Search Results (4,301)

Lymphoid neoplasms such as multiple myeloma (MM), indolent non-Hodgkin lymphoma, and chronic lymphocytic leukemia are increasingly managed as chronic, relapsing conditions characterized by prolonged surveillance, repeated treatment transitions, and cumulative self-management demands. These trajectories expose patients and caregivers to persistent illness uncertainty, fluctuating fear of progression, symptom and comorbidity burden, communication challenges, and treatment-related workload. This theory-informed framework development paper uses an overview of selected psycho-oncological, hematological, nursing, theoretical, and patient-reported outcome literature to propose the LUMINA framework: Longitudinal illness trajectory, Uncertainty fields, Multidimensional symptom and comorbidity load, Information and interaction context, Navigation work and self-management load, and Adaptive outcomes and alignment. LUMINA is intended as a hypothesis-generating conceptual structure to organize clinically relevant domains, clarify potential relationships among uncertainty, symptom burden, communication, navigation work, and adaptive outcomes, and guide future assessment, validation, and intervention research in chronic lymphoid neoplasms. The framework builds on prior theories of illness uncertainty, treatment burden, workload–capacity balance, fear of recurrence/progression, and lymphoma-specific qualitative work on uncertainty management and psychosocial adaptation. Potential research applications include structured assessment, shared decision-making research, and domain-matched supportive-care concepts; however, these applications remain theoretical and require empirical testing. Future studies should evaluate feasibility, acceptability, construct validity, domain overlap, predictive validity beyond quality of life, and the clinical utility of LUMINA-informed research profiles. Until such validation is available, LUMINA should be interpreted as a conceptual model rather than a validated clinical tool or care pathway. Full article

Background/Objectives: Hyalinizing clear cell carcinoma (HCCC) and clear cell odontogenic carcinoma (CCOC) are rare clear cell neoplasms with overlapping histopathological features. This study aimed to compare their clinicopathological characteristics, particularly in anatomically challenging sites such as the palate and maxilla. Methods: Three analyses were performed. First, an unpublished series of five HCCC and three CCOC cases was evaluated for diagnostic histopathological features. Second, a PRISMA-ScR-guided literature review of 58 HCCCs and 45 CCOCs restricted to tumours arising in intraoral minor salivary glands, major salivary glands and gnathic bones published between 2000 and 2025 was conducted using PubMed. Third, a sub-analysis compared palatal HCCC and maxillary CCOC (25 vs. 14 cases), integrating literature and unpublished cases. Results: The case series and overall literature review showed that HCCC and CCOC predominantly occurred in adults (mean age, case series: 50.8 years; literature: 56.33 years for HCCC and 61 vs. 54.11 years for CCOC) with a female predilection (case series: 60%; literature: 68%) and generally exhibited clinically indolent behaviour. The site of occurrence, soft tissue (HCCC) versus intraosseous location (CCOC), was the principal distinguishing feature. No marked differences were observed between the two tumours in either the overall literature analysis or the site-specific sub-analysis. However, CCOC at maxillary/palatal sites presented with a higher number of larger lesions and higher number of cases with nodal metastasis compared with HCCC, most probably indicating delayed clinical detection rather than intrinsic aggressiveness of CCOC. Histopathological overlap was considerable; however, diffuse dense hyalinization (4/5), focal glandular differentiation (2/5), mucous-secreting cells (4/5) and salivary gland association (5/5) favoured HCCC, whereas patchy hyalinization (3/3), larger tumour lobules (3/3) and peripheral palisading (2/3) favoured CCOC. Conclusions: HCCC and CCOC demonstrate clinicopathological similarities and shared EWSR1 rearrangement, supporting a close biological relationship. The considerable overlap between these tumours support the hypothesis that CCOC may represent the intraosseous counterpart of HCCC and highlight the importance of integrated clinicopathological assessment and further clarification in future WHO classifications. Full article

