Search Results (3,716)

Antimicrobial peptides are potential alternatives to conventional antibiotics, primarily due to broad-spectrum activity and low propensity for inducing bacterial resistance. However, their clinical translation faces challenges, including peptide stability and potential mammalian cell toxicity. This study centers on DGL13K, an all D-amino acid peptide, which overcomes proteolytic susceptibility and demonstrates notable stability and broad-spectrum bactericidal activity without inducing de novo bacterial resistance. This work aimed to enhance the therapeutic properties of DGL13K by using targeted modifications to increase antimicrobial potency and decrease toxicity, as determined by hemolysis. DGL13K derivatives were synthesized and tested, involving amino acid substitutions, stereochemical alterations, and N-terminal functionalization with polyethylene glycol (PEG) or myristoylate. While some modifications altered bacterial specificity and reduced hemolytic activity, none of the tested alterations resulted in a substantial overall improvement compared to the parent DGL13K sequence. Furthermore, the antibacterial efficacy of DGL13K and its variants was significantly inhibited in the presence of 50% serum, suggesting limitations for systemic applications. The findings suggest that the DGL13K sequence, derived from an evolutionarily selected protein, is already highly optimized. Given its stability, broad-spectrum efficacy, in vivo activity, low resistance profile, and high safety margin, DGL13K is a promising therapeutic candidate for topical/localized infections. Full article

To develop new hybrid anticancer agents, 3,5-bis(benzylidene)-4-piperidone scaffolds (compounds 1–6) were functionalized with (1R)-borneoyl chloroacetate (8) or (1S)-camphorsulfonyl chloride (10). Covalent attachment of the camphorsulfonyl moiety via N-sulfonylation yielded hybrid molecules (16–21) that exhibited selective cytotoxic and cytostatic activity against cancer cells, with submicromolar IC₅₀ values. In silico ADME analysis indicated that these camphorsulfonyl-conjugated piperidones have improved drug-like properties (enhanced absorption, metabolism, and bioavailability) compared to curcumin. The most potent analogs were halogen-substituted and trimethoxy-substituted analogs, which showed the strongest tumor cell growth inhibition while sparing normal cells. Overall, this terpene-functionalization strategy addresses curcumin’s pharmacokinetic limitations and improves its anticancer profile. These hybrid molecules hold promise as potential anticancer agents. Full article

The antigenic relationship between Eurasian avian-like H1N1 swine influenza viruses (EA H1N1) and human pandemic 2009 H1N1 viruses (2009/H1N1) remains a critical question for influenza surveillance and vaccine efficacy. This study systematically investigated the antigenic differences between strains A/swine/Tianjin/312/2016 (TJ312, EA H1N1) and A/Guangdong-Maonan/SWL1536/2019 (GD1536, 2009/H1N1). Cross-hemagglutination inhibition (HI) assays revealed a significant antigenic disparity, with a 16-fold reduction in heterologous versus homologous HI titers. Comparative sequence analysis identified 22 amino acid differences across the five major antigenic sites (Sa, Sb, Ca1, Ca2, and Cb) of the HA1 subunit. Using reverse genetics, a panel of mutant viruses was generated. This study revealed that a single histidine (H)-to-asparagine (N) substitution at residue 128 (H3 numbering) in the Sa antigenic site acts as a primary determinant of antigenic variation, sufficient to cause a four-fold change in HI titers and a measurable drift in antigenic distance. Structural modeling via AlphaFold3 and PyMOL software suggests that the H128N mutation may alter the local conformation of the antigenic site. It is plausible that H at position 128 could exert electrostatic repulsion with adjacent amino acids, whereas N might facilitate hydrogen bond formation with neighboring residues. These interactions would potentially lead to structural changes in the antigenic site. Our findings confirm that residue 128 is a critical molecular marker for the antigenic differentiation of EA H1N1 and 2009/H1N1 viruses. The study underscores the necessity of monitoring specific HA mutations that could reduce cross-reactivity and provides valuable insights for refining vaccine strain selection and pandemic preparedness strategies. Full article

