Search Results (48,790)

The cell membrane serves as the first line of defense against adverse environmental factors and is first to adapt to changing conditions. Cell membranes in both coral and its symbionts, which use different membrane adaptation strategies, have to acclimatize to various abiotic stressors. As our molecular-genetics analysis showed, colonies of Junceella fragilis were associated with dinoflagellates Cladocopium thermophilum, Gerakladium endoclionum and Breviolum minutum. We analyzed the phospholipid (PL) molecular species of the wild and cultivated Junceella fragilis and their dinoflagellates (phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidylinositol (PI), ceramideaminoethylphosphonate (CAEP)), as well as thylakoid membrane lipids of dinoflagellates (glycolipids and betaine lipids). When comparing wild and cultivated J. fragilis colonies, there were no significant differences in thylakoid lipids, but there were differences in host membrane phospholipids, namely in PC, PE and PS. Thus, the profile of PL molecular species of the membrane is very sensitive to environmental factors, which probably explains the observed differences in the profiles of molecular PL species in this study. Full article

Background: Fascicular turnover flap (FTF) is a donor-sparing option for segmental facial nerve repair. This study compared autologous nerve grafting with proximally based and distally based FTF in a rat facial nerve model. Methods: Adult male Wistar rats were randomized to autograft, proximal FTF, or distal FTF (n = 8 per group). A single additional animal with an untreated defect served as a qualitative histological reference. The prespecified primary endpoint was whisker motion amplitude at week 8; the secondary endpoints were central section histomorphometry (nerve tissue area, µm²) and variability metrics (IQR, SD, and coefficient of variation) as measures of reproducibility. Non-parametric tests (Kruskal–Wallis; Mann–Whitney U) were used; pairwise functional comparisons were Holm-corrected; and effect sizes were expressed as Cliff’s δ. Results: At week 8, the overall functional comparison was significant (Kruskal–Wallis p = 0.047), but no pairwise contrast remained significant after Holm correction. Functional recovery was highest in the autograft group, followed by proximal FTF and distal FTF. Both FTF groups showed lower inter-animal variability than autograft for the week-8 functional endpoint, with the distal FTF showing the lowest dispersion. Central section nerve area comparisons did not reach global significance; effect sizes and descriptive statistics favored autograft, and a single unadjusted pairwise contrast (autograft > proximal FTF) should be interpreted cautiously. Conclusions: Both FTF configurations achieved measurable functional and structural regeneration while avoiding an additional free donor nerve graft. Within an 8-week window, autograft remained the benchmark. Between FTF variants, distal FTF produced more stable functional outcomes, but this did not translate into superior functional recovery. Confirmation in larger, balanced cohorts with longer follow-up and vascular/neural labeling is warranted. Full article

Fetal hypoxia and maternal stress during pregnancy are major risk factors for neurological disorders. The effects of maternal hypoxia may be transmitted to the next generation through persistent alterations in maternal endocrine and metabolic regulation. In this study, using immunohistochemistry, quantitative RT-PCR, and Western blotting, we assessed morphological features and HIF1-dependent processes in the fetal and adult brains of progeny of female rats exposed to maternal hypoxia (PMH). We identified a delay in progenitor cell differentiation into neurons at embryonic day 14, a decreased number of neurons in the hippocampus, an increased number of astrocytes in the prefrontal cortex, and a decreased number of astrocytes in the raphe nuclei of the PMH rats. However, no significant changes were observed in HIF1α protein levels or in the protein levels of HIF1-dependent gene products in the examined brain structures. Thus, the transgenerational effect of maternal hypoxia is manifested as structural disturbances of brain development but is not accompanied by changes in HIF1-dependent metabolism. Full article

