Crossing of the Cystic Barriers of Toxoplasma gondii by the Fluorescent Coumarin Tetra-Cyclopeptide

FR235222 is a natural tetra-cyclopeptide with a strong inhibition effect on histone deacetylases, effective on mammalian cells as well as on intracellular apicomplexan parasites, such as Toxoplasma gondii, in the tachyzoite and bradyzoite stages. This molecule is characterized by two parts: the zinc-binding group, responsible for the binding to the histone deacetylase, and the cyclic tetrapeptide moiety, which plays a crucial role in cell permeability. Recently, we have shown that the cyclic tetrapeptide coupled with a fluorescent diethyl-amino-coumarin was able to maintain properties of cellular penetration on human cells. Here, we show that this property can be extended to the crossing of the Toxoplasma gondii cystic cell wall and the cell membrane of the parasite in its bradyzoite form, while maintaining a high efficacy as a histone deacetylase inhibitor. The investigation by molecular modeling allows a better understanding of the penetration mechanism.

The Trp-rich Antimicrobial Amphiphiles With Intramolecular Aromatic Interactions for the Treatment of Bacterial Infection

Antibiotic resistance is emerging as a hot issue with the abuse and overuse of antibiotics, and the shortage of effective antimicrobial agents against multidrug resistant bacteria creates a huge problem to treat the threatening nosocomial skin and soft tissue infection. Antimicrobial peptides (AMPs) exhibite enormous potential as one of the most promising candidates of antibiotic to fight against pathogenic infections because of its unique membrane penetration mechanism to kill pathogens, whereas the clinical application of AMPs still faces the challenges of production cost, stability, safety, and design strategy. Herein, a series of Trp-rich peptides was designed following the principle of paired Trp plated at the ith and ith+4 position on the backbone of peptides, based on the template (VKKX)4, where X represents W, A, or L, to study the effect of intramolecular aromatic interactions on the bioactivity of AMPs. Through comparing the antimicrobial performance, hemolysis, cytotoxicity, and stability, VW5 which is equipped with the characters of direct antimicrobial efficacy (GM=1.68μM) and physical destruction of bacterial membrane (SEM and electron microscopy) stood out from the engineering peptides. VW5 also performed well in mice models, which could significantly decrease the bacterial colony (VW5 vs infection group, 12.72±2.26 vs 5.52±2.01×109CFU/abscess), the area of dermo-necrosis (VW5 vs infection group, 0.74±0.29 vs 1.86±0.98mm2) and the inflammation cytokine levels at the abscess site without causing toxicity to the skin. Overall, this study provides a strategy and template to diminish the randomness in the exploration and design of novel peptides.

Mechanical properties of a female reproductive tract of a beetle and implications for penile penetration

Coevolution of male and female genitalia is widespread in animals. Nevertheless, few studies have examined the mechanics of genital interactions during mating. We characterized the mechanical properties of the elongated female genitalia, the spermathecal duct, of the small cassidine beetle, Cassida rubiginosa . The data were compared with the mechanical properties of the elongated male genitalia, the flagellum. We analysed the material distributions of the spermathecal duct using a microscopy technique, established a tensile test setup under a light microscope and conducted tensile tests. Diameter and tensile stiffness gradients were present along the spermathecal duct, but its Young's modulus and material distribution were more or less homogeneous. The results confirmed the hypothesis based on numerical simulations that the spermathecal duct is more rigid than the flagellum. In the study species, the penile penetration force is simply applied to the base of the hyper-elongated flagellum and conveyed along the flagellum to its tip. Considering this simple penetration mechanism, the relatively low flexibility of the spermathecal duct, compared to the flagellum, is likely to be essential for effective penetration of the flagellum.

