Search Results (130,456)

Ethylene is a key phytohormone regulating fruit ripening, the senescence of ornamental plants, and the post-harvest quality of horticultural products. Although numerous studies have described compounds that inhibit ethylene biosynthesis or perception, the available evidence remains fragmented across chemical groups, plant species, and pre- and post-harvest applications. This review addresses that gap by critically integrating current knowledge on the principal inhibitors of ethylene biosynthesis and perception used in horticulture, with emphasis on their sites of action, practical effectiveness, and limitations. Biosynthesis inhibitors, including aminoethoxyvinylglycine (AVG), aminooxyacetic acid (AOA), daminozide, benzyl isothiocyanate (BITC), and oxalic acid (OA), reduce ethylene production at different stages of the ethylene pathway, whereas perception inhibitors such as 1-methylcyclopropene, 1-DCP, silver compounds, alkenes, and diazocyclopentadiene interfere with receptor binding and downstream ripening responses. The available literature indicates that 1-methylcyclopropene remains the most widely used commercial inhibitor, while oxalic acid is emerging as a promising natural modulator of ethylene-related processes. However, the efficacy of these compounds is strongly dependent on species, maturity stage, dose, temperature, and storage conditions, and some are additionally constrained by regulatory concerns, incomplete mechanistic understanding, or inconsistent performance. Overall, ethylene inhibitors are important tools for extending shelf life, maintaining firmness, delaying senescence, and reducing post-harvest losses. Further comparative and crop-specific studies are needed to optimize application strategies, improve environmental safety, and support the development of effective natural alternatives. Full article

This systematic review synthesises the qualitative literature on Māori leadership to examine how leadership is conceptualised, enacted, and constrained, and what this implies for Aotearoa New Zealand’s health system. Across included studies, Māori leadership is grounded in whakapapa-based legitimacy, tikanga and mātauranga Māori, and collective responsibility for relational, cultural, and intergenerational wellbeing; these foundations persist across “traditional” and “contemporary” settings, with differences reflecting institutional conditions rather than shifts in core values. Interpreting the literature through a Māori cultural lens, the review shows that leadership is often exercised within Crown-dominated organisations where Māori authority is not the default, requiring leaders to navigate multiple accountabilities to iwi and communities, organisational mandates, and statutory obligations. Hybridity emerges as a structurally produced feature of practice, integrating Māori relational ethics with bureaucratic, professional, and governance requirements and ongoing translation work to make Māori priorities legible within institutional systems. Health-sector evidence illustrates how commissioning, funding, and accountability arrangements can limit Māori decision-making, increase leadership burden, and constrain sustainability and leadership pipelines. The review concludes that strengthening Māori leadership in health requires organisational and system change—such as clearer Māori decision rights, resourced Māori-led priority setting, and accountability mechanisms that operationalise equity and anti-racism—alongside targeted research on governance, commissioning, and system design. Full article

The Aedes aegypti mosquito exhibits a critical behavioral adaptation through its oviposition strategy, laying eggs in dry and wet environments just above the water level, allowing eggs to resist desiccation and hatch only when submerged by rain. To investigate this mechanism, we developed a nonlinear dynamic model incorporating climate-driven parameters affecting egg hatching and adult emergence. Theoretical analysis revealed an imperfect pitchfork bifurcation giving rise to a phenomenon we term basin-mediated hysteresis. Unlike classical hysteresis, which relies on coexisting stable states, this mechanism results from the progressive collapse of the extinction basin boundary. As the control parameter approaches its critical value, the basin of attraction of the trivial equilibrium shrinks. Once the population establishes itself above the threshold, returning the parameter below unity does not restore extinction, leading to an irreversible transition governing population persistence. The model was validated using field data from mosquito traps in a Brazilian city, showing strong agreement with observed seasonal patterns of female captures. Parameters were optimized using the Differential Evolution algorithm, yielding high correlation between model and field data. The results demonstrate that the dual oviposition strategy underlies population persistence and seasonal peaks, providing information for planning interventions amid global arbovirus expansion. Full article

