Search Results (319)

Early and accurate diagnosis of Parkinson’s disease (PD) remains challenging in routine practice, as cardinal motor symptoms emerge only after substantial neurodegeneration has occurred. Blood-based biomarkers are therefore of considerable interest for identifying prodromal disease, enabling biologically stratified clinical trials, and supporting longitudinal monitoring. Among candidate markers, α-synuclein (α-Syn) is centrally relevant due to its fundamental role in PD pathogenesis. However, its peripheral measurement is complicated by marked molecular heterogeneity, uneven compartmental distribution, and analytical variability. In this narrative review, we examine the current evidence on blood-based α-Syn biomarkers with a focus on molecular diversity, compartmental biology, analytical platforms, and mechanisms governing central-peripheral exchange. We critically compare plasma, erythrocytes, and extracellular vesicle-based measurements and discuss the diagnostic implications of total, oligomeric, phosphorylated, and seeding-competent species. Recent advances in immunoassays, ultrasensitive technologies, mass spectrometry, and seed amplification assays (SAA) are also reviewed. Current evidence suggests that blood-based α-Syn assays hold promise, but their interpretation remains constrained by hemolysis, compartment-specific biology, assay heterogeneity, and limited longitudinal validation. Critically, no single blood-based α-Syn assay currently meets the performance standards required for standalone clinical application. Future progress will depend on methodological harmonization, multi-center and multi-ethnic studies, and integration with complementary biomarkers. A mechanistically grounded understanding of peripheral α-Syn dynamics is essential for developing clinically useful biomarker strategies for PD. Full article

Radioguided surgery has become a key component of contemporary breast cancer care, supporting less invasive approaches while maintaining oncologic safety. This narrative review summarizes current practice and recent developments in radioguided breast and axillary surgery, from established molecular imaging workflows to emerging three-dimensional and intraoperative technologies. Modern breast cancer management is increasingly shaped by tumor biology and the widespread use of neoadjuvant systemic therapy, which is transforming surgical decision-making and driving a shift toward personalized, patient-tailored pathways. In this context, radioguided techniques help maintain procedural accuracy despite therapy-induced changes in breast and nodal anatomy, enabling reliable lesion localization and targeted management of the axilla. We discuss sentinel lymph node strategies and de-escalation concepts, including targeted axillary dissection (TAD) after neoadjuvant therapy using marked nodes and selective removal approaches. We also review localization methods, including radioactive seed–based techniques, and the expanding role of molecular imaging–guided surgery to support intraoperative decision-making. Particular attention is paid to technologies aimed at improving surgical precision and margin assessment, including portable/freehand SPECT concepts and intraoperative PET/CT-based specimen imaging for immediate evaluation of excised tissue. Finally, we highlight how artificial intelligence and digital tools may enable workflow optimization, navigation, image interpretation, and decision support, accelerating the transition toward individualized treatment. Overall, integrating molecular information with real-time 3D guidance can help tailor breast and axillary management to each patient while reducing morbidity. Full article

Cannabis sativa L. is an economically significant multi-use crop valued for fiber, seed, and phytochemical production. Compared with other crops, advancement in Cannabis sativa has been slow due to regulatory constraints and genetic resource limitations. Recent advances in technology have transformed the research landscape, supporting a deeper understanding of the genetic architecture underlying key agronomic traits. This review summarizes current progress in Cannabis sativa genetics and genomics, mainly focusing on structural genome organization, including chromosome-level assemblies and emerging pangenomic resources that capture species-wide diversity. We explore the molecular basis of key agronomic traits, including sex determination, cannabinoid biosynthesis, fiber quality, seed composition, disease resistance, and abiotic stress tolerance, highlighting their complex regulatory networks. Functional genomics tools including virus-induced gene silencing, transient expression systems, and CRISPR/Cas9 genome editing are reviewed as approaches enabling direct gene functional validation. We further review integration of these resources with molecular breeding strategies, including marker-assisted and genomic selection, to accelerate elite genotype development. Finally, we address persistent challenges such as genomic complexity, reference bias, and phenotyping limitations while outlining future research directions. Together, these advances position C. sativa as a compelling system for both fundamental plant biology and applied crop improvement. Full article

