Benzodiazepines in complex biological matrices: Recent updates on pretreatment and detection methods

Benzodiazepines(BDZs)are used in clinics for anxiolysis,anticonvulsants,sedative hypnosis,and muscle relaxation.They have high consumptions worldwide because of their easy availability and potential addiction.They are often used for suicide or criminal practices such as abduction and drug-facilitated sexual assault.The pharmacological effects of using small doses of BDZs and their detections from complex biological matrices are challenging.Efficient pretreatment methods followed by accurate and sensitive detections are necessary.Herein,pretreatment methods for the extraction,enrichment,and preconcentration of BDZs as well as the strategies for their screening,identification,and quantitation developed in the past five years have been reviewed.Moreover,recent advances in various methods are summarized.Characteristics and advantages of each method are encompassed.Future directions of the pretreatment and detection methods for BDZs are also reviewed.

Release Model of Water-soluble Chitosan Nanoparticles for Protein Delivery

[Objective] The experiment aimed to explore release rule of water-soluble chitosan (WSC) in vitro. [Method]The bovine serum albumin(BSA) was taken as a model protein drug and some existing release models such as Kinetics model, Gompertz model, Weibull model, Higuchi model and Logistic model were used to fit the BSA release profile from WSC carriers. [Result] Except Higuchi model and Logistic model, other models could fit BSA release profile better. [Conclusion] Gompertz two-order kinetics model could fit the release of WSC nano-particles better and model parameters had practical physical meaning.

A study of the properties of hydrophobically associating water-soluble polymers used in drilling fluids

Hydrophobically associating water-soluble polymers (HPAP) have been synthesized from acrylamide(AM), acrylate (AA), 2-acrylamido-2-methyl propane sulfonic acid (AMPS) and hydrophobic monomer (AP) in aqueous solution by radical polymerization. New polymer drilling fluids are made up of HPAP, which is used as viscosifiers and encapsulation agents. Properties of this system are reported in this paper. Results indicate that this system has a high value of yield point to plastic viscosity (YP/PV≥0.7), high viscosity at a low-shear rate (LSRV≥30000mPa·s), excellent shear thinning behavior, good solid-carrying behavior, resistance to shear, good thermal stability (as high as 140℃) and salt resistance. The system has excellent behavior in high-density solution of NaCl and in calcium and magnesium rich saline solutions. Hence, HPAP also can be used in saltwater polymer drilling fluids.

Effect of Different Environmental Conditions on Algicidal Effect of Water-soluble Extracts of Chinese Chive

[Objective] The paper was to study the algicidal effect of water-soluble extracts of Chinese chive under different environmental conditions, so as to provide reference for further study and development of new algicidal substances. [Method] The effects of water-soluble extracts of Chinese chive on the growth of Microcystis aeruginosa under different pH, light and aeration conditions were compared and studied. [Result] The growth inhibition rate of water-soluble extracts of Chinese chive on M. aeruginosa was greater than 90% under different pH conditions. With the growth of M. aeruginosa, the culture liquid with different initial pH was finally tended to 9-9.5. The growth inhibition rate of water-soluble extracts of Chinese chive on algae cell increased with the prolongation of culture time within the light intensity range of 1 000-4 000 lx. The inhibition effect of water-soluble extracts of Chinese chive on M. aeruginosa under low light intensity（1 000 lx）was better than that under high light intensity, the best light intensity for growth was not conducive to the exertion of allelopathic effect. Meanwhile, aeration condition was more conducive to the inhibition effect of water-soluble extracts of Chinese chive on the growth of M. aeruginosa. [Conclusion] pH, light and aeration conditions all affected the inhibition effect of water-soluble extracts of Chinese chive treated by high temperature on M. aeruginosa. Understanding the effect of these environmental factors on algicidal effect of allelochemicals could provide reference for further study and development of new algicidal substances.

Effect of thatch on water-soluble phosphorus of pasture soil fertilized with broiler litter

The presence of a thatch layer in established pastures could reduce the contact between broiler litter and soil, thus increasing the potential for surface runoff contamination with litter P. We conducted a laboratory study to evaluate the effect of a thatch layer on the dynamics of water-soluble P in undisturbed cores taken from a pasture. Cores with and without a thatch layer received a surface application of broiler litter (5 thm-2) and were incubated at 25 oC for 56 d. The result showed that on the soil surface the contents of water soluble-P (39 kghm-2) of the cores with the thatch layer was higher than that (20 kghm-2) of the cores without the thatch layer. Therefore on well-established pastures fertilized with broiler litter, the presence of a thatch layer might lead to high concentrations of water-soluble P on the soil surface.