Background: Glioblastoma (GBM) exhibits marked cellular heterogeneity and resistance to therapy. Calcium (Ca²⁺) signaling at endoplasmic reticulum (ER)–mitochondria contact sites has emerged as a key regulator of mitochondrial function and cell fate; however, its lineage-specific role and therapeutic relevance in GBM remain unclear. Methods: ITPR1 expression was analyzed using single-cell and bulk RNA sequencing (RNA-seq) datasets and validated by immunohistochemistry and survival analyses. Functional studies were conducted using genetic silencing or CRISPR-mediated activation of ITPR1, combined with DRP1 knockdown, Ca²⁺ imaging, transmission electron microscopy, co-immunoprecipitation, mitochondrial fractionation, and mitochondrial functional assays. Therapeutic efficacy was evaluated in orthotopic GBM xenograft models treated with 2-aminoethoxydiphenyl borate (2-APB), temozolomide (TMZ), or their combination. Results: ITPR1 was enriched in mesenchymal-like malignant cell states and associated with higher tumor grade, recurrence, and poor prognosis. ITPR1 knockdown suppressed GBM cell proliferation and tumor growth while promoting intrinsic apoptosis. Mechanistically, loss of ITPR1 impaired ER-to-mitochondria Ca²⁺ transfer, disrupted ER–mitochondria contacts, and altered mitochondrial ultrastructure. This was accompanied by reduced DRP1 Ser616 phosphorylation and mitochondrial recruitment, as well as decreased autophagy and mitophagy activity. Consequently, ITPR1 knockdown led to mitochondrial depolarization, increased mitochondrial reactive oxygen species (ROS) accumulation, and activation of mitochondria-dependent apoptosis. Conversely, DRP1 knockdown attenuated the mitochondrial and pro-survival effects induced by ITPR1 overexpression. In vivo, combined treatment with 2-APB and TMZ resulted in greater tumor suppression and prolonged survival compared with either treatment alone, accompanied by increased apoptosis and reduced proliferation in tumor tissues. Conclusions: ITPR1 promotes GBM progression by sustaining ER–mitochondria Ca²⁺ coupling and DRP1-dependent mitochondrial quality control, thereby maintaining mitochondrial homeostasis and cell survival. Targeting inositol 1,4,5-trisphosphate receptor (IP₃R)-mediated Ca²⁺ signaling with 2-APB enhances the therapeutic efficacy of TMZ, suggesting that ITPR1-centered Ca²⁺ signaling may represent a potential therapeutic vulnerability in aggressive GBM. Full article

RNA–protein interactions (RPIs), mediated primarily by RNA-binding proteins (RBPs), are central to post-transcriptional gene regulation and govern RNA splicing, transport, localization, translation, and decay. Dysregulation of RBPs and their associated RNA networks contributes to diverse pathologies, including cancer, neurodegenerative disorders, and viral infections. However, profiling RPIs remains a challenge due to their inherent transience, low binding affinity, and shifting spatial dynamics. This review provides a comprehensive and systematic overview of current methodologies for investigating RPIs. We discuss RNA-centric and protein-centric strategies. In addition, imaging-based approaches are evaluated for their capacity to resolve spatial and temporal dynamics of RBP–RNA interactions in situ. We compare these methodologies in terms of resolution, sensitivity, specificity, and biological applicability, emphasizing the importance of integrative strategies for constructing high-resolution, context-dependent RPI maps in physiological and disease settings. Full article

Background: Pulsed field ablation (PFA) has shown promising results for atrial fibrillation (AF), with efficacy comparable to established ablation techniques. High-power short-duration (HPSD) ablation has also emerged as a potential alternative. However, the relative superiority between these approaches remains uncertain. We performed a systematic review and meta-analysis to address this gap. Methods: Three databases were searched. The primary outcome was freedom from AF recurrence. Secondary outcomes included tamponade and other complications, procedure and fluoroscopy durations. Time-to-event data were reconstructed, and a random-effects model was employed. Given variability in post-ablation blanking periods across studies, landmark analyses were performed using a 3-month cut-off to account for the potential under-detection of early recurrence events. Results: Eight studies (1369 patients [PFA: 642; HPSD: 727]) were included. PFA was associated with greater freedom from AF recurrence (HR 0.751; 95% CI 0.57 to 0.99; p = 0.044). Landmark analyses showed no difference in the 0–3 month period; a significant benefit of PFA was observed thereafter (HR 0.72; 95% CI 0.54 to 0.98; p = 0.033). There were no significant differences between groups in the incidence of tamponade (p = 0.73) or overall complications (p = 0.99). PFA was associated with shorter procedure duration (MD 37.05; 95% CI 27.69 to 46.41; p < 0.01), whereas fluoroscopy duration was significantly shorter in the HPSD group (MD −9.04; 95% CI −11.71 to −6.37; p < 0.001). Conclusion: PFA was associated with a lower risk of AF recurrence compared to HPSD, particularly beyond the late post-ablation period, with similar rates of complications. Although PFA was associated with shorter procedure duration, HPSD demonstrated reduced fluoroscopy time. Full article

