Search Results (82,113)

Background: KMT2A rearrangements are a frequent genetic abnormality associated with Acute myeloid leukemia (AML), historically linked to varied prognoses and outcomes. The prognosis for patients with this rearrangement remains controversial, necessitating further research to stratify risk and guide treatment. Methods: In this retrospective study, a total of 3468 adolescent and adult AML patients were screened, and 181 patients harboring KMT2A rearrangements were analyzed. We used FISH, RT-PCR, and next-generation sequencing, including transcriptome and targeted panels, for diagnosis and mutation profiling. All patients received intensive chemotherapy. We evaluated overall survival and event-free survival using Kaplan–Meier and Cox regression models, with HSCT analyzed as a time-dependent variable. Results: The incidence of KMT2A-rearranged AML in our newly diagnosed cohort was 5.9%. Among the 181 patients included in the final analysis, 89 (49.2%) were male and 92 (50.8%) were female, with a median age of 33 years (range: 13–65). The distribution of fusion partners included KMT2A::MLLT3 (n = 39), KMT2A::AFDN (n = 27), KMT2A::MLLT10 (n = 25), KMT2A::ELL (n = 24), and others (n = 12). Seventy-four patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first complete remission (CR1). The median follow-up for survivors was 17.53 months (range 1.47–112.57), and the 3-year overall survival (OS) and event-free survival (EFS) for the entire cohort were 42.0% and 32.1%, respectively. Patients with KMT2A::ELL exhibited superior OS compared to other subtypes (3-year OS [ELL vs. non-ELL]: 59.8% vs. 39.3%, p = 0.023). Concomitant mutations did not significantly impact the prognosis of KMT2A-rearranged AML patients. In multivariate analysis, age and HSCT in CR1 were independently associated with OS and EFS (OS: HR = 1.022, p = 0.026 [age]; HR = 0.238, p < 0.001 [HSCT]; EFS: HR = 1.027, p = 0.002 [age]; HR = 0.155, p < 0.001 [HSCT]). Patients aged over 20 years were more likely to benefit from HSCT than those aged 20 years or younger (p < 0.001 [age > 20], p = 0.780 [age ≤ 20]). Conclusions: Our study revealed the heterogeneous outcomes of KMT2A-rearranged AML patients and clarified the impact of HSCT across different age groups. Full article

Whole-genome duplication (WGD) is a powerful evolutionary force, yet the mechanisms by which neopolyploids achieve transcriptomic stability and phenotypic success remain poorly understood. This study investigated the phenotypic and transcriptomic consequences of ploidy changes in the flatworm Macrostomum lignano, a “successful” neopolyploid model. We exploited two established sublines derived from the inbred DV1 line: the euploid DV1_8 (hidden tetraploid, SSL₁L₂) and the aneuploid DV1_10 (hidden hexaploid, SSL₁L₁L₂L₂). By integrating whole-genome sequencing (WGS)-informed normalization with RNA-seq analysis, we differentiated true regulatory shifts from gene-dosage effects. We revealed that while most genes scale linearly with ploidy, 1308 genes exhibited a nonlinear aneuploidy-induced transcriptional response. The remarkable trans-acting effects were observed across subgenome S encoded by disomic small chromosomes. Differentially expressed genes (DEGs) were enriched in pathways essential for homeostasis and growth: mTOR signaling, ubiquitin-mediated proteolysis, and the Hippo/Wnt pathways. Phenotypes of the DV1_10 worms exhibited increased body size, enhanced cell proliferation, and higher viability in comparison to the DV1_8 worms (60.25% vs. 21.5%). These findings suggest that M. lignano possesses mechanisms for dosage compensation to mitigate the deleterious effects of aneuploidy. Ultimately, this study demonstrates how genomic plasticity and rewiring of the transcriptome may facilitate the evolutionary success of animal neopolyploids. Full article

Numerous publications on forest genetic monitoring (FGM) and related topics in genetics and gene conservation have been published over the past three decades. This paper reviews the methods used in FGM and, more broadly, related scientific findings published to date, of which general conclusions can be applied worldwide in FGM. In the strict sense, long-term FGM projects have been established only in a few regions in Europe. The methodological basis (guidelines) for FGM has already been developed, specifically for European tree species and forest communities. In genetic analyses, traditional SSR markers are predominantly used, but SNP markers from new-generation sequencing are increasingly available. Nonetheless, there is a high level of variation in monitoring activities such as biodiversity, forest health, and forest genetics, likely due to the efforts of national (governmental) and international professional organizations. Early evaluation of the first FGM projects has already been published. Scientific evidence for FGM has been limited because of the low number of projects that represent a few geographic regions and species. Full article

