Search Results (640)

Salicylic acid (SA) is involved in plant defense responses to environmental stressors by modulating gene expression and specialized metabolites production, enhancing plant adaptive resilience through systemic signaling pathways. This study investigates the impact of exogenous application of SA on the metabolism of iridoids and phenolic compounds—characteristic specialized metabolites of the Nepeta species, associated with diverse biological activities. Nepetalactone (NL) is a characteristic monoterpene iridoid, while rosmarinic acid (RA) represents the most abundant phenolic compound within the genus. We explored the effects of varying SA concentrations (2 µM, 5 µM, 10 µM, and 20 µM) on iridoid and phenolic metabolism in in vitro-grown Nepeta nuda, following 7 days and 28 days of elicitation. A significant increase in trans,trans-NL content was observed after 7-day exposure to 2 µM SA, while prolonged exposure led to a decrease in its levels, particularly at higher SA concentrations. Gene expression analysis revealed that 7 days of exposure to lower concentrations of SA upregulated genes coding for NAD-dependent nepetalactol-related short-chain dehydrogenase/reductases (NEPSs), key regulatory enzymes catalyzing the final steps of NL biosynthesis. In contrast, prolonged exposure to 20 µM SA downregulated genes coding for geraniol 8-hydroxylase (NnG8H) and 8-hydroxygeraniol oxidoreductase (Nn8HGO), which resulted in reduced iridoid content. Conversely, SA treatment notably increased RA content after prolonged exposure to 20 µM SA, which is a result of the enhanced expression of all analyzed RA biosynthesis-related genes. These findings demonstrate that both concentration and duration of SA treatment are critical determinants of elicitation outcomes in N. nuda. Strategic manipulation of these parameters can redirect metabolic flux toward either iridoid or phenolic compounds production, and enhance biotechnological production of specialized metabolites in N. nuda. Full article

Legal element recognition, which identifies discrete factual elements in Chinese court judgments to support judicial analysis and case retrieval, faces a severe long-tail challenge: head-to-tail label-frequency ratios exceed 100:1, and over 60% of sentences carry no label, starving rare elements of training signal. Static reweighting methods assign fixed weights prior to training and cannot respond to the model’s evolving confidence; sample-level meta-learning couples all co-occurring label gradients to a single scalar, preventing independent tail-label amplification. We propose BML-Trans, a boundary-aware meta-learning framework that addresses both limitations. A label-wise meta-weighting mechanism maintains per-label gradient weights updated via bilevel hypergradient descent, decoupling tail-label amplification from co-occurring head labels. A boundary-aware meta-set concentrates calibration signal on high-uncertainty, tail-triggering sentences rather than on easy negatives, and a lightweight Multi-Scale Adapter sharpens the warm-up probability estimates on which boundary selection depends. Concretely, BML-Trans achieves an average Avg-F1 of 82.5% on CAIL2019 across the labor, divorce, and loan domains, outperforming the strongest baseline by 1.2 percentage points overall and by up to 5.7 percentage points on tail-label Macro-F1, at only 14% additional training cost. Ablation confirms a cascade dependency among the three components, establishing that the gains are structural rather than incidental to threshold selection or initialization. Full article

