Search Results (6,093)

Background: Bronchial asthma is a chronic inflammatory airway disease characterized by acute bronchoconstriction and type 2-driven inflammation. This study investigated whether inhaled amitriptyline, a functional inhibitor of acid sphingomyelinase, exerts both bronchodilatory and immunomodulatory effects in experimental murine models of allergic airway inflammation (AAI) and human cellular systems. Methods: Acute AAI was induced in mice using ovalbumin (OVA) and house dust mite (HDM) protocols, respectively. Inhaled amitriptyline (3.3 mg/mL) was administered for either 20 days (short-term) or 36 days (long-term). Lung function was assessed using FlexiVent^®, and inflammatory markers including IgE, eosinophils, and type 2 cytokines were measured in bronchoalveolar lavage fluid and lung tissue. Complementary experiments were included using passively sensitized PCLSs and human type 2-differentiated CD4⁺ T cells. Results: Inhaled amitriptyline improved lung mechanics in both the OVA and HDM models, reducing total respiratory resistance and elastance. In the OVA model, eosinophil and T cell counts in BALF were decreased, whereas immunomodulatory effects were less pronounced in the short-term HDM model. In human T_H2 cells, no significant changes in cytokine production or gene expression were observed. Ex vivo, amitriptyline dose-dependently inhibited allergen-induced bronchoconstriction in PCLSs. Conclusions: Inhaled amitriptyline improves lung function across murine models of AAI, supporting its potential in exhibiting model-dependent immunomodulatory effects, and directly attenuates allergen-induced bronchoconstriction, supporting its potential as a bronchodilator with context-dependent immunomodulatory properties. Full article

The inappropriate utilization of traditional antimicrobials has expedited the development of multidrug-resistant bacterial strains, thereby generating an urgent demand for innovative, safe, and efficacious alternatives. Graphene oxide (GO), characterized by its distinctive physicochemical properties, holds significant potential for a wide range of biomedical applications, such as the prevention of oral diseases, periodontal therapy, control of gastrointestinal infections, wound healing, antibacterial therapy for the respiratory tract, and management of urogenital infections. The antimicrobial mechanisms of GO include physical disruption of microbial membranes, induction of reactive oxygen species (ROS), and its role as a photosensitizer. Moreover, improving the dispersion, stability, release behavior, and reusability of GO-based composites can markedly enhance their effectiveness. The antimicrobial activity of GO is further modulated by its physicochemical properties, synthesis methods, bacterial characteristics, and environmental conditions, while potential synergistic or antagonistic interactions remain to be elucidated. This review synthesizes recent advancements in GO-based antimicrobial strategies, elucidates key mechanisms and influencing factors, and addresses major challenges and future research directions, with the objective of facilitating the clinical translation of GO as a next-generation antimicrobial material. Full article

Glioblastoma remains the most lethal primary malignancy of the central nervous system, and the modest gains achieved with maximal surgery, radiotherapy and temozolomide have not been matched by the immune checkpoint inhibitors and antigen-specific vaccines that reshaped the treatment of many extracranial cancers. The recurrent disappointment of these approaches has been attributed less to a single molecular lesion than to a confluence of obstacles: profound intratumoural heterogeneity, a densely immunosuppressive and myeloid-rich microenvironment, sequestration and exhaustion of conventional T cells, and the practical difficulty of delivering effectors across the blood–brain barrier. Against this background, γδ T cells have attracted interest as an unconventional effector population that recognises transformed cells through stress-associated and metabolic cues rather than peptide–major histocompatibility complex (MHC) complexes, that kills in an MHC-unrestricted manner, and that can be expanded from healthy donors for allogeneic, off-the-shelf use with little expectation of graft-versus-host disease. This narrative review examines, with a deliberately critical lens, the biological rationale and the experimental evidence for γδ T cell-based immunotherapy of glioblastoma. We summarise the developmental biology and functional subsets of human γδ T cells, the natural killer group 2 member D (NKG2D)-, DNAX accessory molecule 1 (DNAM-1)- and T-cell-receptor-dependent mechanisms through which they engage glioblastoma cells and glioma stem-like cells, and the in vitro and animal-model studies that underpin the field, taking care not to overstate efficacy that has so far been demonstrated only in preclinical or early-phase settings. We then weigh the principal opportunities—locoregional and repeated dosing, combination with chemoradiotherapy, checkpoint blockade and antibody-based redirection—against barriers that include limited persistence, uncertain intratumoural trafficking, donor and manufacturing variability, and the unsettled requirements of potency testing and trial design. We give particular weight to what becomes of γδ T cells inside a hostile tumour—the exhaustion-like dysfunction that follows chronic stimulation, the oxygen and glucose dependence of their effector programme, the interleukin-17-polarising signals generated by activated microglia and by genotoxic therapy, and the confounding effect of corticosteroids—together with the engineering and pharmacological strategies proposed to counter them. The first peer-reviewed phase 1 report of intracranially delivered, drug-resistant γδ T cells has now appeared and documents tolerability in a small, single-arm cohort without establishing survival benefit. Throughout, γδ T cells are presented as a biologically plausible but still investigational strategy whose clinical value will be determined by adequately powered trials rather than by mechanistic appeal alone. Full article

