Search Results (4,276)

Background/Objectives: Numerous studies have demonstrated that dietary plant-derived polyphenols suppress signaling and metabolic pathways in various malignancies, including neuroblastoma. In the present study, we compared the inhibitory activities of selected polyphenols and their combinations on key metabolic and signaling pathways in two human neuroblastoma cell lines and two noncancerous cell lines—mesenchymal stem cells (MSCs). Methods: The influence of polyphenols on neuroblastoma cells and MSCs were studied via an MTT-assay, cell cycle analysis, and an apoptosis assay (flow cytometry). Chou-Talalay algorithms were used to quantify drug interactions. SeaHorse energy profiling was applied to study energy metabolism. The influence of the compounds on metabolic enzymes and signaling pathways was examined using immunoblotting. Total protein biosynthesis was assessed using o-propargyl-puromycin labeling (flow cytometry). Results: While most of the studied polyphenols displayed a more significant inhibitory effect on neuroblastoma cells than on mesenchymal stem cells (MSCs), we found that the combinations of curcumin and quercetin (CQ) and curcumin, quercetin, and resveratrol (CQR) were significantly superior to the individual compounds. These combinations displayed synergistic effects and inhibited the cell cycle while inducing apoptosis. The CQ and CQR combinations effectively suppressed metabolic reprogramming by downregulating key enzymes of glycolysis, respiration, one-carbon metabolism, glutaminolysis, and fatty acid biosynthesis, as well as N-Myc and c-Myc, which are master regulators of metabolic processes. Furthermore, CQ and CQR inhibited AKT/mTOR, MAPK/ERK, and WNT/β-catenin signaling pathways and total protein biosynthesis and sensitized malignant cells to doxorubicin. Conclusions: Polyphenol combinations exert multifaceted inhibitory effects on metabolic rewiring and signaling networks in neuroblastoma cells. Full article

Background/Objectives: Allergic diseases are highly prevalent worldwide and represent a significant public health burden. Current therapies mainly alleviate symptoms without addressing underlying immune dysfunction, which has increased interest in nutritional bioactive compounds as preventive or modulatory agents. This review summarizes evidence on omega-3 polyunsaturated fatty acids, vitamin D, curcumin, ginger bioactives, quercetin, and epigallocatechin gallate (EGCG) in allergy prevention and management. Methods: A comprehensive literature search was conducted in PubMed, Scopus, and Web of Science up to July 2025, including preclinical and clinical studies reporting immunological, mechanistic, and clinical outcomes. Results: Omega-3 fatty acids modulate Th2 responses, promote regulatory T cells, and generate specialized pro-resolving mediators, with modest clinical benefits observed in pregnancy and early life. Vitamin D contributes to immune tolerance and epithelial integrity, although supplementation trials remain heterogeneous. Curcumin inhibits NF-κB/MAPK signaling, enhances barrier function, and improves allergic rhinitis and dermatitis despite limited bioavailability. Ginger constituents ([6]-gingerol, [6]-shogaol) modulate Th1/Th2 balance, mast-cell activity, and oxidative stress, with early clinical evidence in rhinitis and asthma. Quercetin stabilizes mast cells, inhibits Lyn/PLCγ pathways, and improves rhinitis symptoms in small randomized trials using bioavailable formulations. EGCG stabilizes mast cells, attenuates FcεRI signaling, and reduces airway inflammation in preclinical models, though clinical data are scarce. Conclusions: Overall, preclinical findings consistently support the immunomodulatory potential of these compounds, while clinical results are promising but heterogeneous. Standardized formulations, long-term trials, and exploration of synergistic effects are required to confirm efficacy and safety, providing future research directions in allergy prevention. Full article