Corn, paddy, wheat, sorghum, and cassava serve as the primary energy sources in both human and animal diets. This study aimed to evaluate their nutrient release patterns in a simulated gastrointestinal environment and to assess the in vitro biological activity of the metabolites produced during digestion. The results showed that wheat exhibited the highest dry matter degradation in the stomach–jejunum–ileum digestion stage, while wheat and paddy showed the highest crude protein degradation compared with the other starch sources. In addition, wheat had a higher total free sugar concentration than paddy, sorghum, and cassava. Among the individual free sugars, such as D-sorbitol and D-(+)-trehalose, were found to have the highest concentrations in wheat, whereas cassava had the highest D(−)-fructose concentration. Several differential metabolites, including valeric acid, caproic acid, octanoic acid, and azelaic acid were highly released in paddy, whereas glucaric acid, threonic acid, phenylacetic acid, and shikimic acid were highly released in cassava, and 4-hydroxycinnamic acid was highly released in paddy and sorghum. Four unique metabolites were identified during the digestion process of five starch sources. Particularly, isocitric acid and trans-cinnamic acid were released only from cassava; caffeic acid was released only from sorghum and corn; and pimelic acid was released only from paddy and wheat. Furthermore, cassava was distinct from the other starch sources, displaying a higher abundance of differential metabolites within the glucagon signaling pathways as mapped in KEGG pathway analysis. In summary, compared with other starch sources, wheat provides more dry matter, protein, and sugars for the body. Cassava is unlikely to offer any advantage in glycemic regulation, while paddy and cassava possess stronger biological activity in terms of differential metabolites. Full article

Chemotherapy- and/or radiotherapy-induced oral mucositis (CRIOM) is a common complication in patients with head and neck cancer, driven largely by excessive proinflammatory cytokine signalling and treatment-associated bacterial dysbiosis. This narrative review synthesizes current mechanistic evidence and summarizes emerging therapeutic strategies targeting these pathways. Research indicates that elevated levels of IL-1β, IL-6, TNF, iNOS, and nitric oxide amplify tissue injury and ulceration, while disruption of oral and gut microbial communities, characterized by loss of beneficial commensals and enrichment of pathogenic taxa, further exacerbates mucosal inflammation. Anti-inflammatory agents, including pentoxifylline, atorvastatin, trans-caryophyllene, azilsartan, recombinant human IL-11, and low-level laser therapy have been shown in preclinical models to reduce cytokine levels and promote mucosal healing. Similarly, microbiome-targeted approaches, such as oral microbiota transplantation and multi-strain probiotic formulations, have demonstrated potential in restoring microbial balance and attenuating CRIOM severity, with current evidence including both preclinical and clinical studies. Overall, current findings highlight cytokine toxicity and dysbiosis as synergistic drivers of CRIOM and support anti-inflammatory and microbiome-modulating strategies as promising adjunctive approaches; however, further well-designed clinical studies are required to validate their efficacy and guide clinical translation. Full article

The high incidence of thrombosis in lymphoma is largely due to chronic inflammation and endothelial dysfunction. To elucidate the mechanisms underlying thrombus formation and fibrinolysis, we investigated interactions between circulating endothelial cells and peripheral blood mononuclear cells (MNCs), along with inflammatory signaling pathways, in patients with follicular lymphoma (FL), Hodgkin lymphoma (HL), and diffuse large B-cell lymphoma (DLBCL), independent of the presence of thrombosis, compared to healthy controls by flow cytometry, immunoblotting, and fluorometric assays. We observed increased tissue factor (TF) expression on CD31+ endothelial cells in DLBCL and FL. In DLBCL, inducible nitric oxide synthase expression was elevated in MNCs, while reduced nitrite levels correlated with an advanced clinical stage in patients with thrombosis. In lymphoma, nuclear factor kappa B (NFκB) signaling was activated in MNCs, while signal transducer and activator of transcription 3 (STAT3) activation was increased in DLBCL with thrombosis. Trans-endothelial migration of MNC was enhanced in HL, FL and DLBCL with thrombosis and reduced by inflammatory cytokine tumor necrosis factor alpha (TNF-α) that promoted platelet aggregation like interleukin-6 (IL-6) in HL and FL. Fibrinolytic analyses showed reduced tissue type plasminogen activator in lymphoma, whereas increased urokinase-type plasminogen activator (uPA) was linked to poorer total survival in DLBCL with thrombosis, suggesting a compensatory role in early thrombus resolution. These findings indicate that chronic inflammation promotes endothelial activation, dysregulated fibrinolysis, and increased vascular permeability, contributing to heightened thrombotic risk. This study provides mechanistic insight into lymphoma-associated thrombosis and identifies TF, uPA, and the inflammatory signaling pathways as potential biomarkers and therapeutic targets. Full article

