Search Results (36,608)

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

Sexually transmitted infections (STIs) remain a global health burden. Beyond classical pathogens, dermatophytes are increasingly identified within sexually linked transmission networks. Genital dermatophytosis is a superficial fungal infection of the genital area, primarily caused by anthropophilic and zoophilic dermatophytes. Recently, Trichophyton mentagrophytes genotype VII and Trichophyton indotineae have emerged as clinically significant dermatophytes, increasingly linked to human-to-human and sexually associated transmission within highly interconnected sexual networks. These infections are often marked by inflammatory, persistent, and treatment-refractory presentations, with prominent genital involvement and rising antifungal resistance—particularly to terbinafine—posing growing diagnostic and therapeutic challenges. Doxycycline post-exposure prophylaxis (Doxy-PEP) has recently emerged as a novel preventive strategy for bacterial STIs, involving the administration of 200 mg doxycycline within 24–72 h after activities associated with increased infection exposure, particularly among men who have sex with men (MSM) and transgender women. While effective in reducing infections such as syphilis and chlamydia, its broader implementation raises concerns regarding antimicrobial resistance. Chemsex is an increasingly prevalent behavioural phenomenon, defined as the intentional use of psychoactive substances during sexual activity to enhance or prolong the experience, particularly among MSM. It is associated with multiple adverse effects, including increased STI transmission, substance dependence, drug toxicity, psychological disturbances, and significant challenges in treatment adherence and healthcare engagement. This review aims to provide a comprehensive and clinically oriented overview of emerging trends in STIs, with a particular focus on dermatophyte infections as pathogens with potential sexually associated transmission, alongside evolving prevention strategies and behavioral factors influencing transmission. Full article

The development of fractional-order control has been derived from the mathematical generalization of classical calculus and has become an important tool in the modeling and control of dynamical systems with memory and hereditary effects. In spite of the rapid development of this area of control theory and applications, the overall scientific development, structure, and engineering relevance of fractional-order control remain insufficiently understood. In this paper, we address this problem by combining large-scale bibliometric analysis with representative controller performance studies. A total of 6482 publications indexed in the Web of Science database during the period 2010–2026 are analyzed. The bibliometric results indicate that fractional-order control is an increasingly connected global research field with strong roots in fractional calculus, advanced control theory, and growing interdisciplinary links with applied mathematics, automation, and computer science. To further illustrate controller level behavior, representative simulations are performed on a fractional-order time-delay process and an uncertain nonlinear system. For the fractional-order time-delay process, a well-tuned PID controller is compared with a realizable FOPID controller implemented through Oustaloup recursive approximation. The results show that the FOPID controller improves several performance measures, including overshoot, settling time, control energy, total variation, and sensitivity peak, while the comparison is interpreted as a performance trade-off rather than universal superiority. For the uncertain nonlinear system, fractional-order sliding mode control produces smoother control action and substantially reduces chattering. By combining bibliometric mapping with representative performance evaluation, this paper provides a comprehensive overview of fractional-order control as a globally active and practically relevant discipline in control engineering. Full article

Ferroptosis is a regulated form of cell death driven by iron-dependent lipid peroxidation and is mechanistically distinct from apoptosis, necrosis and pyroptosis. Increasing evidence indicates that ferroptosis plays a critical role in cancer biology, including lymphoproliferative disorders, where chronic redox imbalance, dysregulated iron metabolism, and metabolic rewiring create a permissive environment for ferroptotic vulnerability. In these malignancies, altered iron handling, elevated reactive oxygen species, and a strong reliance on antioxidant systems such as glutathione and glutathione peroxidase 4 tightly control ferroptotic sensitivity. Dysregulation of key components, including SLC7A11, lipid metabolism pathways, and intracellular iron homeostasis, further shapes the susceptibility of malignant lymphoid cells to ferroptosis. Importantly, emerging preclinical studies suggest that therapeutic targeting of ferroptosis may overcome resistance to conventional chemotherapy, targeted agents, and immunotherapy, offering novel opportunities particularly in relapsed or refractory disease. This review provides a comprehensive overview of the molecular mechanisms governing ferroptosis in lymphoproliferative disorders, highlights the interplay between ferroptosis and major cellular and metabolic pathways, and discusses current and emerging strategies to pharmacologically induce ferroptosis, with an emphasis on biomarker-driven clinical translation. Full article

