Synthesis, lipophilicity study and in vitro evaluation of some rodenticides as acetylcholinesterase reversible inhibitors

The anti-AChE activity of phosphoramidates has been noticed for many years. Because of the wide application of phosphoramidates in recent years, there has been a continuing research for synthesis, purification and identification of effective and safe derivatives. In this study some rodenticides with the general formula Me(2)NP(O)(p-OC(6)H(4)-X)(2), where X = H, CH(3), Cl, have been synthesized in water (without organic solvent) and characterized by (31)P, (31)P {(1)H}, (13)C and (1)H NMR spectroscopy. Since lipophilicity has been recognized for its importance in QSAR studies, efforts have been made to determine the logP values. The ability of these rodenticides to inhibit human acetylcholinesterase (hAChE) has been predicted with PASS (Prediction of Activity Spectra for Substances) software (version 1.917) and then has been evaluated by a modified Ellman's assay and spectrophotometric measurements.     

Land Use as a Driver of Patterns of Rodenticide Exposure in Modeled Kit Fox Populations

Although rodenticides are increasingly regulated, they nonetheless cause poisonings in many non-target wildlife species. Second-generation anticoagulant rodenticide use is common in agricultural and residential landscapes. Here, we use an individual-based population model to assess potential population-wide effects of rodenticide exposures on the endangered San Joaquin kit fox (Vulpes macrotis mutica). We estimate likelihood of rodenticide exposure across the species range for each land cover type based on a database of reported pesticide use and literature. Using a spatially-explicit population model, we find that 36% of modeled kit foxes are likely exposed, resulting in a 7-18% decline in the range-wide modeled kit fox population that can be linked to rodenticide use. Exposures of kit foxes in low-density developed areas accounted for 70% of the population-wide exposures to rodenticides. We conclude that exposures of non-target kit foxes could be greatly mitigated by reducing the use of second-generation anticoagulant rodenticides in low-density developed areas near vulnerable populations.     

Biomaterials of PVA and PVP in medical and pharmaceutical applications: Perspectives and challenges

Poly(vinyl alcohol) (PVA) has attracted considerable research interest and is recognized among the largest volume of synthetic polymers that have been produced worldwide for almost one century. This is due to its exceptional properties which dictated its extensive use in a wide variety of applications, especially in medical and pharmaceutical fields. However, studies revealed that PVA-based biomaterials present some limitations that can restrict their use or performances. To overcome these limitations, various methods have been reported, among which blending with poly(vinylpyrrolidone) (PVP) showed promising results. Thus, our aim was to offer a systematic overview on the current state concerning the preparation, properties and various applications of biomaterials based on synergistic effect of mixtures between PVA and PVP. Future trends towards where the biomaterials research is headed were discussed, showing the promising opportunities that PVA and PVP can offer.     

Living scaffolds (specialized and unspecialized) for regenerative and therapeutic medicine

The physical sciences have increasingly demonstrated a significant influence on the life sciences. Engineering in particular has shown its input through the development of novel medical devices and processes having significance to the biomedical field. This review introduces and discusses several fiber generation protocols, which have recently undergone development and exploration for directly handling living cells from which continuous cell-bearing or living threads to scaffolds and membranes have been fabricated. In doing so these protocols have not only demonstrated their versatility but also opened several unique possibilities for the use of these scaffolds in a plethora of biological and medical applications. In particular, these living fibrous structural units could be explored for regeneration purposes, e.g., from accelerated wound healing to combating a wide range of pathologies when coupled with gene therapy. Thus, "living entities" such as these scaffolds could be most useful in surgery/medicine, including its exploration with stem cells for the preparation of unspecialized living scaffolds and membranes.     

Overview of bacterial cellulose composites: A multipurpose advanced material

Bacterial cellulose (BC) has received substantial interest owing to its unique structural features and impressive physico-mechanical properties. BC has a variety of applications in biomedical fields, including use as biomaterial for artificial skin, artificial blood vessels, vascular grafts, scaffolds for tissue engineering, and wound dressing. However, pristine BC lacks certain properties, which limits its applications in various fields; therefore, synthesis of BC composites has been conducted to address these limitations. A variety of BC composite synthetic strategies have been developed based on the nature and relevant applications of the combined materials. BC composites are primarily synthesized through in situ addition of reinforcement materials to BC synthetic media or the ex situ penetration of such materials into BC microfibrils. Polymer blending and solution mixing are less frequently used synthetic approaches. BC composites have been synthesized using numerous materials ranging from organic polymers to inorganic nanoparticles. In medical fields, these composites are used for tissue regeneration, healing of deep wounds, enzyme immobilization, and synthesis of medical devices that could replace cardiovascular and other connective tissues. Various electrical products, including biosensors, biocatalysts, E-papers, display devices, electrical instruments, and optoelectronic devices, are prepared from BC composites with conductive materials. In this review, we compiled various synthetic approaches for BC composite synthesis, classes of BC composites, and applications of BC composites. This study will increase interest in BC composites and the development of new ideas in this field.     

