Search Results (2,655)

Background: Vulvar cancer is a rare gynecologic malignancy comprising 1–3% of all cases. No established standard exists for advanced disease, and treatment is often extrapolated from cervical cancer. Although HER2 overexpression is well defined in breast cancer and recognized across multiple solid tumors, its prevalence and significance in vulvar cancer remain unclear. Recent activity of HER2-directed antibody–drug conjugate Trastuzumab deruxtecan in solid tumors with an objective response rate (ORR) of around 37% highlights the need to better characterize HER2 expression in vulvar cancer. Methods: We performed a systematic search of Medline, Embase, and the Cochrane Library up to May 2025. Eligible studies included ≥10 vulvar cancer cases, predominantly vulvar squamous cell carcinoma (VSCC), excluding vulvar Paget’s disease, with available HER2 assessment by immunohistochemistry and/or in situ hybridization. Two reviewers independently screened the studies. A random-effects model was used to estimate pooled HER2 positivity. Heterogeneity was assessed using Cochrane’s Q and Higgins’s I². Results: Of 506 records, nine retrospective studies including 769 patients with predominantly squamous cell carcinoma histology (98%, n = 752) met inclusion criteria. A total of 50 HER2-positive cases were observed. Median age at diagnosis of vulvar cancer was between 55 and 78, reported in three studies. Molecular profiling was limited. Among three studies with known TP53 status (n = 206), 59% of the tumors expressed TP53 (n = 122), and among two studies with known human papilloma virus (HPV) status (n = 128), 21% (n = 27) were HPV-positive. Six studies used American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) HER2 testing guidelines in breast cancer. Pooled HER2-positive expression across ASCO/CAP-based studies was 2% (95% CI: 1%, 3%) and for non-ASCO/CAP-based studies was 21% (95% CI: 2%, 52%). Exploratory pooled estimated proportion of HER2-positive expression was 5% (95% CI: 0.4%, 14%). There was substantial heterogeneity across studies, I² value of 91.1% [95% CI: 85.4%; 94.6%], and no significant publication bias was observed (Egger’s test p = 0.364). This study could not assess prognostic value of HER2 overexpression in VSCC. Conclusions: HER2 positivity in VSCC appears uncommon but it remains to be fully explored. Standardized assessment using contemporary ASCO/CAP breast, endometrial-specific and/or gastric criteria are needed to clarify the prevalence of HER2-positive versus HER2-low/ultralow disease to inform potential use of HER2-targeted therapy. Full article

(1) Background: Over the past few decades, the number and chromosomal arrangement of rDNA loci have been successfully used as cytogenetic markers in comparative studies of many insect taxa, including the hemipteran suborder Heteroptera (or true bugs). Of the seven generally accepted infraorders of true bugs, such data are available only for three: one of the early branching infraorders Nepomorpha and the sister infraorders Cimicomorpha and Pentatomomorpha. To address this gap, we obtained rDNA-FISH data for another “early” evolutionary lineage of true bugs, the infraorder Gerromorpha, in which we studied four species belonging to the families Gerridae and Mesoveliidae. (2) Methods: Standard karyotypes were studied using the Schiff–Giemsa method. To study the chromosomal distribution of the major rDNA (45S rDNA), the Fluorescence In Situ Hybridization (FISH) method was used with an 18S rDNA probe. (3) Results: Three variants of the chromosomal arrangement of 18S rDNA were identified in the studied species. The rDNA loci were located on one pair of autosomes in Aquarius paludum (n = 11AA + X) and Gerris lacustris (n = 10AA + X); on one pair of autosomes and on the X chromosome in Limnoporus rufoscutellatus (n = 10AA + X) (Gerridae); on one of the four X chromosomes and on the Y chromosome in Mesovelia furcata (n = 15AA + X₁X₂X₃X₄Y) (Mesoveliidae). The karyotype of L. rufoscutellatus was studied for the first time. (4) Conclusions: Our study provides the first data on the rDNA-FISH location for the infraorder Gerromorpha and expands current understanding of the chromosomal distribution of rDNA arrays in Heteroptera as a whole. Full article