Highbush blueberry (Vaccinium corymbosum L.) is widely cultivated in southern Chile on acidic Andisols, where aluminum (Al³⁺) toxicity and water deficit frequently occur simultaneously and limit plant performance. However, the integrated physiological responses to these stresses and the potential protective role of methyl jasmonate (MeJA) remain poorly understood. This study evaluated the physiological, biochemical, and hormonal responses of two cultivars with contrasting resistance, Legacy (Al-resistant) and Star (Al-sensitive), exposed to Al³⁺ stress, water deficit, and their combination, with or without MeJA application. Plants were grown in Andisol soil under greenhouse conditions and subjected to eight treatments, with measurements performed at 7, 14, and 21 days. Exposure to stress conditions resulted in decreased growth, reduced leaf water status, diminished photosynthetic performance, lower pigment stability, and decreased auxin concentration as estimated by Salkowski-reactive indolic compounds. Conversely, stress conditions led to increased aluminum (Al) accumulation, elevated proline levels, enhanced lipid peroxidation, and heightened antioxidant responses. Water deficit produced the strongest reductions in photosynthesis, about 48% in Legacy and 65% in Star, whereas Al accumulated mainly in the roots of Star (14-fold). The combined stress intensified physiological limitations and oxidative damage, particularly in the Star cultivar (4-fold), which showed stronger reductions in photosynthetic parameters, higher Al accumulation, and greater lipid peroxidation. In contrast, Legacy maintained more stable physiological performance. Exogenous MeJA mitigated stress effects by reducing Al accumulation (30–35%) and oxidative damage, improving photosynthetic performance (40–60%) and water status, and partially restoring auxin levels and growth in both cultivars, being more evident in the resistant cultivar Legacy. These results indicate that MeJA contributes to the regulation of physiological and antioxidant responses associated with resistance to combined Al toxicity and water deficit in highbush blueberry. Full article

Seasonal variation in aroma quality is critical for commercial grading of Xinyang Maojian (XYMJ) green tea, and how seasonal changes shape its volatile composition and aroma profile remains unclear. This study investigated the volatile profiles of XYMJ harvested in spring, summer, and autumn using headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) and odor activity value (OAV) analysis. A total of 93 volatile compounds were identified, with alkenes, alcohols, and esters being the most numerous chemical classes. Total volatile content decreased significantly seasonally (p < 0.05), being highest in spring (1716.68 μg/kg), followed by summer (1566.72 μg/kg) and autumn (1378.21 μg/kg). PCA and PLS-DA clearly distinguished seasons. Using a dual-filtering strategy (variable importance in the projection > 1.0 and p < 0.01), 14 differential volatile metabolites were identified as core seasonal markers. Geraniol, cis-jasmone, and indole were identified as key drivers of the premium floral fragrance in spring XYMJ, while cis-3-hexenyl hexanoate and linalool peaked in the summer harvest. OAV results and cross-modal sensory interaction principles suggest that the superior flavor of spring XYMJ arises from both higher aromatic intensity and an optimized aroma-taste balance. These findings provide useful insights into the seasonal variations in the metabolic and chemical profiles of XYMJ, enhancing our understanding of the biochemical markers associated with its production timeline. Full article

Hepatocellular carcinoma (HCC) is the most frequent type of primary liver cancer and one of the leading causes of cancer-related mortality globally, with its incidence increasingly driven not only by viral hepatitis and alcohol-related etiologies but also by metabolic dysfunction-associated steatotic liver disease. Dietary intake can modify gut microbial activity and the production of microbial metabolites, which in turn may regulate hepatic immune signaling and metabolic pathways along the gut–liver axis. Microbiota-derived metabolites have emerged as important immunometabolic mediators linking dietary factors to hepatic immune responses and metabolic reprogramming. These metabolites, which have been shown to influence hepatic immune cell function and inflammatory signaling, include short-chain fatty acids, secondary bile acids, and tryptophan-derived indoles. Changes in the production and composition of these metabolites have been associated with immune dysregulation, chronic inflammation, and metabolic reprogramming that promote hepatocellular carcinoma development. This review highlights how diet–microbiota interactions reshape hepatic immunometabolism and discusses their potential translational relevance for prevention and therapeutic strategies in hepatocellular carcinoma. Full article