Artificial intelligence and machine learning for medical imaging: A technology review

Artificial intelligence (AI) has recently become a very popular buzzword, as a consequence of disruptive technical advances and impressive experimental results, notably in the field of image analysis and processing. In medicine, specialties where images are central, like radiology, pathology or oncology, have seized the opportunity and considerable efforts in research and development have been deployed to transfer the potential of AI to clinical applications. With AI becoming a more mainstream tool for typical medical imaging analysis tasks, such as diagnosis, segmentation, or classification, the key for a safe and efficient use of clinical AI applications relies, in part, on informed practitioners. The aim of this review is to present the basic technological pillars of AI, together with the state-of-the-art machine learning methods and their application to medical imaging. In addition, we discuss the new trends and future research directions. This will help the reader to understand how AI methods are now becoming an ubiquitous tool in any medical image analysis workflow and pave the way for the clinical implementation of AI-based solutions.     

Rational engineering and applications of functional bioadhesives in biomedical engineering

For the past decades, several bioadhesives have been developed to replace conventional wound closure medical tools such as sutures, staples, and clips. The bioadhesives are easy to use and can minimize tissue damage. They are designed to provide strong adhesion with stable mechanical support on tissue surfaces. However, this monofunctionality of the bioadhesives hinders their practical applications. In particular, a bioadhesive can lose its intended function under harsh tissue environments or delay tissue regeneration during wound healing. Based on several natural and synthetic biomaterials, functional bioadhesives have been developed to overcome the aforementioned limitations. The functional bioadhesives are designed to have specific characteristics such as antimicrobial, cell infiltrative, stimuli-responsive, electrically conductive, and self-healing to ensure stability under harsh tissue conditions, facilitate tissue regeneration, and effectively monitor biosignals. Herein, we thoroughly review the functional bioadhesives from their fundamental background to recent progress with their practical applications for the enhancement of tissue healing and effective biosignal sensing. Furthermore, the future perspectives on the applications of functional bioadhesives and current challenges in their commercialization are also discussed.     

Conductive polymer-based sensors for biomedical applications

A class of organic polymers, known as conducting polymers (CPs), has become increasingly popular due to its unique electrical and optical properties. Material characteristics of CPs are similar to those of some metals and inorganic semiconductors, while retaining polymer properties such as flexibility, and ease of processing and synthesis, generally associated with conventional polymers. Owing to these characteristics, research efforts in CPs have gained significant traction to produce several types of CPs since its discovery four decades ago. CPs are often categorised into different types based on the type of electric charges (e.g., delocalized pi electrons, ions, or conductive nanomaterials) responsible for conduction. Several CPs are known to interact with biological samples while maintaining good biocompatibility and hence, they qualify as interesting candidates for use in a numerous biological and medical applications. In this paper, we focus on CP-based sensor elements and the state-of-art of CP-based sensing devices that have potential applications as tools in clinical diagnosis and surgical interventions. Representative applications of CP-based sensors (electrochemical biosensor, tactile sensing 'skins', and thermal sensors) are briefly discussed. Finally, some of the key issues related to CP-based sensors are highlighted.     

Glycosidase inhibitors: update and perspectives on practical use

About 40 years have passed since the classical glycosidase inhibitor nojirimycin was discovered from the cultured broth of the Streptomyces species. Since then, over 100 glycosidase inhibitors have been isolated from plants and microorganisms. Modifying or blocking biological processes by specific glycosidase inhibitors has revealed the vital functions of glycosidases in living systems. Because enzyme-catalyzed carbohydrate hydrolysis is a biologically widespread process, glycosidase inhibitors have many potential applications as agrochemicals and therapeutic agents. Glycosidases are involved in the biosynthesis of the oligosaccharide chains and quality control mechanisms in the endoplasmic reticulum of the N-linked glycoproteins. Inhibition of these glycosidases can have profound effects on quality control, maturation, transport, and secretion of glycoproteins and can alter cell-cell or cell-virus recognition processes. This principle is the basis for the potential use of glycosidase inhibitors in viral infection, cancer, and genetic disorders. In this review, the past and current applications of glycosidase inhibitors to agricultural and medical fields and the prospect for new therapeutic applications are reconsidered.     