Brewer’s spent grain (BSG), the main by-product of the brewing industry, is a rich source of arabinoxylans (AXs) and hydroxycinnamic acids, particularly ferulic acid (FA), which contribute to its prebiotic potential. This study evaluates the prebiotic properties of residual solid from an enzymatically treated BSG, compared to the properties of BSG as a non-enzymatically hydrolyzed control. Although the residual solid exhibited total polyphenol (2581.96 ± 70.63 mg/100 g dry weight) and FA (180.84 ± 3.28 mg/100 g dry weight) contents comparable to those of the non-hydrolyzed control (2500.38 ± 284.20 and 179.59 ± 3.30 mg/100 g dry weight, respectively), the AX content was significantly higher (14,084.81 ± 185.72 mg/100 g), accompanied by a lower degree of feruloylation (12.84 ± 0.23 mg FA/g AX), higher antioxidant activity (64,825.35 ± 4011.24 μmol TE/100 g), and structural changes visualized by scanning electron microscopy. In addition, in vitro colonic fermentation showed a delayed butyrogenic profile, with increased butyrate production compared to the control (3.17 ± 1.44 mM). Microbiota analysis by fluorescence in situ hybridization (FISH) coupled with flow cytometry indicated an increase in butyrate-producing bacteria, including Faecalibacterium prausnitzii (+5.90) and Eubacterium rectale (+6.88). Growth of Bacteroides, Lactobacillus, and Bifidobacterium spp. was also promoted. Overall, these findings suggest that enzymatic processing of BSG can generate a residual solid with modified structural characteristics and potential prebiotic functionality, supporting its potential application as a fermentable flour ingredient in functional foods. Full article

Telomerase reverse transcriptase (TERT) plays a regulatory role in the induction, activation, and hair growth of human and mouse hair follicles. However, the effects of mutations in this gene on sheep hair follicle development and wool traits remain unclear. In this study, the TERT gene (TERT) was investigated using Kompetitive Allele-Specific PCR (KASP) technology and in situ hybridization. The results revealed six single nucleotide polymorphisms (SNPs) across the four exons of TERT, two of which were non-synonymous. The TERT mRNA showed weak positive expression in the stratum corneum, inner root sheath, hair follicle medulla, and sebaceous glands; moderate positive expression in the outer root sheath; and strong positive expression in the dermal papilla. An association analysis between wool trait variation and the SNPs revealed that the two non-synonymous changes were associated with mean wool staple strength (MSS), thus TERT could potentially serve as a candidate gene for this trait. Full article

A biological/synthetic hybrid graft copolymer was obtained by grafting poly(acrylic acid) (PAA, synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization) to amylopectin (AMP). The novel graft copolymer presents amphiphilic properties due to the inherent insolubility of AMP in water and was further utilized as a mediator for the synthesis of gold nanoparticles (AuNPs) following an environmentally friendly in situ procedure. The AMP-g-PAA copolymer formation by the interaction of the PAA end groups with the C(6)-OH groups on an AMP backbone was confirmed by Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR) and 1D (proton (¹H NMR) and carbon (¹³C NMR) nuclear magnetic resonance, and Distortionless Enhancement by Polarization Transfer (DEPT)) and 2D (correlation (COSY) and heteronuclear single quantum coherence (HSQC)) spectroscopies. The calculated degree of substitution of 1.17 suggests that the grafting was done at one OH from the three in an anhydroglycosidic unit (AGU) (preferably at that in C6 position), with a mean grafting efficiency of 76%. Additional information obtained using thermogravimetric analysis shows that the thermal decomposition of AMP-g-PAA occurs in two steps, with a residual mass of ~16 wt% at 700 °C, higher than AMP or PAA, indicating increased thermal stability of the copolymer. Dynamic and electrophoretic light scattering (DLS and ELS) measurements were used to determine the hydrodynamic size and ionic charge of the AMP-g-PAA self-assemblies in aqueous solution as well as their stability. The AMP-g-PAA was subsequently tested as a reducing agent in the environmentally friendly synthesis of AuNPs in aqueous solution, at different incubation temperatures, reaction duration, and inorganic/polymer weight ratios. The development of the surface plasmon resonance band of AuNPs, observed in UV–vis spectra, was consistently monitored over the reaction time. DLS analysis indicated time-dependent changes in the AuNPs’ particle size distributions, while scanning transmission electron microscopy confirmed that the AuNPs formed at the inorganic/polymer weight ratio of 0.36 and at 60 °C were predominantly well-dispersed, spherical-shaped nanoparticles. The AuNPs synthesized in situ within the copolymer matrix did not introduce additional cytotoxicity compared to the parent copolymer alone, with the composites representing a promising safety baseline for further investigation in biomedical applications. Full article