Breast cancer, especially triple-negative breast cancer (TNBC) and endocrine-resistant disease, remains difficult to treat because of limited effective targeted therapies. In this study, we evaluated the antitumor activity and potential mechanism of MHO7, a marine-derived ophiobolin metabolite, in ER-positive ZR-75-30 cells, tamoxifen-resistant LCC2 cells, and TNBC MDA-MB-231 models. MHO7 dose-dependently reduced cell viability, wound closure, and clonogenic growth in ZR-75-30 and LCC2 cells, with IC₅₀ values of 11.53 and 10.43 μM, respectively. MHO7 also promoted apoptotic cell death, accompanied by increased reactive oxygen species accumulation and altered expression of apoptosis-related proteins, including Bcl-2 and caspase-3. N-acetyl-L-cysteine partially attenuated MHO7-induced apoptosis and YAP reduction in MDA-MB-231 cells, suggesting a contribution of oxidative stress. Molecular docking predicted that MHO7 could occupy the conserved TEAD palmitoylation pocket, and subsequent in vitro analyses showed suppression of YAP/TAZ-TEAD signaling, including reduced YAP nuclear accumulation and decreased TEAD4 expression. In an MDA-MB-231 xenograft model, MHO7 significantly inhibited tumor growth, reduced CD31-positive microvessel density, and decreased Hippo pathway-related transcriptional readouts. These findings indicate that MHO7 exerts broad antitumor activity in breast cancer models through oxidative stress-associated apoptosis and modulation of YAP/TAZ-TEAD signaling, supporting its further development as a lead compound for treatment-resistant breast cancer. Full article

Manual visual diagnosis of apple diseases suffers from low efficiency, strong subjectivity and poor scalability for large commercial orchards. Existing research mainly targets diseases on single plant organs, whereas full-growth-cycle detection has to cope with extreme multi-scale differences among lesions. For instance, Valsa canker on tree trunks leads to extensive cortical necrosis, while early-stage anthracnose on fruits appears as tiny spots spanning only a few pixels. These significant scale gaps necessitate robust spatial feature aggregation and anti-noise ability to resist complex background interference. Aiming to achieve rapid and precise detection of diseases on multiple apple organs including leaves, fruits, trunks and branches, this work presents an enhanced YOLOv11 model equipped with the Information Integration Attention (IIA) module. The IIA module is embedded into the key fusion layers of the backbone and neck networks. It strengthens the extraction of fine-grained lesion features, recovers spatial location information via a bidirectional attention mechanism, and suppresses noise induced by uneven lighting and intricate backgrounds. To guarantee stable convergence on low-resource computing devices, a tailored training scheme is designed. Experimental results on a seven-category dataset with 7406 images demonstrate that YOLOv11-IIA reaches a precision of 0.763, a recall of 0.819, mAP@50 of 0.857 and mAP@50-95 of 0.699, which achieves clear performance improvements over the original YOLOv11 (mAP@50 improved from 0.485 to 0.857) and other attention-augmented detectors. The model operates stably on an NVIDIA GTX 1050 4GB GPU with an inference speed of 16 FPS for 640 × 640 input images; comprehensive quantitative computational metrics including parameter count, FLOPs and memory consumption will be fully measured in subsequent UAV deployment experiments. The proposed method provides a reliable technical reference for intelligent apple disease monitoring in smart orchard systems. Full article