Advances in organoid and other three-dimensional culture systems, single-cell and spatial transcriptomics, multi-omics, and high-resolution imaging are reshaping our understanding of the cellular origins and evolutionary trajectories of glioblastoma. When integrated with modern data science approaches, these technologies enable the construction of increasingly detailed molecular biographies of normal neural stem and progenitor cells as well as malignant stem-like cellular states. Such molecular biographies illuminate how developmental programs, cellular plasticity, and microenvironmental cues are co-opted during gliomagenesis. At the same time, progress in machine learning, immunotherapy, and precision molecular targeting is beginning to translate these biological insights into therapeutic strategies that specifically disrupt glioblastoma stem-like states. Together, these converging approaches provide a conceptual and technological framework for improved tumor modeling, earlier detection, and increasingly personalized therapies for malignant gliomas. Full article

Urinary epidermal growth factor (uEGF) and clusterin (uCLU) are emerging biomarkers in chronic kidney disease (CKD), but rigorous analytical validation is required before clinical implementation. We evaluated intra-individual variability and long-term storage stability of uEGF and uCLU in CKD. In the prospective, multicenter UVALID study, 60 adults with CKD stages 2–4 underwent urine sampling at three visits over 8 weeks. First-morning and 24-h urine samples were collected to assess intra-individual variability over 24 h, 3 days and 8 weeks. Biomarkers were measured in duplicate by ELISA and normalized to urinary creatinine (/Cr). Inter-laboratory performance was assessed using quality control samples. Stability after 12 and 15 months of storage at −20 °C and −80 °C and the influence of pH were evaluated. Over 24 h, 3 days, and 8 weeks, uEGF/Cr demonstrated low variability and remained stable after long-term storage at both temperatures. In contrast, uCLU/Cr showed greater variability and pronounced instability at −20 °C, whereas stability was preserved at −80 °C. Samples with pH > 6 partially preserved uCLU stability at −20 °C. Inter-laboratory reproducibility was acceptable for uEGF but suboptimal for uCLU at low concentrations. Thus, uEGF showed robust analytical performance, supporting its potential clinical applicability in CKD, whereas uCLU exhibited important analytical and pre-analytical limitations, warranting further assay optimization. These findings underscore the need for rigorous validation to facilitate biomarker implementation in clinical practice. Full article

This study re-examines the monetary “black box” in India by investigating whether monetary-policy transmission is state-dependent across different interest-rate environments. Using quarterly data spanning 1993Q1–2024Q2, it constructs a Taylor rule-based monetary-policy shock to mitigate the endogeneity of raw policy rates and estimates dynamic discrete-threshold regressions with endogenously determined regimes. The results provide strong evidence of nonlinearity and structural instability in India’s transmission process. For real output, the weighted average call money rate (WACR) emerges as the more informative threshold variable, while wholesale price inflation is more effectively segmented by the 91-day Treasury bill yield. The findings show that the contractionary effect of monetary policy on output is most evident in the intermediate-rate regime, whereas low- and high-rate regimes exhibit weaker or counterintuitive short-run responses, consistent with crisis accommodation, delayed pass-through, and state-specific frictions. For inflation, monetary tightening is associated with a short-run price puzzle in low- and intermediate-yield regimes but produces the expected disinflationary effect in the high-yield regime. Across channels, the credit and asset-price channels matter selectively for output, while the exchange-rate channel is the most relevant for inflation only in the intermediate regime. Overall, the evidence suggests that monetary-policy transmission in India is regime-dependent and that policy assessment should distinguish between operating-rate conditions and broader market-rate regimes. Full article