Extracellular vesicles (EVs) of human origin show promise for regenerative medicine and wound healing. However, they have limitations regarding scalability, variability, safety, and costs. Plant-derived EVs may represent a valid alternative. This study investigated the regenerative potential of EVs extracted from orange juice (oEVs). oEVs obtained by standard ultracentrifugation were compared with oEVs purified by tangential flow filtration (TFF), a scalable technique suitable for large-scale and regulatory-compliant manufacturing. Comparisons included size, morphology, pH, Zeta potential, protein and RNA content, Raman spectroscopy, and proteomic, metabolomic, and RNA sequencing. The regenerative potential of oEVs was tested in vitro, with cell migration, endothelial tube formation, and proliferation assays performed. Antioxidant ability was tested on endothelial cells stressed by hyperglycemia or pro-inflammatory cytokine cocktails. Next, oEVs were formulated with different hydrogels and tested at different doses on skin ulcers on healthy and diabetic mice. TFF oEVs showed the same physio-chemical characteristics and a comparable molecular content as those isolated by ultracentrifugation, confirming the path to scalability. In vitro oEVs promoted cell migration, formation of capillary-like structures, cell proliferation, and strong antioxidant activity. Moreover, oEVs effectively accelerated in vivo wound closure in healthy and diabetic mice. Thus, oEVs may provide a useful and cost-effective ingredient for improved and effective wound treatment strategies. Full article

G-quadruplex (G4) DNA structures have recently emerged as promising chiral scaffolds for enantioselective catalysis. This study investigates how thymidine loop modifications influence the catalytic performance of the telomeric G4 sequence HT21 in the asymmetric sulfoxidation of thioanisole. To this end, several singly or doubly modified HT21 derivatives were synthesized by using β-L-2′-deoxythymidine, 5-hydroxymethyl-2′-deoxyuridine, and 5-bromo-2′-deoxyuridine instead of a T residue, or β-L-2′-deoxyadonesine instead of an A residue, in specific positions within the TTA loops. The catalytic activity of these analogues was evaluated in the Cu(II)-mediated oxidation of thioanisole using hydrogen peroxide as oxidant. All modified sequences maintained complete substrate conversion, but their enantioselectivities varied markedly. Whereas the highest enantiomeric excess (84% ee) had previously been achieved with the HT21 analogue bearing a β-L-2′-deoxyadenosine in the first loop, the thymidine-based modifications, either alone or in combination, resulted in lower ee values, suggesting that loop alterations critically affect the chiral microenvironment, not all loop positions are functionally equivalent, and single substitutions within the same loop can result in different enantioselectivities. These findings highlight new insights on how individual loop residues contribute to asymmetric induction and offer further details for tuning G4-based catalytic scaffolds. Full article

Background and Objectives: Sternocleidomastoid (SCM) dysfunction is commonly implicated in several musculoskeletal conditions. Accordingly, shear-wave elastography has been used to characterize SCM stiffness in asymptomatic and clinical cohorts. However, the only reproducibility study available reported limited reliability, so clinical interpretations should be made with caution. Therefore, this study revisits key methodological aspects of that protocol to assess intra-examiner reliability and includes two examiners with different levels of expertise to evaluate inter-examiner reliability. Materials and Methods: A longitudinal observational study was conducted, recruiting twenty-five asymptomatic participants. Two examiners with different experience levels participated in this study after following structured training. For each side, images were obtained in immediate succession in the sequence experienced–novice–experienced–novice (with side order randomized), using an ROI spanning full muscle thickness, stabilizing approximately 10 s before freezing to record Young’s modulus and shear-wave speed. Results: Inter-examiner agreement was good–excellent: single-measurement ICCs were 0.77–0.86, improving to 0.79–0.87 when averaging two trials, which also reduced the standard error of measurement (SEM) and minimal detectable changes (MDCs). Between-examiner mean differences were small and nonsignificant (p ≥ 0.068). Intra-examiner reliability was excellent (ICC ≈ 0.93–0.94) with small absolute errors. Precision was high (SEM ~5–6 kPa; 0.22 m/s), and MDCs were ~15–16 kPa and ~0.60 m/s, with no trial-to-trial bias (all p ≥ 0.311). Conclusions: The revised protocol showed excellent intra-examiner repeatability and good–excellent inter-examiner reliability with minimal bias. Averaging two acquisitions improved precision, while a single operator optimized longitudinal stability. Full article