Insulin resistance (IR) is a well-established metabolic disorder characterized by reduced responsiveness of peripheral tissues to insulin, leading to hyperglycemia and compensatory hyperinsulinemia. Background: In older adults, IR tends to develop gradually and may remain undiagnosed for years due to the insidious nature of the condition, which often lacks overt symptoms. Non-pharmacological interventions refer to the sum of all measures taken in order to improve a certain biological determination or physical parameter and they consist of lifestyle and dietary modifications. Although insulin resistance is recognized as a central mechanism involved in the development of numerous chronic diseases associated with aging, its impact on intrinsic capacity and the mechanisms underlying this relationship are insufficiently synthesized in the literature. In this context, the present narrative review aims to integrate the current evidence on the interaction between insulin resistance and intrinsic capacity, highlighting common biological mechanisms and potential therapeutic and preventive strategies to promote healthy aging. Methods: We conducted a literature search in PubMed, Scopus and Web of Science databases, screening the literature published between 2010 and January 2026. The search strategy included keywords and Boolean operators in order to refine the suggestions. Relevant articles, reviews, studies and guidelines were selected based on their relevance to the objective of this review. Results and Conclusions: The results of the review highlight that insulin resistance represents a central mechanism contributing to the decline in intrinsic capacity through chronic inflammation, oxidative stress, mitochondrial dysfunction and alteration of the gut microbiota. Current evidence suggests that nutritional interventions, in particular the Mediterranean diet and the DASH diet, can improve insulin sensitivity by modulating the microbiota and reducing systemic inflammation, with the potential to contribute to maintaining functional capacity and promoting healthy aging. Full article

Background/Objectives: Adenomyosis is a chronic gynecological disorder characterized by the presence of endometrial tissue within the myometrium, causing pelvic pain, abnormal uterine bleeding, and infertility. Despite its high prevalence, the molecular mechanisms underlying disease initiation and progression remain incompletely understood. Current evidence implicates disruption of the endometrial–myometrial interface, epithelial–mesenchymal transition, and progesterone resistance in driving tissue invasion and remodeling. Diagnosis relies mainly on imaging modalities, while reliable non-invasive biomarkers are lacking. MicroRNAs, as stable post-transcriptional regulators of gene expression, have emerged as key modulators of proliferation, inflammation, and hormonal signaling, and represent promising candidates for novel diagnostic strategies. Methods: A systematic review was conducted in accordance with PRISMA guidelines and registered with PROSPERO (CRD42025637752). A comprehensive search of the Medline, Embase, Scopus, and Cochrane databases was performed in April 2025. Studies investigating miRNA expression in patients with adenomyosis compared with controls were included. The quality of the studies and the risk of bias were assessed using the Newcastle–Ottawa scale. Two reviewers independently performed study selection, data extraction, and quality assessment. Results: Twenty-seven studies published between 2015 and 2025 met the inclusion criteria. Thirty-nine distinct miRNAs were reported as significantly dysregulated in adenomyosis. Recurrently altered miRNAs included let-7a, miR-145, miR-10b, miR-30c-5p, miR-141-3p, miR-143, and miR-191. Functional analyses have consistently implicated miRNAs in key pathogenic pathways, including Hippo-YAP, PI3K/AKT, MAPK/ERK, JAK/STAT, and Wnt/β-catenin signaling. These alterations were associated with enhanced epithelial–mesenchymal transition, increased cellular proliferation and migration, progesterone resistance, chronic inflammation, and immune modulation. Emerging evidence highlights exosomal and circulating miRNAs as promising non-invasive biomarkers, with a few studies already demonstrating diagnostic potential using serum, plasma, or urine samples. However, substantial heterogeneity in tissue types, sampling timing, and analytical methods precluded meta-analysis. Conclusions: MiRNAs play a central role in the molecular pathogenesis of adenomyosis and show strong potential as non-invasive diagnostic biomarkers. However, large-scale validation studies and standardized methodologies are required before clinical implementation. Full article