Nineteen monoterpene indole alkaloids, including twelve new ones, were successfully isolated and identified from the stems and leaves of Uncaria hirsuta (Havil.). The planar structures were elucidated by nuclear magnetic resonance (NMR), high-resolution mass (HRMS), and ultraviolet (UV) analyses. The absolute configurations of new compounds were determined using electron circular dichroism calculations in conjunction with NMR calculations. The acetylcholinesterase inhibitory activity of the isolated compounds was evaluated in vitro. In further biological evaluation, the isolated compounds were evaluated for their neuroprotective effects on HT22 neuronal cells. Six compounds demonstrated significant protective activity. Their intracellular reactive oxygen species (ROS) levels were measured using the DCFH-DA fluorescent probe, which markedly attenuated glutamate-induced ROS accumulation. The results not only enrich the knowledge on the structural diversity of monoterpene indole alkaloids but also offer substantial evidence for further pharmacological exploration. Full article

The scaffold protein RACK1 (Receptor for Activated C Kinase 1) integrates signaling and translation, acting as a core component of the 40S ribosomal subunit. It binds activated Protein Kinase C (PKC) isoforms and membrane receptors. We used an auxin-inducible degron (AID2) system in human HAP1 cells to selectively deplete the free (cytoplasmic) pool of RACK1. The engineered RACK1–mAID–mClover3 fusion was rapidly degraded in the cytoplasm upon addition of 5-phenyl-indole-3-acetic acid (5-Ph-IAA), while the ribosome-bound pool remained detectable in ribosomal fractions, indicating that ribosome association makes RACK1 relatively less accessible to AID2-mediated proteolysis. Upon activation of PKCβII with phorbol-12-myristate-13-acetate (PMA), imaging at defined time points revealed closely matched kinetics of PKCβII membrane recruitment and membrane-proximal enrichment of ribosome-bound RACK1, peaking at ~10 min. Our data support a model in which activated PKCβII engages ribosome-bound RACK1 at membrane-proximal sites, consistent with a diffusion–capture mechanism in which PKCβII first accumulates at the membrane and then captures ribosome-bound RACK1, thereby recruiting the translational machinery to sites of signal input for membrane-proximal translation. These findings provide new insights into the spatial organization of translation. Full article

Annulated organic molecular structures with planar, fused backbones exhibit superior properties compared to non-fused systems, including high crystallinity, strong π–π stacking, and excellent charge transport characteristics. The rational design of annulated compounds with targeted characteristics presents a significant challenge that requires a comprehensive understanding of structure–property relationships. This work addresses this by synthesizing a series of novel push–pull systems featuring benzothieno[3,2-b]benzothiophene (BT) or its nitrogen-rich analogue, indolo[3,2-b]indole (ID), as electron-donating units, connected via a phenylene π-spacer to two distinct electron-accepting groups (carbonyl or dicyanovinyl). The thermal, structural, optical and electrochemical properties of these compounds were thoroughly investigated. Computational studies of the optical and electrochemical properties, including those of unsubstituted ID and BT model cores, showed excellent agreement with experimental data, validating the theoretical models. Notably, ID-based derivatives exhibited remarkably high photoluminescence quantum yield and enhanced solubility compared to their BT counterparts, along with thermal properties that are more favorable for device fabrication. This work provides the first systematic comparison of these annulated cores, offering novel structure–property insights that may support the rational design of organic functional materials and contribute to the further development of organic electronics. Full article

Camptotheca acuminata, the primary botanical source of camptothecin (CPT), employs this monoterpenoid indole alkaloid as a key chemical defense against herbivores in addition to its established clinical pharmaceutical importance. Given that Spodoptera frugiperda infestations pose a severe threat to C. acuminata seedlings, we examined integrated, multi-layered defense mechanisms that combine physical barriers with chemical toxins to bolster plant resistance. Physiological analyses revealed that herbivory induces antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT), alongside broader metabolic reprogramming. These responses are orchestrated by differential activation of jasmonic acid (JA) and salicylic acid (SA) signaling pathways, which together drive complex defense mobilization, including a marked increase in trichome density. Concurrently, insect herbivory activates the MYB-bHLH-WD40 (MBW) transcriptional complex to promote trichome development while upregulating core CPT biosynthetic genes. In particular, two cytochrome P450 genes, Ca32236 and CaCYP81BQ18, mediate the accumulation of 10-hydroxycamptothecin (10-HCPT), a derivative that is sparingly soluble in water, which enables alkaloid transport and sequestration to specialized storage sites, including trichomes. Collectively, these stress-responsive strategies confer potent insecticidal activity against S. frugiperda and provide valuable insights for improving protection in C. acuminata seedling plantations. Full article