Nanocrystals for enhancement of oral bioavailability of poorly water-soluble drugs

Nanocrystals,a carrier-free colloidal delivery system in nano-sized range,is an interesting approach for poorly soluble drugs.Nanocrystals provide special features including enhancement of saturation solubility,dissolution velocity and adhesiveness to surface/cell membranes.Several strategies are applied for nanocrystals production including precipitation,milling,high pressure homogenization and combination methods such as Nano-Edge^(TM),SmartCrystal and Precipitation-lyophilization-homogenization(PLH)technology.For oral administration,many publications reported useful advantages of nanocrystals to improve in vivo performances i.e.pharmacokinetics,pharmacodynamics,safety and targeted delivery which were discussed in this review.Additionally,transformation of nanocrystals to final formulations and future trends of nanocrystals were also described.

Application of ion chromatography to the determination of water-soluble inorganic and organic ions in atmospheric aerosols

A simple, sensitive and convenient ion chromatography(IC) method was established for the simultaneous determination of twelve water-soluble inorganic anions(F -, Cl -, NO - 2, NO - 3, SO 2- 3, SO 2- 4, PO 3- 4), and fifteen water-soluble organic ions(formate, acetate, MSA, oxalate, malonate, succinate, phthalates, etc.) in atmospheric aerosols. The linear concentrations ranged from 0.005 μg/m 3 to 500 μg/m 3(r = 0.999—0.9999). The relative standard deviation(RSD) were 0.43%—2.00% and the detection limits were from 2.7 ng/m 3 to 88 ng/m 3. The proposed method was successfully applied to the simultaneous determination of those inorganic ions and organic ions in PM 2.5 of Beijing.

On-line Measurement of Water-Soluble Ions in Ambient Particles

Combining the system of rapid collection of ambient particles and ion chromatography, the system of rapid collection of fine particles and ion chromatography （RCFP-IC） was established to automatically analyze on-line the concentrations of water-soluble ions in ambient particles. Here, the general scheme of RCFP-IC is described and its basic performance is tested. The detection limit of RCFP-IC for SO4^2-, NO3^-, NO2^-, Cl^- and F- is below 0.3μg m^-3. The collection efficiency of RCFP-IC increases rapidly with increasing sized particles. For particles larger than 300 nm, the collection efficiency approaches 100%. The precision of RCFP-IC is more than 90% over 28 repetitions. The response of RCFP-IC is very sensitive and no obvious cross-pollution is found during measurement. A comparison of RCFP-IC with an integrated filter measurement indicates that the measurement of RCFP-IC is comparable in both laboratory experiments and field observations. The results of the field experiment prove that RCFP-IC is an effective on-line monitoring system and is helpful in source apportionment and pollution episode monitoring.

Adverse effects of metal exposure on chemotaxis towards water-soluble attractants regulated mainly by ASE sensory neuron in nematode Caenorhabditis elegans

Chemotaxis to water-soluble attractants is mainly controlled by ASE sensory neuron whose specification is regulated by che-1 in Caenorhabditis elegans. Our data suggested that exposure to high concentrations of metals, such as Pb, Cu, Ag, and Cr, would result in severe defects of chemotaxis to water-soluble attractants of NaCl, cAMP, and biotin. Moreover, the morphology of ASE neuron structures as observed by relative fluorescent intensities and relative size of fluorescent puncta of cell bodies, relative lengths of sensory endings in ASE neurons, and the expression patterns of che-1 were obviously altered in metal exposed animals when they meanwhile exhibited obvious chemotaxis defects to water-soluble attractants. In addition, the dendrite morphology could be noticeably changed in animals exposed to 150 μmol/L of Pb, Cu, and Ag. Furthermore, we observed significant decreases of chemotaxis to water-soluble attractants in Pb exposed che-1 mutant at concentrations more than 2.5 μmol/L, and in Cu, Ag, and Cr exposed che-1 mutant at concentrations more than 50 μmol/L. Therefore, impairment of the ASE neuron structures and functions may largely contribute to the appearance of chemotaxis defects to water-soluble attractants in metal exposed nematodes.