Alternaria alternata causes severe foliar disease and substantial yield losses in mung bean (Vigna radiata (L.) R. Wilczek). However, the physiological and hormonal mechanisms driving resistance in locally adapted varieties remain largely unknown. We evaluated nine genotypes of Uzbekistan under controlled A. alternata inoculation across four growth stages (budding, flowering, podding, harvest), measuring salicylic acid (SA), jasmonic acid (JA), photosynthetic pigments, leaf water relations, morphology, and yield components. Infection triggered highly variable SA responses. Surprisingly, strong SA induction offered no yield protection: Barqaror showed a 212% SA increase but suffered the most severe grain weight loss (−62.6%). Conversely, Turon maintained high baseline JA and was the only genotype to increase chlorophyll a at podding (+16.8%). Disease stress did not significantly affect 1000-seed weight (p = 0.184), indicating that A. alternata primarily disrupts early pod formation rather than the seed-filling process. Zilola demonstrated the best overall yield stability, exhibiting near-complete pod retention (−0.8%) and moderate grain weight loss (−26.7%) while maintaining acceptable seed size. These findings emphasize that protecting early pod set is more critical than seed-filling capacity under infection. Consequently, Zilola represents a highly promising parental line for breeding A. alternata-tolerant mung beans in Central Asia. Full article

Colorectal cancer (CRC) remains one of the leading causes of cancer-related morbidity and mortality worldwide despite substantial advances in surgery, chemotherapy, targeted therapies, and immunotherapy. The limited efficacy of current treatment strategies in advanced disease and the emergence of therapeutic resistance highlight the urgent need for novel adjunctive therapeutic approaches. Increasing evidence indicates that chronic stress and sustained activation of β-adrenergic signaling promote colorectal tumor initiation, progression, angiogenesis, metastatic dissemination, and immune evasion, thereby identifying this pathway as a potential therapeutic target. Drug repurposing has emerged as an attractive strategy for accelerating the development of new anticancer therapies by identifying novel applications for clinically approved drugs with well-established safety profiles. Among these, β-blockers have gained considerable attention because of their ability to inhibit β-adrenergic signaling and modulate multiple oncogenic pathways implicated in CRC progression. Although accumulating preclinical and observational clinical evidence suggests that β-blockers may possess anticancer potential, the underlying molecular mechanisms and their translational relevance have not yet been comprehensively integrated. This review provides a critical overview of the current evidence regarding the therapeutic potential of β-blockers in CRC by integrating findings from preclinical and clinical studies. Particular emphasis is placed on the regulation of key signaling pathways, including cAMP/PKA/CREB, PI3K/AKT/mTOR, and RAS/RAF/MEK/ERK, as well as on the effects of β-blockers on tumor cell proliferation, apoptosis, angiogenesis, epithelial–mesenchymal transition, metastasis, and modulation of the tumor microenvironment and antitumor immune responses. However, significant barriers limit the translation of these findings into routine clinical practice, including the limited representativeness of preclinical models, potential hemodynamic adverse effects, and the inherent limitations of observational studies. Importantly, owing to the lack of prospective randomized clinical trials, the current evidence remains insufficient to establish the clinical efficacy of β-blockers in colorectal cancer. Although β-blockers possess several characteristics that make them attractive candidates for drug repurposing, including a well-established safety profile, widespread availability, and low cost, further mechanistic studies, prospective randomized clinical trials, and biomarker-based patient stratification are essential to determine their clinical efficacy and define their role in personalized CRC therapy. Full article

Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide and remains a major therapeutic challenge due to its marked inter- and intratumoral heterogeneity, diverse etiologies, and high propensity for therapeutic resistance. This review summarizes the biological complexity of HCC and current therapeutic challenges, with a particular focus on the RNA-binding protein human antigen R (HuR) as an emerging therapeutic target. Methods: A comprehensive narrative review of peer-reviewed literature was conducted, focusing on HCC pathogenesis, molecular heterogeneity, tumor microenvironment, mechanisms of therapeutic resistance, and recent advances in treatment. Emphasis was placed on studies investigating the biological functions of HuR and its therapeutic potential in HCC. Results: HCC progression is driven by complex interactions among genetic, epigenetic, metabolic, and environmental factors, resulting in substantial tumor heterogeneity and variable therapeutic responses. Dysregulated oncogenic signaling and immunosuppressive tumor microenvironment collectively contribute to resistance against current therapies, including multikinase inhibitors and immune checkpoint inhibitors. Although emerging strategies, such as combination immunotherapy, metabolic targeting, epigenetic modulation, and precision medicine, have shown encouraging preclinical and clinical results, their efficacy remains limited by tumor complexity and adaptive resistance. HuR functions as a master post-transcriptional regulator that stabilizes and promotes the translation of numerous mRNAs encoding oncogenic, inflammatory, and pro-survival factors. Accumulating preclinical evidence demonstrates that pharmacological inhibition of HuR suppresses multiple tumor-promoting pathways and enhances therapeutic sensitivity, supporting its potential as a novel therapeutic strategy for HCC. Conclusions: The biological complexity of HCC necessitates multifaceted, precision-based therapeutic approaches. Although additional HCC-specific mechanistic and translational studies are needed, targeting HuR represents a promising strategy to overcome tumor heterogeneity, therapeutic resistance, and disease progression. Continued integration of molecular profiling, advanced omics technologies, and rational combination therapies will be essential for translating these advances into improved clinical outcomes for patients with HCC. Full article