Ultra-high-temperature materials (UHMs) are indispensable for extreme thermal environments (e.g., temperatures exceeding 2000 °C); however, their practical implementation remains severely constrained by demanding processing conditions, including extreme sintering temperatures, prolonged cycles, densification barriers and high equipment cost. In order to meet the low-cost and ablation-resistant requirements of aircraft nose cones, a facile organic–inorganic hybrid strategy is proposed to fabricate ZrB₂–HfC–SiC composites using a high-char-yield 1,2-dicyanobenzene (DCB) binder, enabling low-temperature moulding at merely 250 °C (2 h; 20 MPa). Upon high-temperature oxidative exposure, the DCB matrix undergoes in situ pyrolysis and synergistic co-sintering with the ceramic powders, producing a multi-layered, self-protective structural architecture. A comprehensive structure–temperature map correlating temperature-dependent phase evolution with flexural strength and thermal conductivity is established, thereby elucidating the underlying self-healing and ablation-resistance mechanisms. The hybrid material in this work exhibits excellent flexural strength, ablation resistance and thermal stability. This study successfully reconciles the long-standing contradiction between low-temperature processability and ultra-high-temperature (2600 °C) service durability, offering a scalable route for next-generation thermal protection systems. Full article

Background/Objectives: Cytokinin and auxin are essential for vascular development in plants. This study aims to explore whether these two hormones exhibit crosstalk in the cambium, analogous to that observed in the apical meristem. Methods: Using the hybrid poplar (Populus alba × Purshia glandulosa clone ‘84K’), we integrated gravitropic induction with transcriptomic analysis and identified the cytokinin biosynthesis gene PagIPT5 as differentially expressed in a tension wood induction system. PagIPT5 overexpression lines were generated and assessed for growth-related phenotypes. The interaction between cytokinin and auxin was investigated via anatomical observation, cell proliferation assays, in situ PCR, and immunofluorescence detection of auxin and cytokinin. Results: Compared with the wild type, PagIPT5 overexpression lines showed growth inhibition and an auxin-deficient phenotype. High PagIPT5 expression in the vascular cambium elevated cytokinin levels while reducing auxin levels, leading to decreased cambial cell proliferation and suppressed xylem development. However, in the tension wood induction system, both auxin and cytokinin levels increased in the vascular cambium of tension wood relative to opposite wood. Treatment with a superoxide anion activator promotes the accumulation of both auxin and cytokinin in 84K plants. Conclusions: These results revealed an antagonistic interaction between the two hormones in the cambium zone. However, this antagonism is attenuated in tension wood, which may be induced by the accumulation of superoxide anion in tension wood. Full article