Rodenticide-humic acid adsorption mechanisms and role of humic acid on their toxicity on human keratinocytes: chromatographic approach to support the biological data

Humic substances are the most important soil components affecting the behaviour and performances of herbicides in the soil-water-organism system. In this paper, a chromatographic approach was used for analysis of anticoagulant rodenticide-humic acid adsorption mechanisms. Using an equilibrium perturbation method, it was clearly shown that: (i) humic acid can be adsorbed on the C18 stationary phase, and (ii) all the rodenticides can be adsorbed on the humic acid adsorbed on the C18 stationary phase. This approach allowed the determination of the adsorption constant values between the anticoagulant rodenticides and humic acid as well as the corresponding thermodynamic data of this adsorption mechanism. The role of humic acid on the toxicity of these rodenticides on human keratinocytes was also clearly described in relation to these physico-chemical data.     

Tight modulation of Escherichia coli bacterial biofilm formation through controlled expression of adhesion factors

Despite the economic and sanitary problems caused by harmful biofilms, biofilms are nonetheless used empirically in industrial environmental and bioremediation processes and may be of potential use in medical settings for interfering with pathogen development. Escherichia coli is one of the bacteria with which biofilm formation has been studied in great detail, and it is especially appreciated for biotechnology applications because of its genetic amenability. Here we describe the development of two new genetic tools enabling the constitutive and inducible expression of any gene or operon of interest at its native locus. In addition to providing valuable tools for complementation and overexpression experiments, these two compact genetic cassettes were used to modulate the biofilm formation capacities of E. coli by taking control of two biofilm-promoting factors, autotransported antigen 43 adhesin and the bscABZC cellulose operon. The modulation of the biofilm formation capacities of E. coli or those of other bacteria capable of being genetically manipulated may be of use both for reducing and for improving the impact of biofilms in a number of industrial and medical applications.     

Phycobiliproteins: Molecular structure,production, applications,and prospects

Phycobiliproteins (PBPs) are the main component of light-harvesting complexes in cyanobacteria and red algae. In addition to their important role in photosynthesis, PBPs have many potential applications in foods, cosmetics, medical diagnosis and treatment of diseases. However, basic researches and technological innovations are urgently needed for exploring those potentials, such as structure and function, their biosynthesis as well as downstream purification. For medical use and application, mechanisms underlying their therapeutic effects must be elucidated. Focusing on these issues, this article gives a critical review on the current status on PBPs, including their structures and functions, preparation processes and applications. In addition, key technical challenges and possible solutions are prospected.     

人羊膜上皮细胞和胚胎干细胞

人胚胎干细胞有着巨大的医学应用前景,但人胚胎干细胞要求的生长条件很高,体外很难模拟其生长的体内环境,因此控制人胚胎干细胞的生长常不理想,而使用鼠胚胎成纤维细胞(MEF)作为滋养层则存在动物源性污染的问题。该文阐述人羊膜上皮细胞(HAEC)的特点及其作为滋养层培养胚胎干细胞的现状,并探讨基因组DNA甲基化修饰在胚胎干细胞分化过程中的作用,为建立更优化的培养系统提供依据。     

Potential of sponges and microalgae for marine biotechnology

Marine organisms can be used to produce several novel products that have applications in new medical technologies, in food and feed ingredients and as biofuels. In this paper two examples are described: the development of marine drugs from sponges and the use of microalgae to produce bulk chemicals and biofuels. Many sponges produce bioactive compounds with important potential applications as medical drugs. Recent developments in metagenomics, in the culturing of associated microorganisms from sponges and in the development of sponge cell-lines have the potential to solve the issue of supply, which is the main limitation for sponge exploitation. For the production of microalgal products at larger scales and the production of biofuels, major technological breakthroughs need to be realized to increase the product yield.     

Development of an electrochemical polypyrrole-based DNA sensor and subsequent studies on the effects of probe and target length on performance

DNA sensors have a wide scope of applications in the present and emerging medical and scientific fields, such as medical diagnostics and forensic investigations. However, much research-to-date on DNA sensor development has focused on short target DNA strands as model genes. In this communication we study the effect of the length of oligonucleotide probe and target strands as a significant step towards real world applications for DNA detection. The sensor technology described uses the conducting polymer polypyrrole as both a sensing element and transducer of sensing events - namely the hybridization of complementary target oligonucleotide to probe oligonucleotide. Detection is performed using electrical impedance spectroscopy. Initially sensor development is performed, wherein we demonstrate an improvement in stability and sensitivity as well as show a reduction in non-specific DNA binding for fabricated sensors, through use of a specific dopant and post-growth treatment. Subsequently, we show that longer target DNA strands display increased response, as do sensors containing longer probe DNA strands. It is suggested that these results are a feature of the increase in negative charges associated with the longer DNA strands. The results of this comparative study are aimed to guide future design of analogous sensors.     