Hydrogels have gained prominence as a class of biomaterials in biomedicine due to their excellent biocompatibility, biodegradability, and high water retention. Among them, hydrogels derived from natural polysaccharides sourced from plants, animals, and microbes are attracting growing interest due to their renewable nature, low toxicity, low immunogenicity, and diverse functional properties. While several recent reviews have addressed polysaccharide-based hydrogels, they have largely focused on isolated aspects—such as 3D bioprinting formulations, double-network mechanical reinforcement, rheological behavior, or single-source polysaccharides—without establishing an integrated framework that links raw material selection, structural diversity, chemical modification, and crosslinking design to clinical translation. This review distinguishes itself by providing a systematic, end-to-end perspective that spans from the structural diversity of plant- and microbe-derived polysaccharides through recent advances in chemical modification and novel cross-linking strategies, to the fine-tuning of physicochemical properties for enhanced therapeutic outcomes. This article provides an overview of the progress made in the emerging biomedical applications and material design of natural polysaccharide hydrogels in terms of raw material selection, chemical modification, cross-linking mechanisms, and functional utilization. It aims to fully explore the potential of these materials and promote integration into advanced biomedical practices. Full article

Background: Myelomeningocele (MMC) is a severe neural tube defect resulting from primary neurulation failure. Despite advanced multidisciplinary paradigms, long-term morbidity remains substantial. Population-based longitudinal data from small European cohorts are scarce. This study evaluates long-term clinical and functional outcomes within a complete national cohort in Slovenia. Methods: A retrospective cohort study was conducted on all children born with MMC in Slovenia between 2007 and 2023. Patients were managed via a centralized, standardized multidisciplinary program. Phenotypic severity was stratified by anatomical lesion levels, and outcomes were assessed using standardized functional measures. Results: Over an 18-year period, 32 children were treated (prevalence: ~1 per 10,000 live births; mean follow-up: 13.2 years). All underwent anatomical closure within 24 h of birth. Hydrocephalus developed in 71.8% (n = 23), with 65.6% requiring ventriculoperitoneal shunting. Independent ambulation was achieved by 28.1%, while 46.8% were wheelchair-dependent and paraplegic. Neurogenic bladder dysfunction occurred in 87.5%. Subgroup analysis demonstrated that thoracolumbar lesions were significantly associated with lower ambulation rates and higher shunt dependency compared to lumbosacral lesions (p < 0.05). Long-term survival was 96.9%. Conclusions: This study represents the first comprehensive national analysis of myelomeningocele outcomes in Slovenia. Despite the relatively small number of patients, complete national coverage and centralized multidisciplinary management provide a unique overview of long-term outcomes. The findings demonstrate that outcomes achieved within the Slovenian healthcare system are comparable to those reported internationally, thereby establishing an important national benchmark for future evaluation of preventive measures and evolving treatment strategies. Full article

The emergence of CRISPR-Cas editing systems—comprising clustered regularly interspaced short palindromic repeats and associated Cas proteins—marked a breakthrough in genetic engineering, owing to the simplicity, efficiency, and adaptability of the method. Despite continuous improvements and the incorporation of innovative discoveries to develop reliable, fine-tuned tools, the effective application of CRISPR-Cas technology in cereals remains challenging. This review provides a technically oriented overview of CRISPR-Cas-mediated genome editing in wheat (Triticum aestivum L.), one of the world’s fundamental crops. While focusing on established solutions and progressive methodological modifications, we also discuss pertinent topics, including plant genetic transformation, prospective innovations, and compliance considerations. Full article

With the rapid development of general artificial intelligence, large models have gradually become the key force driving the digital transformation of the field. Agriculture has distinct domain characteristics, and traditional deep learning models are difficult to meet its cross-regional and cross-task requirements. Large models specifically designed for the agricultural field can integrate multi-source data and prior knowledge to break through this bottleneck. Therefore, tracking the development trend of large agricultural models is an important prerequisite for building new, quality productive forces in smart agriculture and promoting the digital transformation of agriculture. This article conducts a literature search and review around the research on large agricultural models, following the PRISMA guidelines. It combines the keywords of large models, crops, livestock breeding, etc., and only includes journal papers from 2022 to 2026, totaling 713 articles. Then, it performs topic modeling to deeply clarify the current research and application status, and summarizes the challenges faced and makes future research prospects. Existing evidence indicates that current large agricultural models are gradually developing towards agents and embodied intelligence, and are widely applied in scenarios such as agricultural knowledge services, pest and disease diagnosis and prevention, livestock and fishery breeding, and smart agricultural machinery control. However, they still face many key challenges, and further exploration is needed in theoretical methods and practical applications. In the future, research can be further deepened and expanded in areas such as the construction of high-quality data sets, the construction of domain evaluation systems, strengthening model reliability, building multi-agent systems, and lightweight deployment of large models and embodied intelligence. Full article