Butterworts (Pinguicula spp.) are carnivorous plants often restricted to small, isolated populations in mountainous microclimates, making them vulnerable to inbreeding and demographic decline. In Mexico, the global hotspot for Pinguicula diversity (>50 species, 90% endemic), conservation is limited by scarce data on population biology, demography, and vulnerability. This study provides the first population size estimate for the endemic P. gracilis and evaluates how patch and population size influence biological fitness components across three localities in northeastern Mexico. Using a multi-component fitness framework and statistical models, we found that smaller populations and patches exhibit significantly reduced reproductive fitness, particularly in fruit set and seed quality. Patch size showed strong positive correlations with fruit production (r = 0.45–0.53), while isolation negatively affected seed output (r = −0.48). These results highlight the role of landscape structure in shaping fitness components, with patch size influencing reproductive effort and connectivity determining reproductive success. Our findings provide the first germplasm and population baseline for P. gracilis and a framework to identify vulnerable populations, prioritize conservation actions, and guide restoration strategies. Full article

Reproductive biology is fundamental for understanding fish population dynamics and for guiding fisheries management and aquaculture practices. Key reproductive and fishery-related variables such as catch size, age at maturity, spawning season, aggregation behavior, and the implementation of seasonal closures are critical to ensuring fish population sustainability. Snappers have been targeted for commercial aquaculture development due to their plasticity and ability to adapt to captive conditions. In Mexico, reproductive biology information on snappers remains fragmented and largely species-specific along both Pacific and Gulf coasts. This review reveals a lack of integrated perspective on snappers’ reproductive biology and identifies key knowledge gaps that may limit the development of effective conservation measures and aquaculture strategies. The absence of species-specific regulations for many snapper species along the Mexican Pacific coast reflects limited biological information and restricts the development of effective management policies. Increasing catch rates may indicate overexploitation, highlighting the need for targeted research to address existing information gaps and support effective conservation strategies for snapper populations. This review synthesizes available information on snapper reproductive biology and discusses how these traits can inform broodstock management, spawning control, and seed production in snappers from the Mexican coastal regions. Full article

Chemical hybridization agents (CHAs) enable efficient, large-scale hybrid seed production, yet their mechanisms remain poorly understood. Understanding how CHAs induce male sterility at the metabolic level is important for both basic pollen biology and crop breeding. Here, we performed integrated metabolomic analyses to investigate the metabolic basis of the action of trifluoromethanesulfonamide (TFMSA) across multiple species and tissues. TFMSA treatment induced systemic metabolic reprogramming across species, prominently affecting amino acid metabolism, central carbon metabolism, and one-carbon metabolism. Although individual metabolite responses varied among species, pathway-level analyses consistently revealed coordinated modulation of carbon–nitrogen metabolic networks. In reproductive tissues, TFMSA induced tissue-specific metabolic changes. In cowpea anthers, proline was the only metabolite significantly altered and was strongly depleted, whereas in floral tissues several amino acids, including phenylalanine and tyrosine, were accumulated. Pathway analysis revealed altered amino acid metabolism, suggesting that systemic metabolic responses accompanied the proline reduction in anthers. These findings indicate that TFMSA induces male sterility through coordinated metabolic reprogramming across tissues and species, leading to depletion of key metabolites required for pollen development. This study provides a metabolic framework for understanding CHA-induced male sterility and highlights TFMSA as a powerful tool for probing metabolic regulation of pollen development. Full article

Chronic inflammation accelerates the aging process, and targeted clearance of senescent cells shows potential in alleviating age-related decline. PCC1, a potent senescent cell clearance agent in grape seed extract (GSE), has limited applications due to its low oral bioavailability. This study introduced a novel GSE formulation, Natural Senolytics PCC1 (NSPCC1), which significantly enhanced PCC1 absorption and metabolic characteristics. Validation in two mouse aging models demonstrated that oral administration of NSPCC1 markedly extended lifespan and promoted healthy aging. The formulation improved the capacity for hematopoietic stem/progenitor cell differentiation and reduced age-related myeloid cell bias. Comprehensive histological analysis revealed attenuated aging phenotypes in bone marrow and skin, improved peripheral blood erythroid parameters, and a partial increase in blood antioxidant capacity, alongside reduced M1 macrophage infiltration and fibrosis in liver, kidney, and lung tissues. These effects were validated through histological assessments, including H&E, Masson, F4/80, and iNOS staining. This study highlighted the pivotal role of hematopoietic stem cells in aging and established NSPCC1 as a promising natural intervention for age-related pathologies. Its enhanced efficacy lays the groundwork for deeper exploration of natural products in aging biology and provides crucial support for the development of safe and effective anti-aging therapies. Full article

