Search Results (60)

Ultra-high dose-rate (FLASH) irradiation can transiently deplete oxygen and modulate radical-mediated chemistry in irradiated cells. Cellular antioxidants also contribute to mitigating oxidative damage in a manner dependent on linear energy transfer (LET), as suggested by recent experimental studies. In this work, we employed our multi-track Monte Carlo simulation framework (IONLYS-IRT) to investigate how LET influences transient radiation-induced oxygen depletion (ROD) in a cell-like aqueous environment under FLASH irradiation conditions. FLASH exposures were modeled as single, instantaneous pulses of protons with energies from 300 MeV to 150 keV, corresponding to LET values of ~0.3 to 71 keV/μm. Our simulations revealed a marked decline in oxygen depletion with increasing LET, in agreement with experimental observations. For an intracellular O₂ concentration of 30 μM, the oxygen consumption yield, G(–O₂), decreased from ~4.0 molecules/100 eV at low LET (~0.3 keV/μm) to ~1.6 molecules/100 eV at high LET (~71 keV/μm), representing a ~60% reduction. To assess whether ROD depends solely on LET or is also governed by ion track structure, we systematically compared multiple ion species (protons, ⁴He²⁺, ¹⁰B⁵⁺, ¹²C⁶⁺, ¹⁶O⁸⁺, ²⁰Ne¹⁰⁺, ²⁸Si¹⁴⁺, ³²S¹⁶⁺, and ⁴⁰Ar¹⁸⁺) at comparable LET values. At ~70 keV/μm, heavier ions produced significantly higher G(−O₂) values than protons—though still below those at low LET—suggesting that track structure plays a key role beyond LET alone. These findings highlight the dual importance of LET and ion-specific track structure in modulating ROD under FLASH conditions. Notably, enhanced ROD in surrounding normal tissues (low-LET plateau regions) may contribute to radioprotective effects, whereas reduced ROD in tumor tissues (high-LET Bragg peak regions) would be expected to preserve tumoricidal efficacy. Together, these results provide a mechanistic framework for optimizing proton and heavy-ion approaches in FLASH radiotherapy. Full article

We present a novel approach for the synthesis of crystalline zinc oxide (ZnO) nanopowders based on the direct interaction of high-power microwave radiation with a zinc wire in atmospheric air. The process utilizes a localized microwave-induced plasma to rapidly vaporize the metal, followed by oxidation and condensation, resulting in the deposition of ZnO nanostructures on glass substrates. Plasma diagnostics confirmed the generation of a plasma in local thermodynamic equilibrium (LTE), characterized by high electron temperatures. Optical emission spectroscopy highlighted atomic species such as ZnI, ZnII, OI, OII, and NI, as well as molecular species including OH, N₂ and O₂. The spectral fingerprint of N₂ molecules reveals the presence of high energy electrons, while the persistent occurrence of OI and OII emission lines throughout the plasma spectrum reveals that ZnO formation is mainly driven by the continuous dissociation of molecular oxygen. High crystallinity and chemical purity of the synthesized ZnO nanoparticles were confirmed through SEM, TEM, XRD, FTIR, and EDX characterization. The resulting nanorods exhibit a rod-like morphology, with diameters ranging from 12 nm to 63 nm and lengths between 58 nm and 354 nm. This low-cost, high-yield method offers a scalable and efficient route for metal oxide nanomaterial fabrication via direct metal–microwave coupling, providing a promising alternative to conventional physical and chemical synthesis techniques. Full article

Mild traumatic brain injury (mTBI) affects over 40 million people every year. One of its features includes the activation of microglia, the resident immune cells of the brain. Microglia assume different morphological states depending on their level of activation, such as surveilling ramified and activated hypertrophic, ameboid, and rod-like microglia. These states can be distinguished by multiple features, including the shape, span, and branching of microglia. Male Sprague–Dawley rats sustained mTBI using the Closed-Head Impact Model of Engineered Rotational Acceleration (CHIMERA) (3 times, 1.5 J per impact) or sham treatment. Four days after the injury, brains were collected and stained for microglia using the ionized calcium-binding adapter molecule-1 (Iba-1) antibody. Cortical injury sites were identified in a subset of CHIMERA animals. Using the MicrogliaMorphology ImageJ plugin and the MicrogliaMorphologyR package, 27 morphological features were quantified from individual microglia, and k-means clustering was used to classify microglia as ramified, rod-like, ameboid, and hypertrophic states. The CHIMERA injury altered microglia morphology features, which contributed to increased hypertrophic (activated) and decreased ramified (inactive) microglia compared to the sham controls. Combined with the clinically relevant mTBI paradigm and semi-automated/unbiased approach, the current findings may contribute to microglia morphology classification. Full article

