing platform. Fabrication of PEDOT-PG nanocomposites was achieved through a simple liquid-liquid interfacial polymerization. Subsequently, poly-l-lysine (PLL) functionalization was employed to enhance the dispersibility and stability of the prepared PEDOT-PG, as well as promote its adhesion on the sensor surface. In the presence of DBP, the imprinted poly(o-phenylenediamine) film was formed on the surface of PLL/PEDOT-PG. Investigation of the physical properties and electrochemical behavior of the MIP/PLL/PEDOT-PG indicates that the incorporation of PG into PEDOT, with PLL uniformly wrapping its surface, significantly enhanced conductivity, carrier mobility, stability, and provided a larger surface area for specific recognition sites. Under optimal experimental conditions, the electrochemical response exhibited a linear relationship with a logarithm of DBP concentration within the range of 1 fM to 5 µM, with the detection limit as low as 0.88 fM. The method demonstrated exceptional stability and repeatability and has been successfully applied to quantify DBP in plastic packaging materials.

Discovery of benzopyridone cyanoacetates as new type of potential broad-spectrum antibacterial candidates.

Unique benzopyridone cyanoacetates (BCs) as new type of promising broad-spectrum antibacterial candidates were discovered with large potential to combat the lethal multidrug-resistant bacterial infections. Many prepared BCs showed broad antibacterial spectrum with low MIC values against the tested strains. Some highly active BCs exhibited rapid sterilization capacity, low resistant trend and good predictive pharmacokinetic properties. Furthermore, the highly active sodium BCs (NaBCs) displayed low hemolysis and cytotoxicity, and especially octyl NaBC 5g also showed in vivo potent anti-infective potential and appreciable pharmacokinetic profiles. A series of preliminary mechanistic explorations indicated that these active BCs could effectively eliminate bacterial biofilm and destroy membrane integrity, thus resulting in the leakage of bacterial cytoplasm. Moreover, their unique structures might further bind to intracellular DNA, DNA gyrase and topoisomerase IV through various direct noncovalent interactions to hinder bacterial reproduction. Meanwhile, the active BCs also induced bacterial oxidative stress and metabolic disturbance, thereby accelerating bacterial apoptosis. These results provided a bright hope for benzopyridone cyanoacetates as potential novel multitargeting broad-spectrum antibacterial candidates to conquer drug resistance.

Effects of evodiamine on ROS/TXNIP/NLRP3 pathway against gouty arthritis.

Evodiamine (EVO) was tested on acute gouty arthritis rats to investigate its anti-inflammatory effect. Seventy-two male Sprague-Dawley (SD) rats were randomly assigned into the control, model, high, medium, and low dose of EVO groups and colchicine group. The ankle swelling degrees were measured at 2 h, 6 h, and 24 h following sodium urate injection into ankle joint. Histopathological examination was performed 24 h after injection. Reactive oxygen species (ROS) content in the ankle joint was detected using chemical fluorescence. Serum interleukin-1ß (IL-1ß), interleukin-18 (IL-18), and tumor necrosis factor-α (TNF-α) content were determined by ELISA. Serum xanthine oxidase (XOD), superoxide dismutase (SOD), and malondialdehyde (MDA) were determined by spectrophotometry. The expressions of thioredoxin-interacting protein (TXNIP), NOD-like receptor thermal protein domain associated protein 3 (NLRP3), pro-caspase-1, caspase-1, and apoptosis-related spot like protein (ASC) in synovium were detected by Western blot. Evodiamine alleviated the ankle swelling of the affected foot in gouty arthritis rats and reduced inflammatory cell infiltration in joint synovial tissue. Evodiamine also decreased the content of serum inflammatory factors including IL-1ß, IL-18, and TNF-α, and increased serum SOD activity, while it decreased serum XOD, MDA activity, and ROS level. Moreover, evodiamine downregulated the protein expression levels of TXNIP, NLRP3, pro-caspase-1, cleaved caspae-1, and ASC. The mechanism of EVO in treating gouty arthritis is associated with the inhibition of NLRP3 inflammasome by regulating the ROS/TXNIP/NLRP3 signaling pathway.

Comprehensive Insights into Medicinal Research on Imidazole-Based Supramolecular Complexes.