A novel Ag(I) coordination polymer, [Ag₂(bipy)(btca)]_n, (SCP 1) was synthesized using 4,4′-bipyridyl (bipy) and 1,2,4,5-benzene-tetracarboxylic acid (H₄BTC). Characterization by FT-IR, ¹H/¹³C NMR, and single-crystal X-ray diffraction confirmed its 3D network structure. The structure of SCP 1 consists of two chains arranged in …ABAB… fashion. Chain A is one-dimensional, containing [Ag(4,4′-bipy)]_n chain, while chain B is free, containing uncoordinated 1,2,4,5-benzene tetracarboxylate and water molecules. The stacking and argentophilic interactions extend the chain A of [Ag(4,4′-bipy)]_n into a two-dimensional layer. In contrast, chain B of uncoordinated 1,2,4,5-benzene tetracarboxylate and water molecules form a 1-D chain through extensive hydrogen bonds between water molecules and BTC ions and between water molecules themselves. Chains A and B are connected through extensive hydrogen bonds, generating a three-dimensional network structure. This Silver I supramolecular coordination polymer (SCP 1) demonstrated high catalytic activity as a recyclable heterogeneous catalyst for the synthesis of 5-substituted 1H-tetrazoles via [3+2] cycloaddition of NaN₃ and terminal nitriles under solvent-free conditions in a Q-tube pressure reactor (yields: 94–99%). A mechanistic proposal involving cooperative Lewis acidic Ag(I) sites and Brønsted acidic -COOH groups facilitates the cycloaddition and protonation steps. SCP 1 catalyst exhibits reusability up to 4 cycles without significant loss of activity. The structural stability of the SCP 1 catalyst was assessed based on PXRD and FTIR analyses of the catalyst after usage, confirming its integrity during the recycling process. Full article

The ability of common carp to withstand both short-term and long-term oxygen deprivation has been well documented; however, the potential genetic mechanisms behind common carp’s hypoxia response remain unclear. Therefore, to understand the possible genetic foundation of their response to hypoxia, comparative genomic analyses were conducted among six common carp varieties: Color, Songpu, European, Yellow, Mirror, and Hebao common carps. We identified 118 single-copy orthologous positively selected genes (PSGs) (dN/dS > 1) in all common carps under study, with GO functions directly related to the cellular responses to hypoxia in Color and European common carp PSGs, such as oxygen transport activity, oxygen binding activity, respiratory burst activity, and superoxide anion production. The Bayes Empirical Bayes (BEB) technique identified possible amino acid substitutions in mitochondrial and hypoxic genes under positive selection. Exonic and intronic structural variations (SVs) were discovered in the CYGB2 hypoxia-related gene of Color and European common carps, as well as in several mitochondrial genes, including MRPL20, MRPL32, NSUN3, GUF1, TMEM17B, PDE12, ACAD6, and COX10 of Color, European, Songpu, Yellow, and Hebao common carps. Moreover, Color common carp and Songpu common carp were found to share the greatest percentage of collinear genes (49.8%), with seven Songpu common carp chromosomes (chr A2, chr A9, chr A13, chr B13, chr B15, chr B2, and chr B12) showing distinct translocation events with the corresponding chromosomes of Color common carp. Additionally, we found 570 translocation sites that contained 3572 translocation-related genes in Color common carp, some of which are directly relevant to mitochondrial and hypoxic GO functions and KEGG pathways. Our results offer strong genome-wide evidence of the possible evolutionary response of Cyprinus carpio to hypoxia, providing important insights into the potential molecular mechanisms that explain their survival in hypoxic environments and guiding future research into carp hypoxia tolerance. Full article