Plasma electrolytic oxidation (PEO) has emerged as a leading surface engineering technology for improving the tribological and corrosion performance of lightweight structural alloys, including aluminum, magnesium, titanium, and zirconium. Unlike conventional anodizing or line-of-sight deposition processes, PEO forms thick, multiphase ceramic oxide coatings metallurgically bonded to the substrate through plasma-assisted in situ oxidation, enabling treatment of complex and internal geometries that competing technologies cannot reach. The tribological performance of PEO coatings is governed by coupled interactions among electrolyte chemistry, electrical discharge behavior, phase evolution, porosity development, and residual stress state. This review critically evaluates the friction, wear, and tribo-corrosion behavior of PEO coatings under dry sliding, lubricated, high-temperature, marine, and vacuum environments, and systematically examines the influence of processing parameters, microstructural evolution, transfer layer formation, and counterface interactions on coating performance. Hybrid and duplex systems incorporating solid lubricants, polymer impregnation, sol–gel sealing, and multilayer architectures are discussed as strategies to overcome limitations associated with brittleness and surface porosity. Current research challenges, including fatigue degradation, coating defect control, limited cross-study standardization, and incomplete mechanistic understanding of process–microstructure, tribological relationships, are critically assessed. Emerging directions encompassing self-lubricating adaptive coatings, AI-guided process optimization, and multifunctional hybrid architectures are highlighted as pathways toward next-generation surface systems. This review provides a mechanism-based framework for understanding tribological behavior in PEO coatings and identifies critical opportunities for future industrial implementation in aerospace, automotive, marine, biomedical, and energy applications. Full article

Sea cucumber Apostichopus japonicus is one of the few animals capable of synthesizing saponins, which are critical components of its nutritional quality and health-beneficial properties. However, the specific mechanism underlying saponin biosynthesis in sea cucumbers remains unclear despite previous investigations. This study aimed to characterize the molecular pathway and regulatory mechanism of saponin biosynthesis in A. japonicus. Thirteen candidate genes involved in de novo saponin skeleton synthesis were identified from the A. japonicus genome, and their full-length cDNAs were obtained via PCR-RACE. Sequence analysis predicted the intracellular localization of these genes. Combined in situ hybridization and quantitative real-time PCR analyses revealed their high expression in coelomocytes, indicating coelomocytes as the primary saponin synthesis sites. Knockdown of mevalonate kinase (AjMVK) and two oxidosqualene cyclases (AjPS and AjLS) caused a more obvious decrease in saponin levels, identifying them as key biosynthetic enzymes. Yeast two-hybrid assays revealed that AjPS and AjLS interact with ficolins, complement component 3-2, O-linked β-N-acetylglucosamine transferase, and α-L-fucosidase, whose regulatory effects were further validated by RNA interference and saponin content measurements. These results suggest that saponin biosynthesis in A. japonicus is regulated by the complement lectin pathway and modulated by glycosylation enzymes, providing a molecular foundation for enhancing bioactive saponin production for pharmaceutical and nutraceutical applications. Full article

The intratumoral microbiota has emerged as a critical component of the tumor microenvironment (TME), with accumulating evidence indicating that its biological functions are influenced not only by microbial composition but also by their spatial organization within tumor tissues. This review summarizes the historical development and potential origins of intratumoral microbiota, and elaborates on the concept and biological significance of spatial heterogeneity. Based on recurrent spatial distribution patterns reported across different tumor types, we propose a conceptual framework comprising several putative spatial niches, including hypoxic/necrotic, immune-enriched, stromal-associated, invasive/metastatic, and intracellular niches. We further discuss the potential mechanisms contributing to the establishment and maintenance of spatial heterogeneity. The clinical significance of spatial microbial signatures is critically evaluated, alongside a comprehensive overview of spatial analytical methodologies, ranging from in situ hybridization and immunology-based approaches to emerging spatial omics and multi-omics integration strategies. Finally, we address key challenges and limitations, including contamination control, causal inference, barriers to clinical translation, and the underexplored spatial dimensions of the intratumoral mycobiome and virome. By synthesizing current knowledge and identifying critical gaps, this review aims to provide a conceptual and methodological framework for advancing spatially resolved investigations of intratumoral microbiota and facilitating their potential translational applications in precision oncology. Full article