The electron-rich five-membered aromatic aza-heterocyclic imidazole, which contains two nitrogen atoms, is an important functional fragment widely present in a large number of biomolecules and medicinal drugs; its unique structure is beneficial to easily bind with various inorganic or organic ions and molecules through noncovalent interactions to form a variety of supramolecular complexes with broad medicinal potential, which is being paid an increasing amount of attention regarding more and more contributions to imidazole-based supramolecular complexes for possible medicinal application. This work gives systematical and comprehensive insights into medicinal research on imidazole-based supramolecular complexes, including anticancer, antibacterial, antifungal, antiparasitic, antidiabetic, antihypertensive, and anti-inflammatory aspects as well as ion receptors, imaging agents, and pathologic probes. The new trend of the foreseeable research in the near future toward imidazole-based supramolecular medicinal chemistry is also prospected. It is hoped that this work provides beneficial help for the rational design of imidazole-based drug molecules and supramolecular medicinal agents and more effective diagnostic agents and pathological probes.

Azolylpyrimidinediols as Novel Structural Scaffolds of DNA-Groove Binders against Intractable Acinetobacter baumannii.

A unique class of antibacterial azolylpyrimidinediols (APDs) and their analogues were developed. Some synthesized compounds showed excellent bacteriostatic potency; especially, triazolylpyrimidinediol (triazolyl PD) 7a exhibited good anti-Acinetobacter baumannii potential with a low MIC of 0.002 mmol/L. Triazolyl PD 7a with inconspicuous cytotoxicity and hemolytic activity could eradicate the established biofilm, showed low resistance, and exhibited favorable drug-likeness. Mechanistic explorations revealed that compound 7a without membrane-targeting ability could decrease metabolic activity, interact with DNA through groove binding action to block DNA replication rather than intercalate into and cleave DNA, and thus inhibit bacterial growth. Further computations displayed that the low EHOMO and large energy gap might help triazolyl PD 7a binding to biological targets more easily. Moreover, compound 7a gave appreciable in vivo pharmacokinetic properties and pharmacodynamics. These findings of azolylpyrimidinediols as novel structural scaffolds of DNA-groove binders might imply a large promise for the treatments of Acinetobacter baumannii infection.

Kaolin-loaded carboxymethyl chitosan/sodium alginate composite sponges for rapid hemostasis.

There are several factors that contribute to the mortality of people who suffer from unmanageable bleeding. Therefore, the development of rapid hemostatic materials is necessary. Herein, novel rapid hemostatic composite sponges were developed by incorporation of kaolin (K) into carboxymethyl chitosan (CMCS)/sodium alginate (SA) via a combination of methods that includes ionic crosslinking, polyelectrolyte action, and freeze-drying. The CMCS/SA-K composite sponges were cross-linked with calcium ions provided by a sustained-release system consisting of D-gluconolactone (GDL) and Ca-EDTA, and the hemostatic ability of the sponges was enhanced by loading the inorganic hemostatic agent-kaolin (K). It was demonstrated that the CMCS/SA-K composite sponges had a good porous structure and water absorption properties, excellent mechanical properties, outstanding biodegradability, and biocompatibility. Simultaneously, they exhibited rapid hemostatic properties, both in vitro and in vivo. Significantly, the hemostatic time of the CMCS/SA-K60 sponge was improved by 82.76 %, 191.82 %, and 153.05 %, compared with those of commercially available gelatin sponges in the rat tail amputation, femoral vein, and liver injury hemorrhage models respectively, indicating that its hemostatic ability was superior to that of commercially available hemostatic materials. Therefore, CMCS/SA-K composite sponges show great promise for rapid hemostasis.

Chitosan-based packaging films with an integrated antimicrobial peptide: Characterization, in vitro release and application to fresh pork preservation.

Chitosan (CS) films were developed incorporating peptide HX-12C. The films were studied to determine their microstructures, physical properties, release properties of peptide HX-12C and functional properties. The results indicated that there may be hydrogen bonding interactions between CS and peptide HX-12C, thereby creating a homogeneous internal microstructure and lower crystallinity (10.8-12.8 %). Compared with CS film, CS-HX-12C films displayed lower light transmission, MC (20.8-19.9 %), WVP (8.82-8.59 × 10-11·g·m-1·s-1·Pa-1), OTR (0.015-0.037 cc/(m2.day)) and higher WS (15.7-32.4 %) values. Moreover, controlled-release experiments showed that pH, ionic strength and temperature could all significantly affect the release of peptide HX-12C from the films. Finally, the increase of pH value and TVC and lipid oxidation of fresh pork were delayed due to the treatment with CS-2%HX-12C film. However, incorporating peptide HX-12C into CS films did not improve the mechanical properties of the films and their effects against protein oxidation. Our results suggest that the CS-based antimicrobial packaging films integrated with peptide HX-12C exhibit the potential for fresh pork preservation.

