Search Results (3,822)

A novel efficient method to evaluate time-periodic flows is applied to turbomachinery configurations in this paper (PSpTM). The technique reduces the overall computational cost of unsteady CFD calculations relative to conventional implicit approaches. The method is based on a pseudo-spectral definition of the time derivative rearranged in a time-marching fashion. The key advantage of this novel formulation compared with classical harmonic methods is that it requires minor modifications in the CFD solver structure. The method was implemented into an existing unstructured edge-based, second-order, compressible RANS solver. To benchmark the method, a well-established implicit time scheme based on a second-order backward implicit approach (BDF2) is used. Sample unsteady turbomachinery configurations are used to determine the accuracy and efficiency of the method. The accuracy of the solution is highly linked to the number of harmonics prescribed for the solution. An adequate level of accuracy was obtained while retaining a reduced number of harmonics, with approximately twice the number of harmonics of the unsteady perturbation. Notable savings in computational cost were observed when the PSpTM method was used with speed-up factors of between 2 and 10 with respect to the BDF2, depending on the case. However, the PSpTM method exhibits a poor periodic convergence rate, leaving room for further improvements in efficiency. However, even in its current form and with the current understanding, the method has a remarkable performance. Full article

Acute lymphoblastic leukemia (ALL) is a heterogeneous hematologic malignancy defined by the uncontrolled proliferation of lymphoid precursors. Accurate diagnosis and effective therapeutic strategies hinge on a comprehensive understanding of the genetic and molecular landscape of ALL. This review synthesizes the latest updates in cytogenetic and molecular classifications, emphasizing the 2022 World Health Organization (WHO) and International Consensus Classification (ICC) revisions. Key chromosomal alterations such as BCR::ABL1 and ETV6::RUNX1 and emerging subtypes including Ph-like ALL, DUX4, and MEF2D rearrangements are examined for their prognostic significance. Furthermore, we assess novel diagnostic tools, notably next-generation sequencing (NGS) and optical genome mapping (OGM). While NGS excels at identifying point mutations and small indels, OGM offers high-resolution structural variant detection with 100% sensitivity in multiple validation studies. These advancements enhance our grasp of leukemogenesis and pave the way for precision medicine in both B- and T-cell ALL. Ultimately, integrating these innovations into routine diagnostics is crucial for personalized patient management and improving clinical outcomes. Full article

Introduction: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a very rare subtype of cutaneous T-cell lymphoma. It is characterized by the neoplastic infiltration of subcutaneous adipose tissue. Its clinical presentation, including subcutaneous nodules, fever, and systemic symptoms, often mimics inflammatory panniculitis, making diagnosis difficult. Case Presentation: This case report describes a 14-year-old female presenting with fever, limb pain, swelling, and subcutaneous nodules, who was ultimately diagnosed with SPTCL via punch biopsy and BIOMED-2 clonality assays, confirming positive T-cell receptor-γ chain gene rearrangement. Positron emission tomography–computed tomography revealed diffuse subcutaneous involvement across multiple body regions. Methylprednisolone and cyclosporine A treatment rapidly resolved her symptoms, with laboratory parameters, including ferritin and inflammatory markers, showing significant improvement. Next-generation sequencing identified a heterozygous C9 gene mutation (c.346C>T, p.Arg116Ter), adding a novel genetic dimension to the case. Following a tapered discontinuation of immunosuppressive therapy, the patient achieved sustained remission without relapse for over 1 year. Conclusions: We report a case of adolescent SPTCL treated with immunosuppressive therapy and suggest that immunosuppressive therapy should be considered before chemotherapy in pediatric patients with SPTCL but without HLH. Full article

Protein–polyelectrolyte nanostructures assembled via electrostatic interactions offer versatile applications in biomedicine, tissue engineering, and food science. However, several open questions remain regarding their intermolecular interactions and the influence of external conditions—such as temperature and pH—on their assembly, stability, and responsiveness. This study explores the formation and stability of networks between poly(acrylic acid) (PAA) and lysozyme (LYZ) at the nanoscale upon thermal treatment, using a combination of experimental and simulation measures. Experimental techniques of static and dynamic light scattering (SLS and DLS), Fourier transform infrared spectroscopy (FTIR), and circular dichroism (CD) are combined with all-atom molecular dynamics simulations. Model systems consisting of multiple PAA and LYZ molecules explore collective assembly and complexation in aqueous solution. Experimental results indicate that electrostatic complexation occurs between PAA and LYZ at pH values below LYZ’s isoelectric point. This leads to the formation of nanoparticles (NPs) with radii ranging from 100 to 200 nm, most pronounced at a PAA/LYZ mass ratio of 0.1. These complexes disassemble at pH 12, where both LYZ and PAA are negatively charged. However, when complexes are thermally treated (TT), they remain stable, which is consistent with earlier findings. Atomistic simulations demonstrate that thermal treatment induces partially reversible structural changes, revealing key microscopic features involved in the stabilization of the formed network. Although electrostatic interactions dominate under all pH and temperature conditions, thermally induced conformational changes reorganize the binding pattern, resulting in an increased number of contacts between LYZ and PAA upon thermal treatment. The altered hydration associated with conformational rearrangements emerges as a key contributor to the stability of the thermally treated complexes, particularly under conditions of strong electrostatic repulsion at pH 12. Moreover, enhanced polymer chain associations within the network are observed, which play a crucial role in complex stabilization. These insights contribute to the rational design of protein–polyelectrolyte materials, revealing the origins of association under thermally induced structural rearrangements. Full article