Experimental study of the mechanism of grouting colloidal nano-silica in over-broken coal mass

The grouting process is an important subject for stability control of unfavourable geology. A multi-parameter grouting monitoring device was designed to monitor pump pressure, inlet density, outlet density, outlet electrical resistance and osmotic pressure. Taking the multi-source information as the indication, this paper presented an experimental study about the process of grouting colloidal nano-silica into over-broken coal mass, which was verified by percolation mechanics theory and numerical simulation simultaneously. The porosity and permeability of the injected sample were 15.34% and 5.45 mD. The results showed that the variation of pump pressure generally presented an obvious three-stage regularity. The time-dependent curves of outlet density and outlet resistance were consistent with that of pump pressure, while the curve of inlet density was opposite to pump pressure. The law of the dominated penetration mechanism was as follows: miscible displacement mechanism in the 1st stage (0-46th minute), Darcy flow in the 2nd stage (46th∼200th minute) and filtration flow in the 3rd stage. This research can guide grouting theory study and design in the over-broken rock mass.

Improved Dermal and Transdermal Delivery of Curcumin with SmartFilms and Nanocrystals

Poor aqueous solubility of active compounds is a major issue in today’s drug delivery. In this study the smartFilm-technology was exploited to improve the dermal penetration efficacy of a poorly soluble active compound (curcumin). Results were compared to the dermal penetration efficacy of curcumin from curcumin bulk suspensions and nanocrystals, respectively. The smartFilms enabled an effective dermal and transdermal penetration of curcumin, whereas curcumin bulk- and nanosuspensions were less efficient when the curcumin content was similar to the curcumin content in the smartFilms. Interestingly, it was found that increasing numbers of curcumin particles within the suspensions increased the passive dermal penetration of curcumin. The effect is caused by an aqueous meniscus that is created between particle and skin if the dispersion medium evaporates. The connecting liquid meniscus causes a local swelling of the stratum corneum and maintains a high local concentration gradient between drug particles and skin. Thus, leading to a high local passive dermal penetration of curcumin. The findings suggest a new dermal penetration mechanism for active compounds from nano-particulate drug delivery systems, which can be the base for the development of topical drug products with improved penetration efficacy in the future.

Study on the Penetration Performance of a 5.8 mm Ceramic Composite Projectile

The penetration ability of a 5.8 mm standard projectile can be improved by inserting a ZrO2 ceramic ball with high hardness, high temperature, and pressure resistance at its head. Thereby, a ceramic composite projectile can be formed. A depth of penetration (DOP) experiment and numerical simulation were conducted under the same condition to study the armor-piercing effectiveness of a standard projectile and ceramic composite projectile on 10 mm Rolled Homogeneous Armor (RHA) and ceramic/Kevlar composite armor, respectively. The results show that both the ceramic composite and standard projectiles penetrated the armor steel target at the same velocity (850 m/s). The perforated areas of the former (φ5 mm & φ2 mm) were 2.32 and 2.16 times larger, respectively, than those of the latter. The residual core masses of these two projectiles (φ5 mm & φ2 mm) were enhanced by 30.45% and 22.23%. Both projectiles penetrated the ceramic/Kevlar composite armor at the same velocity (750 m/s). Compared with the standard projectile, the residual core masses of the ceramic composite one (Ø5 mm & Ø2 mm) were enhanced by 12.4% and 3.6%, respectively. This paper also analyzes the penetration mechanism of the ceramic composite projectile on target plates by calculating its impact pressure. The results show that the ceramic composite projectile outperformed the standard projectile in penetration tests. The research results are instructive in promoting the application of the ZrO2 ceramic composite in an armor-piercing projectile design.

Oblique penetration mechanism of hybrid composite laminates

Hybrid fiber composites are widely used to improve the anti-penetration performance. Carbon/Kevlar hybrid composites are used in aircrafts and safety devices, thanks to the strong toughness of Kevlar fibers and high strength of carbon fibers. In the present work, the contact force of hybrid composites under oblique impact is derived. The viscoelastic constitutive model of Kevlar layer is investigated and the dissipation energies of composites for different high velocity oblique impacts are simulated. The results show that hybrid composites have good bullet-proof performance, the contact forces are fluctuant in short time and the frictional dissipation energy allows us to prevent penetration.