In the history as well as historiography of Chinese Buddhism, the tradition has often been closely associated with death-related cultural practices and ideas, an association that has frequently carried negative connotations. Early twentieth-century reformers such as Taixu famously criticized Buddhism as a religion of ghosts and funerals and sought to redirect Mahāyāna Buddhism toward engagement with an urban, modernizing society. Contemporary Taiwanese Buddhists have realized many aspects of this socially engaged vision. Yet concern with death remains deeply embedded in Buddhist life. Far from standing in contradiction to social engagement, this concern has become one of its central expressions, most visibly in the emergence of modern Buddhist palliative care. Focusing on the writings of the scholar-monk Shi Huimin, this article examines the development of Buddhist palliative care in Taiwan in response to a secular, multireligious, and rapidly aging society, with primary attention to Huimin’s conceptual work. Rather than treating death in isolation, Huimin situates dying within a broader ethical horizon that links good death to good aging, good living, and community formation. Through his reinterpretation of the Five Śīlas and his notion of a Community Pure Land, he extends prevailing concerns with dying well toward a more comprehensive reflection on everyday moral cultivation, healthy lifestyles, and communal responsibility. In this sense, the study reads Buddhist palliative care as a site that “provincializes” dominant Euro-American frameworks of spiritual and palliative care, highlighting their particular historical and Christian-inflected origins while tracing how they are reconfigured and made productive in a multireligious, secular context. By foregrounding Huimin’s conceptual contributions, this study highlights how palliative and spiritual care are localized and reworked within Taiwanese Buddhism, connecting end-of-life care to broader questions of life, aging, and community well-being. Full article

Background: Neuroinflammation is recognized as a key contributor to Parkinson’s disease (PD), but the relationships between inflammatory signaling, immune-state alterations, and cell-type-specific transcriptional programs remain unclear. Methods: Public transcriptomic datasets, including GSE20141 (discovery cohort) and the substantia nigra subset of GSE114517 (external validation cohort), were analyzed. Genes identified by exploratory differential-expression screening in the discovery cohort were intersected with predefined inflammation- and chemokine-related gene sets to define a candidate space for downstream prioritization. Protein–protein interaction, Gene Ontology, KEGG, and immune-signature analyses were performed, followed by machine learning-based feature prioritization using Elastic Net, support vector machine-recursive feature elimination, and random forest. Prioritized candidates were further evaluated by cross-platform validation, single-nucleus transcriptomic mapping, and a hypothesis-generating in silico perturbation analysis in PD astrocytes. Results: Seventeen genes were retained at the intersection of PD-related differentially expressed genes and inflammation-/chemokine-associated gene sets. These candidates formed a response module enriched in mitochondrial organization, oxidative phosphorylation, and mitophagy pathways. Immune-signature analysis suggested an altered transcriptome-derived immune landscape in PD, with changes in NK cell-related signatures and significant correlations between immune-state scores and the candidate genes. Machine learning-based prioritization yielded five shared candidates, of which only CCL2 and PAK6 showed same-direction support with nominal significance in the external validation cohort. Single-nucleus transcriptomic analysis localized CCL2 predominantly to astrocytes, whereas PAK6 was more strongly associated with neuronal populations, particularly OTX2-positive ventral midbrain neurons. In silico perturbation analysis further predicted that CCL2 suppression in PD astrocytes may be associated with translational- and ribosome-related regulatory programs. Conclusions: CCL2 and PAK6 emerged as prioritized candidate biomarkers associated with PD-related inflammatory and chemokine-linked transcriptional alterations in the substantia nigra. More broadly, this study provides a multi-layered framework for candidate prioritization, cross-platform validation, and cell-type-level contextualization in PD neuroinflammation. Because the study is computational and the perturbation analysis is predictive, orthogonal experimental validation will be required to determine whether CCL2 and PAK6 are biomarkers of disease-associated transcriptional states, functional contributors to PD pathogenesis, or both. Full article