Chromosome rearrangements during plant evolution can lead to alterations in genome structure and gene function, thereby influencing species adaptation and evolutionary processes. Gymnosperms, as an ancient group of plants, offer valuable insights into the morphological, physiological, and ecological characteristics of early terrestrial flora. The reconstruction of ancestral karyotypes in gymnosperms may provide critical clues for understanding their evolutionary history. In this study, we inferred the ancestral gymnosperm karyotype (AGK), which comprises 12 chromosomes, and conducted a collinearity analysis with existing gymnosperm genomes. Our findings indicate that chromosome numbers have remained remarkably stable throughout the evolution of gymnosperms. For species with multiplied chromosome numbers, such as gnetophytes, weak collinearities with the AGK were observed. Comparisons between the AGK and gnetophyte genomes revealed a biased pattern regarding retained duplication blocks. Furthermore, our analysis of transposable elements in Welwitschia mirabilis identified enriched regions containing LINE-1 retrotransposons within the syntenic blocks. Syntenic analysis between the AGK and angiosperms also demonstrated a biased distribution across chromosomes. These results provide a fundamental resource for further characterization of chromosomal evolution in gymnosperms. Full article

It is well-known that the necessary and sufficient condition for a connected graph to be unicyclic is that its omega invariant, a recently introduced graph invariant useful in combinatorial and topological calculations, is zero. This condition could be stated as the condition that the order and the size of the graph are equal. Using a recent result saying that the length of the unique cycle could be any integer between 1 and n − a₁ where a₁ is the number of pendant vertices in the graph, two explicit labeling algorithms are provided that attain these extremal values of the first and second Zagreb indices by means of an application of the well-known rearrangement inequality. When the cycle has the maximum length, we obtain the situation where all the pendant vertices are adjacent to the support vertices, the neighbors of the pendant vertices, which are placed only on the unique cycle. This makes it easy to calculate the second Zagreb index, as the contribution of the pendant edges to such indices is fixed, implying that we can only calculate these indices for the edges on the cycle. Full article

Background/Objectives: Optical genome mapping (OGM) has recently emerged as a new technology in the clinical cytogenomics laboratories. This methodology has the ability to detect balanced and unbalanced structural rearrangements using ultra-high molecular weight DNA. This article discusses the uses of this new technology in both constitutional and somatic settings, its advantages as well as opportunity for improvements. Methods: We reviewed the medical and scientific literature for methodology and current clinical uses of OGM. Results: OGM is a recent addition to the methods used in cytogenomics laboratories and can detect a wide range of structural and copy number variations across a plethora of diseases. Conclusions: Clinical cytogenomics is an important laboratory specialty for which various technologies have been validated over the last several decades to improve detection of copy number and structural variations and their association to human disease. OGM has proven to be a powerful tool in the arsenal of clinical laboratories and provides a unified workflow for the detection of chromosomal aberrations across a wide range of diseases. Full article

Understanding the early-stage physical interactions between polymeric membranes and supersaturated salt solutions is crucial for advancing membrane-assisted crystallization (MCr) processes. In this study, we employed molecular dynamics (MD) simulations to investigate the short-term morphological response of an isotactic polypropylene (PP) membrane in contact with LiF solutions at different concentrations (5.8 M and 8.9 M) and temperatures (300–353 K), across multiple time points (0, 150, and 300 ns). These data were used as input for computational fluid dynamics (CFD) analysis to evaluate structural descriptors of the membrane, including tortuosity, connectivity, void fraction, anisotropy, and deviatoric anisotropy, under varying thermodynamic conditions. The results show subtle but consistent rearrangements of polymer chains upon exposure to the hypersaline environment, with a marked reduction in anisotropy and connectivity, indicating a more compact and isotropic local structure. Surface charge density analyses further suggest a temperature- and concentration-dependent modulation of chain mobility and terminal group orientation at the membrane–solution interface. Despite localized rearrangements, the membrane consistently maintains a net negative surface charge. This electrostatic feature may influence ion–membrane interactions during the crystallization process. While these non-reactive, short-timescale simulations do not capture long-term degradation or fouling mechanisms, they provide mechanistic insight into the initial physical response of PP membranes under MCr-relevant conditions. This study lays a computational foundation for future investigations bridging atomistic modeling and membrane performance in real-world applications. Full article