Familial thoracic aortic aneurysm and dissection (FTAAD), caused by the pathogenic Myh11 K1256del variant, is characterized by impaired aortic contractility; however, how reduced contractility predisposes the aorta to dissection remains incompletely understood. In this study, we performed a data-driven trans-omic upstream analysis using Genome Enhancer to identify key regulatory mechanisms in aortas from Myh11 K1256del mice under baseline conditions, without exposure to exogenous pathological stimuli. Transcriptome analysis revealed enrichment of genes related to smooth muscle contraction and regulation of myosin light chain phosphatase activity. Upstream computational analysis of regulatory regions identified nuclear factor of activated T cells 1 and lymphoid enhancer-binding factor 1 as major transcription factors, and further highlighted Rho-associated, coiled-coil-containing protein kinase 1 (ROCK1) as a predicted central regulator of the dysregulated transcriptional network. Druggability analysis suggested ROCK1 and the JunB proto-oncogene AP-1 transcription factor subunit as potential therapeutic targets. Furthermore, it predicted 51 candidate therapeutants, including atorvastatin, GSK-269962A, and atovaquone. These findings indicate that even in the absence of overt pathological stimulation, aortic tissue carrying the Myh11 K1256del variant exhibits a transcriptional program centered on ROCK signaling, which may prime the aorta for maladaptive responses to additional stress and may enhance susceptibility to dissection. This computational analysis requires experimental validation, but may provide a hypothesis-generating framework for development of preventive pharmacological interventions against FTAAD. Full article

We developed a Python-integrated closed-loop industrial safety system that bridges real-time helmet-compliance detection with immediate machine control. The custom Python application serves as critical middleware, orchestrating the complete pipeline from You Only Look Once Version 8 computer vision inference to industrial automation by trans-lating AI detection results into Object Linking and Embedding for Process Control Unified Architecture communications with a Mitsubishi programmable logic controller (PLC). The Python framework implements configurable safety policies through polygonal zones with authorized helmet colors, incorporates persistence filtering to prevent nuisance trips, and ensures deterministic translation from probabilistic AI outputs to Boolean PLC con-trol signals. Validation demonstrates reliable, low-latency safety actuation with clear ar-chitectural separation between vision processing, Python-mediated policy enforcement, and PLC-based deterministic control. Full article

Human induced pluripotent stem cell (iPSC)-derived brain organoids have emerged as powerful three-dimensional (3D) platforms for modeling human neurodevelopment and neurological disorders. However, the absence of a functional vascular network remains a critical limitation, restricting oxygen and nutrient delivery, impairing metabolic stability, and constraining long-term maturation. Conventional extracellular matrix (ECM) mimetics, such as Matrigel and other static synthetic hydrogels, provide biochemical support but fail to recapitulate the dynamic remodeling that characterizes the developing neurovascular niche. Recent advances in stimuli-responsive hydrogels offer spatiotemporal control over matrix stiffness, degradability, viscoelasticity, and biochemical cue presentation. In this review, we discuss dynamic hydrogel systems within a structure–property–function framework, highlighting how network chemistry and architecture may regulate endothelial sprouting, lumen formation, vascular stabilization, and neurovascular unit maturation in vascularized brain organoid models, based on evidence from both organoid studies and related biomaterial or vascular systems. Photoresponsive, enzyme-cleavable, thermo-responsive, supramolecular, bio-orthogonal click-based, and bioprinted platforms are discussed with emphasis on mechanotransduction, angiocrine signaling, and barrier specialization. Functional outcomes, including trans-endothelial electrical resistance, selective permeability, transporter expression, electrophysiological integration, and sustained perfusion, are discussed alongside translational challenges such as cytocompatibility, oxidative stress, scalability, and regulatory feasibility. Collectively, dynamic hydrogels provide a versatile biomaterial strategy for improving vascularization and aspects of functional maturation in brain organoid models with enhanced physiological relevance. Ultimately, stimuli-responsive hydrogel systems may serve as enabling platforms for engineering vascularized brain organoids and advancing human-relevant neurovascular disease modeling. Full article