A 54-year-old female patient presented with a gradually enlarging mass on the ulnar side of the left wrist. Magnetic resonance imaging demonstrated a fat-containing lesion deep within the flexor carpi ulnaris that showed heterogeneous signal intensity, as well as weak internal and peripheral enhancement, which are not typical for atypical spindle cell/pleomorphic lipomatous tumors (ASPLTs). The imaging appearance overlapped with spindle cell lipoma (SCL), atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL), and hibernoma, which made preoperative diagnosis challenging. The mass was excised en bloc. Histologically, the tumor consisted of mature adipocytes with substantial size variation, mild atypical spindle cells within a myxoid stroma, and scattered lipoblasts. Immunohistochemistry showed CD34 positivity and loss of RB1, while MDM2 amplification was absent on fluorescence in situ hybridization analysis, supporting a diagnosis of ASPLT. ASPLT is known for its broad range of morphological and radiological presentations, and this case further highlights the difficulty inherent in distinguishing it from SCL and ALT/WDL based on imaging alone. Recognition of its diverse features and the use of molecular testing are essential for accurately diagnosing ASPLT. Surgical excision remains the standard treatment. Although recurrence has been reported, metastasis of ASPLT is exceedingly rare. Full article

Pediatric acute myeloid leukemia (AML) is biologically heterogeneous, and genomic profiling increasingly informs risk stratification and treatment. We evaluated the relationship between induction response, genomic risk, transplant allocation, and survival in pediatric AML. We retrospectively analyzed 38 pediatric patients with newly diagnosed AML, treated between 2020 and 2025. Clinical, cytogenetic, molecular, treatment, and outcome data were collected. Genomic alterations were assessed using cytogenetics, fluorescence in situ hybridization (FISH), molecular testing, and next-generation sequencing (NGS). Survival was estimated by Kaplan–Meier analysis, and prognostic factors for event-free survival (EFS) were assessed using univariable Cox regression. This study is exploratory given the limited sample size and should be interpreted accordingly. Complete remission (CR) after the first course of induction was achieved in 25/38 patients (65.8%), partial remission (PR) in 3/38 (7.9%), and refractory disease in 10/38 (26.3%). Twenty-four patients underwent allogeneic hematopoietic stem cell transplantation; 17/24 (70.8%) were alive at last follow-up, with a 2-year overall survival rate of 72.9%. Both induction response and genomic risk stratification showed suggestive associations with outcome; descriptively, induction response showed the strongest prognostic discrimination, with achievement of CR associated with markedly improved survival. High cytogenetic risk and FLT3-ITD were significantly associated with inferior EFS. Post-induction measurable residual disease (MRD) positivity was detected in 16 of 38 patients (42.1%) and was associated with suboptimal induction response; MRD negativity did not uniformly preclude adverse outcomes, particularly in the high-risk genomic subgroup. Genomic profiling refined biological risk and post-remission treatment allocation. Integrated assessment of genomic risk, induction response, and MRD status may improve therapeutic stratification in pediatric AML. Full article

Background/Objectives: The Y chromosome plays a crucial role in male fertility, sex determination, and spermatogenesis, yet it remains poorly characterized in Mediterranean river buffalo (Bubalus bubalis, 2n = 50) because of its high repeat content, extensive heterochromatin, and complex palindromic structures. Although a chromosome-level Y assembly is available for swamp buffalo (2n = 48), no equivalent reference exists for the river type. Methods: To address this gap, Y chromosomes from 10 Mediterranean buffalo bulls were isolated by laser microdissection following peripheral blood culture and whole-chromosome amplification. Probe specificity was verified by FISH, and amplified Y chromosomes were sequenced using Illumina NovaSeq 6000 (Illumina, San Diego, CA, USA). Sequencing data were assembled and analysed through de novo assembly, repeat identification, sequence alignment, and variant detection. Comparative analyses included alignment to the swamp buffalo Y chromosome and annotation of Y-linked genes using the Bos taurus reference genome. Results: FISH confirmed the specificity of the isolated material, showing strong signals on the Y chromosome and on X/Y PAR and heterochromatic regions. Sequencing generated over 240 million paired-end reads, and de novo assembly produced 566,815 contigs. Repeat analysis identified 3.91% repetitive elements, mainly SINEs, while variant calling detected more than 23,000 variants. Comparative analyses mapped several contigs to the swamp buffalo Y chromosome and Y-linked genes. Annotation against the B. taurus genome identified 26 unique genes, including homologs shared with the X chromosome, and revealed MSY gene duplications, including 10 copies of TSPY and 3 of HSFY. Conclusions: These findings show that laser microdissection with NGS enables effective access to the buffalo Y chromosome, representing a milestone in the characterization of the river type genome, and providing a basis for studies on buffalo male fertility and breeding programs. Full article

