Search Results (739)

Extensive research on amphibians has focused on areas such as morphological and molecular taxonomy, ecology, embryology, and molecular phylogeny. However, the structure and biotechnological potential of egg jelly—which plays a protective and nutritive role for embryos—have remained largely unexplored. This study presents, for the first time, a detailed physicochemical analysis of the egg jelly of Pelophylax ridibundus, an amphibian species, using Fourier Transform Infrared Spectroscopy, Thermogravimetric Analyzer, X-ray Diffraction, and elemental analysis. The carbohydrate content was determined via High-Performance Liquid Chromatography analysis, and the protein content was identified using Liquid Chromatography-Tandem Mass Spectrometry analysis. Additionally, it was revealed that this jelly exhibits a significant cytotoxic effect on melanoma cells (viability < 30%) while showing no cytotoxicity on healthy dermal fibroblast cells (viability > 70%). Consequently, this non-toxic, biologically derived, and cultivable material is proposed as a promising candidate for cancer applications, paving the way for further research in the field. Full article

Bacteriophages (phages), the most abundant biological entities on Earth, have long served as both model systems and therapeutic tools. Recent advances in synthetic biology and genetic engineering have revolutionized the capacity to tailor phages with enhanced functionality beyond their natural capabilities. This review outlines the current landscape of synthetic and functional engineering of phages, encompassing both in-vivo and in-vitro strategies. We describe in-vivo approaches such as phage recombineering systems, CRISPR-Cas-assisted editing, and bacterial retron-based methods, as well as synthetic assembly platforms including yeast-based artificial chromosomes, Gibson, Golden Gate, and iPac assemblies. In addition, we explore in-vitro rebooting using TXTL (transcription–translation) systems, which offer a flexible alternative to cell-based rebooting but are less effective for large genomes or structurally complex phages. Special focus is given to the design of customized phages for targeted applications, including host range expansion via receptor-binding protein modifications, delivery of antimicrobial proteins or CRISPR payloads, and the construction of biocontained, non-replicative capsid systems for safe clinical use. Through illustrative examples, we highlight how these technologies enable the transformation of phages into programmable bactericidal agents, precision diagnostic tools, and drug delivery vehicles. Together, these advances establish a powerful foundation for next-generation antimicrobial platforms and synthetic microbiology. Full article

Background: Sodium–glucose cotransporter 2 (SGLT2) inhibitors have transformed type 2 diabetes mellitus (T2DM) management by promoting glucosuria, lowering glycated hemoglobin (HbA1c), blood pressure, and weight; however, their use is limited by genitourinary infections and ketoacidosis. Phytocannabinoids—bioactive compounds from Cannabis sativa—exhibit multi-target pharmacology, including interactions with cannabinoid receptors, Peroxisome Proliferator-Activated Receptors (PPARs), Transient Receptor Potential (TRP) channels, and potentially SGLT2. Objective: To evaluate the potential of phytocannabinoids as novel modulators of renal glucose reabsorption via SGLT2 and to compare their efficacy, safety, and pharmacological profiles with synthetic SGLT2 inhibitors. Methods: We performed a narrative review encompassing the following: (1) the molecular and physiological roles of SGLT2; (2) chemical classification, natural sources, and pharmacokinetics/pharmacodynamics of major phytocannabinoids (Δ⁹-Tetrahydrocannabinol or Δ⁹-THC, Cannabidiol or CBD, Cannabigerol or CBG, Cannabichromene or CBC, Tetrahydrocannabivarin or THCV, and β-caryophyllene); (3) in silico docking and drug-likeness assessments; (4) in vitro assays of receptor binding, TRP channel modulation, and glucose transport; (5) in vivo rodent models evaluating glycemic control, weight change, and organ protection; (6) pilot clinical studies of THCV and case reports of CBD/BCP; (7) comparative analysis with established synthetic inhibitors. Results: In silico studies identify high-affinity binding of several phytocannabinoids within the SGLT2 substrate pocket. In vitro, CBG and THCV modulate SGLT2-related pathways indirectly via TRP channels and CB receptors; direct IC₅₀ values for SGLT2 remain to be determined. In vivo, THCV and CBD demonstrate glucose-lowering, insulin-sensitizing, weight-reducing, anti-inflammatory, and organ-protective effects. Pilot clinical data (n = 62) show that THCV decreases fasting glucose, enhances β-cell function, and lacks psychoactive side effects. Compared to synthetic inhibitors, phytocannabinoids offer pleiotropic benefits but face challenges of low oral bioavailability, polypharmacology, inter-individual variability, and limited large-scale trials. Discussion: While preclinical and early clinical data highlight phytocannabinoids’ potential in SGLT2 modulation and broader metabolic improvement, their translation is impeded by significant challenges. These include low oral bioavailability, inconsistent pharmacokinetic profiles, and the absence of standardized formulations, necessitating advanced delivery system development. Furthermore, the inherent polypharmacology of these compounds, while beneficial, demands comprehensive safety assessments for potential off-target effects and drug interactions. The scarcity of large-scale, well-controlled clinical trials and the need for clear regulatory frameworks remain critical hurdles. Addressing these aspects is paramount to fully realize the therapeutic utility of phytocannabinoids as a comprehensive approach to T2DM management. Conclusion: Phytocannabinoids represent promising multi-target agents for T2DM through potential SGLT2 modulation and complementary metabolic effects. Future work should focus on pharmacokinetic optimization, precise quantification of SGLT2 inhibition, and robust clinical trials to establish efficacy and safety profiles relative to synthetic inhibitors. Full article