Mono- and bis-guanyl hydrazone-functionalized tricyclic compounds were here designed and investigated as putative G-quadruplex ligands in the context of anticancer drug development. The G-quadruplex on Controlled Pore Glass (G4-CPG) assay, a fast and easy screening method based on affinity chromatography for identifying potential G-quadruplex binders, together with biophysical techniques such as circular dichroism and fluorescence spectroscopy, demonstrated a higher selectivity of mono- with respect to disubstituted derivatives in recognizing G-quadruplexes from telomeric and oncogenic DNA regions vs. duplexes. Among the mono-substituted compounds, higher G-quadruplex selectivity was found for those containing the pyrido[3,4-b]indole and dibenzofuran scaffolds compared to the 9H-fluorene, 9H-carbazole, and dibenzothiophene ones. Molecular docking studies suggested that the investigated ligands bound the hybrid telomeric G-quadruplex model by adopting a coplanar arrangement of the core and guanyl hydrazone moieties, both stacked on the 5′-G-quartet, while in the interaction with the parallel oncogenic G-quadruplex model the guanyl hydrazone moieties pointed towards the grooves/loops. Finally, biological assays highlighted the higher potential of mono-guanyl hydrazone-derivatized tricyclic compounds as selective anticancer agents, showing higher anticancer activity and selectivity of action than the bis-guanyl hydrazone derivatives. Full article

Inflammatory bowel disease (IBD; Crohn’s disease and ulcerative colitis) arises from convergent dysfunction of the epithelial barrier, mucosal immunity, and gut microbiome on a background of genetic susceptibility and environmental exposures. Diet is among the most modifiable of these exposures, yet much of the diet–microbiome research in IBD remains descriptive and poorly aligned with the molecular pathways linking food to mucosal effects. This comprehensive review reframes the field around functional dysbiosis, in which altered microbial metabolic capacity (rather than taxonomic shifts alone) drives disease-relevant biology. We trace how dietary substrates and additives are converted by gut microbes into bioactive metabolites (short-chain fatty acids, secondary bile acids, tryptophan-derived indoles, sulfur compounds, and polyphenol-derived molecules) and map these to host receptors and signaling pathways governing barrier function, mucus and antimicrobial peptide production, and Treg/Th17 balance. Defined dietary therapies (exclusive enteral nutrition, the Crohn’s disease exclusion diet plus partial enteral nutrition, and Mediterranean-style patterns) are reinterpreted as interventions that reshape microbial metabolic output, and candidate biomarkers for microbiome-informed precision nutrition are evaluated. Microbiota-derived metabolites provide the molecular interface between diet and mucosal immunity in IBD; personalized dietary algorithms remain a research goal, not a validated clinical tool, and diet is best framed as adjunctive to pharmacotherapy and dietitian care. Full article

