Search Results (28,488)

Polyfarnesene, a bio-based polymer, was epoxidized in situ using performic acid to investigate oxirane ring formation, stability, and the role of its bottlebrush architecture in the kinetics. The reaction reached a maximum epoxidation degree of ~20% after 6 h but underwent side reactions, producing hydroxyl and formic ester groups. FTIR and ¹H NMR revealed that ring opening began within the first hour, whereas residual unsaturated bonds persisted after prolonged reaction, owing to steric shielding by the polymer’s long C11–C13 side chains. Unlike smaller polydiene homologues, polyfarnesene exhibited slower ring-opening kinetics, retaining approximately 10% of oxirane groups after 20 h. GPC showed minimal molecular weight changes but an increase in polydispersity, confirming structural rearrangements without chain scission or crosslinking. DSC demonstrated that oxirane incorporation increased the T_g; however, side reactions reduced this effect by limiting chain mobility. These findings establish that the spatial constraints imposed by the bottlebrush architecture of polyfarnesene govern the reaction kinetics, restricting epoxidation efficiency and favoring esterification pathways. This interplay provides a basis for designing bio-based polymers with tunable thermal properties. Controlling the reaction environment to suppress side reactions is key to producing high-T_g epoxidized derivatives suitable for rubber technologies and sustainable materials. Full article

Background/Objectives: Non-indigenous species are increasingly reshaping Mediterranean marine ecosystems, particularly under ongoing climate warming. The rayed pearl oyster Pinctada radiata, a thermophilic species originating from the Indo-Pacific region, is one of the earliest and most successful invaders in the Mediterranean Sea and has recently established populations in the Adriatic Sea. Methods: This study integrates preliminary shell morphometric data with molecular genetic analyses based on mitochondrial cytochrome c oxidase subunit I (COI) and nuclear internal transcribed spacer 2 (ITS2) markers to confirm species identity and examine patterns of genetic variation in comparison with other Mediterranean Sea regions and the Persian Gulf. Results: Phylogenetic analyses based on COI confirmed P. radiata as a distinct and well-supported monophyletic lineage, whereas the nuclear ITS2 marker showed limited resolution and interspecific overlap. Mediterranean and Adriatic populations showed low COI haplotype and nucleotide diversity and weak genetic structuring, consistent with recent colonization and secondary expansion, whereas Persian Gulf populations were more genetically diverse. Conclusions: Future studies should employ larger sample sizes and broader geographic sampling across both the Mediterranean Sea and the full native range of P. radiata, combined with high-resolution genome-wide nuclear markers, to better resolve connectivity and invasion dynamics. Full article

Thoracic aortopathies, including aneurysm and dissection, are complex vascular disorders characterized by structural alterations of the aortic wall that disrupt normal haemodynamics. Altered shear stress, turbulent flow, and endothelial dysfunction promote thrombus formation and modulate systemic hemostasis via platelet activation and the von Willebrand factor–ADAMTS13 axis. The Total Thrombus-Formation Analysis System (T-TAS) is a microfluidic, flow-dependent assay that quantitatively evaluates thrombus formation under physiological shear conditions. Although studied in various cardiovascular contexts, its application in aortopathies remains largely unexplored, and no prospective studies have validated its clinical utility. Integrating T-TAS with computational haemodynamic approaches, such as two-way fluid–structure interaction simulations, enables assessment of the interplay between blood flow, vessel wall mechanics, pulse wave propagation, and local shear patterns. Patient-specific modelling, including individualized flow profiles, pressure distributions, and wall properties, may enhance mechanistic insights. Genetic variants in Fibrillin-1 gene (FBN1), Transforming Growth Factor Beta Receptor 1/2 (TGFBR1/2), Actin Alpha 2 (ACTA 2), and Myosin Heavy Chain 11 (MYH11) further contribute to structural vascular heterogeneity and diverse systemic haemostatic phenotypes, highlighting the need for personalized assessment. T-TAS should currently be considered an exploratory research tool rather than a validated diagnostic or prognostic method. This narrative review proposes a hypothesis-generating framework integrating structural, haemodynamic, molecular, and functional perspectives. Combining flow-based thrombosis assays with advanced modelling may inform future translational studies, improve mechanistic understanding of thrombus formation, and support personalized risk stratification and management in patients with thoracic aortopathies. Full article