Electroporation-mediated gene delivery is a cornerstone of synthetic biology, offering several advantages over other methods: higher efficiencies, broader applicability, and simpler sample preparation. Yet, electroporation protocols are often challenging to integrate into highly multiplexed workflows, owing to limitations in their scalability and tunability. These challenges ultimately increase the time and cost per transformation. As a result, rapidly screening genetic libraries, exploring combinatorial designs, or optimizing electroporation parameters requires extensive iterations, consuming large quantities of expensive custom-made DNA and cell lines or primary cells. To address these limitations, we have developed a High-Throughput Microfluidic Electroporation (HTME) platform that includes a 384-well electroporation plate (E-Plate) and control electronics capable of rapidly electroporating all wells in under a minute with individual control of each well. Fabricated using scalable and cost-effective printed-circuit-board (PCB) technology, the E-Plate significantly reduces consumable costs and reagent consumption by operating on nano to microliter volumes. Furthermore, individually addressable wells facilitate rapid exploration of large sets of experimental conditions to optimize electroporation for different cell types and plasmid concentrations/types. Use of the standard 384-well footprint makes the platform easily integrable into automated workflows, thereby enabling end-to-end automation. We demonstrate transformation of E. coli with pUC19 to validate the HTME’s core functionality, achieving at least a single colony forming unit in more than 99% of wells and confirming the platform’s ability to rapidly perform hundreds of electroporations with customizable conditions. This work highlights the HTME’s potential to significantly accelerate synthetic biology Design-Build-Test-Learn (DBTL) cycles by mitigating the transformation/transfection bottleneck. Full article

Positron emission tomography (PET) and liquid biopsy have independently transformed prostate cancer management. This review explores the complementary roles of PET imaging and liquid biopsy in prostate cancer, focusing on their combined diagnostic, monitoring, and prognostic potential. A systematic search of PubMed, Scopus, and Cochrane Library databases was conducted to identify human studies published in English up to January 2025. Seventeen studies met the inclusion criteria and were analyzed according to PRISMA guidelines. Across the included studies, PET-derived imaging metrics, such as metabolic activity and radiotracer uptake, correlated consistently with liquid biopsy biomarkers, including circulating tumor cells and cell-free DNA. Their joint application demonstrated added value in early detection, treatment monitoring, and outcome prediction, particularly in castration-resistant prostate cancer. Independent and synergistic prognostic value was noted for both modalities, including survival outcomes such as overall survival and progression-free survival. Combining PET imaging and liquid biopsy emerges as a promising, non-invasive strategy for improving prostate cancer diagnosis, monitoring, and therapeutic stratification. While preliminary findings are encouraging, large-scale prospective studies are essential to validate their integrated clinical utility. Full article

The ability to study mature neuronal cells ex vivo is complicated by their non-dividing nature and difficulty in obtaining large numbers of primary cells from organisms. Thus, numerous transformed progenitor models have been developed that can be routinely cultured, then scaled, and differentiated to mature neurons. In this paper, we present a new method for differentiating one such model, the Lund human mesencephalic (LUHMES) dopaminergic neurons. This method is two days faster than some established protocols, results in nearly five times greater numbers of mature neurons, and involves fewer handling steps that could introduce technical variability. Moreover, it overcomes the problem of cell aggregate formation that commonly impedes high-resolution imaging, cell dissociation, and downstream analysis. While recently established for herpes simplex virus type 1, we demonstrate that LUHMES neurons can facilitate studies of other herpesviruses, as well as RNA viruses associated with childhood encephalitis and hemorrhagic fever. This protocol provides an improvement in the generation of large-scale neuronal cultures, which may be readily applicable to other neuronal 2D cell culture models and provides a system for studying neurotrophic viruses. We named this method the Streamlined Protocol for Enhanced Expansion and Differentiation Yield, or SPEEDY, method. Full article