Aquaporins (AQPs) are increasingly recognized as key regulators of tumor progression, influencing key hallmarks of cancer progression and cellular homeostasis. Their frequent overexpression in malignancies highlights their potential as therapeutic targets, yet the development of selective synthetic inhibitors remains challenging due to structural conservation and off-target toxicity. Natural compounds have recently emerged as promising modulators of AQP expression and function, offering greater molecular diversity and generally favorable safety profiles. This review synthesizes current evidence on phytochemicals, including bacopaside II, curcumin, resveratrol, quercetin, EGCG, all-trans retinoic acid, chrysin, and rottlerin, that interact with AQP isoforms relevant to cancer biology. These agents regulate AQPs through transcriptional control, redox modulation, signaling-pathway interference, or direct pore blockade, thereby attenuating oncogenic processes such as migration, angiogenesis, inflammation, and metabolic adaptation. Several compounds, notably bacopaside II and rottlerin, display isoform-selective inhibitory properties that directly impair AQP1- and AQP3-mediated permeability. Collectively, available evidence positions natural AQP modulators as promising lead compounds providing scaffolds for further drug development in oncology. Continued structural, mechanistic, and preclinical research is required to optimize isoform specificity and therapeutic efficacy, paving the way for their integration into future anticancer strategies. Full article

Steroid-resistant nephrotic syndrome (SRNS) in childhood frequently reflects monogenic podocytopathies in which immunosuppression is ineffective. Biallelic variants in MYO1E, encoding the class I myosin Myo1E, cause a distinctive form of focal segmental glomerulosclerosis (FSGS) often accompanied by “Alport-like” multilamination of the glomerular basement membrane (GBM). Early recognition has therapeutic and prognostic implications. A previously healthy 4-year-old boy presented with generalized edema and nephrotic-range proteinuria. Glucocorticoids induced no remission; sequential calcineurin inhibition (cyclosporine, then tacrolimus) and a single dose of ofatumumab yielded only transient, partial reductions in proteinuria. A first biopsy elsewhere showed FSGS with nonspecific IgM/C3 trapping; electron microscopy (EM) was not performed. At age 10, repeat biopsy with EM revealed ~30% segmental foot-process effacement, focal GBM thickening (to 1740 nm), irregular lamina densa multilamination, and lamellar duplications without immune-complex deposits—features highly suggestive of hereditary GBM disease. Targeted sequencing identified compound-heterozygous MYO1E variants segregating in trans: a canonical splice-donor change (c.2785+1G>A) and a frameshift (c.3094_3097del; p.Thr1032Profs*73). Each parent was an unaffected heterozygous carrier; the sibling was negative. Supportive therapy with ramipril was continued. At last follow-up (January 2025), renal function was normal (serum creatinine 0.5 mg/dL; creatinine clearance 122 mL/min) with stable sub-nephrotic proteinuria (0.52 g/day; 16 mg/m² per hour) and normotension. This case broadens clinicopathologic recognition of MYO1E-associated nephropathy and highlights the teaching point that Alport-like GBM changes are not pathognomonic for type IV collagen disorders but may signal defects in podocyte cytoskeletal anchoring. Full article