Traditional drug discovery processes are typically expensive, time-consuming, and have a very high failure rate. Artificial intelligence (AI) is currently reshaping this field in unprecedented ways, promising to significantly improve the efficiency and success rate of drug development. This article systematically compares and analyzes the application of AI for two major drug types: small molecule vs. peptide drugs. It explores their applications in several key stages of drug development, including virtual screening, lead compound optimization, de novo drug design, ADMET (absorption, distribution, metabolism, excretion, and toxicity) property prediction, and chemical synthesis planning. While both drug types benefit from AI-driven approaches, fundamental differences exist in molecular representation, data availability, key challenges, and model adaptability. For small molecule drugs, AI focuses on drug efficacy, synthetic feasibility, and accurate structure–activity relationship prediction. In contrast, for peptide drugs, AI faces more unique biological challenges, such as inherent flexibility, complex biological functions, stability, and immunogenicity. Finally, this article provides a forward-looking perspective on the future of AI-driven drug discovery, highlighting the immense potential of basic models, multimodal integrated systems, and autonomous discovery platforms, which will collectively drive the next wave of precision drug development. Full article

The gastrointestinal mucus barrier (GIMB) is a gelatinous structure consisting primarily of mucins, water, and cathelicidin. Such a structure is the first line of defense against pathogens in the intestinal cavity and acts an important environment for the survival and reproduction of symbiotic flora. Mucin is mainly synthesized and secreted by intestinal goblet cells, forming a slime layer with different structures throughout the intestinal tract. The process of mucin synthesis and secretion is regulated by many factors, and there are some differences in the physical and chemical properties of the GIMB among animal species. Furthermore, recent studies have shown a close relationship among the mucus barrier, gastrointestinal diseases, and tumors. Soybean agglutinin (SBA) is a major glycoprotein in soybean that is closely related with the detection, prevention, and treatment of disease and cancer. Current studies indicate a close relationship between SBA and the GIMB, particularly at the molecular level and through species-specific differences in mucin glycan structures. Existing evidence shows that these differences affect the binding affinity and antinutritional effects of SBA. The novel relations between SBA and GIMB may become new targets for disease treatment. Full article

Background: Vascular malformations are congenital structural abnormalities of the blood vessels that may present at any age. In the vulvovaginal region, these lesions are uncommon and frequently misdiagnosed because their clinical appearance overlaps with common gynecologic conditions, particularly Bartholin’s gland cyst or abscess. Inappropriate surgical intervention without prior vascular evaluation may result in hemorrhage, incomplete treatment, and recurrence. Methods: A structured narrative review of the literature was performed using PubMed/MEDLINE and EMBASE databases (January 2000–April 2024) to summarize the classification, pathophysiology, clinical presentation, imaging characteristics, differential diagnosis, and management of vulvovaginal vascular malformations. Publications addressing vascular anomalies in other anatomical locations were also included when clinically relevant. A representative clinical case confirmed by histopathologic and molecular analysis is presented to illustrate the diagnostic pitfalls. Results: Vulvovaginal vascular malformations are predominantly low-flow venous lesions but may include high-flow arteriovenous malformations. A clinical examination alone is insufficient for diagnosis. Doppler ultrasonography is the recommended initial imaging modality, followed by magnetic resonance imaging to define the lesion extent and flow characteristics. Misdiagnosis most commonly occurs when lesions are treated as Bartholin’s gland pathology without prior imaging. Low-flow lesions are generally managed with sclerotherapy or planned surgical excision, whereas high-flow lesions require embolization and multidisciplinary care. Hormonal and hemodynamic changes, including pregnancy, may precipitate enlargement or thrombosis. Conclusions: Vascular malformations should be considered in the differential diagnosis of atypical vulvar masses. Preoperative imaging is essential in order to avoid inappropriate surgical procedures. A structured diagnostic approach combining clinical assessment and imaging enables correct classification and guides treatment. The presented case demonstrates a typical diagnostic pitfall and emphasizes the importance of recognizing vascular lesions in gynecologic practice. Full article

