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Various proteins introduced into living modified organism (LMO) crops function in plant defense mechanisms against target insect pests or herbicides. This study analyzed the antifungal effects of an introduced LMO protein, 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) from Agrobacterium sp. strain CP4 (CP4-EPSPS). Pure recombinant CP4-EPSPS protein, expressed in Escherichia coli, inhibited the growth of human and plant fungal pathogens (Candida albicans, C. tropicalis, C. krusei, Colletotrichum gloeosporioides, Fusarium solani, F. graminearum, and Trichoderma virens), at minimum inhibitory concentrations (MICs) that ranged from 62.5 to 250 µg/mL. It inhibited fungal spore germination as well as cell proliferation on C. gloeosporioides. Rhodamine-labeled CP4-EPSPS accumulated on the fungal cell wall and within intracellular cytosol. In addition, the protein induced uptake of SYTOX Green into cells, but not into intracellular mitochondrial reactive oxygen species (ROS), indicating that its antifungal action was due to inducing the permeability of the fungal cell wall. Its antifungal action showed cell surface damage, as observed from fungal cell morphology. This study provided information on the effects of the LMO protein, EPSPS, on fungal growth.

Biofilms are resistant to antibiotics and are a major source of persistent and recurring infections by clinically important pathogens. Drugs used for biofilm-associated infections are limited because biofilm-embedded or biofilm-matrix bacteria are difficult to kill or eradiate. Therefore, many researchers are developing new and effective antibiofilm agents. Among them, antimicrobial peptides have an attractive interest in the development of antibiofilm agents. The present study evaluated the effects of 10 synthetic peptides on growth inhibition, inhibition of biofilm formation, and biofilm elimination in drug-resistant Pseudomonas aeruginosa. The planktonic cell growth and biofilm formation were dose-dependently inhibited by most of the peptides. WIK-14 eliminated preformed biofilm masses by removing carbohydrates, extracellular nucleic acids, proteins, and lipids constituting extracellular polymeric substances. The results demonstrated that WIK-14 and WIKE-14 peptides might provide novel therapeutic drugs to overcome multidrug resistance in biofilm-associated infections.

Clinically, fungal pneumonia rarely occurs in adults, and invasive fungal infections can cause substantial morbidity, and mortality due to sepsis and septic shock. In the present study, we have designed peptides that exhibit potent antifungal activities against fluconazole-resistant Candida albicans in physiological monovalent, and divalent ionic buffers, with minimal fungicidal concentrations ranging from 16 to 32 µM. None of these tested peptides resulted in the development of drug resistance similar to fluconazole. Among them, the PS1-2 peptide did not induce stimulation of macrophages by C. albicans, and it exerted antifungal and anti-inflammatory effects against C. albicans-induced intratracheal infection, in an acute lung injury mouse model. PS1-2 is likely a novel therapeutic agent for the control, and prevention of drug-resistant C. albicans infection, and our findings may be useful for designing antimicrobial peptides to combat fungal infection.

Antimicrobial peptides (AMPs) can combat drug-resistant bacteria with their unique membrane-disruptive mechanisms. This study aimed to investigate the antibacterial effects of several membrane-acting peptides with amphipathic structures and positional alterations of two tryptophan residues. The synthetic peptides exhibited potent antibacterial activities in a length-dependent manner against various pathogenic drug-resistant and susceptible bacteria. In particular, the location of tryptophan near the N-terminus of AMPs simultaneously increases their antibacterial activity and toxicity. Furthermore, the growth inhibition mechanisms of these newly designed peptides involve cell penetration and destabilization of the cell membrane. These findings provide new insights into the design of peptides as antimicrobial agents and suggest that these peptides can be used as substitutes for conventional antibiotics.