This report discusses the impact of nanoparticles on glass-forming systems composed of a liquid crystalline (LC) mixture E7 and paraelectric BaTiO₃ particles ($d\approx 50 \mathrm{n}\mathrm{m}$, globular), tested via broadband dielectric spectroscopy. In the isotropic phase, critical changes in the dielectric constant are shown. They are related to the weakly discontinuous nature of the isotropic–nematic transition. In the nematic phase, two primary relaxation times/processes and DC electric conductivity are considered, down to the glass temperature $T_g$. The prevalence of portrayals via the ‘double exponential’ MYEGA equation and the critical & activated Drozd-Rzoska relation for dynamic properties are shown. For the primary loss curve, critical-like changes of its maximum (peak) are evidenced: ${\epsilon }_{peak}^{″}\propto 1/\left(T-T_g^{*}\right)$ for $T_g<T<\left(T_g+25 \mathrm{K}\right)$, where $T_g^{*}<T_g$ denotes the extrapolated singular temperature. Dielectric constant monitoring revealed the permanent arrangement of rod-like LC molecules by nanoparticles’ endogenic impact in the nematic phase. The heuristic model regarding this unique behavior is presented. It considers a hypothetical link between the glass transition and a hidden near-critical discontinuous phase transition, uniquely avoiding a symmetry change. The uniaxiality of LC molecules enables the detection of critical-like features when approaching the glass transition, hypothetically associated with a specific ‘amorphous’ phase transition. Full article

The EFR3 (Eighty-Five Requiring 3) protein and its homologs are rather poorly understood eukaryotic plasma membrane peripheral proteins. They belong to the armadillo-like family of superhelical proteins. In higher vertebrates two paralog genes, A and B were found, each expressing at least 2–3 protein isoforms. EFR3s are involved in several physiological functions, mostly including phosphatidyl inositide phosphates, e.g., phototransduction (insects), GPCRs, and insulin receptors regulated processes (mammals). Mutations in the EFR3A were linked to several types of human disorders, i.e., neurological, cardiovascular, and several tumors. Structural data on the atomic level indicate the extended superhelical rod-like structure of the first two-thirds of the molecule with a typical armadillo repeat motif (ARM) in the N-terminal part and a triple helical motif in its C-terminal part. EFR3s’ best-known molecular function is anchoring the giant phosphatidylinositol 4-kinase A complex to the plasma membrane crucial for cell signaling, also linked directly to the KRAS mutant oncogenic function. Another function connected to the newly uncovered interaction of EFR3A with flotillin-2 may be the participation of the former in the organization and regulation of the membrane raft domain. This review presents EFR3A as an intriguing subject of future studies. Full article

Self-assembly of amphiphilic molecules is an important phenomenon attracting a broad range of research. In this work, we study the self-assembly of KTOF₄ sphere–rod amphiphilic molecules in mixed water–dioxane solvents. The molecules are of a T-shaped geometry, comprised of a hydrophilic spherical Keggin-type cluster attached by a flexible bridge to the center of a hydrophobic rod-like oligodialkylfluorene (OF), which consists of four OF units. Transmission electron microscopy (TEM) uncovers self-assembled spherical structures of KTOF₄ in dilute solutions. These spheres are filled with smectic-like layers of KTOF₄ separated by layers of the solution. There are two types of layer packings: (i) concentric spheres and (ii) flat layers. The concentric spheres form when the dioxane volume fraction in the solution is 35–50 vol%. The flat layers are formed when the dioxane volume fraction is either below (20 and 30 vol%.) or above (55 and 60 vol%.) the indicated range. The layered structures show no in-plane orientational order and thus resemble thermotropic smectic A liquid crystals and their lyotropic analogs. The layered packings reveal edge and screw dislocations. Evaporation of the solvent produces a bulk birefringent liquid crystal phase with textures resembling the ones of uniaxial nematic liquid crystals. These findings demonstrate that sphere–rod molecules produce a variety of self-assembled structures that are controlled by the solvent properties. Full article