Background: Subarachnoid hemorrhage (SAH) has high mortality and disability rates. The timely and precise assessment of SAH severity is of critical importance in predicting life-threatening complications. Several CT-based radiological grading systems have been proposed, but a comprehensive meta-analysis of their inter-rater reliability (IRR) has not been conducted. Methods: This study followed the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Two authors performed a systematic search of original articles in the PubMed database. Methodological quality of the studies was assessed using the Quality Appraisal of Reliability Studies (QAREL). Meta-analyses of Cohen’s kappa and intra-class correlation coefficient (ICC) were performed using R packages “metafor” and “meta”. Results: A systematic literature analysis was performed for twenty articles that met the inclusion criteria. The methodological quality was moderate in 14 of 20 studies; five studies were of low quality. Only eight articles were suitable for meta-analysis. Cohen’s kappa of the binarized Fisher scale was 0.85 (95% CI 0.70–0.93), though it was based on only two studies and 109 patients. The Hijdra scale had an ICC of 0.75 (95% CI 0.29–0.93). The original and modified Graeb scales proposed for the assessment of concomitant intra-ventricular hemorrhage demonstrated ICC of 0.83 (95% CI 0.59–0.94) and 0.93 (95% CI 0.84–0.97), respectively. For other scales, meta-analysis was not possible due to incomplete reporting or single evaluations. Conclusions: The current evidence on IRR of radiological grading scales for SAH is limited, emphasizing the need for further high-quality research to validate their reliability and clinical applicability. Full article

Background: Untargeted metabolomics enables comprehensive profiling of biological systems, but accurate metabolite annotation remains a critical bottleneck due to incomplete spectral libraries and structural isomerism. The use of in silico annotation tools can increase the coverage of annotated compounds, but it remains unclear whether these tools, in the absence of reference standards, can reliably annotate real-world experimental LC-HRMS data and whether they are sufficient for this task. Methods: This study assesses the performance and limitations of four widely used in silico structure prediction tools (MassFrontier, MetFrag, MS-FINDER, and SIRIUS/CSI:FingerID) when applied to an experimentally acquired feature set previously used to differentiate patients with depressive disorders from healthy controls. To ensure uniform evaluation across tools under realistic but optimized conditions, the quality of MS/MS data was improved using a parallel reaction monitoring method, allowing acquisition of interpretable fragmentation spectra for 26 of the 28 detected features. Results: For most features, all tools were able to suggest structure candidates. However, none of the tools proved sufficient as a standalone solution for reliable metabolite annotation. Due to their different algorithms, each tool had strengths and weaknesses in fragmentation interpretation, candidate generation, and ranking, resulting in incomplete or inconsistent annotations. While the combined application of all four tools provided a substantial improvement in putative annotation over conventional spectral library matching, the in silico structure prediction tools often prioritized chemically implausible, biologically irrelevant, or artifactual candidates. Consequently, manual expert evaluation was required to assess the chemical plausibility and biological relevance of the proposed structures. This ultimately reduced the number of biologically plausible metabolites putatively associated with disease to ten. Conclusions: Overall, these results demonstrate that existing in silico annotation tools can substantially support the annotation of experimental metabolomics data, but are insufficient on their own. Reliable identification of metabolites in complex biological matrices still depends on high-quality MS/MS data acquisition, the combined use of complementary tools, and mandatory post-annotation expert curation. Full article

In the biodegradable metal class, Mg-based alloys are considered the most promising candidates for temporary implant manufacture. However, their high corrosion rate in physiological media is considered a main drawback for clinical translation. Conversion coatings address the limitations of Mg-based alloys and provide a strategy to control corrosion and improve surface biocompatibility. In this review paper, a detailed analysis of various conversion coating techniques, including ceramic conversion coatings based on metals, polymeric conversion coatings, bioactive conversion coatings, and hybrid conversion coatings, is performed. Attention is devoted to the corrosion process and parameters, as well as to the biological response in relation to bioactivity or biocompatibility. The main angiogenic and osteogenic signaling pathways are described based on the analyzed conversion coatings, and the evolution of the cellular response is estimated. Although significant progress has been made in the field, there are still challenges associated with synchronizing Mg alloy degradation with new bone formation and with precisely guiding cell signaling responses to achieve a desired biological response. An overall conclusion of the paper consists of the fact that conversion coatings are an important topic, as they can enhance the surface of Mg-based alloys, making them prone to clinical translation. Full article