Although considerable scientific research data is available for sepsis and cytokine storm syndrome, there is a need to develop new treatments or drugs for sepsis management. Antimicrobial peptides (AMPs) possess anti-bacterial and anti-inflammatory activity, neutralizing toxins such as lipopolysaccharides (LPS, endotoxin). Most AMPs have been designed as a substitute for conventional antibiotics, which kill drug-resistant pathogens. The present study aimed to determine the anti-inflammatory potential of 10 designed XIW (X: lysine, arginine, or glutamic acid) α-helical peptides in macrophages and a mouse model in the presence of LPS. Among them, WIKE-14, a peptide with a helix-to-helix structure, having the 12th amino acid substituted with glutamic acid, suppressed pro-inflammatory cytokines in RAW 264.7 macrophages. This reaction was mediated by the inhibition of the binding between LPS and macrophages. In addition, the WIKE-14 peptide exhibited a potent anti-inflammatory activity in mice ears and lungs inflamed using LPS. Thus, our results may provide useful insights for the development of anti-sepsis agents via the sequence and structure information of the WIKE-14 peptide.

Cancer cells are more vulnerable to reactive oxygen species (ROS)-mediated oxidative stress than normal cells due to disturbed redox balance. It can be postulated that ROS-generating drug carriers exert anticancer actions, leading to combination anticancer therapy with drug payloads. Here, we report a ROS-generating polyprodrug of cinnamaldehyde (CA) that not only serves as a drug carrier but also synergizes with drug payloads. The polyprodrug of CA (pCA) incorporates ROS-generating CA in the backbone of an amphiphilic polymer through an acid-cleavable acetal linkage. pCA could self-assemble with tumor-targeting lipopeptide (DSPE-PEG-RGD) and encapsulate doxorubicin (DOX) to form T-pCAD micelles. At acidic pH, T-pCAD micelles release both CA and DOX to exert synergistic anticancer actions. Animal studies using mouse xenograft models revealed that T-pCAD micelles accumulate in tumors preferentially and suppress the tumor growth significantly. Based on the oxidative stress amplification and acid-responsiveness, ROS-generating pCAD micelles hold tremendous potential as drug carriers for combination anticancer therapy.

Profilins (PFNs) are actin monomer-binding proteins that function as antimicrobial agents in plant phloem sap. Although the roles of

Infectious diseases induced by multidrug-resistant bacteria are a challenging problem in medicine because of global rise in the drug resistance to pathogenic bacteria. Despite great efforts on the development of antibiotics and antimicrobial agents, there is still a great need to develop a strategy to early detect bacterial infections and eradicate bacteria effectively and simultaneously. The innate immune systems of various organisms produce antimicrobial peptides, which kill a broad range of bacteria with minimal cytotoxicity to mammalian cells. Therefore, antimicrobial peptides have recently attracted increasing attention as an alternative to conventional antibiotics in antibacterial medications. Here, we report a new family of antibacterial agents, which is formulated from self-assembly of a chimeric antimicrobial lipopeptide (DSPE-HnMc) and amphiphilic biodegradable polymers. HnMc micelles could effectively bind the bacterial membrane to kill a wide spectrum of bacteria and bacterial biofilms. In the studies of mouse models of drug-resistant bacterial infections, HnMc micelles could target bacterial infections with high specificity and also kill drug-resistant bacteria effectively, demonstrating the great potential of HnMc micelles as imaging and targeted antibacterial agents. These findings also provide new insight into the design of antimicrobial peptide-based nanomedicine for detection and treatment of bacterial infections.

Purpose To evaluate the effect of the location of the femoral tunnel on 3-dimensional (3D) computed tomography (CT) upon the postoperative tunnel widening after anterior cruciate ligament (ACL) reconstructions. Methods Inclusion criteria were patients who underwent hamstring ACL reconstructions using an adjustable-loop cortical suspension device, underwent 3D CT at the day after surgery, and were followed for a minimum of 2 years after surgery. Exclusion criteria were patients with combined ligament injury and reinjury after reconstruction. Using 3D CT, the center of the femoral tunnel aperture was located on a standardized grid system. The center of the ACL footprint was defined from the literature. The femoral tunnel location was classified as anatomic if it located within 2 standard deviations of the center position. If it was outside the 2 standard deviations, the tunnel was classified as nonanatomic. The patients were divided into either anatomic or nonanatomic groups. Femoral tunnel angles on both sagittal and coronal planes were measured. Both femoral and tibial tunnels measured on anteroposterior and lateral radiographs at immediate postoperative day and at 2 years after surgery. Postoperative knee stability and patient-reported outcomes were evaluated. Results There were 37 patients in anatomical group and 52 patients in nonanatomical group among enrolled 87 patients. There were no differences in demographics between the 2 groups. There were no differences in the femoral tunnel angles and postoperative tunnel widening between the 2 groups. A higher position correlated to the femoral tunnel widening at 2 years postoperatively. Postoperative knee stability and patient-reported outcomes showed no statistically significant differences between the 2 groups. Conclusions There was no significant difference in postoperative tunnel widening or clinical outcomes between anatomic and nonanatomic femoral tunnel location after hamstring ACL reconstructions. A higher position correlated to the femoral tunnel widening at 2 years postoperatively. Level of Evidence Level III, Retrospective comparative study.