Background: Botulinum neurotoxin is widely regarded as a “wonder medicine” due to its therapeutic efficacy in treating a variety of conditions. While it is traditionally classified as a neurotoxin, it is arguably more appropriate to refer to it as a neuromedicine. All FDA-approved formulations of botulinum neurotoxin are currently administered through intramuscular injections, with no other delivery methods widely used. The primary reasons for this include the following: (a) the extremely high potency of the toxin, (b) the potential for diffusion to adjacent muscles, (c) factors related to the site of administration (e.g., muscle thickness), (d) the large size of the molecule, (e) the impermeability of skin to large protein molecules, and (f) safety concerns. Despite these challenges, there is growing interest in the development of an effective transdermal formulation of botulinum neurotoxin. Refining and standardizing the delivery technology for topical or transdermal use remains an important goal for the future. Methods: The aim of this study was to develop a nanoemulsion-based transdermal formulation capable of delivering active botulinum neurotoxin (BoNT) through human skin. The goal was to demonstrate its efficacy in a mouse model, highlighting the therapeutic effects on both neuromuscular activity and hyperhidrosis. We successfully developed a nanoemulsion-based formulation that facilitates the transdermal delivery of BoNT. The formulation was homogeneous, stable, and efficacious. In a mouse model, we evaluated the neurotoxin’s impact on neuromuscular function using the Digital Abduction Score (DAS) for toe-spread and rota-rod assay to assess motor coordination. Results: The results confirmed the successful paralytic effect of the neuotoxin. The formulation significantly reduced sweating in the hyperhidrosis mouse model, indicating the therapeutic potential for this indication. Beyond the neurotoxin’s paralyzing effect, we also observed the recovery of nerve function, showing that the neurotoxin does not cause permanent damage, further underscoring its safety and efficacy. Conclusions: This formulation is the first of its kind to successfully deliver a large biomolecule like BoNT across the skin and produce a therapeutic effect. The ability to deliver large biomolecules transdermally has the potential to serve as a platform technology for treating a variety of conditions, including neuromuscular disorders, skin conditions, and localized pain management. Full article

The crystal structures of rod-like molecules with nitro-biphenyl or nitro-phenyl end groups and attached n-alkyl units with terminal acid or ester groups are determined by single crystal analysis and their arrangements are compared. The molecules are linked by head-to-tail arrangements and form strings. They point in a single or two different directions and are placed side by side to create the crystal structure. Some of the space groups of the structures can only be determined by a statistical routine because strongly disordered structures prevent the use of extinction methods, since many extinction violations occur for monoclinic and orthorhombic unit cells. An agreement between experimental and calculated X-ray reflection intensities serves as proof of the correctness of the method as well as a test of the existence of an inversion center. The single crystals are grown in solution with ethanol, isopropanol, DMAc, and toluene as solvents. Cocrystals are formed in DMAc solutions by the dissolved acid compounds. The two-molecule asymmetric unit of the acid compound is reduced to a one-molecule asymmetric unit with one DMAc included which forms a hydrogen bond with the acid group of the biphenyl molecule. These changes alter the hydrogen bonding scheme along a string. Some structural similarities as the head-to-tail arrangement in the strings are maintained between the terminal acid and ester compounds despite disordered ester groups in the compounds and the ester molecules themselves at ambient temperature. Full article

Bio-based eco-friendly cellulose nanocrystals (CNCs) gain an increasing interest for diverse applications. We report the results of an investigation of hydrogels spontaneously formed by the self-assembly of carboxylated CNCs in the presence of CaCl₂ using several complementary techniques: rheometry, isothermal titration calorimetry, FTIR-spectroscopy, cryo-electron microscopy, cryo-electron tomography, and polarized optical microscopy. Increasing CaCl₂ concentration was shown to induce a strong increase in the storage modulus of CNC hydrogels accompanied by the growth of CNC aggregates included in the network. Comparison of the rheological data at the same ionic strength provided by NaCl and CaCl₂ shows much higher dynamic moduli in the presence of CaCl₂, which implies that calcium cations not only screen the repulsion between similarly charged nanocrystals favoring their self-assembly, but also crosslink the polyanionic nanocrystals. Crosslinking is endothermic and driven by increasing entropy, which is most likely due to the release of water molecules surrounding the interacting COO⁻ and Ca²⁺ ions. The hydrogels can be easily destroyed by increasing the shear rate because of the alignment of rodlike nanocrystals along the direction of flow and then quickly recover up to 90% of their viscosity in 15 s, when the shear rate is decreased. Full article