There has been extensive research on the KSHV/HHV8 virus, which has led to a better understanding of viral transmission, pathogenesis, viral-driven lymphoid proliferation, neoplastic transformation, and how we might combat these processes clinically. On an extensive review of the literature, only two true KSHV/HHV8-positive lymphoid neoplasms are described: primary effusion lymphoma (PEL), which can also present as solid or extracavitary primary effusion lymphoma (EC-PEL) and diffuse large B-cell lymphoma (DLBCL). Two lymphoproliferative disorders have also been described, and while they are not true monotypic neoplasms, these lesions can transform into neoplasms: KSHV/HHV8-positive germinotropic lymphoproliferative disorder (GLPD) and multicentric Castleman disease (MCD). This review provides a somewhat concise overview of information related to KSHV/HHV8-positive lymphoid neoplasms and pertinent associated lymphoproliferative lesions. Full article

Ovarian cancer, the most lethal form of gynecological cancer worldwide with a poor prognosis, is largely driven by an immunosuppressive tumor microenvironment. In this study, we investigated the anticancer effects of hydnocarpin, a natural flavonolignan derived from the flowers of Pueraria lobata, focusing on its effects on ovarian cancer and tumor-associated immune cells, including ovarian cancer-stimulated macrophages (MQs) and T cells. Hydnocarpin exhibited potent cytotoxicity against multiple ovarian cancer cell lines but only minimal toxicity against normal ovarian surface epithelial cells. Mechanistically, hydnocarpin triggered caspase-dependent apoptosis, as evidenced by the activation of caspase-9 and -3, with limited involvement of caspase-8, indicating the activation of the intrinsic apoptotic pathway. Experimental data implicated reactive oxygen species generation as a key mediator of hydnocarpin cytotoxicity, and reactive oxygen species inhibition significantly inhibited this cytotoxicity. In addition to its direct tumoricidal effects, hydnocarpin reprogrammed the tumor-associated immune cells, ovarian cancer-stimulated macrophages and T cells, by downregulating the levels of M2 MQ markers and pro-tumoral factors (matrix metalloproteinase-2/9, C–C motif chemokine ligand 5, transforming growth factor-β, and vascular endothelial growth factor) and enhancing MQ phagocytosis. Additionally, hydnocarpin promoted T-cell activation (interferon-γ and interleukin-2) and reduced the expression levels of immune evasion markers (CD80, CD86, and VISTA). Overall, this study demonstrated the dual anti-tumor effects of hydnocarpin on both ovarian cancer cells and immunosuppressive immune components in the tumor microenvironment, highlighting its potential as a novel therapeutic candidate for ovarian cancer. Full article

Background: Endometriosis is a complex, estrogen-dependent condition that can significantly impact women’s quality of life and fertility. Current diagnostic strategies remain invasive and often prolonged, demonstrating the need for reliable, non-invasive biomarkers. In this context, microRNAs (miRNAs), due to their stability in blood and regulatory roles in inflammation and cell proliferation, have emerged as promising candidates. Methods: This review systematically analyzes 17 studies published between 2010 and 2025 that investigated the diagnostic utility of circulating and tissue-based miRNAs in endometriosis. Results: A wide range of dysregulated miRNAs was identified, with miR-125b-5p, miR-451a, and miR-3613-5p showing the most consistent alterations across studies. However, diagnostic performance varied considerably—largely due to methodological heterogeneity. Key differences were observed in sample type (serum, plasma, endometrium), patient selection, and control group definition. The menstrual cycle phase and hormonal status were often not matched or reported, limiting reproducibility. Conclusions: Despite encouraging findings, the current evidence base is weakened by inconsistent protocols and limited validation. Standardized, multicenter research with well-characterized patient cohorts is essential to the establishment of clinically applicable miRNA-based diagnostics. If validated, miRNAs may offer a transformative, non-invasive approach for earlier detection and improved management of endometriosis. Full article