Peritoneal dialysis (PD)-associated peritonitis in children represents a complex interplay between microbial virulence, host immune activation and progressive peritoneal membrane remodeling. It should not be viewed solely as an acute infectious episode, but as a process unfolding within a chronically conditioned immune environment shaped by prolonged exposure to glucose-based dialysis solutions, oxidative stress and persistent biofilm formation on the Tenckhoff catheter. Mesothelial cells act as immunologically active sentinel cells, recognizing pathogen-associated molecular patterns through Toll-like receptors and related innate pathways. Subsequent activation of nuclear factor kappa B, inflammasome signaling and neutrophil extracellular trap formation further amplifies local inflammatory responses. Repeated inflammatory stimulation promotes mesothelial–mesenchymal transition, angiogenesis and extracellular matrix deposition driven by transforming growth factor beta 1 and interconnected profibrotic networks. In pediatric patients, prolonged PD vintage during critical stages of growth may intensify cumulative structural injury and increase the risk of ultrafiltration failure or encapsulating peritoneal sclerosis. Emerging strategies targeting inflammation, fibrosis and biofilm persistence, together with earlier molecular risk detection, may support preservation of the peritoneal membrane. A unified host–pathogen framework may therefore deepen pathophysiological insight and facilitate more individualized therapeutic strategies in pediatric PD. Full article

Mitochondria regulate nuclear genomes and their own genetic material, primarily to provide energy in eukaryotes. Currently, high-throughput sequencing technologies are being used to resolve the mitochondrial genomes of various edible fungi. However, the application of pan-genomes for the analysis of edible mushroom mitochondrial genomes remains unexplored. In this study, we conducted a comparative mitochondrial genome analysis of 31 Hypsizygus marmoreus strains (four newly sequenced monotypes and 27 public datasets), ranging from 98,284 to 111,087 bp. This variation was determined to be primarily driven by dynamic changes in non-coding regions, particularly intronic polymorphisms in the cox1 gene. Further, transfer RNA (tRNA) secondary structures exhibited atypical globular and elongated conformations alongside copy number variations. Additionally, codon usage showed a pronounced A/T bias, whereas core respiratory chain genes demonstrated an evolutionary pattern of strong purifying selection. Furthermore, the 31 mitochondrial genomes of H. marmoreus were found to harbor eight gene rearrangement patterns and five genetic clusters, and the pan-genome analysis (220,364 bp, 217 nodes) captured abundant single-nucleotide polymorphisms (SNPs), insertions/deletions (InDels), and structural variations. This study provides breeding-relevant genetic markers and a genomic framework for H. marmoreus germplasm classification, genetic improvements, and the molecular breeding of stress-resilient varieties. Full article

The presence of an unbalanced gut microbiome and the dysregulation of bile acid signalling are considered pivotal causes of various inflammation-based diseases. The Takeda G protein-coupled receptor (TGR5), TGR5 is a bile acid-responsive receptor that modulates inflammatory signalling pathways, making it an enticing molecular target for the discovery of novel anti-inflammatory agents. Herein, a comprehensive in silico approach was employed to identify potential TGR5 agonists from sterol-rich phytocompounds present in Triphala, a traditional polyherbal formulation. Using in silico computational methods, such as molecular docking and molecular dynamics simulations (MDS), we screened the putative agonistic potential of 10 phytocompounds obtained from Terminalia chebula, Terminalia bellirica, and Phyllanthus emblica against the crystal structure of human TGR5 (PDB ID: 7XTQ). Based on binding energy and molecular interactions, ergosterol (−12.34 ± 0.17 kcal/mol) and stigmasterol (−10.35 ± 0.04 kcal/mol) were predicted to be the top and best compounds. Furthermore, the stability of these two compounds in the docked complex was analysed using MDS for 200 ns. The mean Cα RMSD values were 0.22 ± 0.02 nm for both ergosterol- and stigmasterol-bound complexes, compared to 0.21 ± 0.02 nm for the unbound apo protein. Further, the molecular mechanics/Poisson–Boltzmann surface area (MMPBSA) analysis revealed that ergosterol exhibited binding free energy (−139.868 ± 12.318 kJ/mol) comparable to that of the co-crystallised ligand R399 −93.424 ± 8.919 kJ/mol. In silico ADMET predictions indicated acceptable drug-like properties and low toxicity for both compounds. Collectively, these computational findings suggest that ergosterol is a promising putative TGR5 agonist, warranting further experimental validation of its potential role in modulating inflammation-related pathways. Full article