The flowers of Panax ginseng C. A. Mey. (PG) and Panax notoginseng (Burkill) F. H. Chen ex C. H. Chow (PN) are morphologically indistinguishable after drying, leading to prevalent adulteration that compromises product quality and consumer safety. To address this issue, we developed a rapid, closed-tube molecular authentication method based on high-resolution melting (HRM) analysis. Species-specific primer pairs were designed to target the conserved ITS and rbcL-accD regions, with PNG-2 selected as the optimal candidate owing to its stable genotyping performance and moderate GC content. Our results established GC content, rather than amplicon length, as the primary determinant of the melting temperature (Tm). Notably, the experimentally measured Tm values were consistently 0.7–1.5 °C higher than theoretical predictions, a discrepancy attributable to the stabilizing effect of the saturated fluorescent dye. To ensure maximum diagnostic reliability, the HRM results were cross-validated through a three-tier system comprising ITS2 phylogenetic analysis, agarose gel electrophoresis, and Sanger sequencing. The practical utility and matrix robustness of the assay were further verified using a diversified validation cohort of 30 commercial samples, including 24 floral batches and 6 root-derived products (root slices and ultramicro powders). The HRM profiles demonstrated 100% concordance with DNA barcoding results, effectively identifying mislabeled products across different botanical matrices and processing forms. This methodology, which can be completed within 3 h, provides a significantly more cost-effective and rapid alternative to traditional sequencing-based methods for large-scale market surveillance and industrial quality control. Full article

Basidiomycete mushrooms contain complex β-D-glucans which act as immunomodulator, immune stimulants and anti-cancer agents, which can be either free or bound to proteins. The present report consists of a novel and intrinsic synchronous fluorescence and phosphorescence assay method for β-D-glucans. This analytical technique was carried out by a spectrofluorometer in the range of 250 to 750 nm with a Δλ range of 5–30 nm which exhibited peaks at 492, 540 and 550 nm by using β-D-glucan from Euglena gracilis as a standard. A micro and high-throughput method based on a microplate fluorescence reader was devised with a excitation and emissions λ of 420 nm and 528 nm, respectively. This assay method revealed some advantages over the reported colorimetric methods, since it is a non-destructive assay method of β-D-glucans in samples with a linearity range of 0–14 μg/well, correlation coefficient (r2) of 0.9961, LOD of 0.973 μg/well, LOQ of 2.919 μg/well, greater sensitivity, fast, a high-throughput method and very economical. β-D-glucans of several mushrooms (i.e., Poria coccus, Auricularia auricula, Ganoderma lucidium, Pleurotus ostreatus, Cordyceps sinensis, Agaricus blazei, Polyporus umbellatus, Inonotus obliquee) were purified by using a sequence of various solvent extractions, quantified by either spectrofluorometer or fluorescence microtiter plate reader assay and compared with Congo red assay method. Three-dimensional spectra measurements were carried out on β-D-glucans from commercial sources and medicinal mushroom strains. FTIR spectroscopy was selected to investigate the structural properties of β-D-glucans in these mushroom samples. Therefore, the present assay method is simple, fast, cheap and non-destructive for β-D-glucans from medicinal mushrooms as well as from commercial sources. Full article

Runx2 plays essential roles in osteoblast differentiation and chondrocyte maturation. Runx2 in the perichondrium has been reported to inhibit chondrocyte maturation through Fgf18 induction. To further investigate the functions of Runx2 in the perichondrium, we generated Runx2^fl/−Cre mice by crossing Runx2^fl/+, Runx2^+/−, and 2.3-kb Col1a1 Cre mice and compared them with Runx2^fl/− mice at E15.5, when the endochondral bones were cartilaginous. Skeletal preparation of the upper limbs in Runx2^fl/−Cre mice showed reduced mineralization of the humerus and scapula, and histological analysis of the femurs showed delays in the terminal differentiation of chondrocytes, as indicated by the absence of mineralization and Spp1 expression in the cartilage and osteoblast differentiation in the perichondrium, compared to those in Runx2^fl/− mice. mRNA sequence analysis showed that the expression of Nell1, which encodes a secreted protein that enhances chondrocyte maturation, in Runx2^fl/−Cre femurs was more than two-fold lower than that in Runx2^fl/− femurs. Nell1 expression was reduced in the perichondrium of Runx2^fl/−Cre femurs compared to that in Runx2^fl/− femurs. Nell1 expression was upregulated by Runx2 overexpression and downregulated by Runx2 siRNA. These findings indicate that Runx2 in perichondrial osteoblasts enhances the terminal differentiation of chondrocytes by inducing Nell1 expression. Full article