Halictidae, as a major pollinator family in bees, has significant ecological value. However, the insufficient molecular data for this group has limited our understanding of the evolutionary history of this group. Herein, we newly sequenced and assembled four mitogenomes of Halictidae, including three species of Nomiinae and one species of Rophitinae. We analyzed the characters of the newly obtained mitogenomes, including nucleotide composition, sequence length, and gene rearrangements. The length of the newly sequenced mitogenomes ranged from 16,492 to 21,192 bp, and all newly obtained mitogenomes contained 22 tRNAs, 13 protein-coding genes, two rRNAs, and one control region. Their AT content (%) ranged from 82.55 to 86.44. Relative synonymous codon usage analysis showed that UUU, UUA, and AUU were the preferred codons. The relative synonymous codon usage > 2 of mostly newly sequenced species was as follows: UUA > UCA > CGA. All newly obtained mitogenomes show gene rearrangement; we found five gene rearrangement patterns in total. Notably, ND4-trnP-ND4L-trnT was the first reported gene rearrangement pattern in bees. In addition, we reconstructed the phylogenetic relationships of Halictidae based on 10 species (eight ingroups and two outgroups), using Bayesian Inference and Maximum Likelihood approaches. Phylogenetic analysis showed that Rophitinae was the basal group within Halictidae. Full article

AAA+ ATPases are ring-shaped hexameric protein complexes that operate as elaborate macromolecular motors, driving a variety of ATP-dependent cellular processes. AAA+ ATPases undergo large-scale conformational changes that lead to the conversion of chemical energy from ATP into mechanical work to perform a wide range of functions, such as unfolding and translocation of the protein substrate inside a proteolysis chamber of an AAA+-associated protease. Despite extensive biochemical studies on these macromolecular assemblies, the mechanism of substrate unfolding and degradation has long remained elusive. Indeed, until recently, structural characterization of AAA+ protease complexes remained hampered by the size and complexity of the machinery, harboring multiple protein subunits acting together to process proteins to be degraded. Additionally, the major structural rearrangements involved in the mechanism of this complex represent a crucial challenge for structural biology. Here, we report the main advances in deciphering molecular details of the proteolytic reaction performed by AAA+ proteases, based on the remarkable progress in structural biology techniques. Particular emphasis is placed on the latest findings from high-resolution structural analysis of the ClpXP proteolytic complex, using crystallographic and cryo-EM investigations. In addition, this review presents some additional dynamic information obtained using solution-state NMR. This information provides molecular details that help to explain the protein degradation process by such molecular machines. Full article

We present a 48-year-old female with a past medical history of endometrioid adenocarcinoma who presented with symptoms of spontaneous gum bleeding, post-coital bleeding, and upper extremities–lower extremities-abdomen ecchymosis. Initial laboratory findings were significant for cytopenia and disseminated intravascular coagulation (DIC). Due to a suspected case of acute promyelocytic leukemia (APL), conventional karyotyping and fluorescence in situ hybridization (FISH) were performed. FISH analysis confirmed an unusual chromosome rearrangement that affected chromosomes 3, 15, and 17. This t(3;15;17)(q29;q24;q21) was characterized by the presence of PML::RARA fusion on the derivative chromosome 15. Treatment at the hospital with standard APL therapy of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) was complicated by the development of differentiation syndrome, which necessitated the temporary stoppage of ATO. However, complete remission was achieved despite complications after starting consolidation treatment. Full article

Structural variations (SVs) represent genomic variations that involve breakage and rejoining of DNA segments. SVs can alter normal gene dosage, lead to rearrangements of genes and regulatory elements within a topologically associated domain, and potentially contribute to physical traits, genomic disorders, or complex traits. Recent advances in sequencing technologies and bioinformatics have greatly improved SV detection and interpretation at unprecedented resolution and scale. Despite these advances, the functional impact of SVs, the underlying SV mechanism(s) contributing to complex traits, and the technical challenges associated with SV detection and annotation remain active areas of research. This review aims to provide an overview of structural variations, their mutagenesis mechanisms, and their detection in the genomics era, focusing on the biological significance, methodologies, and future directions in the field. Full article