Rheumatoid arthritis (RA) has traditionally been managed after the onset of clinically apparent synovitis; however, accumulating evidence indicates that disease-related immune abnormalities precede clinical diagnosis by several years. This preclinical phase is characterized by systemic autoimmunity, early musculoskeletal symptoms, and subclinical inflammation in genetically and environmentally susceptible individuals. In this review, we summarize current concepts regarding the pathogenesis, risk stratification, and therapeutic interception of preclinical RA. Particular attention is given to the mucosal origin hypothesis and to the roles of immunosenescence, peripheral helper T cells, and fibroblast-like synoviocytes in early disease evolution. Recent advances in clinical, serological, and imaging-based risk stratification have improved the identification of individuals at high risk of progression to clinical RA, and emerging intervention trials have shown that selected therapies may delay disease onset or reduce early inflammatory burden. Although complete prevention of RA has not yet been achieved, these findings support a paradigm shift from the treatment of established RA toward earlier, risk-adapted intervention before irreversible joint damage occurs. Future efforts should focus on refining predictive biomarkers, optimizing the timing and intensity of intervention, and establishing safe, individualized preventive strategies. Full article

Background: Photodynamic therapy (PDT) has emerged as a powerful minimally invasive modality for cancer treatment. However, its efficacy as a monotherapy is often limited by oxygen dependence and limited light penetration. Combining PDT with systemic anticancer drug therapies offers a promising strategy to achieve synergistic effects and overcome resistance. Objective: This review aims to provide a systematic analysis of the mechanisms and clinical potential of combining PDT with chemotherapy, targeted therapy, and immunotherapy, focusing on recent advancements and nanotechnology-based delivery systems. Methods: A comprehensive literature search was performed using PubMed and Scopus databases. The analysis focused on peer-reviewed studies published over the last 10 years addressing synergistic molecular pathways, co-delivery nanoplatforms, and clinical trial outcomes. Results: The combination of PDT with chemotherapy enhances drug accumulation via vascular photosensitization and can overcome multi-drug resistance. Integration with immunotherapy, particularly immune checkpoint inhibitors and tumor vaccines, triggers immunogenic cell death (ICD), leading to systemic antitumor responses. Nanotechnology provides a versatile platform for the targeted co-delivery of photosensitizers and pharmacological agents, significantly reducing systemic toxicity. Conclusions: Combined PDT–drug regimens demonstrate superior therapeutic efficacy compared to monotherapies. Future clinical translation requires the standardization of dosimetry and the development of multifunctional nanomedicines to enable personalized treatment protocols. Full article

Ceramides are central bioactive sphingolipids that regulate diverse cellular processes, including membrane organization, energy metabolism, and stress signaling. Emerging evidence has implicated that ceramide dysregulation is associated with the onset and progression of heart failure. This review introduces the understanding of ceramide metabolism, focusing on its biosynthesis, and functional roles in cardiomyocytes. In addition, the contribution of systemic ceramides derived from circulating lipoproteins and peripheral tissues to cardiovascular risk is also discussed. In parallel, it is highlighted that cardiomyocyte-intrinsic ceramide synthesis plays physiological and pathological roles in the heart. Particularly, excessive ceramide accumulation is detrimental for cardiac function, through multiple mechanisms, such as lipotoxic effects, mitochondrial impairment, inflammation, and cell death. The current review discusses the potential diagnostic and therapeutic strategies targeting ceramide metabolism, as well as the open questions about ceramide association with heart disease. Full article

Plant-derived sweet proteins are promising low-calorie natural sweeteners that may reduce dietary sugar intake and prevent non-communicable diseases. Although seven have been identified—thaumatin, miraculin, monellin, mabinlin, brazzein, pentadin, and curculin (neoculin)—only thaumatin is currently approved as a food additive. The development of others requires comprehensive safety assessments, particularly regarding allergenicity. This systematic review aims to investigate and synthesize allergenicity assessment methods (in silico, in vitro, in vivo, and clinical) applied to these seven sweet proteins. The literature searches were conducted following PRISMA guidelines across Scopus, PubMed, and Wiley Online Library databases, up to 30 November 2025, with no time restrictions. The risk of bias in selected studies was evaluated using GRADE. After the selection process, 14 out of 2634 studies met the inclusion criteria. Thaumatin, miraculin, monellin, and brazzein emerged as the most extensively studied proteins. In silico approaches (sequence and structural homology) and in vitro assays (digestibility and cell-based methods) were the most commonly employed methods. In contrast, in vivo studies (animal models) and clinical evaluations (skin prick tests, oral food challenges) were rarely reported. Allergenicity studies on pentadin, mabinlin, and curculin (neoculin) are limited, indicating a research gap that requires further study to support regulatory approval and consumer acceptance. Full article