Preparation of Ultrafine Water-soluble Polymers Nanofiber Mats via Electrospinning

A series of water-soluble polymers such as poly（ethylene oxide）（PEO）, polyacrylamide（PAM） and poly（vinyl pyrrilidone）（PVP） was successfully prepared via the electrospinning of their aqueous solutions without the use of a surfactant. The effects of solution properties on the electrospinning of PEO, PAM and PVP solutions were investigated. The viscosity of the solution, charge density carried by the jet, and the surface tension of the solution are the key factors that influence the morphology and diameter size of the fibers. The viscosity of the solution was measured on a modular compact rheometer. The morphology and the diameter size distribution of the fibers were observed under an environmental scanning electron microscope（ESEM）. The results show that the diameters of the nanofibers electro spun from the solutions of these water soluble polymers were uniform and less than 300 nm.

Effect of kaolin on tensile strength and humidity resistance of a water-soluble potassium carbonate sand core

Water soluble cores(WSCs) have been widely applied in manufacture of complex metal components with hollow configurations or internal channels. However, the WSCs without any additons have low tensile strength and low humidity resistance. The purpose of this study is to prepare a water-soluble potassium carbonate sand core with addition of kaolin by the hot-temping method. The effects of kaolin on tensile strength, humidity resistance, fracture mechanism, as well as the gas evolution and collapsibility of WSCs were investigated. Results show that both the crystal morphology and the fracture mechanism of the inorganic salt are changed under the participation of kaolin, contributing to the increase of the tensile strength and the humidity resistance of the core. With the addition of 3wt.% kaolin, the tensile strength could be increased by a factor of 2, reached 1.50 MPa and the hygroscopic rate could be decreased by 14%, achieved 0.559%(after stored for 8 h), respectively. As the addition amount of kaolin increases from 0wt.% to 3wt.%, the main fracture mechanism changes from a adhesive to a cohesive fracture mechanism. The water-soluble potassium carbonate core obtained has the low gas evolution and excellent collapsibility, which makes it suitable for casting low melting metal with complex cavities and crooked channels.

Study on Dyeing Performance of Cationic Water-soluble Sulphur Black on Silk

A novel polyquaternaryammonium cationic sulphur black dye was synthesized and its dyeing behavior on silk was studied. The dye exhibited excellent dyeing fixation of up to 98.2 %, as well as excellent dyeing fastness on silk.

Phosphoryl choline-grafted water-soluble carbon nanotube

Water-soluble property is the precondition of biomedical evaluation and application of carbon nanotube （CNT）. Novel water- soluble CNT was synthesized in this letter by grafting phosphoryl choline （PC） onto multi-wall CNTs. Utilizing FTIR, XPS, TGA and TEM, the title CNTs were characterized and it was found that the target products could facilely dissolve in water. 2007 Tao Zhang. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

Effects of Different Analog Water-soluble Fertilizers on Flue-cured Tobacco

This study aimed to investigate the application effect of analog water-soluble fertilizer as an alternative of flue-cured tobacco-specific topdressing fertilizer. A field experiment was conducted, and the dry matter accumulation, intrinsic chemical composition, smoking quality and economic benefit of flue-cured tobacco were compared between analog water-soluble fertilizer and conventional fertilizer, The results showed compared with conventional fertilizer, analog water-soluble fertilizer increased the dry matter accumulation in flue-cured tobacco by 4.90%-16.70%, increased the yield of flue-cured tobacco by 6%-15%, and increased the output of flue-cured tobacco by 5%-14%. In terms of chemical composition, the flue-cured tobacco applied with analog water-soluble fertilizer was better than that applied with conventional fertilizer, except the nicotine content in the upper leaves, the potassium content in the middle leaves and the reducing sugar content. The smoking quality of both the upper and middle leaves of flue-cured tobacco in the analog water-soluble fertilizer treatment groups was better than that in the conventional fertilizer treatment group. In short, analog water-soluble fertilizer was better than conventional fertilizer, with advantages of lower cost （reduced by 381.60 yuan/hm2）, lower application amount （reduced by 165 kg/hm2） and higher utilization efficiency.

The FDA Mandate to Reassess Benzodiazepines: Alprazolam Induces a Positive Conditioned Place-Preference in Male Rats

On September 23, 2020, in order “To address the serious risks of abuse, addiction, physical dependence, and withdrawal reactions, the U.S. Food and Drug Administration (FDA) is requiring the Boxed Warning be updated for all benzodiazepine medicines”. With this announcement, the FDA proclaimed that much more needs to be known about the initiation, continuation, and discontinuation of these widely-used drugs. Unfortunately, relevant information is lacking, since for many years, there has been a notable sparsity in the funding and conduct of basic and clinical research on these drugs. In order to begin to fill the void, it is valuable to (re)examine animal models. We here describe a model of conditioned place-preference (CPP) for rats and for the first time, to our knowledge, show that the representative benzodiazepine alprazolam induces positive place-preference in male rats.