Pathogen and rodenticide exposure in American badgers (Taxidea taxus) in California

Urban and agricultural land use may increase the risk of disease transmission among wildlife, domestic animals, and humans as we share ever-shrinking and fragmented habitat. American badgers (Taxidae taxus), a species of special concern in California, USA, live in proximity to urban development and often share habitat with livestock and small peridomestic mammals. As such, they may be susceptible to pathogens commonly transmitted at this interface and to anticoagulant rodenticides used to control nuisance wildlife on agricultural lands. We evaluated free-ranging badgers in California for exposure to pathogens and anticoagulant rodenticides that pose a risk to wildlife, domestic animals, or public health. We found serologic evidence of badger exposure to Francisella tularensis, Toxoplasma gondii, Anaplasma phagocytophilum, canine distemper virus, and three Bartonella species: B. henselae, B. clarridgeiae, and B. vinsonii subsp. berkhoffii. Badger tissues contained anticoagulant rodenticides brodifacoum and bromadiolone, commonly used to control periurban rodent pests. These data provide a preliminary investigation of pathogen and toxicant exposure in the wild badger population.     

Applications of carbon nanotubes for cancer research

Carbon nanotubes have many unique properties such as high surface area, hollow cavities, and excellent mechanical and electrical properties. Interfacing carbon nanotubes with biological systems could lead to significant applications in various disease diagnoses. Significant progress in interfacing carbon nanotubes with biological materials has been made in key areas such as aqueous solubility, chemical and biological functionalization for biocompatibility and specificity, and electronic sensing of proteins. In addition, the bioconjugated nanotubes combined with the sensitive nanotube-based electronic devices would enable sensitive biosensors toward medical diagnostics. Furthermore, recent findings of improved cell membrane permeability for carbon nanotubes would also expand medical applications to therapeutics using carbon nanotubes as carriers in gene delivery systems. This article reviews the current trends in biological functionalization of carbon nanotubes and their potential applications for breast cancer diagnostics. The article also reports the applications of confocal microscopy for use in understanding the interactions of biological materials such as antibodies on carbon nanotubes that are specific to surface receptors in breast cancer cells. Furthermore, a nanotube-field-effect transistor is demonstrated for electronic sensing of antibodies that are specific to surface receptors in cancer cells.     

Bacterial cellulose-based materials and medical devices: current state and perspectives

Bacterial cellulose (BC) is a unique and promising material for use as implants and scaffolds in tissue engineering. It is composed of a pure cellulose nanofiber mesh spun by bacteria. It is remarkable for its strength and its ability to be engineered structurally and chemically at nano-, micro-, and macroscales. Its high water content and purity make the material biocompatible for multiple medical applications. Its biocompatibility, mechanical strength, chemical and morphologic controllability make it a natural choice for use in the body in biomedical devices with broader application than has yet been utilized. This paper reviews the current state of understanding of bacterial cellulose, known methods for controlling its physical and chemical structure (e.g., porosity, fiber alignment, etc.), biomedical applications for which it is currently being used, or investigated for use, challenges yet to be overcome, and future possibilities for BC.     

The influence of nano MgO and BaSO4 particle size additives on properties of PMMA bone cement

A common technique to aid in implant fixation into surrounding bone is to inject bone cement into the space between the implant and surrounding bone. The most common bone cement material used clinically today is poly(methyl methacrylate), or PMMA. Although promising, there are numerous disadvantages of using PMMA in bone fixation applications which has limited its wide spread use. Specifically, the PMMA polymerization reaction is highly exothermic in situ, thus, damaging surrounding bone tissue while curing. In addition, PMMA by itself is not visible using typical medical imaging techniques (such as X-rays required to assess new bone formation surrounding the implant). Lastly, although PMMA does support new bone growth, studies have highlighted decreased osteoblast (bone forming cell) functions on PMMA compared to other common orthopedic coating materials, such as calcium phosphates and hydroxyapatite. For these reasons, the goal of this study was to begin to investigate novel additives to PMMA which can enhance its cytocompatibility properties with osteoblasts, decrease its exothermic reaction when curing, and increase its radiopacity. Results of this study demonstrated that compared to conventional (or micron) equivalents, PMMA with nanoparticles of MgO and BaSO4 reduced harmful exothermic reactions of PMMA during solidification and increased radiopacity, respectively. Moreover, osteoblast adhesion increased on PMMA with nanoparticles of MgO and BaSO4 compared with PMMA alone. This study, thus, suggests that nanoparticles of MgO and BaSO4 should be further studied for improving properties of PMMA for orthopedic applications.