Pollen development is a complex process that is highly sensitive to environmental stresses. Abscisic acid (ABA), a key hormone mediating plant growth and stress responses, has been implicated in the regulation of sexual reproduction, especially pollen development, yet its precise regulatory role remains unclear. This study investigated the effects of exogenous ABA on Arabidopsis thaliana pollen development and function through integrated phenotypic, cytological, and transcriptomic approaches. ABA treatment specifically impaired pollen function by reducing germination rates and inhibiting pollen tube elongation, which resulted in shortened siliques and decreased seed set, without affecting pollen morphology or viability. Transcriptome analysis of mature anthers revealed a transient and time-dependent transcriptional response, with the number of differentially expressed genes (DEGs) peaking at 8 h post-ABA treatment and markedly declining by 22 h. These DEGs were enriched in stress-response pathways (e.g., salt, cold, and dehydration), hormone signaling, and carbohydrate metabolism. Moreover, we identified 25 differentially expressed transcription factors and 16 pollen development and function-related genes, highlighting their key roles in ABA-mediated regulation. In parallel, 146 differentially expressed lncRNAs (DELs) were identified, which formed 144 cis-regulatory pairs with genes involved in ABA response and pollen tube growth, with their predicted targets enriched in pathways such as hormone and MAPK signaling, carbohydrate metabolism and stress response. Trans-regulatory analysis further revealed that these DELs co-expressed with DEGs in modules enriched for stress response, pollen development, and tube growth pathways. Notably, key pollen function genes showed strong co-expression with DELs, indicating that lncRNAs participate in ABA-induced transcriptional reprogramming that shifts metabolic resources from growth to defense, thereby suppressing pollen germination and tube elongation. Together, these findings elucidate a coordinated regulatory network involving mRNAs, lncRNAs and transcription factors roles in modulating ABA responses during pollen/anther development. Full article

Chronic obstructive pulmonary disease, interstitial lung disease, and post-lung trans-plantation are often accompanied by skeletal muscle dysfunction that worsens the quality of life. Such physiological changes are driven by physical inactivity, systemic inflammation, oxidative stress, anabolic and hormonal resistance, and medication effects. Structural changes include impaired capillarization, fiber-type shifts (slow-to-fast in limb muscle and fast-to-slow in respiratory muscles), mitochondrial dysfunction, reduced oxidative capacity, and early lactate accumulation. Electromyography and dynamometry, both isokinetic and isometric, quantify neuromuscular drive through measuring strength, power, and endurance and are associated with functional outcomes (6-min walk, sit-to-stand, stair climbing tests). Pulmonary rehabilitation (PR) improves neuromuscular efficiency, dyspnea, exercise tolerance, and quality of life by combining resistance, endurance, and eccentric training. The effects of PR generally plateau at three months, emphasizing the need for maintenance and the personalization of rehabilitation plans. While nutritional optimization is important, supplements have shown little benefit. Future priorities include defining EMG/dynamometry thresholds to allow standardized routine testing for comparable benchmarks and more precise PR protocols. Future research targeting mitochondrial remodeling, inflammatory signaling, and anabolic resistance offer potential pathways for preventing and reversing muscle wasting. Full article

This study presents the development and evaluation of surface functionalized solidly mounted resonators (SMRs), including custom developed at the University of Warwick (UWAR) devices and commercial Sorex sensors, for the detection and classification of plant-emitted volatile organic compounds (VOCs). The sensors were tested against linalool, trans-2-hexenal (T2H), and D-limonene at different concentrations under both dry and humid conditions (30% ± 3% RH). A Python-based (v3.13.5) signal-processing workflow was established to filter frequency responses and extract key features, such as baseline, saturation point, and frequency shift ($\Delta f$). Adsorption behaviour was modelled using the Freundlich isotherm, showing good agreement with experimental data and suggesting heterogeneous, multilayer adsorption on CH₃-terminated EC surfaces. A 2D polar classification framework combining vector-normalized $\Delta f$ values from UWAR and Sorex sensors enabled a clear separation of the VOCs. The results highlight the complementary performance of the two types of SMR sensors and demonstrate that feature-engineered resonant devices, combined with computational classification, offer strong potential for future use in plant health monitoring systems. Full article