Background: Therapeutic resistance following cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) plus endocrine therapy (ET) represents a key unmet need in hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2−) metastatic breast cancer (mBC). Treatment paradigms have advanced from non-targeted options, such as fulvestrant monotherapy or everolimus-based combinations, to precision medicine strategies, including inhibitors of the PI3K/AKT pathway, oral selective estrogen receptor degraders (SERDs), and novel ER-modulating agents, often guided by biomarkers and molecular surveillance. Methods: This narrative review synthesizes evidence from randomized clinical trials, real-world studies, and biomarker-driven analyses published from 2010 to 2026, with emphasis on next-generation sequencing (NGS)-guided genomic profiling, targeted pathway therapies, and circulating tumor DNA (ctDNA)-based proactive interventions in the post-CDK4/6i setting. This review was conducted and reported in accordance with the SANRA recommendations for narrative reviews. Results: Early second-line standards, including fulvestrant and alpelisib for PIK3CA-mutated tumors, established the basis for biomarker-guided treatment in hormone receptor–positive, HER2-negative metastatic breast cancer. With the widespread use of CDK4/6 inhibitors in the first-line setting, the optimal post-progression strategy has shifted toward molecularly selected combination approaches rather than single-agent endocrine therapy, as endocrine monotherapy has shown limited efficacy in acquired resistance. Multiple randomized studies have demonstrated that adding targeted agents to endocrine therapy improves progression-free survival compared with hormonal therapy alone, supporting combination regimens as the preferred strategy after CDK4/6 inhibitor progression, except in carefully selected patients with low disease burden, indolent biology, or frailty where tolerability is a major concern. Precision-based trials have further refined this approach. Elacestrant improved progression-free survival in ESR1-mutated disease in the EMERALD trial, capivasertib plus fulvestrant demonstrated significant benefit in tumors harboring AKT/PIK3CA/PTEN pathway alterations in CAPItello-291, and inavolisib plus palbociclib and fulvestrant achieved both progression-free and overall survival improvement in PIK3CA-mutated patients with early relapse in INAVO120. Real-world analyses further support the effectiveness of these biomarker-directed strategies across diverse clinical subgroups. Comprehensive genomic profiling has identified multiple resistance mechanisms, including ESR1 mutations, PI3K/AKT/mTOR pathway activation, RB1 loss, and FGFR alterations, which may co-occur and reduce sensitivity to endocrine monotherapy. While ESR1 and PI3K pathway alterations now guide approved therapies, FGFR alterations remain investigational targets, with ongoing trials evaluating selective FGFR inhibitors. Proactive switching approaches evaluated in SERENA-6 and PADA-1 demonstrate that serial circulating tumor DNA (ctDNA) monitoring can detect emergent ESR1 mutations before radiographic progression, providing a clinically actionable lead time for early therapeutic modification and extending endocrine-based disease control by approximately 5 to 7 months. Conclusions: Post-CDK4/6i management increasingly relies on NGS-guided precision approaches, integrating pathway-specific therapies and ctDNA surveillance to tailor sequencing based on resistance profiles, prior ET response, and tumor heterogeneity. Future investigations into novel ER degraders and multi-targeted combinations hold potential to further optimize algorithms, extend non-chemotherapy options, and enhance survival in HR+/HER2− mBC. Full article

Tomato is susceptible to various fungal pathogens, including Alternaria alternata and Curvularia spicifera, which can cause extensive post-harvest losses. Chemical fungicides have limited effectiveness in controlling post-harvest fungal pathogens and pose risk to human health and the environment. Therefore, this study assessed indigenous isolates of three species of Trichoderma (Tr1: T. longibrachiatum; Tr2: T. harzianum; and Tr3: T. asperellum) as biocontrol agents against two fungal pathogens in vitro and in vivo and determined their physicochemical analysis and plant-growth-promoting traits. The three species of Trichoderma exhibited catalase production in vitro, while T. longibrachiatum and T. asperellum showed the highest potential for plant-growth promotion by producing indole-3-acetic acid and phosphate solubilization but not nitrogen-fixing capability. T. harzianum showed lower potential in these traits. Mycelial growth was found to be maximum (5.77–12.27 cm) at 30 °C and a pH of 7–9, but inhibition (2.60–5.13 cm) was recorded at the highest temperature (45 °C) and pH (11). In vivo, studies on tomato fruits indicated that T. longibrachiatum and T. asperellum significantly (p < 0.05) reduced lesion diameters of A. alternata by 53.60% and 48.71%, respectively, and C. spicifera by 55.58% and 56.19%, respectively, relative to the infected control. Besides their antifungal efficacy, the three species of Trichoderma enhanced tomato seedling growth, particularly at 1/10 filtrate dilution, and improved fruit quality parameters by increasing firmness and nitrate content, while reducing oxidative stress. Physicochemical analysis indicated that Trichoderma-treated fruits had better firmness, pH, and nitrate value coupled with a reduction in oxidative stress (reduced malondialdehyde content) compared to pathogen-infected controls. The indigenous isolates of the three species of Trichoderma provided high efficacy as biocontrol agents of the two fungal pathogens that cause post-harvest losses of tomato, suggesting that biological control can replace synthetic chemicals in preserving tomato under storage conditions and contribute to agricultural sustainability. Full article