Human astroviruses are small, non-enveloped RNA viruses belonging to the family Astroviridae. Among the four species known to infect humans, the species Mamastrovirus hominis (the classical human astroviruses, formerly MAstV1) is associated with gastrointestinal illness worldwide, while three more recently identified species have been linked to lethal central nervous system infections. High substitution rates and recombination drive their rapid evolution, yet recombination patterns in classical human astroviruses remain poorly characterized. This study systematically analyzes patterns and temporal dynamics of natural recombination in classical human astroviruses. Publicly available genomes of classical human astroviruses were analyzed to identify recombination hotspots. Recombinant forms were defined as stable phylogenetic lineages unaffected by recombination, and their half-lives were estimated based on time-scaled phylogenies (BEAST2v2.7.7). Recombination in classical human astroviruses occurred most frequently at the ORF1b/ORF2 junction, but also within ORF1a, at the ORF1a/ORF1b junction, and within ORF2. Only the 3′-part of ORF1a and a fragment of ORF1b exhibited robust temporal signal, yielding substitution rates of 2.35 × 10⁻³ and 2.14 × 10⁻³ s/s/y, respectively. The half-lives of recombinant forms varied considerably by genomic region: longest for exchanges between the parts of ORF1a (21 years), intermediate for ORF1a/ORF1b recombinants (7–9 years), and shortest for ORF1ab/ORF2 recombinants (2.5–3.6 years). The estimated half-lives for recombinants align with those reported for human enteroviruses and noroviruses. These findings highlight the dynamics of the generation of astrovirus diversity and may inform advanced surveillance of emerging strains. Full article

MYO16 has previously been identified as a candidate gene in studies of meat productivity in sheep, but its complete sequence and the potential impact of polymorphisms on the functional properties of the gene in sheep remain understudied. The aim of this study was to analyze genetic variation in the MYO16 gene region in sheep and to identify polymorphisms that, according to bioinformatic prediction, are capable of changing the amino acid sequence of the protein or are associated with allele-specific differences in transcription factor binding motifs potentially significant for gene regulation or protein structure. Whole-genome sequencing was performed for genomic DNA from Manych Merino rams (n = 30) on an Illumina NovaSeq 6000 platform. Variants within the MYO16 region were extracted and annotated. For each variant, ±30 bp reference and alternative sequences were scanned with FIMO using the JASPAR 2020 Vertebrates PWMs to detect allele-specific gain or loss of significant motif hits. TFLink (Mus musculus) was used to retain only TFs with MYO16 listed as a target. In the MYO16 gene region, 10,318 variants were detected. The coding region contained 54 SNPs, including 15 missense variants. In silico TFBS scanning identified 23 variants showing allele-specific gain or loss of significant motif hits, involving motifs for EBF1, CTCF, NRF1, SPI1, NFE2L2, JUN, and GFI1. We examined polymorphism in the ovine MYO16 gene region and identified candidate variants to be tested for association with productivity traits in future genotype–phenotype studies. Full article

The skin serves as the first line barrier of innate immunity, protecting the body from external influences and maintaining its homeostasis. Exogenous and endogenous stress factors alter the structure and functional properties of the skin. The search for compounds capable of counteracting these processes has allowed the identification of peptides as promising ingredients of products for medicinal and cosmetic applications. This review comprehensively examines the mechanisms of action and dermatological applications of two distinct classes of natural products—endogenous human peptides and those derived from marine organisms. Human peptides exhibit numerous biological functions, including antimicrobial and immunomodulatory ones, as well as promoting antioxidant protection and wound healing. Microbiome-associated peptides are an underestimated but powerful regulator of skin aging through immunomodulation, inflammation control, barrier function maintenance, and selection of the proper microbial community. Peptides from marine organisms exhibit significant structural diversity and a broad spectrum of biological activity, including regenerative effects and effects on antibiotic-resistant microorganisms. This review summarizes current data obtained from in vitro, ex vivo, and clinical studies demonstrating a broad potential of peptides for maintaining skin health. Both peptide classes represent powerful, targeted strategies for innovative dermatological interventions aimed at promoting skin rejuvenation, protection, and overall homeostasis. Full article