Wild carnivores are increasingly recognized as hosts or reservoirs of canine parvovirus (CPV), a major pathogen of dogs. To investigate CPV circulation in Central Europe, we examined 221 red foxes (Vulpes vulpes) and 53 European badgers (Meles meles) from seven Slovakian regions. Small intestines (n = 86), rectal swabs (n = 123), and feces (n = 65) were tested by real-time PCR, and positives were sequenced for the VP2 gene. Virus isolation was performed on MDCK cells. CPV was detected in 10.9% (30/274) of samples, with a prevalence of 10.9% (24/221) in foxes and 11.3% (6/53) in badgers. Phylogenetic analysis revealed co-circulation of CPV-2a, CPV-2b, and CPV-2c, with CPV-2b being prevalent (20/30, 66.7%) and CPV-2c detected in a single sample (1/30, 3.3%). CPV-2a/2b isolates clustered with European strains, while CPV-2c grouped within the “Asian” lineage. Several sequences carried “Asian-like” signatures (5G, 267Y, 324I, 370R), suggesting transboundary introduction and spillover into wildlife. Two infrequent substitutions were identified: S552I in CPV-2b and I447M in CPV-2a. Viable virus was isolated from all positives, with characteristic CPV-cytopathic effects. This study provides the first molecular and virological evidence of CPV in Central European wildlife. Our findings expand our understanding of CPV diversity in Europe, and underscore wildlife as an integral component of European ecology. Full article

Aromatic ring systems appear ubiquitously in active pharmaceutical substances, such as FDA-approved histone deacetylase inhibitors. However, these rings reduce the water solubility of the molecules, which is a disadvantage during application. To address this problem, azaborine rings may be substituted for conventional aromatic ring systems. These are obtained by replacing two adjacent carbon atoms with boron and nitrogen. Incorporating B–N analogs in place of aromatic rings not only enhances structural diversity but also provides a strategy to navigate around patent-protected scaffolds. We synthesized azaborines, which are isosteric to naphthalene and indole, and utilized them as capping units for HDAC inhibitors. These molecules were attached to various aliphatic and aromatic linkers with different zinc-binding units, used in established active compounds. Nearly half of the twenty-four molecules tested exhibited inhibitory activity against at least one of the enzymes HDAC1, HDAC4, or HDAC8, with three compounds displaying IC₅₀ values in the nanomolar range. We have therefore demonstrated that azaborine building blocks can be successfully incorporated into HDACis, resulting in a highly active profile. Consequently, it should be feasible to develop active substances containing azaborine rings against other targets. Full article

Object detection has a vital impact on the analysis and interpretation of visual scenes. It is widely utilized in various fields, including healthcare, autonomous driving, and vehicle surveillance. However, complex scenes containing small, occluded, and multiscale objects present significant difficulties for object detection. This paper introduces a lightweight object detection algorithm, utilizing YOLOv8n as the baseline model, to address these problems. Our method focuses on four steps. Firstly, we add a layer for small object detection to enhance the feature expression capability of small objects. Secondly, to handle complex forms and appearances, we employ the C2f-DCNv2 module. This module integrates advanced DCNv2 (Deformable Convolutional Networks v2) by substituting the final C2f module in the backbone. Thirdly, we designed the CBAM, a lightweight attention module. We integrate it into the neck section to address missed detections. Finally, we use Ghost Convolution (GhostConv) as a light convolutional layer. This alternates with ordinary convolution in the neck. It ensures good detection performance while decreasing the number of parameters. Experimental performance on the PASCAL VOC dataset demonstrates that our approach lowers the number of model parameters by approximately 9.37%. The mAP@0.5:0.95 increased by 0.9%, recall (R) increased by 0.8%, mAP@0.5 increased by 0.3%, and precision (P) increased by 0.1% compared to the baseline model. To better evaluate the model’s generalization performance in real-world driving scenarios, we conducted additional experiments using the KITTI dataset. Compared to the baseline model, our approach yielded a 0.8% improvement in mAP@0.5 and 1.3% in mAP@0.5:0.95. This result indicates strong performance in more dynamic and challenging conditions. Full article

In this article, we present density functional theory (DFT) calculations for $Z{n}_{(1-x)}{M}_{x}O$, where M represents one of the following substitutional metallic impurities: Ga, Cd, Cu, Pd, Ag, In, or Sn. Our study is based on the wurtzite structure of pristine ZnO. We employ the Quantum Espresso package, using a fully unconstrained implementation of the generalized gradient approximation (GGA) with an additional U correction for exchange and correlation effects. We analyze the density of states, energy gaps, and absorption spectra for these doped systems, considering the limitations of a finite-size cell approximation. Rather than focusing on precise numerical values, we highlight the following two key aspects: the location of impurity-induced electronic states and the overall trends in optical properties across the eight systems, including pristine ZnO. Our results indicate that certain dopants introduce electronic levels within the band gap, which enhance optical absorption in the visible, near-infrared, and near-ultraviolet regions. For instance, Sn-doped ZnO shows a pronounced absorption peak at ∼2.5 eV, which is in the middle of the visible spectrum. In the case of Ag and Pd impurities, they lead to increased electromagnetic radiation absorption at the near ultra-violet spectrum. This represents a promising performance for efficient solar radiation absorption, both at the Earth’s surface and in outer space. Furthermore, Ga- and In-doped ZnO present bandgaps of ∼0.9 eV, promising an interesting performance in the near infrared region. These findings suggest potential applications in solar energy harvesting and selective sensors. Full article

CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated protein) nucleases enable precise genome editing, but off-target cleavage remains a critical challenge. Here, we report the development of MAD7_HF, a high-fidelity variant of the MAD7 nuclease engineered through a bacterial screening system leveraging the DNA gyrase-targeting toxic gene ccdB. This system couples survival to efficient on-target cleavage and minimal off-target activity, mimicking the transient action required for high-precision editing. Through iterative selection and sequencing validation, we identified MAD7_HF, harboring three substitutions (R187C, S350T, K1019N) that enhanced discrimination between on- and off-target sites. In Escherichia coli assays, MAD7_HF exhibited a >20-fold reduction in off-target cleavage across multiple mismatch contexts while maintaining on-target efficiency comparable to wild-type MAD7. Structural modeling revealed that these mutations stabilize the guide RNA-DNA hybrid at on-target sites and weaken interactions with mismatched sequences. This work establishes a high-throughput bacterial screening strategy that allows the identification of Cas12a variants with improved specificity at a given target site, providing a useful framework for future efforts to develop precision genome-editing tools. Full article

We systematically investigated the parent anthracene (abbreviated as en-1, C₁₄H₁₀) and three N,N′-disubstituted derivatives: the 1,5-diethylanthracene (en-2, C₁₈H₁₈), the 1,5-divinylanthracene (en-3, C₁₈H₁₄), and the 1,5-diphenylanthracene (en-4, C₂₆H₁₈), using a rigorous density functional theory (DFT)/time-dependent density functional theory (TD-DFT) approach. Following full geometric optimization and frequency validation (no imaginary frequencies), frontier molecular orbital analysis revealed an inverse correlation between conjugation extent and the HOMO-LUMO energy gap. Electrostatic potential (ESP) analysis further indicated a progressive increase in surface potential variance upon substitution, reflecting charge redistribution. TD-DFT calculations yielded vertical excitation wavelengths of 438 nm, 441 nm, 464 nm, and 496 nm for en-1, en-2, en-3, and en-4, respectively. Complementary color theory predicts visual colors of yellow, yellow, red, and orange for these compounds based on their absorption characteristics. This work establishes a closed-loop “computation-spectra-color” model for anthracene-based dyes, providing a transferable design paradigm for novel functional pigments with high molar extinction coefficients. Full article

In this study, low-viscosity (<5 mm²·s⁻¹, fits European Biodiesel Standard-EN 14214) quaternary microemulsification fuels were developed and tested in a CRDI diesel engine to evaluate their effects on engine performance, injection, combustion, and emission characteristics. The fuels were formulated using 50% petro-diesel, 30% waste frying oil (without converting biodiesel), and a combination of 10% n-butanol with either 10% methanol or 10% ethanol. Engine tests were conducted at constant speed of 2000 rpm and five different engine loads. The results indicated that both microemulsified fuels exhibited increased brake specific fuel consumption by about 20% and brake specific energy consumption by around 8% compared to petro-diesel, while thermal efficiency decreased by about 8%. Injection timing for both pilot and main injections occurred earlier with the emulsification fuels, and higher injection amount and injection rate values were observed at all loads. As engine load increased, the peak cylinder pressures of the emulsified fuels surpassed those of petro-diesel, although the crank angles at which these peak values were attained were similar. The combustion duration was shorter for both quaternary fuels, with similar maximum pressure rise rates to petro-diesel. Emulsification fuels caused higher exhaust emissions (especially THC) and this difference increased with increasing load. When comparing two formulations, the methanol-containing fuel demonstrated slightly better results than the ethanol-containing blend. These findings suggest that microemulsified fuels containing bio-alcohols and waste frying oil can be sustainable fuel alternatives for partial petro-diesel substitution if the injection settings are adapted in accordance with the properties of these fuels. Full article