Precision medicine is transforming hematologic cancer care by tailoring treatments to individual patient profiles and moving beyond the traditional “one-size-fits-all” model. This review outlines foundational technologies, disease-specific advances, and emerging directions in precision hematology. The field is enabled by molecular profiling techniques, including next-generation sequencing (NGS), whole-exome sequencing (WES), and RNA sequencing (RNA-seq), as well as epigenomic and proteomic analyses. Complementary tools such as liquid biopsy and minimal residual disease (MRD) monitoring have improved diagnosis, risk stratification, and therapeutic decision making. We discuss major molecular targets and personalized strategies across hematologic malignancies: FLT3 and IDH1/2 in acute myeloid leukemia (AML); Philadelphia chromosome–positive and Ph-like subtypes in acute lymphoblastic leukemia (ALL); BCR-ABL1 in chronic myeloid leukemia (CML); TP53 and IGHV mutations in chronic lymphocytic leukemia (CLL); molecular subtypes and immune targets in diffuse large B-cell lymphoma (DLBCL) and other lymphomas; and B-cell maturation antigen (BCMA) in multiple myeloma. Despite significant progress, challenges remain, including high costs, disparities in access, a lack of standardization, and integration barriers in clinical practice. However, advances in single-cell sequencing, spatial transcriptomics, drug repurposing, immunotherapies, pan-cancer trials, precision prevention, and AI-guided algorithms offer promising avenues to refine treatment and improve outcomes. Overcoming these barriers will be critical for ensuring the equitable and widespread implementation of precision medicine in routine hematologic oncology care. Full article

Sediment fingerprinting was utilized to identify potential hotspots of soil erosion and sediment transport pathways in the Nile Nyabarongo Upper Catchment (NNYU) in Rwanda, where rivers and reservoirs are suffering from alarmingly high levels of sedimentation. Sediment fingerprinting is a practical approach used to identify erosional hotspots and sediment transport processes in highly mountainous regions undergoing swift land use transformation. This technique involves a statistical comparison of the elemental composition of suspended sediments in river water with the elemental composition of soils belonging to different geological formations present in the catchment, thereby determining the sources of the suspended sediment. Suspended sediments were sampled five times over dry and wet seasons in all major headwater tributaries, as well as the main river channel, and compared with soils from respective delineated watersheds. Elemental composition was obtained using laser ablation inductively coupled plasma mass spectrometry, and elements were chosen that could reliably distinguish between the various geological types. The final results indicate different levels of sediment contribution from different geological types. A three-level intervention priority system was devised, with Level 1 indicating the areas with the most serious erosion. Potential sources were located on an administrative map, with the highest likely erosion over the study period (Level 1) occurring in Kabuga cell in the Mwogo sub-catchment, Nganzo and Nyamirama cells in the Nyagako sub-catchment and Kanyana cell in the NNYU downstream sub-catchment. This map enables the pinpointing of site visits in an extensive and rugged terrain to verify the areas and causes of erosion and the pathways of sediment transport. Sediment concentrations (mg L⁻¹) were the highest in the Secoko and Satinsyi tributaries. The composition of suspended sediment was seen to be temporally and spatially dynamic at each sampling point, suggesting the need for an adequate number of sampling locations to identify erosion hotspots in a large mountainous watershed. Apart from prioritizing rehabilitation locations, the detailed understanding of critical zone soil–land cover–climate processes is an important input for developing region-specific watershed management and policy guidelines. Full article

Background/Objectives: ALK+ Anaplastic Large Cell Lymphoma (ALCL) is an aggressive T-cell lymphoma that is characterized by expression of the Anaplastic Lymphoma Kinase (ALK), which is induced by the t(2;5) chromosomal rearrangement, leading to the expression of the NPM-ALK fusion oncogene. Most previous preclinical models of ALK+ ALCL were based on overexpression of the NPM-ALK cDNA from heterologous promoters. Due to the enforced expression, this approach is prone to artifacts arising from synthetic overexpression, promoter competition and insertional variation. Methods: To improve the existing ALCL models and more closely recapitulate the oncogenic events in ALK+ ALCL, we employed CRISPR/Cas-based chromosomal engineering to selectively introduce translocations between the Npm1 and Alk gene loci in murine cells. Results: By inducing precise DNA cleavage at the syntenic loci on chromosome 11 and 17 in a murine IL-3-dependent Ba/F3 reporter cell line, we generated de novo Npm-Alk translocations in vivo, leading to IL-3-independent cell growth. To verify efficient recombination, we analyzed the expression of the NPM-ALK fusion protein in the recombined cells and could also show the t(11;17) in the IL-3 independent Ba/F3 cells. Subsequent functional testing of these cells using an Alk-inhibitor showed exquisite responsiveness towards Crizotinib, demonstrating strong dependence on the newly generated ALK fusion oncoprotein. Furthermore, a comparison of the gene expression pattern between Ba/F3 cells overexpressing the Npm-Alk cDNA with Ba/F3 cells transformed by CRISPR-mediated Npm-Alk translocation indicated that, while broadly overlapping, a set of pathways including the unfolded protein response pathway was increased in the Npm-Alk overexpression model, suggesting increased reactive changes induced by exogenous overexpression of Npm-Alk. Furthermore, we observed clustered expression changes in genes located in chromosomal regions close to the breakpoint in the new CRISPR-based model, indicating positional effects on gene expression mediated by the translocation event, which are not part of the older models. Conclusions: Thus, CRISPR-mediated recombination provides a novel and more faithful approach to model oncogenic translocations, which may lead to an improved understanding of the molecular pathogenesis of ALCL and enable more accurate therapeutic models of malignancies driven by oncogenic fusion proteins. Full article