Natural polyphenols, particularly tannins, are of interest due to their complex composition and multi-target biological activities. A highly purified tannin fraction was isolated from Aronia melanocarpa fruits, and its composition was characterized by HPLC-MS and IR spectroscopy. The Aronia tannin fraction exhibited comprehensive antioxidant properties, demonstrating superior DPPH radical scavenging activity compared to quercetin and a membrane-protective effect exceeding reference antioxidants. In vivo, Aronia tannins showed a delayed but potent antioxidant effect against cyclophosphamide (CP)-induced oxidative stress, significantly reducing malondialdehyde (MDA) levels, with the maximum effect observed at days 14–21. The immunomodulatory effect involved a complex regulation of the phagocytic system: selective activation of the monocytic arm with simultaneous modulation of neutrophilic activity. Crucially, a high phagocytic completion rate was maintained, indicating support for both bacterial uptake and intracellular killing. Tannins accelerated recovery post-CP, restoring leukocyte and platelet counts. Modulation of neutrophil oxidative metabolism, measured by chemiluminescence, indicates an ability to balance defense activation with prevention of excessive oxidative stress. These findings confirm the potential of the Aronia melanocarpa tannin fraction for correcting oxidative stress and immune dysfunction. Full article

Background: Centaurium erythraea Rafn. (C. erythraea) is a medicinal plant traditionally used in European folk medicine for the treatment of wounds, skin inflammations, and other dermatological conditions, in addition to its well-documented systemic antioxidant and anti-inflammatory effects. However, its topical applications remain insufficiently investigated, particularly using plant material collected from Romania. The purpose of this study was to prepare different ointment formulations containing C. erythraea Rafn. extract obtained from the aerial parts of the plant, using various excipients, and to evaluate their in vitro and in vivo efficacy. Methods: The phytochemical profile of C. erythraea extract was characterized using liquid chromatography–tandem mass spectrometry (LC–MS/MS). The lyophilized extract was pre-dissolved in different solubilizing agents—Transcutol^® P (diethylene glycol monoethyl ether), Capryol^® 90 (propylene glycol monocaprylate), or a combination of both—and then incorporated into five ointment formulations. Texture analysis and an in vitro membrane diffusion study were performed. The antioxidant capacity of the formulations was assessed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, ferric reducing antioxidant power (FRAP), and total phenolic content (TPC) assays. Anti-inflammatory activity was evaluated in vitro using tumor necrosis factor-alpha (TNF-α)-induced interleukin-1 beta (IL-1β) production in human keratinocyte (HaCaT) cells, and in vivo using a carrageenan-induced rat paw edema model. Results: LC–MS/MS identified 18 polyphenolic compounds, with hyperoside (3.78 ± 0.05 µg/mL), protocatechuic acid (1.13 ± 0.06 µg/mL), chlorogenic acid (1.07 ± 0.06 µg/mL), and quercetin (0.53 ± 0.03 µg/mL) as the principal constituents. The formulation containing both Transcutol^® P and Capryol^® 90 exhibited the most pronounced antioxidant activity (65% DPPH inhibition; 69.71 ± 0.83 mg gallic acid equivalent/mL) and significantly reduced IL-1β levels by 45.7% compared to the inflamed control. In vivo, this formulation showed comparable anti-edematous effects to a methylprednisolone ointment. Furthermore, it demonstrated the highest skin permeation efficiency, with a quercetin diffusion coefficient of 35.12 × 10⁻⁵ cm²/min. Conclusions: These findings highlight the therapeutic potential of C. erythraea extract from aerial parts in topical formulations and underscore the enhancing role of Transcutol^® P and Capryol^® 90 in improving both the pharmacodynamic and pharmacokinetic properties of bioactive compounds. Full article