H. pylori infection induces oxidative stress and inflammatory responses in gastric epithelial cells, which are key factors in the pathogenesis of gastritis and ulcers. Given the increasing threat of antibiotic resistance, non-antibiotic approaches that target host cell injury mechanisms are gaining considerable interest. While peptides derived from corn protein are known for their antioxidant and anti-inflammatory activities, whether they can alleviate H. pylori-induced gastric epithelial injury remains unclear. In this study, we evaluated the preventive effects of corn protein-derived bioactive peptides (CPDP-N), prepared by neutral protease hydrolysis, against H. pylori-triggered injury in human GES-1 cells. CPDP-N exhibited no cytotoxic effects, reduced H. pylori-induced intracellular ROS accumulation in a dose-dependent manner, and markedly increased the activities of intracellular antioxidant enzymes. Flow cytometry and fluorescence imaging demonstrated that CPDP-N attenuated the loss of mitochondrial membrane potential and relieved G0/G1 cell cycle arrest. CPDP-N markedly suppressed the secretion of the pro-inflammatory cytokines TNF-α, IL-1β, and IL-8, attenuated LDH release, and upregulated the anti-inflammatory cytokine IL-10. Moreover, CPDP-N markedly lowered the H. pylori-induced elevation of nuclear factor kappa-B (NF-κB) p65 protein, a key regulator of inflammatory signaling. These protective effects were accompanied by reduced intracellular ROS levels and lower NF-κB p65 abundance, suggesting the involvement of oxidative stress and NF-κB pathways. Collectively, these findings demonstrate that corn protein-derived peptides can protect gastric epithelial cells from H. pylori-induced oxidative and inflammatory injury, highlighting their potential as a dietary intervention for H. pylori-associated gastric diseases. Full article

Prostate cancer remains one of the most frequently diagnosed malignancies in men worldwide, and despite favorable outcomes for localized disease, progression to castration-resistant prostate cancer (CRPC) represents a major clinical challenge associated with poor prognosis. CRPC is characterized by disease progression despite castrate levels of circulating testosterone and is most commonly diagnosed in the metastatic setting. Although the introduction of second-generation androgen receptor-targeted therapies has improved survival, resistance inevitably emerges. This review overviews the most recent findings in the field of CRPC with particular emphasis on the current understanding of the biological mechanisms of hormone-resistant cancer as well as the evidence on treatment strategies. A comprehensive literature search was conducted across PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar, focusing mainly on studies published between 2015 and 2025 that investigated molecular and cellular mechanisms of resistance to androgen deprivation therapy and androgen receptor (AR)-targeted treatments. Seventy-eight relevant articles were included in the final synthesis. The reviewed evidence highlights four major categories of resistance mechanisms. First, AR-dependent alterations remain predominant, including AR gene amplification, activating mutations, dysregulation of co-regulators, and expression of constitutively active AR splice variants such as AR-V7. Second, AR-independent or bypass pathways, most notably PI3K/AKT/mTOR, Wnt/β-catenin, MAPK, and glucocorticoid receptor signaling, enable tumor survival despite AR blockade. Third, lineage plasticity and transdifferentiation to neuroendocrine prostate cancer represent a distinct and increasingly recognized resistance mechanism driven by loss of TP53 and RB1 and epigenetic reprogramming. Finally, additional contributors, including intratumoral androgen synthesis, metabolic reprogramming, and tumor microenvironment interactions, further support disease progression. Together, these interconnected mechanisms underscore the biological complexity of CRPC and emphasize the need for biomarker-guided, combination-based therapeutic strategies to overcome resistance and improve patient outcomes. Full article