Despite the success of artificial neural networks in solving numerous tasks, they face significant challenges, including difficulties in online adaptation and rapidly increasing energy consumption. As a biologically plausible alternative, spiking neural networks offer promising capabilities for efficient cognitive computing. Recently, a three-element spiking neuron model consisting of a threshold selector, a tunnel diode, and a capacitor was proposed. In this work, we experimentally validate this model using a threshold selector hardware emulator and demonstrate its dynamical equivalence to the biologically plausible Izhikevich neuron model. To evaluate the novel neuron’s applicability for cognitive computing, we implement a liquid state machine (LSM) reservoir architecture with spatially dependent random topology for synaptic weight distribution. Our simulations on the MNIST and Fashion-MNIST benchmarks demonstrate competitive classification accuracy (97.9% and 89.5%, respectively) while offering estimated energy efficiency and processing speed enhancements compared to existing FPGA-based and memristor-based spiking reservoir implementations. The developed reservoir is feasible for processing neuromorphic sensors output, including visual perception tasks. Full article

Pharmacological chaperones (PCs)—small molecules that normalize the 3D structure of mutant protein molecules—are promising substances for pharmacological treatment of grave hereditary pathologies. In this study, possible chaperone-like effects of the Fe(II) with tris(1-pyrasolyl)methane complex, [Fe(TPM)₂]Cl₂, on the mutant 447R form of mouse tryptophan hydroxylase 2 (TPH2) in vitro and in vivo were investigated. The experiments were carried out on Balb/c mice homozygous for the mutant TPH2. This complex in concentrations of 0.01, 0.05 and 0.1 mM markedly increased the temperature (T₅₀) and free energy (ΔG) of the mutant TPH2 thermal denaturation in vitro. Seven intramuscular administrations of 30 and 60 mg/kg of [Fe(TPM)₂]Cl₂ markedly increased the TPH2 activity in the midbrain of Balb/c mice. This increase in the TPH2 activity was not accompanied with an increase in the Tph2 gene mRNA and TPH2 protein levels. It is the first demonstration of chaperone-like activity of [Fe(TPM)₂]Cl₂. This complex is a promising chemical for correction of genetic alterations in TPH2 and the associated hereditary psychic disorders. Full article

Viral infections of grapevines reduce plantation productivity and planting material quality, necessitating the development of effective sanitization methods and comprehensive systems for monitoring plant physiological status. This study conducted a comprehensive analysis of the physiological–biochemical status of grapevine microplants (morphometric parameters, activity of key antioxidant enzymes, dehydrogenase activity, pigment composition, and relative copy number of mitochondrial and chloroplast DNA) in microclones of the rootstock Vitis riparia × Vitis berlandieri ‘Kober 5 BB’ in vitro, depending on the presence of viral infection and sanitization using thermo- and cryotherapy. Four plant variants were investigated: healthy (VIRUS FREE), infected (VIRUS), sanitized via thermotherapy (V.F.T.), and cryotherapy (V.F.K.). It was shown that, despite the absence of pronounced suppression of morphometric parameters, viral infection causes a significant increase in total protein content, catalase, polyphenol oxidase, and total dehydrogenase activity in tissues, as well as pigment imbalance (changes in the chlorophyll coefficient) and modulation of the carotenoid profile, along with alterations in the relative copy number of mitochondrial and chloroplast DNA. The relative copy number of mitochondrial and chloroplast DNA decreased in infected plants and was restored to a greater extent after cryotherapy rather than after thermotherapy. The results indicate the formation of stress-related changes (stress imprint) that persist in sanitized microclones and can serve as a multilevel marker system for assessing sanitization efficacy and monitoring the physiological status of grapevine microplants in vitro. Full article