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne zoonotic pathogen of significant public health concern in South Korea, where human cases continue to occur at high levels; however, information on the molecular epidemiology and genotype diversity of SFTSV in goats—an increasingly important livestock species—remains limited. In this study, blood samples were collected from 750 clinically healthy goats during nationwide surveillance in 2024. Viral RNA was detected by RT-PCR targeting the S and M genomic segments. Epidemiological characteristics were analyzed according to season, region, farm size, breed, and sex. Positive samples were subjected to sequencing and phylogenetic analysis to determine SFTSV genotypes. SFTSV RNA was detected in 10 of 750 goats (1.3%), with significantly higher detection rates in autumn compared with summer, in southern regions compared with northern regions, and in female goats compared with males, while no significant association was observed with farm size or breed. Phylogenetic analysis showed that goat-derived SFTSV strains belonged to genotypes B2, D, and F; notably, genotypes D and F were identified in goats for the first time in South Korea. These findings indicate that goats are exposed to genetically diverse SFTSV strains circulating in tick populations and exhibit epidemiological patterns consistent with tick ecology and human SFTS incidence, supporting the role of goats as incidental or sentinel hosts. Continuous molecular surveillance of goats, integrated with vector monitoring programs, may enhance understanding of regional SFTSV transmission dynamics and facilitate early detection of emerging genotypes with public health implication. Full article

Non invasive prenatal testing, NIPT, is widely used for fetal aneuploidy screening, but its clinical utility depends on gestational timing and maternal characteristics. Low fetal fraction can lead to unreportable tests and increased false negative risk, while GC-content-related sequencing bias may contribute to both false positive and false negative findings. We propose a Bayesian decision-theoretic optimization framework to recommend personalized NIPT timing across maternal body mass index (BMI) strata, explicitly incorporating test credibility and detection errors. We performed a retrospective analysis of de-identified NIPT records from a hospital in Guangdong Province, China, covering 1 January 2023 to 18 February 2024, including 1082 male fetus tests. Y chromosome concentration was used as a proxy for test reportability, with a 4 percent reporting threshold. Detection state proportions were empirically summarized from clinical reference information, with false positives at 10.35 percent and false negatives at 2.77 percent. A logistic regression model quantified the probability of obtaining a reportable result as a function of gestational week, maternal age, height, and weight, and the estimated probabilities were used to parameterize the Bayesian risk model. The optimized BMI-stratified schedule produced six BMI groups with recommended testing weeks ranging from 11 to 16, and the overall expected risk converged to 0.531. These results indicate a nonlinear BMI–timing relationship and suggest that a single universal testing week is suboptimal. The proposed framework provides quantitative decision support for BMI-stratified NIPT scheduling in clinical practice. Full article

Comparative transcriptomics offers a powerful approach to elucidate host–virus interactions across related pathogens, yet systematic evaluations across species-matched cellular systems remain limited. We performed a cross-species RNA sequencing analysis of respective species’ cells infected with three alphaherpesviruses—herpes simplex virus 1 (HSV-1), bovine alphaherpesvirus 1 (BHV-1), and equid alphaherpesvirus 1 (EHV-1)—to dissect conserved and virus-specific transcriptional responses. We show that certain orthologous genes and orthologous pathways are differentially regulated upon infection among the three species like pathways related to translation rRNA processing and TNF-alpha signalling. We find that the earliest sampled timepoint of infection, 2 h post infection (hpi), shows the most commonly enriched pathways among the three species compared to later timepoints. At 6 h and 9 h post infection, BHV-1- and EHV-1 infections have more in common with each other in terms of enriched pathways than with HSV-1 infections. Moreover, we provide a comprehensive analysis of temporal viral gene expression for all three herpesviruses. Together, these findings provide a comparative framework for understanding alphaherpevirus–host interactions and reveal both conserved core responses and species-specific transcriptional signatures. This work establishes a foundation for identifying broadly acting antiviral targets as well as virus-specific vulnerabilities that may inform host-directed therapies and cross-species disease management. Full article