Tailoring the morphologies and optical properties of the 2D and hierarchical nanostructures self-assembled by the π-conjugated molecules is both interesting and challenging. Herein, a series of 2D ribbon-like nanostructures with single or multiple H-aggregated perylene bisimides (PBI) monolayer and hierarchical nanostructures (including straw-like, dumbbell-shaped, and rod-like nanostructures) are fabricated by solution self-assembly of three chiral alanine-decorated PBI. The influence of the solvent’s dissolving capacity, the chirality of alanine, and the preparation methods on the morphologies and optical properties of the nanostructures were extensively studied. It was observed that the hierarchical nanostructures are formed by the reorganization of the 2D ribbon-like nanostructures. The size of the 2D ribbon-like nanostructures and the amount of the hierarchical nanostructures increase with the decrease in the solvent’s dissolving capacity. The small chiral alanine moiety is unable to induce chirality in the nanostructures, owing to its low steric hindrance and the dominant strong π-π stacking interaction of the PBI skeleton. A weaker π-π stacking interaction and better H-aggregated arrangement of the PBI skeleton could reduce the low-wavelength fluorescence intensity. The process of heating, cooling, and aging promotes the formation of H-aggregation in the PBI skeleton. The region of spectral overlap of the PBI solutions increases with the decrease in the dissolving capacity of the solvent and the steric hindrance of the chiral alanine. This study supplies a view to tailor the morphologies and optical properties of the nanostructures, which could be used as sensors and photocatalysts. Full article

Drug-resistant Morganella morganii, a rod-shaped, Gram-negative, facultatively anaerobic bacillus belonging to the Enterobacteriaceae family, is a growing worldwide health concern due to its association with high morbidity and mortality rates. Recent advancements in machine learning, particularly Alphafold 2’s protein structure prediction using local physics and pattern recognition, have aided research efforts. This study focuses on the enzymatic activity of aminoglycoside N6′-acetyltransferase (aacA7), a critical transferase enzyme in bacteria that confers resistance to aminoglycosides. AacA7 modifies aminoglycoside molecules by catalyzing the acetylation of their 6′-amino group using acetyl-CoA, rendering antibiotics like kanamycin, neomycin, tobramycin, and amikacin inactive. We propose that Doripenem and OncoglabrinolC can interact with aacA7, potentially modifying its enzymatic activity. Molecular docking analysis of aacA7 with 22 drug targets revealed OncoglabrinolC as the most promising candidate, exhibiting a binding energy of −12.82 kcal/mol. These two top candidates, OncoglabrinolC and Doripenem, were then subjected to 100 ns of molecular dynamic simulations to assess their dynamic conformational features. Furthermore, the PredictSNP consensus classifier was used to predict the impact of mutations on aacA7 protein functionality. The study also investigated the interaction of wild-type and mutant aacA7 proteins with both Doripenem and OncoglabrinolC. These findings provide valuable insights into the binding behavior of OncoglabrinolC and Doripenem as potential lead molecules for repurposing against aacA7, potentially reducing the pathogenicity of Morganella morganii. Full article

Bardet–Biedl syndrome (BBS), one of the most common forms of syndromic inherited retinal diseases (IRDs), is characterized by the combination of retinal degeneration with additional extra-ocular manifestations, including obesity, intellectual disability, kidney disease, polydactyly and other skeletal abnormalities. We observed an Israeli patient with autosomal recessive apparently non-syndromic rod–cone dystrophy (RCD). Extra-ocular findings were limited to epilepsy and dental problems. Genetic analysis with a single molecule molecular inversion probes-based panel that targets the exons and splice sites of 113 genes associated with retinitis pigmentosa and Leber congenital amaurosis revealed a homozygous rare missense variant in the BBS9 gene (c.263C>T;p.(Ser88Leu)). This variant, which affects a highly conserved amino acid, is also located in the last base of Exon 3, and predicted to be splice-altering. An in vitro minigene splice assay demonstrated that this variant leads to the partial aberrant splicing of Exon 3. Therefore, we suggest that this variant is likely hypomorphic. This is in agreement with the relatively mild phenotype observed in the patient. Hence, the findings in our study expand the phenotypic spectrum associated with BBS9 variants and indicate that variants in this gene should be considered not only in BBS patients but also in individuals with non-syndromic IRD or IRD with very mild extra-ocular manifestations. Full article