A series of functionalized calix[4]arenes were prepared that contain mono- and bis-(alkoxy)imidazolium groups that are linked to the lower rim of a t-butylcalix[4]arene framework. These molecules have potential as anion-complexation reagents and as precursors to N-heterocyclic carbene complexes that are attached to a calixarene framework. They were prepared by the preliminary reaction α,ω-dibromoalkanes with the parent t-butylcalix[4]arene to give bis-ω-bromoalkoxy groups that are connected to the calix[4]arene framework in the 25- and 27-positions. The reaction of the bis-substituted calixarenes with TiCl₄ led to the removal of one bromoalkoxy group to give mono-substituted derivatives. Both the mono- and bis-functionalized calixarenes were reacted with N-substituted imidazoles to give a series of mono- or bis-imidazolium salts with the imidazolium group tethered to the calix[4]arene via O–(CH₂)_n– linkages (n = 2, 4, or 6). Unexpected bis-calix[4]arene products, in which the calixarenes are linked together via bridging organic groups, were obtained in some of these reactions. One bridge consists of two calixarenes linked together via two –C₂H₄– groups while the other had a –O–C₄H₈–imidazolium-C₄H₈–O– linker tethering the two calix[4]arenes together. Both these species were characterized by single crystal X-ray diffraction studies. The structures both had significant disorder but, nevertheless, the data do establish their structures. That the imidazolium-substituted calix[4]arene cations are precursors to N-heterocyclic carbene complexes of nickel was demonstrated by the reaction of a mono-imidazolium-substituted calix[4]arene with nickelocene to give the fully characterized N-heterocyclic carbene nickel complex linked to the calix[4]arene group. Full article

The removal of nickel from industrial wastewater necessitates efficient sorbent materials. This study investigates nanostructured potassium- and sodium-substituted aluminosilicate-based nanocomposites for this application. Materials were synthesized and characterized using SEM-EDS, XPS, XRD, FTIR, low temperature N₂ adsorption–desorption and Ni²⁺ adsorption experiments. SEM and XRD confirmed an X-ray amorphous structure attributable to fine crystallite size. The sodium-substituted material Na₂Al₂Si₂O₈ exhibited the lowest specific surface area (48.3 m²/g) among the tested composites. However, it demonstrated the highest Ni(II) sorption capacity (64.6 mg/g, 1.1 mmol/g) and the most favorable sorption kinetics, as indicated by a Morris-Weber coefficient of 0.067 ± 0.008 mmol/(g·min¹/²). Potassium-substituted analogs with higher Si/Al ratios showed increased surface area but reduced capacity. Analysis by XPS and SEM-EDS established that Ni(II) uptake occurs through a complex mechanism, involving ion exchange, surface complexation, and chemisorption resulting in the formation of new nickel-containing composite surface phases. The results indicate that optimal sorption performance for Ni(II) is achieved with sodium-based aluminosilicates at a low Si/Al ratio (Si/Al = 1). The functional characteristics of Na₂Al₂Si₂O₈ compare favorably with other silicate-based sorbents, suggesting its potential utility for wastewater treatment. Further investigation is needed to elucidate the precise local coordination environment of the adsorbed nickel. Full article

A straightforward synthetic method is advanced to produce hard-to-reach polycyclic compounds belonging to the [1,2,5]oxadiazolo[3,4-b]quinoxaline ring system. This approach draws on a combination of the nucleophilic aromatic substitution of hydrogen (S_N^H) and Scholl cross-coupling reactions, followed by reduction of the 1,2,5-oxadiazole fragment under mild reaction conditions. All compounds were obtained for the first time with moderate to excellent yields. Electrochemical and photophysical measurements show that the synthesized compounds may serve as narrow-band n-type organic semiconductors, with energy levels ranging from 2.00 to 2.28 eV, comparable to those of the best commercially available electronic semiconductors. Full article