Recent advancements in gene delivery systems that specifically target a variety of cancer types have increased demand for tissue-specific gene therapy. The current study describes the synthesis of a copolymer (GPgWSC) composed of a polyethylenimine (PEI)-grafted water-soluble chitosan (WSC) and gambogic acid (GA). It was validated as a ligand capable of enabling targeted attachment to transferrin receptors in HCT116 cancer cell lines. GPgWSC demonstrated superior antitumor activity in vitro in HCT116 compared to LoVo or MCF-7 cell lines, facilitated by the apoptotic activity of psiRNA-hBCL2. Pre-incubation of transferrin significantly inhibited GFP expression in the GPgWSC polyplex, demonstrating that GA is an extremely effective transferrin receptor targeting molecule. Additionally, in the HCT116-bearing mouse model, the tumor mass of PBS-treated mice increased to 2270 mm2 after 22 days, but the injection of GPgWSC polyplex significantly reduced the mass-increasing rate as a mass size of 248 mm2.

To alleviate water shortage, several water transfer projects have been constructed in China. To further develop the supply chain management of water resources, the Eastern and Central Routes of China's South-to-North Water Transfer Project are considered as two water suppliers. The two suppliers provide water for two distributors in northern China. Based on a two-stage Stackelberg game, we develop a chain-to-chain competition model in three alternating scenarios including under wholesale price contracts, two-part pricing contracts and mixed pricing contracts, and derive the optimal pricing and ordering strategies. We find that each water supply chain member can earn a higher profit under the two-part pricing contract with appropriate parameters compared to that under the wholesale price contract. When the competition is weak, the performance of the supply chain subsystem under the two-part pricing contract is better than that under the wholesale pricing contract. On the contrary, when the competition is strong, the performance of the supply chain under the two-part pricing contract is lower than that under the wholesale price contract. With the two-part pricing contract used for both water supply chains, the two suppliers are in the prisoners' dilemma. The study expands the theory of supply chain management under competition and provides insights for the sustainability of water resource management.

Background It remains an open question whether plant phloem sap proteins are functionally involved in plant defense mechanisms. Methods The antifungal effects of two profilin proteins from Arabidopsis thaliana, AtPFN1 and AtPFN2, were tested against 11 molds and 4 yeast fungal strains. Fluorescence profiling, biophysical, and biochemical analyses were employed to investigate their antifungal mechanism. Results Recombinant AtPFN1 and AtPFN2 proteins, expressed in Escherichia coli, inhibited the cell growth of various pathogenic fungal strains at concentrations ranging from 10 to 160 μg/mL. The proteins showed significant intracellular accumulation and cell-binding affinity for fungal cells. Interestingly, the AtPFN proteins could penetrate the fungal cell wall and membrane and act as inhibitors of fungal growth via generation of cellular reactive oxygen species and mitochondrial superoxide. This triggered the AtPFN variant-induced cell apoptosis, resulting in morphological changes in the cells. Conclusion PFNs may play a critical role as antifungal proteins in the Arabidopsis defense system against fungal pathogen attacks. General significance The present study indicates that two profilin proteins, AtPFN1 and AtPFN2, can act as natural antimicrobial agents in the plant defense system.