Coarse-grained molecular dynamic simulations are employed to investigate the spatiotemporal evolution of vesicles (polymersomes) via self-assembly of randomly distributed amphiphilic diblock copolymers PB-PEO (Poly(Butadiene)-b-Poly(Ethylene Oxide)) in water. The vesiculation pathway consists of several intermediate structures, such as spherical/rodlike aggregates, wormlike micelles, lamellae, and cavities. The lamella-to-vesicle transition occurs at a constant aggregation number and is accompanied by a reduction in the solvent-accessible surface area. Simulation predictions are in qualitative agreement with the mechanism of vesicle formation in which the unfavorable hydrophobic interactions between water molecules and polymer segments, along the edge of the lamella, are eliminated at the expense of gaining curvature energy. However, rod–lamella–vesicle transition is accompanied by an increase in copolymer packing density. Hence, the change in the surface area accompanying vesiculation predicted by the simulations is significantly lower than theoretical estimates. Changes in information entropy, quantified by the expectation of the logarithm of the probability distribution function of the segmental stretch parameter s, defined as the difference between the maximum and instantaneous segmental extension, are statistically insignificant along the vesiculation pathway. For rods, lamellae, and polymersomes, s follows a log normal distribution. This is explained based on the configurational dynamics of a single diblock chain in water. Full article

We have designed new chiral smectic mesogens with the -CH₂O group near the chiral center. We synthesized two unique rod-like compounds. We determined the mesomorphic properties of these mesogens and confirmed the phase identification using dielectric spectroscopy. Depending on the length of the oligomethylene spacer (i.e., the number of methylene groups) in the achiral part of the molecules, the studied materials show different phase sequences. Moreover, the temperature ranges of the observed smectic phases are different. It can be seen that as the length of the alkyl chain increases, the liquid crystalline material shows more mesophases. Additionally, its clearing (isotropization) temperature increases. The studied compounds are compared with the structurally similar smectogens previously synthesized. The helical pitch measurements were performed using the selective reflection method. These materials can be useful and effective as chiral components and dopants in smectic mixtures targeted for optoelectronics and photonics. Full article

The viscoelastic behaviors of aqueous solutions of commercially available methyl cellulose (MC) samples with a degree of substitution of 1.8 and a wide range of weight average molar masses (M_w) were investigated over a wide concentration (c) range at some temperatures from −10 to 25 °C. The viscoelastic parameters useful to discuss the structure and dynamics of MC-forming particles in aqueous solutions were precisely determined, such as the zero-shear viscosity (η₀), the steady-state compliance (J_e), the average relaxation time (τ_w), and the activation energy (E*) of τ_w. Because previously obtained scattering and intrinsic viscosity ([η]) data revealed that the MC samples possess a rigid rod-like structure in dilute aqueous solutions over the entire M_w range examined, the viscoelastic data obtained in this study were discussed in detail based on the concept of rigid rod particle suspension rheology. The obtained J_e⁻¹ was proportional to the number density of sample molecules (ν = cN_AM_w⁻¹, where N_A means the Avogadro’s constant) over the ν range examined irrespective of M_w. The reduced relaxation time (4N_Aτ_w(3νJ_e [η]η_mM_w)⁻¹), where η_m means the medium viscosity, was proportional to (νL³)², L; the average particle length depending on M_w for each sample was determined in a previous study; and the reduced specific viscosity (η_spN_AL³(M_w [η])⁻¹), where η_sp means the specific viscosity, was proportional to (νL³)³ in a range of νL³ < 3 × 10². These findings were typical characteristics of the rigid rod suspension rheology. Therefore, the MC samples behave as entangling rigid rod particles in the νL³ range from rheological points of view. A stepwise increase in E* was clearly observed in a c range higher than the [η]⁻¹ value irrespective of M_w. This observation proposes that contact or entanglement formation between particles formed by MC molecules results in an increase in E*. Full article