More than 160 types of post-transcriptional RNA modifications have been identified, revealing considerable diversity in their types, abundances, distributions, and functional roles across different RNAs, cells, and tissues in humans. Recent advances in high-throughput sequencing technologies have enabled the systematic detection of dynamic RNA modifications, including N6-methyladenosine (m⁶A) and inosine (I). In this review, we focus on RNA modifications in eukaryotic mRNA and provide an overview of current high-throughput methodologies for detecting the most abundant adenosine-related modifications, including m⁶A and adenosine-to-inosine (A-to-I) RNA editing. Finally, we discuss the major challenges that remain in the field and highlight key directions for future research. Full article

Fragrance allergens are widely used in cosmetics and personal care products to make them more attractive to consumers. However, their presence has raised increasing concerns due to their potential to induce allergic contact dermatitis and other adverse health effects. As a result, regulatory authorities have progressively strengthened labelling requirements and restrictions for fragrance allergens in cosmetics, creating new analytical and compliance challenges for both industry and regulatory laboratories. In this context, the development of sensitive, selective, and reliable analytical methodologies has become essential for the identification and quantification of these compounds in complex cosmetic matrices. This review provides a comprehensive overview of analytical methodologies reported between 2015 and 2025 for the determination of fragrance allergens in cosmetic matrices, with a focus on sample preparation. Conventional extraction methodologies are critically discussed together with advanced, miniaturized and microextraction approaches. The advantages, limitations, and applicability for routine quality control and regulatory compliance are critically discussed. Chromatographic developments, including the use of multidimensional approaches, are assessed. Recent regulatory updates are examined, and the challenges related to allergen labelling, low-level detection, matrix complexity, standardization, and harmonization of analytical protocols are also addressed. Finally, future perspectives on innovative analytical tools, and green analytical chemistry approaches are highlighted. Full article

Takotsubo syndrome (TTS) is an acute disorder characterized by transient left ventricular dysfunction with typical regional wall motion abnormalities, most commonly apical ballooning. It accounts for 1–3% of all suspected acute coronary syndromes and up to 5–6% in women presenting with ST-segment elevation myocardial infarction requiring coronary angiography to exclude obstructive coronary artery disease. The pathophysiology of TTS is complex and not fully elucidated, with sympathetic hyperactivation playing a central role through calcium dysregulation, oxidative stress, and metabolic alterations. Both clinical and experimental data demonstrate the importance of inflammation, with cell infiltration and persistent immune activation exceeding the acute phase. Increasing evidence highlights the impact of coronary microvascular disfunction (CMVD) as a secondary phenomenon, with some findings that support its role as a causative substrate. Beyond well-known predisposing conditions such as female sex, postmenopausal age, and neurological and psychiatric disorders with the trigger of a physical or psychological event, numerous case reports associate the syndrome with chronic autoimmune diseases, even if clear experimental evidence remains poor and worthy of further study. Echocardiography and advanced imaging techniques, including cardiac magnetic resonance and positron emission tomography, have provided insights into transient CMVD, reversible myocardial edema, and metabolic impairment, strengthening our knowledge of the syndrome as a dynamic process. It is also of growing interest to perform invasive hemodynamic assessment to explain the increase in microvascular resistance. This review offers a comprehensive and up-to-date overview of these techniques in the context of TTS. Since clinically, TTS may be associated with significant morbidity and mortality, with some unexplained cases of long-term myocardial disfunction or even recurrence, a deeper understanding of the interplay between catecholamines, inflammation, immune substrate, and CMVD may improve risk stratification and lead to the development of targeted therapeutic strategies. Full article

Background: This review aims to provide a comprehensive and practical overview of the evolving role of autologous transplantation in leukaemias, a strategy that was once largely abandoned but has recently regained interest in selected clinical settings. Methods: We reviewed the historical development of autologous transplantation in acute leukaemias, including the early period during which autologous transplantation was considered inferior to allogeneic approaches because of limited graft purification techniques and the inability to induce effective graft-versus-leukaemia (GVL)-like immune responses. We further summarise more recent experimental strategies aimed at improving stem cell purification and enhancing anti-leukaemic immune activity in autologous settings. In addition, we discuss how advances in measurable residual disease (MRD) assessment and molecular risk stratification have contributed to the renewed interest in autologous transplantation in selected subgroups of leukaemia patients. Results: This review identifies clinical situations in which autologous transplantation remains an important therapeutic option, including plasma cell leukaemia, where it continues to represent a standard first-line approach. We also discuss well-defined patient subgroups, particularly selected AML subtypes with intermediate-risk molecular profiles and acute promyelocytic leukaemia (APL) in second remission, in which outcomes following autologous transplantation may be comparable to, or occasionally superior to, those achieved with allogeneic transplantation. In contrast, autologous transplantation currently plays only a limited role in diseases such as chronic lymphocytic leukaemia (CLL) and chronic myeloid leukaemia (CML). Although attempts to induce potent anti-leukaemic immune effects in autologous settings have so far shown limited clinical efficacy, several emerging strategies appear promising and may further expand the role of autologous transplantation, particularly in elderly or frail patients. Discussion: Overall, current molecular and MRD-based risk stratification strategies, together with emerging immunological and graft-manipulation approaches, may redefine the role of autologous transplantation as a personalised therapeutic option in selected subgroups of leukaemia patients. Full article