Indole-3-acetic acid (IAA) is the main natural auxin and a key regulator of plant growth. However, most commercial auxins are synthetically produced from non-renewable resources. Here, we present a minimal synthetic biology platform for microbial IAA production that also serves as a teaching model for genetic circuit design and bioprocess development. We developed codon-optimized versions of the iaaM and iaaH genes, which encode tryptophan 2-monooxygenase and indole-3-acetamide hydrolase, and assembled them into a compact expression cassette in Escherichia coli TOP10. Correct expression of both enzymes was confirmed by SDS-PAGE. The engineered strain was cultivated in a low-cost medium made from avocado seed hydrolysate, an agro-industrial waste, supplemented with tryptophan as a precursor. IAA was quantified using the Salkowski colorimetric assay and further validated by HPLC, reaching approximately 303–313 µg/mL at 48 h, with the medium costing approximately fivefold cheaper locally than traditional LB. The supernatants containing biosynthetic IAA induced root formation in 100% of tobacco leaf explants, outperforming the commercial standard at the same concentration and confirming biological activity. Since this workflow follows the Design–Build–Test–Learn (DBTL) cycle, Design (pathway selection and codon optimization), Build (plasmid assembly), Test (protein expression, metabolite quantification, plant bioassays), and Learn (medium and process optimization), it provides a sustainable production method and an accessible educational platform for synthetic biology. Full article

Tumor-associated macrophages (TAMs) are among the most abundant immune cell populations in breast cancer and have emerged as central regulators of tumor progression, metastatic dissemination, immune evasion, and therapeutic resistance. While TAMs were historically described using a simplified M1/M2 polarization framework, accumulating evidence indicates that TAMs in breast cancer comprise a continuum of phenotypic and functional states shaped by ontogeny (tissue-resident vs monocyte-derived), spatial localization (including hypoxic, perivascular, and invasive niches), tumor-intrinsic programs, and therapy-induced selective pressures. In breast cancer, mechanistic studies integrating lineage tracing, intravital imaging, single-cell and spatial profiling, and clinical analyses have established that TAMs actively coordinate rate-limiting steps of the metastatic cascade. These include promotion of angiogenesis and vascular permeability, orchestration of tumor cell invasion and TMEM-mediated intravasation, facilitation of metastatic seeding and niche formation, and suppression of anti-tumor immunity. TAMs also critically influence therapeutic response by modulating chemotherapy efficacy and limiting the activity of immune checkpoint blockade. Therapeutic strategies targeting TAMs in breast cancer have evolved from depletion approaches (CSF1/CSF1R blockade) to inhibition of monocyte recruitment (CCL2/CCR2 axis), functional reprogramming (CD40 agonism, PI3Kγ inhibition), and macrophage-directed checkpoint modulation (CD47–SIRPα axis). Early clinical studies demonstrate clear pharmacodynamic activity but highlight the need for context-specific and combination-based approaches. This review focuses on TAM biology in breast cancer progression and metastasis, synthesizing key mechanistic and translational evidence and proposing a framework in which spatially and functionally defined macrophage states act as rate-limiting regulators of dissemination and therapy response. We further outline principles for rational TAM-targeting strategies that integrate tumor stage, metastatic niche, and treatment context. Full article