Several antimicrobial peptides (AMPs) have been discovered, developed, and purified from natural sources and peptide engineering, however, the clinical applications of these AMPs are limited owing to their lack of abundance and side effects related to cytotoxicity, immunogenicity, and hemolytic activity. Accordingly, to improve cell selectivity for pseudin-2, an AMP from Pseudis paradoxa skin, in mammalian cells and pathogenic fungi, the sequence of pseudin-2 was modified by alanine or lysine at each position of two amino acids within the leucine-zipper motif. Alanine-substituted variants were highly selective toward fungi over HaCaT and erythrocytes and maintained their antifungal activities and mode of action (membranolysis). However, the antifungal activities of lysine-substituted peptides were reduced, and the compound could penetrate into fungal cells, followed by induction of mitochondrial reactive oxygen species and cell death. In vivo antifungal assays of analogous peptide showed excellent antifungal efficiency in a Candida tropicalis skin infection mouse model. Our results demonstrated the usefulness of selective amino acid substitution in the repeated sequence of the leucine-zipper motif for the design of AMPs with potent antimicrobial activities and low toxicity.

We aimed to assess whether brain volumes may affect the results of deep brain stimulation (DBS) in patients with Parkinson’s disease (PD). Eighty-one consecutive patients with PD (male:female 40:41), treated with DBS between June 2012 and December 2017, were enrolled. Total and regional brain volumes were measured using automated brain volumetry (NeuroQuant). The Unified Parkinson Disease Rating Scale motor score quotient was used to assess changes in clinical outcome and compare the preoperative regional brain volume in patients categorized into the higher motor improvement and lower motor improvement groups based on changes in the postoperative scores. The study groups showed significant volume differences in multiple brain areas. In the higher motor improvement group, the anterior cingulate and right thalamus showed high volumes after false discovery rate (FDR) correction. In the lower motor improvement group, the left caudate, paracentral, right primary sensory and left primary motor cortex showed high volume, but no area showed high volumes after FDR correction. Our data suggest that the effectiveness of DBS in patients with PD may be affected by decreased brain volume in different areas, including the cingulate gyrus and thalamus. Preoperative volumetry could help predict outcomes in patients with PD undergoing DBS.

It is difficult to identify new antifungal agents because of their eukaryotic nature. However, antimicrobial peptides can well differentiate among cell types owing to their variable amino acid content. This study aimed to investigate the antifungal effect of Hn-Mc, a chimeric peptide comprised of the N-terminus of HPA3NT3 and the C-terminus of melittin. We evaluated its potent antifungal activity at low minimal inhibitory concentrations (MICs) ranging from 1&ndash, 16 &mu, M against pathogenic yeast and molds. The cell-type specificity of Hn-Mc was mediated through the formation of a random &alpha, helical structure to mimic the fungal membrane environment. Furthermore, Hn-Mc caused cell death in C. tropicalis and F. oxysporum by inducing apoptosis via the generation of reactive oxygen species (ROS) due to mitochondrial damage. The present results indicate that Hn-Mc has a high affinity for the fungal plasma membrane and induces apoptosis in fungal cells, and provide guidance for the development of new antifungal agents.

The increasing emergence of drug-resistant bacteria creates a requirement for new antibiotics and various types of antibiotic materials such as proteins, peptides, polymers, and chemical compounds. Among these, antimicrobial peptides (AMPs) are considered to be promising antibiotic candidates for clinical treatments. In this study, we have designed a novel series of peptides with repeated sequences of minimum membrane-active motif, ‘XWZX’ basic sequence (X: lysine or arginine, Z: leucine, tyrosine, valine, or glycine), and an α-helical secondary structure. Some peptides displayed a potent antibacterial activity via membranolytic action and high therapeutic index (toxic dose/minimum inhibitory concentration) in vitro. Furthermore, in vivo experiments using bacterial ear-skin infection models verified that these peptides have the potential to be powerful and safe antibiotics. The present study provides a lead sequence for designing peptide antibiotics against bacterial membranes and information for cell-selectivity of hydrophobic amino acids with aromatic side chains such as Trp and Tyr.