Oral diseases, encompassing conditions such as periodontitis, head and neck squamous cell carcinoma, pulpitis, and mucosal infections, remain a major global health burden due to their high prevalence and complex, multifactorial pathophysiology. The unique anatomical structure of the oral cavity, together with persistent microbial challenges and dynamic immune responses, imposes substantial limitations on conventional drug delivery strategies. Biomimetic cell membrane-based materials have recently emerged as a promising class of delivery platforms, leveraging natural biological interfaces to confer inherent biocompatibility, immune evasion, prolonged circulation, specific targeting, and biofilm-interactive capabilities. These features position them as a transformative approach for improving therapeutic precision and efficacy in oral disease management. In this review, we provide a systematic and materials-oriented overview of biomimetic cell membrane-based drug delivery systems. Specifically, we discuss: (1) the biological sources, classification, and physicochemical properties of membrane-coated systems, along with their fabrication and engineering strategies; (2) the mechanistic basis of targeting, immune modulation, and nanobiointerface interactions, and their applications across representative oral diseases; and (3) current challenges, including scalable manufacturing, functional controllability, biosafety, and clinical translation. Furthermore, we highlight emerging directions such as stimuli-responsive membrane systems and multifunctional integrated platforms, aiming to provide a conceptual framework for the rational design and clinical advancement of biomimetic drug delivery systems in complex disease settings. Full article

This essay offers a critical reading of Karen Barad’s and Heinrich Päs’ interpretations of quantum mechanics, using a Categorial Differentiation approach to science and religion, which is inspired by Wittgenstein and van Fraassen. Barad and Päs are ontological realists, but their philosophies of quantum mechanics depart from what I call scientistic realist interpretations of quantum mechanics, which are mainstream in the analytic philosophy of physics. After an overview of the ontological turn in the philosophy of quantum mechanics and explaining the basic difference between scientistic and existential kinds of realism, I examine the central features of Barad’s agential realism and Päs’ quantum monism. The Categorial Differentiation approach, which offers a normative perspective on the relationship between science and religion, is introduced, and its relevance for the philosophy (and theology) of quantum mechanics is explained. I conclude the essay with a critical analysis of Barad’s and Päs’ interpretations from this Wittgensteinian perspective, focusing on the ways in which they relate the science of quantum mechanics with their respective existential–moral visions. Full article

Background: Cardiac hypertrophy, a major feature of heart failure, is closely linked to metabolic remodeling and energy deficiency. Lysine lactylation (Kla), a recently discovered post-translational modification (PTM), has been implicated in various cellular processes. However, its specific role in cardiac hypertrophy remains poorly understood. Methods: We conducted quantitative proteomics and Kla PTM analysis on left ventricular tissues from both sham-operated and aortic banding-induced hypertrophic mouse hearts. Protein samples were extracted, enriched for lactylation, and subjected to mass spectrometry. Bioinformatic analyses were performed to uncover pathways and protein–protein interactions (PPI) related to Kla-modified proteins. Results: Our lactylome analysis identified 159 Kla-modified sites across 80 proteins, with 72 proteins exhibiting elevated Kla levels, particularly in mitochondrial and sarcomeric proteins. Pathway enrichment analysis highlighted significant involvement of fatty acid metabolism, the tricarboxylic acid (TCA) cycle, and cardiomyopathy-related pathways, underscoring the role of Kla in energy metabolism and cardiac remodeling. PPI analysis further revealed the central role of metabolic and structural proteins in the hypertrophic response. Conclusions: Our study provides the comprehensive analysis of Kla in cardiac hypertrophy, revealing its significant role in modulating proteins involved in mitochondrial energy metabolism and sarcomeric structure. Our findings provide a comprehensive overview of the lactylation landscape in cardiac hypertrophy and reveal extensive lactylation changes in proteins associated with mitochondrial metabolism and sarcomeric organization. These observations suggest a potential link between Kla and cardiac hypertrophy, which warrants further functional investigation. Full article