Preparation of fructone catalyzed by water-soluble Brφnsted acid ionic liquids

Fructone （2-methyl-2-ethylacetoacetate-1, 3-dioxolane）, a flavouring material, has been synthesized from ethyl acetoacetate and glycol using five water-soluble Brφnsted acid ionic liquids as catalysts for the first time. The used Brφnsted acid ionic liquids include [Hmim]Tfa, [Hmim]Tsa, [Hmim]BF4, [Bmim]HSO4, [Bmim]H2P04, and [Hmim]BF4 showed the highest catalytic activity for the preparation of fructone. After reaction, the product could be isolated from the reaction system automatically, and the ionic liquid could be directly reused without dehydration.

Structure, properties and application to water-soluble coatings of complex antimicrobial agent Ag-carboxymethyl chitosan-thiabendazole

The structure, properties and application to water-soluble coatings of a new complex antimicrobial agent Ag-carboxylmethyl citosan-thiabendazole （Ag-CMCTS-TBZ） prepared from different materiel ratios were reported. The silver ions were preferably coordinated with the free-NH2 groups and the -OH groups of secondary alcohol and carboxyl in CMCTS. TBZ preferably bonded to carboxyl group in CMCTS by electrostatic force and hydrogen bonding. Increase in silver ions content in the complex agent improved to some limited extent the antibacterial activity, but enhanced coloring and cost of the complex agent. Increase in TBZ content resulted in increase of antifungal activity, but decrease of water solubility of the complex agent. The antimicrobial MICs of the complex agent to Esherichia coil, Staphylococcus aureus, Candida albicans, Aspergillus niger, Mucor sp. were 20 -80, 15 -60, 20 - 55, 40 - 250, and 400 - 1700 mg/kg, respectively. Addition of 0.1% of this complex agent to acrylic emulsion paint made the paint without substantial change in color, luster, viscosity, odor or pH value, but with an excellent and chronically persisting broad-spectra antimicrobial activity.

Inquiry of Water-Soluble Polysaccharide Extraction Conditions from Grapefruit Skin

Water-soluble polysaccharide was isolated from grapefruit with the method of water-dissolving and ethanol-precipitating. By single factor test and orthogonal experimental method, the extraction conditions of the water-soluble polysaccharide were investigated, which contained liquid-solid ratio, temperature, time and pH. The results showed that pH was the most important factor of polysaccharide extraction, followed by temperature. The optimized extraction technology conditions were obtained. The liquid-solid ratio was 1:40, temperature was 90?C, time was 2.0 h, and pH was 2. The highest extraction rate of crude polysaccharide was 8.30%.

Alginate encapsulated mesoporous silica nanospheres as a sustained drug delivery system for the poorly water-soluble drug indomethacin

We applied a combination of inorganic mesoporous silica material,frequently used as drug carriers,and a natural organic polymer alginate(ALG),to establish a sustained drug delivery system for the poorly water-soluble drug Indomethacin(IND).Mesoporous silica nanospheres(MSNs)were synthesized using an organic template method and then functionalized with aminopropyl groups through postsynthesis.After drug loading into the pores of aninopropyl functionalized MSNs(AP-MSNs),IND loaded AP-MSNs(IND-AP-MSNs)were encapsulated by ALG through the ionic interaction.The effects of surface chemical groups and ALG layer on IND release were systematically studied using scanning electron microscopy(SEM),transmission electron microscopy(TEM),nitrogen adsorption,zetapotential analysis and TGA analysis.The surface structure and surface charge changes of the ALG encapsulated AP-MSNs(ALG-AP-MSNs)were also investigated.The results showed that sustained release of IND from the designed drug delivery system was mainly due to the blockage effect from the coated ALG.We believe that this combination will help designing oral sustained drug delivery systems for poorly water-soluble drugs.

Synthesis and Cytotoxic Activity of Novel Water-soluble Prodrugs of Combretastatin A-4

Novel water-soluble prodrugs of combretastatin A-4 （5-8） were synthesized and evaluated for their in vitro cytotoxicity against lung carcinoma A549. Compound 5, bearing phosphoryl choline （PC） moiety, showed 90% inhibition at 32 ktg/mL concentration after 24 h. The findings showed the PC derivative would be a promising candidate for the development of new water-soluble prodrug of cytotoxic combretastatin A-4,