Cutaneous T-cell lymphoma (CTCL), primarily mycosis fungoides (MF) and Sézary syndrome (SS), has long been characterized as a neoplasm of mature memory T cells, based on monoclonal T-cell receptor (TCR) rearrangements and tissue-resident memory (TRM)/central memory (TCM) T-cell phenotypes. This review synthesizes converging population-genetic, multi-omic, and single-cell evidence to argue that this characterization is incomplete and that a progenitor-based model better accounts for the full spectrum of disease biology. We present evidence that initiating mutations arise in hematopoietic stem or early lymphoid progenitor survive thymic selection, and diversify after TCR assembly, resulting in branched evolution across both blood and skin. In SS, paired analyses reveal > 200 shared variants between CD34⁺ progenitors and Sézary cells, as well as signal-joint T-cell receptor excision circle (sjTREC) positivity, providing direct progenitor-level evidence. In MF, convergent signals, multiple malignant clonotypes per lesion, greater blood–skin than skin–skin clonotype overlap, and compartment-specific CNV subclones, implicate hematogenous seeding and reseeding. Population-scale lymphoid clonal hematopoiesis and lymphoid-pattern mosaic chromosomal alterations define a compatible antecedent state. Spatial single-cell atlases and trajectory analyses map site-conditioned programs in skin, including Th2-skewed cytokines, microbial responses, and UV signatures, that select and expand subclones and explain inter- and intra-patient heterogeneity. This framework reconciles mature immunophenotypes with upstream initiation and clarifies why compartment-focused therapies often reshape rather than eradicate disease. It yields testable predictions and actionable implications: trials should pair multicompartment cytoreduction with strategies that attenuate progenitor-derived reservoirs, restore immune balance, and repair skin barrier dysfunction. A progenitor-initiated, niche-adapted model provides a coherent scaffold for more durable control in CTCL. Full article

Seed germination is a critical initial stage of the plant life cycle, regulated by signaling pathways such as phytohormones and reactive oxygen species (ROS). However, the low germination rate of immature grains is a key bottleneck limiting wheat speed breeding. This study used immature grains of the winter wheat cultivar Kenong 199 (KN199) collected 18 days post anthesis to establish an efficient germination protocol. By screening individual and combined treatments of hydrogen peroxide (H₂O₂, 1%), gibberellin (GA₃, 20 μM), and varying concentrations of abscisic acid (ABA) synthesis inhibitor sodium tungstate (Na₂WO₄), alongside transcriptome analysis, we identified the optimal reagent combination and gained preliminary insight into its molecular basis. The triple reagent combination of 0.5 mM Na₂WO₄ + 20 μM GA₃ + 1% H₂O₂ exhibited the highest germination rate of 80%, approximately sevenfold higher than single reagent treatments, with germination rate peaking after 4 days. Transcriptome profiling revealed that this combination modulated the expression of key genes related to dormancy release and germination, including upregulation of GA biosynthesis gene GA3ox2 and ABA catabolism gene TaCYP707A2, and downregulation of ABA biosynthesis and signaling genes (ABI5, TaNCED1, etc.). Additionally, genes associated with energy metabolism and transport pathways were enhanced. This optimized reagent combination significantly improves immature grain germination, shortens the breeding cycle, and provides a practical tool for achieving “five generations per year” speed breeding in winter wheat. Our findings contribute to seed biology by offering a chemical strategy to overcome dormancy in immature cereal grains. Full article

The genus Passiflora includes species important for fruit production, ornamental value, and breeding programs. Conventional methods, such as seed propagation and vegetative cuttings, face challenges like genetic heterogeneity, pathogen transmission, and long juvenile phases, limiting large-scale cultivation and breeding efficiency. In vitro culture technologies are essential for clonal propagation, germplasm conservation, and improving Passiflora species using biotechnology. This review critically evaluates current progress in micropropagation and regeneration systems in Passiflora spp. and examines the prospects of haploid and doubled haploid technologies as future breeding tools. Unlike previous reviews, which primarily focus on summarizing tissue culture protocols, this study integrates regeneration biology, developmental constraints, and emerging biotechnological approaches to provide a broader framework for research. Additionally, this review offers a comparative analysis of various regeneration systems across Passiflora species and highlights the challenges of genotype-dependent methods. By synthesizing recent advancements in haploid technology, it provides new insights into the potential for accelerating breeding programs in Passiflora, a field where robust protocols are still lacking. Full article