Microscopic cell classification is a fundamental challenge in both clinical diagnosis and biological research. However, existing methods still struggle with the complexity and morphological diversity of cellular images, leading to limited accuracy or high computational costs. To overcome these constraints, we propose an efficient classification method that balances strong feature representation with a lightweight design. Specifically, an Inception-Linear Attention-based Lightweight Vision Transformer (ILViT) model is developed for microscopic cell classification. The ILViT integrates two innovative modules: Dynamic Inception Convolution (DIC) and Contrastive Omni-Kolmogorov Attention (COKA). DIC combines dynamic and Inception-style convolutions to replace large kernels with fewer parameters. COKA integrates Omni-Dimensional Dynamic Convolution (ODC), linear attention, and a Kolmogorov-Arnold Network(KAN) structure to enhance feature learning and model interpretability. With only 1.91 GFLOPs and 8.98 million parameters, ILViT achieves high efficiency. Extensive experiments on four public datasets are conducted to validate the effectiveness of the proposed method. It achieves an accuracy of 97.185% on BioMediTech dataset for classifying retinal pigment epithelial cells, 97.436% on ICPR-HEp-2 dataset for diagnosing autoimmune disorders via HEp-2 cell classification, 90.528% on Hematological Malignancy Bone Marrow Cytology Expert Annotation dataset for categorizing bone marrow cells, and 99.758% on a white blood cell dataset for distinguishing leukocyte subtypes. These results show that ILViT outperforms the state-of-the-art models in both accuracy and efficiency, demonstrating strong generalizability and practical potential for cell image classification. Full article

Complex antimony pyrochlores Bi_2.7M_0.46Ni_0.70Sb₂O_10+Δ (M = Zn, Mg) were synthesized from oxide precursors, using the solid-state reaction method. For each composition variant, the pyrochlore phase formation process was studied during solid-state synthesis in the range of 500–1050 °C. The influence of zinc and magnesium on the phase formation process was established. The interaction of oxide precursors occurs at a temperature of 600 °C and higher, resulting in the formation of bismuth stibate (Bi₃SbO₇) as a binary impurity phase. Oxide precursors, including bismuth(III) and antimony(III,V) oxides, are fixed in the samples up to 750 °C, at which point the intermediate cubic phase Bi₃M_2/3Sb_7/3O₁₁ (sp. gr. Pn-3, M = Zn, Ni) is formed in the zinc system. Interacting with transition element oxides, it is transformed into pyrochlore. An intermediate phase with the Bi_4.66Ca_1.09VO_10.5 structure (sp. gr. Pnnm) was found in the magnesium system. The unit cell parameter of pyrochlore for two samples has a minimum value at 800 °C, which is associated with the onset of high-temperature synthesis of pyrochlore. The synthesis of phase-pure pyrochlores is confirmed by high-resolution Raman spectroscopy. The data interpretation showed that the cations in Ni/Zn pyrochlore are more likely to be incorporated into bismuth positions than in Ni/Mg pyrochlore. The nickel–magnesium pyrochlore is characterized by a low-porosity microstructure, with grain sizes of up to 3 μm, according to SEM data. Zinc oxide has a sintering effect on ceramics. Therefore, the grain size in ceramics is large and varies from 2 to 7 μm. Full article

Solitary plasmacytoma refers to a neoplastic, clonal proliferation of plasma cells forming a single mass. They are divided based on their origin site; solitary bone plasmacytomas originate from the bones, and extramedullary plasmacytomas represent extraosseous tumors. These are rare tumors but carry a risk of transforming to multiple myeloma; thus, optimal management and meticulous follow-up are needed. Their rarity poses a major challenge in conducting large-scale clinical trials, leaving important gaps in evidence regarding best practices. Newer imaging techniques have improved the quality of staging, management decisions, and outcomes. Radiation still has a significant role in treatment algorithms, and adjuvant chemotherapy is gaining more importance; trials are underway in this area. Follow-up should contain biochemical tests as the proposed response definition criteria. We aimed to review the key studies and guidelines in this paper. Full article