Lead (Pb²⁺) and cadmium (Cd²⁺) are among the most hazardous heavy metal pollutants in wastewater owing to their high toxicity, environmental persistence, and detrimental impacts on human health and aquatic ecosystems. In this study, a novel ternary magnetic composite, SnFe₂O₄/activated carbon/polypyrrole (SnFe₂O₄/AC/PPy), was effectively synthesized and tested as an effective adsorbent in the removal of Pb²⁺ and Cd²⁺ from aqueous water. The composite was prepared by depositing spinel SnFe₂O₄ nanoparticles on activated carbon, followed by in situ polymerization of polypyrrole to enhance surface functionality and adsorption affinity. The successful fabrication of the porous SnFe₂O₄/AC/PPy hybrid composite was confirmed through FTIR, XRD, SEM–EDS, BET, XPS, and VSM characterization. The composite demonstrated a relatively high surface area (352.3 m²/g) and adequate magnetic responsiveness (12.33 emu/g), ensuring facile magnetic separation following wastewater treatment. Batch adsorption experiments showed great removal efficiency of 95.02 and 92.48% for Pb²⁺ and Cd²⁺ ions, respectively, at optimum conditions. The adsorption equilibrium data followed the Langmuir isotherm model with maximum adsorption capacities of 187.07 mg/g for Pb²⁺ and 96.45 mg/g for Cd²⁺ ions, which were attributed to monolayer adsorption on homogenous active sites. The kinetic and isothermal model indicated that the adsorption process was controlled by the combination of physical and chemical interactions. Thermodynamic parameters showed negative Gibbs free energy and enthalpy changes (ΔH° = −49.74 kJ/mol for Pb²⁺ and −38.82 kJ/mol for Cd²⁺ ions), confirming the spontaneous and exothermic nature of adsorption. Furthermore, the increasingly negative ΔG° values at lower temperatures indicated that the adsorption was thermodynamically more favorable under cooler conditions. According to the regeneration studies, the composite maintained a high removal efficiency after five consecutive cycles. In general, SnFe₂O₄/AC/PPy composite has good potential as a stable, reusable, and high-performance adsorbent to treat heavy metal wastewater. Full article

The limited energy efficiency of sonochemical processes and the high reagent consumption of Fenton-based treatments remain the major challenges for large-scale water treatment. This study investigates a hybrid Sono–Galvano–Fenton (US/GF) process for the degradation of malachite green as a model organic pollutant, using parallel and series coupling configurations for the assessment of the potential synergistic effects of ultrasound and galvanic Fenton reactions. The results show that acoustic streaming can effectively replace mechanical stirring, providing comparable mixing performance while reducing mechanical energy requirements by approximately 20–30%. In addition, in situ sonochemical hydrogen peroxide generation contributes to pollutant degradation, achieving up to 35–50% removal efficiency, although this remains lower than the efficiency obtained with conventional Galvano–Fenton processes, which typically achieve removal efficiencies of 70–90%. In addition, continuous-flow hybrid configurations appear promising to improve in situ reagent production and overall process efficiency. Full article