Diffractive optical elements with a trigonometric phase dependence on radius are considered. They allow the formation of multiple local light segments on the optical axis. The dependence of the focal distribution on the optical element parameters is studied analytically and numerically. It is shown that by varying the parameters, both the positions and relative magnitudes of the foci can be independently changed. A detailed comparison of a sinusoidal lens with a parabolic one is performed. Binarization of a sinusoidal lens leads to non-obvious effects: this process does not create new foci, but significantly changes the energy distribution between the foci. In particular, the intensity can increase at positions where the focal magnitude was very small before binarization. Moreover, the trigonometric elements have very interesting chromatic dispersion features: changing the wavelength leads to significant variations in the ratio of the focal energies, which is not typical of parabolic lenses. The obtained results are promising for the field of multiplexing optical information transmission channels, increasing the depth of focus, laser material processing and optical trapping. Full article

Background/Objectives: Since non-invasive implants and invasive implants (metastases) are a key point of differentiation between serous borderline tumors (SBTs) and low-grade serous carcinoma (LGSC), the correct diagnosis of these two types of extraovarian lesions is crucial for patient treatment and prognosis. However, accurate diagnosis can be challenging even for experienced pathologists. The aim of this study was to evaluate interobserver agreement in the classification of these extraovarian lesions. Methods: Twenty-four cases of ovarian SBT and LGSC with 33 samples of non-invasive implants of SBT and metastasis of LGSC were independently reviewed by three gynecologic pathologists and three general pathologists. Diagnostic criteria included destructive invasion, micropapillary architecture, and retraction clefts. To measure interobserver agreement, Fleiss’ kappa and Cohen’s kappa were calculated, with consensus diagnoses determined by the majority of gynecologic pathologists. Results: According to the consensus, diagnosis 42.4% biopsies were classified as metastases of LGSC and 57.6% as non-invasive implants of SBT. Overall reproducibility was substantial (κ = 0.61). The agreement among gynecologic pathologists, as well as between gynecologic pathologists and the consensus (using leave-one-out reference), was substantial to near-perfect (κ = 0.745–0.821). General pathologists’ agreement with the consensus was moderate (κ = 0.467–0.698). Agreement between general pathologists was also moderate, with κ values ranging from 0.413 to 0.518. The difference in pairwise agreement between the two groups was statistically significant, confirming that gynecologic pathologists outperformed general pathologists in classifying extraovarian lesions. Conclusions: The results showed that current diagnostic reproducibility remains suboptimal, particularly among general pathologists, underscoring the need for improved training and standardized criteria. Ultimately, a multidisciplinary approach combining morphological expertise, immunohistochemical validation and molecular stratification will be essential for optimizing diagnosis and treatment. Full article

The aim of the study was to evaluate the biotechnological potential of thermophilic microorganisms isolated from chernozem soil during composting of poultry manure. The efficiency of the strains was determined by their effect on organic matter degradation, humification intensity, and nitrogen accumulation. The correlation between the quality indicators of the composting process was assessed with the gross values, taking into account the proportion of compost fractions. The strains were identified as: Aeribacillus pallidus KCTC 3564^T (cellulolytic), Neobacillus sedimentimangrovi FJAT-2464^T, Aeribacillus composti N.8^T, Caldifermentibacillus hisashii N-11^T (nitrogen fixers), Acinetobacter pittii CIP 70.29^T, and Pseudomonas plecoglossicida NBRC 103162^T (nitrifies). It was found that all the bacteria increase the proportion of small fractions by 19.0–19.9%. The gross content of humic acids increases under the influence of nitrifiers (15.5%) and nitrogen fixers (5.5%). The total nitrogen content increases under cellulolytics (13.8%) and nitrogen fixers (20.2%). The smallest fraction (≤0.25 mm) in nitrogen fixers and nitrifying variants has the greatest bioreclamation properties, by 16.4% (p < 0.001) and 12.9% (p < 0.001). Targeted microbial strains provide the direction of the transformation processes during biocomposting. It can also be concluded that assessing the quality of composting based on the fraction distribution can be a promising element of the biofermentation process monitoring. Full article