Aside from overstocking, inappropriate grazing management strategies may cause rangeland degradation in commercial scale ranches. In this paper we construct a dynamic model to study the economic and ecological consequences of continuous and multi-paddock (MP) grazing. Simulations on long-term economic profitability and ecological indices were carried out for continuous vs. MP grazing management strategies under different grass growth rates, grass dormant periods, initial ecological conditions and various installation costs for MP grazing. Results show that compared to continuous grazing, MP grazing on large commercial ranches greatly increases the optimal 30-year net present value (NPV) by sustaining much higher stocking rates. At realistic stocking rates, MP grazing both increases long-term economic profit and improves ecological conditions. The advantage of MP grazing is more pronounced under xeric conditions, longer grass dormancy period, and initial prevalence of less palatable grasses and weeds. However, ranch managers for smaller ranches and/or ranches under short-term leases are less likely to adopt MP grazing due to its diminished economic advantages on those ranches.

Biofilm-associated infections are difficult to manage or treat as biofilms or biofilm-embedded bacteria are difficult to eradicate. Antimicrobial peptides have gained increasing attention as a possible alternative to conventional drugs to combat drug-resistant microorganisms because they inhibit the growth of planktonic bacteria by disrupting the cytoplasmic membrane. The current study investigated the effects of synthetic peptides (PS1-2, PS1-5, and PS1-6) and conventional antibiotics on the growth, biofilm formation, and biofilm reduction of drug-resistant Pseudomonas aeruginosa and Staphylococcus aureus. The effects of PS1-2, PS1-5, and PS1-6 were also tested in vivo using a mouse model. All peptides inhibited planktonic cell growth and biofilm formation in a dose-dependent manner. They also reduced preformed biofilm masses by removing the carbohydrates, extracellular DNA, and lipids that comprised extracellular polymeric substances (EPSs) but did not affect proteins. In vivo, PS1-2 showed the greatest efficacy against preformed biofilms with no cytotoxicity. Our findings indicate that the PS1-2 peptide has potential as a next-generation therapeutic drug to overcome multidrug resistance and to regulate inflammatory response in biofilm-associated infections.

Objective Cerebral varices (CVs) without an arteriovenous shunt, so called nonfistulous CVs, are very rare, and their etiology and natural course are not well understood. The aim of this study is to evaluate the clinical outcomes of nonfistulous CVs by the analysis of 39 cases. Methods From 2000 to 2015, 22 patients with 39 nonfistulous CVs (≥5 mm) were found by searching the medical and radiologic records of our institute. Clinical data and radiological data including numbers, sizes and locations of CVs and associated anomalies were retrospectively collected and analyzed. Previously reported cases in literature were reviewed as well. Results The mean age of the patients was 21 years (range, 0-78 years). On average, 1.8±1.2 CVs were found per patient. CVs were categorized as either fusiform or saccular depending on their shapes. Two patients had saccular type CVs, seventeen patients had fusiform types, and three patients had both fusiform and saccular CVs. Eight patients had associated compromise of the vein of Galen and the straight sinus. Four of those patients had sinus pericranii, as well. Five patients had CVs that were distal draining veins of large developmental venous anomalies. One patient had associated migration anomaly, and two patients had Sturge- Weber syndrome. Six patients with an isolated cerebral varix were observed. Of the 39 CVs in 22 patients, 20 lesions in 14 patients were followed up in outpatient clinics with imaging studies. The average follow-up duration was 6.6 years. During this period, no neurological events occurred, and all the lesions were managed conservatively. Conclusion Nonfistulous CVs seemed to be asymptomatic in most cases and remained clinically silent. Hence, we suggest conservative management.

In no-till wheat (Triticum aestivum L.) cropping systems of the US Southern Great Plains, urea fertilizer is commonly surface broadcast and producers rely on unpredictable precipitation in dryland conditions for incorporation into the soil. Several enhanced-efficiency fertilizer technologies are designed to reduce N loss in this scenario, though there are not published reports on evaluations of these in regional wheat systems. Here we report on an evaluation of two enhanced-efficiency fertilizer technologies, polymer-coated urea (PCU) and urease/nitrification inhibitor-stabilized urea (SU), which were compared to untreated urea at different application rates (0, 31.5, and 70 kg N ha–¹) and timings (at-planting and split) in two locations differing in soil type (clay loam and loamy fine sand). The fertilizer was broadcast, except for PCU, which was drilled in-row. The greatest yield was observed with a high at-planting rate of SU, where yield was 26% greater than with untreated urea and 34% greater than with no fertilizer. Yield improvement with SU was associated with greater grain N uptake efficiency and protein content. The high SU rate brought higher net profits than untreated urea at all price points analyzed and surpassed the no-fertilizer control as price increased. As might be expected with seed placement, there was substantial crop damage at the high rate of PCU, but even minor damage at the lower rate. The results suggest that a safe seed-placed rate for PCU in wheat in this environment is somewhat lower than 30 kg N ha–¹. No benefit was observed in splitting the N application.