Heat stress-induced systemic metabolic disorder serves as the core pathological basis of organismal damage. Although mung bean polyphenols (MBPs) had been preliminarily validated in cellular heat-stress models for their intestinal tissue-protective potential, whether they can alleviate heat-stress injury in vivo by remodeling the metabolic crosstalk network between the gut and systemic circulation remains mechanistically unclear. In this study, we innovatively employed an integrated multi-omics approach combining physiological phenotype, gut metabolome, and serum metabolome analyses based on a Balb/c heat stress (41 °C) mouse model, systematically constructing the metabolic phenotype regulatory network of MBPs. The results demonstrated that MBPs not only significantly improved oxidative stress (elevating GSH-Px and T-AOC, reducing MDA), immune-inflammation (down-regulating IL-1β and TNF-α), and stress hormone (lowering cortisol) phenotypes, but also specifically reversed the disturbances in intestinal and serum metabolic profiles induced by heat stress, particularly restoring key pro-inflammatory mediators such as Leukotriene E4 and 5-HETE. Arachidonic acid metabolism, tryptophan metabolism, histidine metabolism, and Fc epsilon RI signaling pathway constituted the core network of heat-stress metabolic disorder and MBP regulation. Furthermore, the study revealed that alterations in hub metabolites—Indolelactic Acid, Trans-Cinnamic Acid, Leukotriene E4, 5-HETE, and N(omega)-Hydroxyarginine—were significantly correlated with phenotypic improvements. This confirms that mung bean polyphenols dynamically dismantle the “pro-inflammatory-oxidative stress” pathological coupling by constructing a novel protective axis centered on the indole metabolism–melatonin–endogenous antioxidant system and successfully established a novel protective axis driven by gut-derived beneficial metabolites that promotes systemic antioxidant function, thereby elucidating the systemic mechanism underlying the alleviation of heat-stress injury at the metabolic network level. Full article

Background: LATERAL ORGAN BOUNDARIES DOMAIN (LBD/AS2) transcription factors integrate developmental and hormonal signals during organogenesis. As a high-value fruit tree crop, blueberries’ rooting ability underpins their vegetative propagation and field performance, yet a genome-wide view of the LBD repertoire and its roles in blueberry has been lacking. Results: We cataloged 153 non-redundant LBD genes (VcLBD) by homology search against the GDV RefTrans V1 genome and domain validation, substantially exceeding counts reported for other fruit crops. Phylogeny resolved the family into the canonical Class I/II and seven subclades, with extensive lineage-specific expansion supported by synteny: 72.31% of loci arose from whole-genome/segmental and tandem duplication. Gene structures were highly heterogeneous (2–24 exons) but conserved within clades; motif profiling (MEME/InterPro) recovered the signature LOB cysteine block, GAS module and a leucine-zipper-like motif with clade-specific combinations. Promoter scanning identified 38 cis-element types, including hormone- (auxin, cytokinin, GA, JA/MeJA, ABA, SA), stress- and meristem-associated motifs, indicating broad regulatory inputs. Public transcriptomes revealed pronounced tissue–stage specificity with a root-centered bias; qRT-PCR across eight organs/stages validated four archetypal expression programs (higher expression in roots, flowers, fruits in stage 1, or mature fruit, respectively), including floral/early-fruit enrichment (e.g., VcLBD39/40) and ripening-associated induction. Hormone assays demonstrated differential responsiveness: IAA up-regulated VcLBD6/16b/33c/40e/41, whereas 6-BA suppressed VcLBD16b/33c/39a/39c/40e and induced VcLBD41/46h; ACC and MeJA produced gene-specific induction or repression. During adventitious rooting (0/4/7/10 DAC), 30 VcLBDs were differentially expressed, forming three temporal patterns. VcLBD16b reaches its peak expression during the early stages of adventitious root development and exhibits a strong response to auxin. VcLBD11 shows dynamic changes synchronized with cytokinin activity, while VcLBD33/40 is associated with primordia growth and vascular-related processes. Conclusions: We identified and characterized 153 VcLBD genes, profiled their transcripts across multiple blueberry tissues, defined stages of adventitious root development, and evaluated hormone responsiveness for representative members. Together, these results establish a foundation for dissecting VcLBD regulatory mechanisms and functions, particularly in organ growth and adventitious rooting. Full article