Bovine mastitis, caused by both contagious and environmental pathogens, represents a major infectious disease burden in the global dairy industry. Antibiotics remain the primary treatment option, but their effectiveness is limited by the blood–milk barrier, drug residues, and the growing threat of multidrug-resistant bacteria. Among the various alternatives, phage therapy has drawn particular attention due to its specificity, ability to disrupt biofilms, low impact on commensal flora, and self-replication at infection sites. In this review, we summarize recent advances in the isolation of lytic phages targeting major mastitis-causing pathogens, their bactericidal mechanisms, and their performance in vitro and in vivo. We also discuss key obstacles to clinical translation including formulation stability, narrow host range, and safety concerns. Moreover, the potential strategies to overcome these issues are explored. This review provides a useful reference for research on phage therapy against bovine mastitis. Full article

Non-coding RNAs (ncRNAs) are increasingly recognized as important regulators of cancer biology. Long non-coding RNAs (lncRNAs), defined as transcripts longer than 200 nucleotides, gain particular attention due to their cancer-specific expression patterns and functional roles in tumor progression, metastasis and therapeutic resistance. Although lncRNAs have been extensively studied as diagnostic, prognostic and predictive biomarkers, growing evidence indicates that they can also act as active mediators of therapeutic resistance, supporting their potential as therapeutic candidates. Here, we summarize how lncRNAs contribute to resistance against radiotherapy, chemotherapy, immunotherapy and targeted therapy, highlighting their molecular mechanisms. Next, we discuss RNA-based therapeutics as a strategy to target disease-relevant transcripts, focusing on antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), microRNA (miRNA) mimics and antimiRs, as well as approved RNA therapeutic agents, oncology-focused candidates in clinical development and emerging preclinical approaches directed against lncRNAs or lncRNA-controlled regulatory axes. Finally, we examine delivery platforms, including lipid-based nanovectors, extracellular vesicles, polymeric systems and other approaches designed to overcome key translational barriers, such as RNA instability, off-target effects, immune activation, renal clearance and inefficient tumor-specific delivery. By connecting lncRNA-mediated resistance mechanisms with RNA therapeutic strategies and delivery technologies, this review highlights lncRNA-directed RNA therapeutics as a promising yet developing approach in oncology. Full article

Ganoderma boninense, a soil-borne pathogenic fungus causing basal stem rot (BSR) disease in oil palm, is the major threat to cultivation in Southeast Asia, with the potential to reduce oil production by up to 80% in severely affected plantations. With a view to marker-assisted selection (MAS) of resistant planting material, we combined genetics and transcriptomics approaches to investigate the defense mechanisms of oil palm against infection by G. boninense. We first performed quantitative trait locus (QTL) mapping of BSR resistance using a multi-locus Bayesian variable selection approach applied to more than 10 years of data collected during pre-nursery tests of Deli and La Mé breeding populations. We found 6 and 5 BSR resistance loci segregating in Deli and La Mé respectively, with no overlap between them. Then we performed an RNA-sequencing approach on libraries of roots and bole of oil palm seedlings inoculated or not with G. boninense, focusing on Deli × La Mé crosses with contrasted BSR resistance. A Bayesian variable selection on predictors obtained by tracing the resistance loci haplotypes in profiled individuals identified 195 differentially expressed genes (DEGs) for the G. boninense inoculation × QTL interaction, among the 551 DEGs found for inoculation effects. The DEGs were located both in cis and trans positions compared to the segregating QTL intervals, enabling the prioritization of candidate genes and resistance mechanisms associated. Focusing on a strong effect QTL region on chromosome 4 in the Deli genetic background, we identified three candidate genes in cis positions that exhibited differential expression both in response to G. boninense inoculation and between resistant and susceptible haplotypes. Our study is the first combining QTL and RNA-seq approaches in oil palm based on genetically connected experimental setup, providing valuable information on the underlying mechanisms and paving the way for MAS of BSR resistant planting material. Full article