Advancements, challenges and future perspectives on peptide-based drugs: Focus on antimicrobial peptides.

Among other health related issues, the rising concerns on drug resistance led to look for alternative pharmaceutical drugs that are effective both against infectious and noninfectious diseases. Antimicrobial peptides (AMPs) emerged as potential therapeutic molecule with wide range of applications. With their limitations, AMPs have gained reputable attentions in research as well as in the pharmaceutical industry. This review highlighted the historical background, research trends, technological advancements, challenges, and future perspectives in the development and applications of peptide drugs. Some vital questions related with the need for pharmaceutical production, factors for the slow and steady journey, the importance of oral bioavailability, and the drug resistance possibilities of AMPs were raised and addressed accordingly. Therefore, the current study is believed to provide a profound understanding in the past and current scenarios and future directions on the therapeutic impacts of peptide drugs.

Anticorrosion behaviour and tribological properties of AZ31 magnesium alloy coated with Nb2O5/Nb2O5-Mg/Mg layer by magnetron sputtering.

Magnesium alloys are attracting increasing attention for the fabrication of temporary implants because of their superior biodegradability and biocompatibility. However, their high degradation rate under physiological conditions limits their clinical applications. In this work, a Nb2O5/Nb2O5-Mg/Mg multilayer coating was prepared on the surface of AZ31 magnesium alloy by magnetron sputtering in order to improve its corrosion resistance. The microstructure and performance of the layers were studied by SEM, AFM, EDS, and XPS, and a scratch tester, nanoindenter, friction tester, and electrochemical workstation, using Nb2O5 monolayer coating as a control. The results show that these two coatings significantly improved the mechanical, tribological, and anticorrosion performance of AZ31 magnesium alloy. Compared with a Nb2O5 monolayer coating, the multilayer coating exhibits an increased adhesion by about 10.6 times, and a decreased wear rate and corrosion current density by one order of magnitude, meaning higher damage resistance. This study provides a feasible strategy for enhancing the properties of ceramic layers on magnesium alloys for medical applications.

Unique iminotetrahydroberberine-corbelled metronidazoles as potential membrane active broad-spectrum antibacterial agents.

In an effort for fighting with dreadful drug resistance, iminotetraberberine was hybridized with metronidazole to construct a unique type of potential broad-spectrum antibacterial iminotetrahydroberberine-corbelled metronidazoles. Some prepared hybrids exerted promising inhibitory effects against the tested microorganisms in comparison to the natural berberine, clinical metronidazole and norfloxacin. Noticeably, phenyl oxime derivative 8e displayed a broad antibacterial spectrum with a quite low MIC value of 0.024 mM against P. aeruginosa, being 63-, 62- and 2-fold to berberine, metronidazole and norfloxacin, respectively. The active compound 8e with low cytotoxicity under effective bacteriostatic concentration could decrease biofilm viability and show much lower trend to induce the resistant development than norfloxacin in the tested period. Mechanism investigation showed that compound 8e could disturb the bacterial membrane to lead to the leakage of cellular contents, thus exerting potent antibacterial potency. It was also revealed that compound 8e could interact with penicillin binding protein via multi-site non-covalent binding in docking simulation. The above results manifested that iminotetrahydroberberine-corbelled metronidazoles might bring hope for the exploitation of new broad-spectrum antibacterial agents with a membrane-destruction mechanism.

Pyrimidine-conjugated fluoroquinolones as new potential broad-spectrum antibacterial agents.