Wildlife trafficking poses a severe threat to global biodiversity and ecosystem stability, necessitating robust forensic tools for tracing the origins of illegally traded taxa. In this study, we developed a method of single-nucleotide polymorphism (SNP)-based molecular markers to enable precise geographical traceability of four animal species native to China: the Tibetan macaque (Macaca thibetana), brown eared pheasant (Crossoptilon mantchuricum), blue eared pheasant (Crossoptilon auritum), and Chinese pangolin (Manis pentadactyla). We studied these four species because their DNA is characterized by distinct population genetic structure, they are subjected to illegal trafficking, and given their diverse evolutionary histories, this allowed us to assess the general applicability of our forensic genetic framework in reducing wildlife crime. Based on whole-genome resequencing data from 26 Tibetan macaques, 51 eared pheasants and 42 Chinese pangolins, we performed population genetic analyses to elucidate their genetic structure and identify population-specific loci. The results indicated that all samples from these four species showed clear genetic differentiation and distinct clustering, allowing us to design primers to facilitate PCR-based traceability. We also assessed the utility of mitochondrial DNA (mtDNA) for tracing Tibetan macaques and both species of eared pheasants. We found that traceability accuracy using mtDNA was lower than when using SNPs. Our research offers a SNP-based traceability framework that accurately determines the geographical origin of wildlife samples to the genetic population level, and this provides a powerful tool for combating illegal trade and aiding conservation efforts. Full article

Background: Retinal and optic nerve disorders are a leading cause of irreversible visual impairment worldwide. Advances in molecular genetics—including next-generation sequencing, genome-wide association studies, and gene-based therapeutic technologies—have reshaped understanding of both inherited and complex retinal diseases. However, translating genetic discovery into sustained clinical benefit remains biologically and practically constrained. Methods: A structured literature search was conducted using PubMed and Scopus to identify relevant studies published between 2015 and 2025. The search focused on molecular genetics, epigenetic modulation, mitochondrial biology, and translational applications in inherited retinal dystrophies and selected complex retinal diseases, prioritizing high-impact original research and systematic reviews addressing diagnostic innovation and therapeutic development. Results: Inherited retinal dystrophies represent the most advanced model of precision ophthalmology, with diagnostic yields approaching 70–80% in well-characterized cohorts. Gene augmentation and genome-editing strategies have demonstrated proof-of-concept efficacy, yet clinical benefit depends on residual cellular viability, delivery efficiency, and durability of expression. Emerging platforms include AAV-mediated gene transfer, in vivo CRISPR-based editing, RNA-directed splice modulation, and mitochondrial-targeted approaches. Persistent barriers include unresolved non-coding and structural variants, variant interpretation uncertainty, and endpoint selection in clinical trials. In contrast, complex retinal diseases such as glaucoma, age-related macular degeneration, and pathological myopia reflect polygenic susceptibility interacting with environmental and aging-related factors. Although polygenic risk scores refine probabilistic prediction, their utility is limited by ancestry bias and incomplete predictive performance. Epigenetic and mitochondrial mechanisms further modulate disease expression but remain largely non-actionable in routine practice. Conclusions: Retinal genetics has progressed from gene discovery to early therapeutic implementation. Future advances will depend on improved variant detection, functional validation, biomarker-guided staging, and integration of genomics with imaging and longitudinal modeling to achieve durable and equitable precision ophthalmology. Full article

Background: Diabetic wounds represent a major clinical challenge due to persistent inflammation, oxidative stress, and impaired angiogenesis. Bone marrow mesenchymal stem cells (BMSCs) have strong regenerative potential, and their therapeutic effects and optimization strategies for diabetic wounds warrant further exploration. Objective: This study aimed to improve the therapeutic efficacy of BMSCs in diabetic wound healing via chrysin pretreatment, as well as to evaluate the healing capacity and molecular mechanisms of the derived chrysin-pretreated BMSC-conditioned medium (Chrysin-CM). Methods: BMSCs were pretreated with 1 μM chrysin for 48 h to generate Chrysin-CM. The therapeutic effects were evaluated in vitro by analyzing the proliferation, migration, and matrix synthesis of human umbilical vein endothelial cells (HUVECs) and human skin fibroblasts (HSFs) under high-glucose (HG) conditions. In vivo, a diabetic mouse model with full-thickness excisional wounds was established and treated topically with Chrysin-CM. Transcriptomic sequencing and immune infiltration analysis of wound tissues were performed on day 14 in order to investigate the underlying mechanisms. Results: Chrysin pretreatment significantly enhanced the functional activity of BMSCs, accompanied by increased proliferative capacity and accelerated cell cycle progression. In vitro, Chrysin-CM demonstrated superior efficacy, robustly protecting HUVECs and HSFs from HG-induced dysfunction. In vivo, Chrysin-CM significantly accelerated wound closure, re-epithelialization, and neovascularization compared to the control. Mechanistically, RNA sequencing (RNA-seq) revealed that Chrysin-CM induced multi-level remodeling, characterized by reduced inflammatory gene expression and immune cell infiltration, along with the upregulation of regenerative genes and alternative splicing events. Conclusions: Chrysin successfully improved the therapeutic efficacy of the BMSC secretome in wound healing. Chrysin-CM effectively accelerated diabetic wound healing by actively resolving chronic inflammation and promoting angiogenesis and structural remodeling, thus providing a potential strategy for stem cell-based cell-free treatment for chronic diabetic wounds. Full article