High temperature during flowering and grain filling severely reduces rice yield and grain quality. Split potassium (K) fertilization can mitigate such heat-induced damage, yet its mechanisms linking grain filling, endogenous hormones and grain performance remain unclear. Here, a two-year pot experiment was conducted to explore the effects of split K application on rice yield, quality and hormonal metabolism under high temperature. Four treatments included ambient temperature with full basal K (AT-K₁₀₀), high temperature with full basal K (HT-K₁₀₀), and two split K regimes under high temperature (HT-K₇₀₊₃₀, HT-K₃₀₊₇₀). Split K application decreased abscisic acid (ABA) levels at 5 days after anthesis (DAA), increased indole-3-acetic acid (IAA), zeatin riboside (ZR) and gibberellin A3 (GA₃) at 5 DAA, and maintained higher IAA and GA₃ levels until 20 DAA. The ratios of ABA/IAA and ABA/GA₃ were also reduced at both 5 and 20 DAA. These hormonal alterations optimized grain-filling dynamics, prolonged active filling duration and improved middle- and late-stage filling rates, thereby promoting grain weight accumulation and suppressing chalkiness formation. Compared with HT-K₁₀₀, HT-K₇₀₊₃₀ increased yield by 8.75%, which was attributed to improved seed-setting rate and 1000-grain weight. HT-K₃₀₊₇₀ enhanced spikelet number per panicle, seed-setting rate and 1000-grain weight, but significantly decreased effective panicles, resulting in no obvious yield advantage. Furthermore, split K application effectively reduced grain chalkiness, with a more pronounced effect at a higher panicle-stage K proportion. Under ongoing global warming, K management can be tailored to production goals: higher basal K is preferable for yield pursuit, while increasing panicle K topdressing effectively improves grain quality. Full article

Tryptophan (TRP) metabolism has emerged as a critical interface linking inflammation, immune regulation, oxidative stress, and cellular energetics. The kynurenine pathway, the predominant route of TRP degradation, is highly responsive to inflammatory stimuli and generates a spectrum of bioactive metabolites with divergent and context-dependent biological effects. Indoleamine 2,3-dioxygenase 1 (IDO1)-mediated TRP catabolism integrates immune activation with downstream metabolic signaling, influencing redox homeostasis, endothelial function, and mitochondrial energetics, in part by regulating nicotinamide adenine dinucleotide (NAD⁺) synthesis. Alterations in TRP metabolism are consistently observed across cardiometabolic diseases, including obesity, type 2 diabetes (T2D), atherosclerosis, myocardial infarction (MI), and heart failure with preserved ejection fraction (HFpEF), where they are associated with disease severity and adverse outcomes. Importantly, emerging data suggest that cardiometabolic phenotypes are determined not by pathway activation alone, but by the relative distribution of flux across downstream metabolic branches. Depending on the tissue compartment and stage of the disease, different biological effects may be contributed by redox-active kynurenine 3-monooxygenase (KMO)/3-hydroxykynurenine (3-HK)/quinolinic acid (QA) pathways, 3-hydroxyanthranilic acid (3-HAA)-mediated lipid and inflammasome regulation, microbiome-derived indoles, and NAD⁺-generating pathways. This review synthesizes current evidence using a branch-specific and context-dependent framework. We discuss the utility and limitations of the kynurenine-to-tryptophan ratio (KTR) as an upstream biomarker, the need for downstream metabolite panels, and therapeutic opportunities aimed at pathway modulation rather than broad inhibition. Future studies integrating temporal profiling, spatial and cell-specific approaches, large-animal models, and pathway-informed clinical trials will be essential to define causal mechanisms and enable precision therapeutic translation. Full article