A thrombus (blood clot), composed mainly of activated platelets and fibrin, obstructs arteries or veins, leading to various life-threatening diseases. Inspired by the distinctive physicochemical characteristics of thrombi such as abundant fibrin and an elevated level of hydrogen peroxide (H2O2), we developed thrombus-specific theranostic (T-FBM) nanoparticles that could provide H2O2-triggered photoacoustic signal amplification and serve as an antithrombotic nanomedicine. T-FBM nanoparticles were designed to target fibrin-rich thrombi and be activated by H2O2 to generate CO2 bubbles to amplify the photoacoustic signal. In the phantom studies, T-FBM nanoparticles showed significant amplification of ultrasound/photoacoustic signals in a H2O2-triggered manner. T-FBM nanoparticles also exerted H2O2-activatable antioxidant, anti-inflammatory, and antiplatelet activities on endothelial cells. In mouse models of carotid arterial injury, T-FBM nanoparticles significantly enhanced the photoacoustic contrast specifi...

Sung In Jeong,1,* Seong-Cheol Park,2,* Sun-Jeong Park,2,* Eun-Ji Kim,2 Hun Heo,2 Jong-Seok Park,1 Hui-Jeong Gwon,1 Youn-Mook Lim,1 Mi-Kyeong Jang2 1Research Division for Industry and Environment, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup, 2Department of Polymer Science and Engineering, College of Engineering, Sunchon National University, Suncheon, Korea *These authors contributed equally to this work Introduction: Although numerous studies have been conducted with the aim of developing drug-delivery systems, chemically synthesized gene carriers have shown limited applications in the biomedical fields due to several problems, such as low-grafting yields, undesirable reactions, difficulties in controlling the reactions, and high-cost production owing to multi-step manufacturing processes. Materials and methods: We developed a 1-step synthesis process to produce 2-aminoethyl methacrylate-grafted water-soluble chitosan (AEMA-g-WSC) as a gene carrier, using gamma irradiation for simultaneous synthesis and sterilization, but no catalysts or photoinitiators. We analyzed the AEMA graft site on WSC using 2-dimensional nuclear magnetic resonance spectroscopy (2D NMR; 1H and 13C NMR), and assayed gene transfection effects in vitro and in vivo. Results: We revealed selective grafting of AEMA onto C6-OH groups of WSC. AEMA-g-WSC effectively condensed plasmid DNA to form polyplexes in the size range of 170 to 282 nm. AEMA-g-WSC polyplexes in combination with psi-hBCL2 (a vector expressing short hairpin RNA against BCL2 mRNA) inhibited tumor cell proliferation and tumor growth in vitro and in vivo, respectively, by inducing apoptosis. Conclusion: The simple grafting process mediated via gamma irradiation is a promising method for synthesizing gene carriers. Keywords: water-soluble chitosan, 2-aminoethyl methacrylate, gamma irradiation, gene delivery

This study investigates smallholder farmers’ participation in and knowledge of village-based water user associations in north-western China, and analyzes their interplay with membership in water as...

The highly conserved SGT1 (suppressor of the G2 alleles of skp1) proteins from Arabidopsis are known to contribute to plant resistance to pathogens. While SGT1 proteins respond to fungal pathogens, their antifungal activity is not reported and the mechanism for this inhibition is not well understood. Therefore, recombinant Arabidopsis SGT1 proteins were cloned, expressed, and purified to evaluate their antifungal activity, resulting in their potent inhibition of pathogen growth. Dye-labeled proteins are localized to the cytosol of Candida albicans cells without the disruption of the cell membrane. Moreover, we showed that entry of the proteins into C. albicans cells resulted in the accumulation of reactive oxygen species (ROS) and cell death via altered mitochondrial potential. Morphological changes of C. albicans cells in the presence of proteins were visualized by scanning electron microscopy. Our data suggest that AtSGT1 proteins play a critical role in plant resistance to pathogenic fungal infection and they can be classified to a new plant antifungal protein.