Background/Objectives: The increasing sensitivity of molecular diagnostic techniques has led to the frequent detection of low-level JAK2 V617F mutations in individuals without overt myeloproliferative neoplasms (MPNs), creating uncertainty regarding their biological and clinical significance. This study aimed to evaluate the clinical relevance, thrombotic risk, and hematologic evolution associated with low JAK2 V617F allele burden. Methods: We conducted a retrospective single-center study including adult patients tested for JAK2 V617F between January 2016 and December 2023. Patients with a variant allele frequency (VAF) <2% who did not meet WHO or 2022 International Consensus Classification diagnostic criteria for MPN at baseline were included. Clinical characteristics, laboratory parameters, molecular findings, thrombotic events, and longitudinal ou--comes were analyzed. Results: Among two-thousand-three-hundred-seventy-two tested subjects, 55 patients (9.2% of JAK2-positive cases) harbored a low-level JAK2 V617F mutation (median VAF 0.35%). Over a median follow-up of 31.7 months, 12 patients (21.8%) progressed to overt MPN. Baseline VAF was significantly higher in patients who evolved to MPN compared to non-progressors. Thrombotic events occurred in 30.9% of patients and were associated with higher VAF values irrespective of MPN diagnosis. Serial molecular analyses showed stable persistence of the mutant clone over time. Conclusions: Low-burden JAK2 V617F mutations represent clinically relevant clonal events associated with thrombotic risk and potential disease evolution. These findings support the need for structured clinical and molecular follow-up even in the absence of initial diagnostic criteria. Full article

Natural product research has experienced substantial growth over the past two decades, driven by a renewed appreciation for the structural complexity and biological relevance of compounds derived from nature. Technological advances in separation science, spectroscopic characterization, and high-sensitivity bioassays have collectively restored natural products to a position of prominence in modern drug discovery efforts. Nature remains the most prolific source of bioactive molecular diversity, drawing from microorganisms, plants, and marine life to offer a vast reservoir of structurally novel scaffolds whose pharmacological potential remains largely unexplored. Effective extraction and isolation remain foundational to natural product research, as the quality and purity of isolated compounds directly govern the reliability of downstream biological evaluation. Recent years have witnessed remarkable innovation in this space, spanning green and designer solvent systems, pressurized and ultrasound-assisted extraction platforms, supercritical fluid techniques, and integrated purification workflows that dramatically reduce processing time while improving compound recovery and analytical throughput. Particularly noteworthy is the growing application of artificial intelligence and machine learning tools for solvent selection, extraction optimization, and metabolite dereplication, which in combination with advanced phase-separation strategies and informatic platforms have substantially expanded the scope of detectable and characterizable metabolites within complex biological matrices. This review summarizes recent progress in extraction and isolation methodologies supporting natural product research, with particular emphasis on combinatorial extraction strategies, next-generation solvent systems, and AI-driven applications that have collectively improved operational efficiency, selectivity, and analytical output over the past five years. Full article

The enzymatic method is the primary focus for alginate oligosaccharide (AOS) production. However, the high viscosity of sodium alginate (SA) substrate often limits enzymatic efficiency. Pretreatment strategies aimed at reducing SA viscosity offer a promising and innovative solution to enhance process efficiency. This study compared the effects of three pretreatment methods—high-pressure vapor (HP-v), high-pressure solution (HP-s), and atmospheric-pressure air (AP-a)—on the physicochemical properties of SA. These pretreatments reduced SA viscosity and induced visible color changes in the order HP-v > HP-s > AP-a. Additionally, the effects of high-pressure treatments on molecular weight, M/G ratio, and chemical structure of SA were analyzed, confirming the feasibility of pretreatment-assisted enzymolysis. Molecular weight distribution and ESI-MS analysis of AOS after enzymolysis demonstrated that brief HP-v treatment maximizes the catalytic potential of alginate lyase, facilitating efficient AOS production without altering its structural characteristics. Full article