Over the past decade, an increasing number of functional microbial-like terpene synthases (MTPSLs) have been reported in non-seed plants. However, whether the traditional Chinese medicinal plant H. serrata harbors such enzymes and their corresponding functions remains unexplored. In this study, we mined the transcriptome of H. serrata and identified a microbial-like terpene synthase, HsMTPSL1, which produces multiple diterpene products. Following isolation and structural elucidation, seven distinct compounds were obtained, representing three skeletal types: spatane, prenylkelsoene-type, and biflorane. Among these, compound 7 is a novel biflorane diterpene. Structural analysis and subsequent mutagenesis revealed critical residues governing the formation of distinct skeletons, uncovering the multifunctional nature of this enzyme. Notably, the S224A mutation significantly enhanced the production of spatane diterpene compound 1 by 11.6-fold, demonstrating the potential for protein engineering to improve the yield of this bioactive marine-specific diterpene. Transcriptomic profiling revealed that HsMTPSL1 is highly expressed in sporangia, and co-expression analysis with cytochrome P450s identified the CYP781 subfamily as candidates potentially involved in the downstream modification of these skeletons. Collectively, we report the first MTPSL from H. serrata and characterize it as a multifunctional diterpene synthase. Through structure-guided mutagenesis, we uncovered the molecular basis of its functional versatility, with the S224A mutation providing a powerful tool for enhancing the yields of all three diterpene skeletons, thereby laying a foundation for future protein engineering and synthetic biology applications. Full article

With the rapid advancement in Generative Artificial Intelligence (GenAI), AI-generated content (AIGC) lacking human cognitive oversight is increasingly permeating open web environments and academic communication systems. This study integrates longitudinal retraction data (Retraction Watch Database, 1990–2026), web-scale analyses of AI-content penetration (Common Crawl, 2013–2026), and bibliometric mapping of governance scholarship (Web of Science Core Collection, Scopus, Google Scholar, 2020–2026) to diagnose the cross-level misalignment between synthetic-content diffusion, AI-related misconduct pressure, and governance attention. On this basis, it proposes a Normalized Coverage Index (NCI) to measure the relative relationship between scholarly attention to AI-related academic misconduct governance and the level of misconduct pressure observed through retraction data across disciplines. The results reveal pronounced asymmetries at the disciplinary level. Fields such as chemistry (0.04), physics, mathematics & statistics (0.11), and life sciences & biology (0.34) exhibit clear governance gaps, whereas Education shows a comparatively excessive level of attention (NCI = 29.26). Since 2022, AIGC has expanded rapidly across open web corpora, accompanied by a sharp rise in AI-related retractions, which also exhibit a longer detection lag than traditional forms of misconduct (2.77 years vs. 1.91 years). Although the volume of academic governance-related research has grown rapidly, its proportion within the broader body of AI-related research has declined, suggesting that scholarly attention to governance has not kept pace with technological diffusion. Consequently, a structural misalignment in governance—closely tied to the allocation of attention—has emerged within the academic system in the era of GenAI. This misalignment may pose potential risks to the robustness of the knowledge production system. Addressing it requires rebuilding epistemic infrastructure through provenance transparency, auditable workflows, and governance-aware seed corpora aligned with empirically concentrated risks. Full article

Synthetic datasets are increasingly used in education research for methodological validation, privacy-preserving data sharing, and reproducible equity analysis; however, most generative approaches prioritize marginal distributional similarity without ensuring preservation of multilevel inferential properties. This limitation is consequential for repeated-measures data analyzed using intersectionality-focused hierarchical models, where conclusions depend on variance partitioning, partial pooling, and stratum-level heterogeneity. We introduce MAI-GAN, a hybrid generative framework that implements a structure–residual decomposition approach combining Bayesian longitudinal MAIHDA with conditional GAN-based residual generation. Inferential fidelity is operationalized with respect to multilevel intersectional models by explicitly targeting the preservation of fixed effects, variance components, and variance partitioning coefficients, while baseline composition is maintained via stratified bootstrap resampling. Applied to a six-semester undergraduate biology dataset (N = 2669 students), MAI-GAN was evaluated across multiple independent random seeds and consistently reproduced baseline-dependent residual structure and key inferential quantities. These results demonstrate that model-aligned generative strategies can produce synthetic longitudinal datasets that remain coherent under intersectionality-focused multilevel analysis, offering a principled foundation for equity-oriented synthetic data generation. Full article