Pyrimidine-conjugated fluoroquinolones were constructed to cope with the dreadful resistance. Most of the target pyrimidine derivatives effectively suppressed the growth of the tested strains, especially, 4-aminopyrimidinyl compound 1c showed a broad antibacterial spectrum and low cytotoxicity and exhibited superior antibacterial potency against Enterococcus faecalis with a low MIC of 0.25 µg/mL to norfloxacin and ciprofloxacin. The active compound 1c with fast bactericidal potency could inhibit the formation of biofilms and showed much lower trend for the development of drug-resistance than norfloxacin and ciprofloxacin. Further exploration revealed that compound 1c could prompt ROS accumulations in bacterial cells and interact with DNA to form a DNA-1c complex, thus facilitating bacterial death. ADME analysis indicated that compound 1c possessed favorable drug-likeness and promising pharmacokinetic properties. These results demonstrated that pyrimidine-conjugated fluoroquinolones held hope as potential antibacterial candidates and deserve further study.

Recent advances and application of whole genome amplification in molecular diagnosis and medicine.

Whole genome amplification (WGA) is a technology for non-selective amplification of the whole genome sequence, first appearing in 1992. Its primary purpose is to amplify and reflect the whole genome of trace tissues and single cells without sequence bias and to provide sufficient DNA template for subsequent multigene and multilocus analysis, along with comprehensive genome research. WGA provides a method to obtain a large amount of genetic information from a small amount of DNA and provides a valuable tool for preserving limited samples in molecular biology. WGA technology is especially suitable for forensic identification and genetic disease research, along with new technologies such as next-generation sequencing (NGS). In addition, WGA is also widely used in single-cell sequencing. Due to the small amount of DNA in a single cell, it is often unable to meet the amount of samples needed for sequencing, so WGA is generally used to achieve the amplification of trace samples. This paper reviews WGA methods based on different principles, summarizes both amplification principle and amplification quality, and discusses the application prospects and challenges of WGA technology in molecular diagnosis and medicine.

Magnetic resonance feature of "paintbrush borders" sign as a novel way to predict recurrence of giant cell tumor of bone after curettage: a pilot study.

Objective To identify the prognostic factors for local recurrence of giant cell tumor of bone (GCTB) through assessment of the preoperative imaging features of the tumor border. Methods Patients with GCTBs treated with intralesional procedures in the proximal tibia and distal femur were prospectively enrolled and then followed up for at least 2 years. The GCTBs were grouped according to their preoperative imaging features. GCTBs treated with en bloc resection were enrolled for investigation of the pathologic basis of specific imaging features. Differences between rates were evaluated by the chi-square test or Fisher's exact test; independent factors were identified by multivariate logistic regression analysis. Results Fifty-three patients were enrolled and successfully followed up. Relapse occurred in 22 patients. Patients with a "paintbrush borders" sign (n = 21) had a significantly higher rate of local recurrence (71.43%) than patients without this sign (21.88%). The "paintbrush borders" sign was identified as an independent prognostic factor for local recurrence. Other imaging features were not significantly associated with recurrence. The "paintbrush borders" sign showed a correlation with local invasion of bone. Conclusion The "paintbrush borders" sign on preoperative magnetic resonance imaging is an independent prognostic factor for local recurrence of GCTB.

[Soil microfauna diversity among Cunninghamia lanceolata plantations based on pyrosequencing].

In order to study the function of soil microfauna and its responses to environmental changes, we used metagenome analyses of the 18S rDNA gene region to identify differences in microfauna diversity and community structure among fifteen soil samples belonging to five different Cunninghamia lanceolate plantations. The plantations were located in Youxian County, Hunan Province in central China. The trees in these plantations were of different ages (3, 13, and 26 years) and belonged to different ecological successions (first, second, and third successions). The total dataset comprised 94922 high quality sequences with an average length of 436 bp. The dominant taxonomic groups across all samples were Chordata, Annelida, Arthropoda, Nematoda, Rotifera and Platyhelminthes with each accounting for 60.8%, 24.0%, 7.4%, 3.6%, 1.5% and 1.2% of the sequences, respectively. There were significant differences in ACE index and Shannon index among the five plantations. The lowest diversity of soil microfauna was in the 13-year old plantation of the first ecological succession. The correlation analysis showed that both ACE and available potassium concentration were negatively correlated to the Chaol index. However, there were no significant correlations between the Shannon, Simpson indices and the physical-chemical properties of soil. Overall, the Jaccard's similarity coefficient was less than 0.4 among samples at each site, and significant differences were found among plantations.