Targeting antitumor drugs to specific tissues or cells has attracted considerable interest in the recent tumor therapy because it can reduce the side effects in the body and the treated drug dosage through homing drug to the desired tissues. To utilize the high affinity of biotin to avidin as a drug carrier for doxorubicin (DOX), biotinylated targeting material (biotin-polyethylene glycol (PEG)-folic acid, BPF) and biotinylated drug with a bioreducible linker (biotin-SS-PEG-DOX, BSPD) were designed in this study. The in vitro cellular uptake of the avidin/biotinylated drug complexes showed that the complexes with BPF were internalized dose-dependently into HeLa cells, while their uptake was not detected in the absence of BPF. Although the anti-tumor activity of the drug complexes with BPF and BSPD were similar to that of free DOX in cervical cancer cells, the cytotoxic effect of DOX was significantly reduced in normal cells. Their targeting antitumor effect revealed the significant inhibition of the increasing tumor size in HeLa-xenograft mouse model. These results show that the strong complexing between avidin and biotin acted as a targeting moiety and the antitumor drug is an adaptable tool in the fields of tumor therapy.

A thrombus (blood clot) is formed in injured vessels to maintain the integrity of vasculature. However, obstruction of blood vessels by thrombosis slows blood flow, leading to death of tissues fed by the artery and is the main culprit of various life-threatening cardiovascular diseases. Herein, we report a rationally designed nanomedicine that could specifically image obstructed vessels and inhibit thrombus formation. On the basis of the physicochemical and biological characteristics of thrombi such as an abundance of fibrin and an elevated level of hydrogen peroxide (H2O2), we developed a fibrin-targeted imaging and antithrombotic nanomedicine, termed FTIAN, as a theranostic system for obstructive thrombosis. FTIAN inhibited the generation of H2O2 and suppressed the expression of tumor necrosis factor-alpha (TNF-α) and soluble CD40 ligand (sCD40L) in activated platelets, demonstrating its intrinsic antioxidant, anti-inflammatory, and antiplatelet activity. In a mouse model of ferric chloride (FeCl3)-indu...

An antifungal protein, AtUSP protein (At3g53990), was isolated from Arabidopsis thaliana leaves by ion and size chromatography and sequenced by N-terminal sequencing. The AtUSP gene amplified from an Arabidopsis leaf cDNA library was transformed to Escherichia coli to express the AtUSP protein. The recombinant protein inhibited the cell growth of various pathogenic fungal strains. The levels of the AtUSP transcripts were increased by various stresses, including pathogenic infection and salt stress. These results suggest that Arabidopsis AtUSP plays a critical role in the plant tolerance to diverse pathogenic infections. The potent antifungal action, which is a new function of AtUSP, was attributed to fungal reactive oxygen species (ROS) generation and mitochondrial potential alteration.

A plant protein with effective antifungal activity was isolated from Arabidopsis thaliana leaves. The results of N-terminal sequencing analysis revealed that the isolated protein matches with a partial fragment of A. thaliana oxidoreductase thioredoxin h type 5; AtTrx-h5 (GenBank accession number AT1G45145). The AtTrx-h5 gene isolated from an Arabidopsis leaf cDNA library was transformed into Escherichia coli to investigate the functional characterizations of AtTrx-h5 protein. Recombinant AtTrx-h5 protein inhibited the conidia germination in 7 filamentous fungal cells and the proliferation in 3 pathogenic yeast cells. In addition, the cellular distribution of recombinant AtTrx-h5 protein in Fusarium solani showed pH-dependent cytosolic accumulation. Interestingly, AtTrx-h5 acted as an inhibitor of fungal growth via cellular reactive oxygen species (ROS) generation. We propose the novel functions of AtTrx-h5 as a potential candidate for natural antifungal material in the study.