This study focuses on the clastic reservoir in the first member of Yaojia Formation within Qijia-Gulong Sag, Songliao Basin. The results indicate that the reservoir in the study area develops within a shallow-water delta sedimentary system. The dominant sedimentary microfacies comprise underwater distributary channels, mouth bars, and sheet sands. Among these, the underwater distributary channel microfacies exhibits primary porosity ranging from 15.97% to 17.71%, showing the optimal reservoir quality, whereas the sheet sand microfacies has a porosity of only 7.45% to 12.08%, indicating inferior physical properties. During diagenesis, compaction notably decreases primary porosity via particle rearrangement and elastic deformation, while calcite cementation and quartz overgrowth further occlude pore throats. Although dissolution can generate secondary porosity (locally up to 40%), the precipitation of clay minerals tends to block pore throats, leading to “ineffective porosity” (permeability generally < 5 mD) and overall low-porosity and low-permeability characteristics. Carbon–oxygen isotope analysis reveals a deficiency in organic acid supply in the study area, restricting the intensity of dissolution alteration. Reservoir quality evolution is dominantly governed by the combined controls of sedimentary microfacies and diagenesis. This study emphasizes that, within shallow-water delta sedimentary settings, the material composition of sedimentary microfacies and the dynamic equilibrium of diagenetic processes jointly govern reservoir property variations. This insight provides critical theoretical support for understanding diagenetic evolution mechanisms in clastic reservoirs and enabling precise prediction of high-quality reservoir distribution. Full article

In this review, we explore the complexities of objectively assessing the response to immunotherapy in mycosis fungoides (MF), a prevalent form of cutaneous T-cell lymphoma. The core challenge lies in distinguishing between reactive and malignant lymphocytes amidst treatment, particularly given the absence of uniform pathological biomarkers for MF. We highlight the vital role of emerging histological technologies, such as multispectral imaging and spatial transcriptomics, in offering a more profound insight into the tumor microenvironment (TME) and its dynamic response to immunomodulatory therapies. Drawing on parallels with melanoma—another immunogenic skin cancer—our review suggests that methodologies and insights from melanoma could be instrumental in refining the approach to MF. We specifically focus on the prognostic implications of various TME cell types, including CD8+ tumor-infiltrating lymphocytes, natural killer (NK) cells, and histiocytes, in predicting therapy responses. The review culminates in a discussion about adapting and evolving treatment response quantification strategies from melanoma research to the distinct context of MF, advocating for the implementation of novel techniques like high-throughput T-cell receptor gene rearrangement analysis. This exploration underscores the urgent need for continued innovation and standardization in evaluating responses to immunotherapies in MF, a field rapidly evolving with new therapeutic strategies. Full article

The Millard’s rat (Dacnomys millardi), a threatened murid endemic to Southeast Asian montane rainforests and the sole member of its monotypic genus, faces escalating endangered risks as a Near Threatened species in China’s Biodiversity Red List. This ecologically specialized rodent exhibits diagnostic morphological adaptations—hypertrophied upper molars and cryptic pelage—that underpin niche differentiation in undisturbed tropical/subtropical forests. Despite its evolutionary distinctiveness, the conservation prioritization given to Dacnomys is hindered due to a deficiency of data and unresolved phylogenetic relationships. Here, we integrated morphological analyses with the first complete mitogenome (16,289 bp in size; no structural rearrangements) of D. millardi to validate its phylogenetic placement within the subfamily Murinae and provide novel insights into genetic diversity erosion. Bayesian and maximum likelihood phylogenies robustly supported Dacnomys as sister to Leopoldamys (PP = 1.0; BS = 100%), with an early Pliocene divergence (~4.8 Mya, 95% HPD: 3.65–5.47 Mya). Additionally, based on its basal phylogenetic position within Murinae, we propose reclassifying Micromys from Rattini to the tribe Micromyini. Codon usage bias analyses revealed pervasive purifying selection (Ka/Ks < 1), constraining mitogenome evolution. Genetic diversity analyses showed low genetic variation (CYTB: π = 0.0135 ± 0.0023; COX1: π = 0.0101 ± 0.0025) in fragmented populations. We propose three new insights into this genetic diversity erosion. (1) Evolutionary constraints: genome-wide evolutionary conservation and shallow evolutionary history (~4.8 Mya) limited mutation accumulation. (2) Anthropogenic pressures: deforestation-driven fragmentation of habitats (>20,000 km²/year loss since 2000) has reduced effective population size, exacerbating genetic drift. (3) Ecological specialization: long-term adaptation to stable niches favored genomic optimization over adaptive flexibility. These findings necessitate suitable conservation action by enforcing protection of core habitats to prevent deforestation-driven population collapses and advocating IUCN reclassification of D. millardi from Data Deficient to Near Threatened. Full article