This study presents the complete sequencing and comparative genomic analysis of Leimania (Viannia) naiffi and Leishmania (Viannia) shawi, species of epidemiological relevance in the Brazilian Amazon. Genome assemblies yielded sizes of 32.13 Mb and 32.51 Mb, with 8170 and 7767 annotated genes, respectively. Predicted gene functions were primarily related to catalytic, binding, and ATP-dependent activities. Pangenome analysis revealed a core genome of 6256 genes alongside notable species-specific differences, including 46 and 25 unique genes in L. naiffi and L. shawi. Functional screening identified pharmacologically promising proteins such as calpains, ABC transporters, and notably, GSK-3. Ploidy analysis indicated tetraploidy on chromosome 8 in L. naiffi and chromosome 2 in L. shawi. Genetic variability assessment detected 34,480 SNPs in L. naiffi and 26,562 in L. shawi, indicating greater genomic diversity in the former. Phylogenetic inference based on the polA1 gene confirmed the placement of both species within the Leishmania (Viannia) subgenus. These findings advance Leishmania genomics knowledge by highlighting unique genetic signatures, regions of high variability, and potential therapeutic targets. This work establishes a foundation for future research on evolution, pathogenicity, and drug development for leishmaniasis. Full article

With the development of space laser networks, miniaturization and lightweight design have become inevitable trends in laser terminal development. In laser links, functions such as spot position measurement, ranging, and data transmission are usually performed by multiple independent units. Integrating these three functions can effectively reduce the size of the opto-mechanical structure and save space within the optical transceiver, thereby supporting the lightweight and compact growth of laser terminals. This paper presents an integrated scheme based on an optical direct-sequence spread-spectrum (DSSS) quadrant detector (QD) and regenerative codes, which enables spot position measurement, ranging, and data transmission through an optical transceiver. The core of this approach involves using a code tracking loop to perform correlation gain calculation, phase comparison, and demodulation of the pseudo-noise code-modulated laser signal, thereby achieving all three functions simultaneously. A desktop experimental system was built to test and verify the scheme’s accuracy and precision. The system achieved a ranging accuracy of 14 mm (1σ), a spot position measurement accuracy of 0.83 μm (1σ) at the target center, and a communication sensitivity of −31 dBm at a 10⁻⁴ bit error rate (BER) with a data rate of 1 Kbps. This study provides a reference for future lightweight optical terminals. Full article

Objectives: Respiratory syncytial virus (RSV) is a leading cause of hospitalization for acute lower respiratory tract infections (ALRIs) in children, with bacterial coinfection complicating diagnosis and often driving antibiotic overuse. This study aimed to develop and validate a clinical prediction model using common laboratory biomarkers to enable early, accurate identification of clinically significant bacterial coinfection in children with RSV infection. Methods: A single-center, retrospective cohort study was conducted at Fujian Children’s Hospital, enrolling 518 hospitalized children with RSV infection, which was confirmed via targeted next-generation sequencing (tNGS). Patients were randomly divided into a training set (n = 363) and a test set (n = 155) at a 7:3 ratio. The primary outcome, bacterial coinfection, was defined by a composite reference standard integrating etiological evidence from tNGS with clinical, inflammatory, and imaging data, and adjudicated by a blinded expert panel. LASSO regression identified independent predictors, followed by multivariable logistic regression modeling. Model performance was assessed via discrimination (AUC), calibration (Hosmer–Lemeshow test), and clinical utility (Decision Curve Analysis) in both sets. Results: Neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP), and serum amyloid A (SAA) were selected as predictors. The model achieved an AUC of 0.832 (95% CI: 0.788–0.875) in the training set and 0.811 (95% CI: 0.737–0.885) in the test set, with well-calibrated predictions (p > 0.05). Decision curve analysis demonstrated net clinical benefit across 10–80% threshold probabilities. A nomogram was developed for practical application. Conclusions: This study established a model integrating NLR, CRP, and SAA. It offers a reliable tool for the early detection of bacterial coinfection in RSV-infected children, enabling targeted antibiotic stewardship and improving clinical outcomes. Full article