Background: The Wnt/β-catenin signaling pathway plays a pivotal role in embryonic development, maintenance of the central nervous system, and the formation of neuronal circuits. Disruption of this pathway is closely associated with oncogenesis and neurodegenerative diseases, notably Alzheimer’s disease. Flavonoids such as quercetin derivatives have emerged as promising neuroprotective agents. This study investigates the impact of 3-O-methylquercetin (3OMQ), a methylated quercetin metabolite, on Wnt/β-catenin signaling and its potential relevance in neurodegenerative disease models. Methods: The ability of 3OMQ to modulate Wnt/β-catenin activity was analyzed using a luciferase-based reporter assay in both neural and non-neural cell lines. Cell viability assays evaluated cytotoxicity at various concentrations. We mapped 3OMQ activity within the pathway using targeted cell signaling experiments. Docking and molecular dynamics simulations suggested glycogen synthase kinase 3β (GSK3β) as a putative target of 3OMQ. Finally, we employed a mouse model of acute amyloid-β oligomer (AβO) toxicity to assess the in vivo effects of 3OMQ on spatial memory and Wnt-related gene expression. Results: We compared the flavonoids quercitrin, quercetin, and 3-O-methylquercitrin (3OMQ) with pharmacologically active compounds in a gene reporter assay (TOPFLASH) using Wnt-sensitive RKO cells treated with Wnt3a-conditioned medium. XAV-939 and PNU-74654 showed inhibitory activity, while BIO, CHIR99021, quercitrin, and 3OMQ enhanced the Wnt/β-catenin pathway. Notably, 3OMQ potentiated this pathway at concentrations 5–10 times lower than quercitrin and outperformed 1 μM BIO at 10 μM without cytotoxicity, highlighting its remarkable potency. Mechanistically, 3OMQ acts downstream of initial membrane activation and upstream of the β-catenin destruction complex. Consistently, molecular docking indicates a strong interaction with GSK3, a central regulator of the pathway. In adult mice, 3OMQ administration prevented AβO-induced recognition memory deficits and favored normalization of Wnt-related gene expression. Conclusions: These findings identify 3OMQ as a potent positive modulator of the Wnt/β-catenin pathway, with both in vitro and in vivo neuroprotective effects. Targeting Wnt signaling with compounds such as 3OMQ holds promise for maintaining neuronal health and developing therapeutic strategies for neurodegenerative conditions. Full article

In this study, an integrated analytical method coupling ultra-high-performance liquid chromatography–photodiode array detection–quadrupole time-of-flight mass spectrometry with total antioxidant capacity determination (UHPLC-PDA-Q-TOF/MS-TACD) was developed for the rapid screening and identification of antioxidants in complex natural extracts. The system enables simultaneous chromatographic separation, mass spectrometric characterization, and on-line activity assessment by combining 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) and ferric ion reducing antioxidant power (FRAP) assays. When applied to Rosa rugosa samples from five different origins, the approach efficiently separated the extract and successfully localized antioxidants directly from the chromatographic profile. A total of 86 compounds were identified, including flavonoids, tannins, and phenolic acids. Among them, 60 exhibited free radical scavenging capacity and 59 showed reducing activity. Activity verification experiments showed that all seven compounds exhibited good antioxidant activity. The IC₅₀ values of gallic acid, ellagic acid, quercetin 3-O-rhamnoside, and rutin were 0.019, 0.025, 0.043, and 0.046 mM, respectively, which were significantly better than the positive control (vitamin C). This method provides methodological and technical support for the rapid discovery of antioxidant components in complex natural products. Full article

RNA triple helices are relatively understudied, including their interactions with small molecules. In this study, we evaluated eight previously reported triplex-binding molecules (TBMs) for their functional effects on the premature and mature MALAT1 triple helix. Based on UV thermal denaturation experiments, the TBMs berberine, coralyne, sanguinarine, berenil, and neomycin selectively stabilize the Hoogsteen interface of the MALAT1 triple helix. Moreover, fisetin, luteolin, and quercetin were more sensitive to nucleotide composition, whereas berberine, coralyne, sanguinarine, and berenil were more sensitive to changes in the length of the major-groove triple helix. Most TBMs could not outcompete MALAT1 triple helix-binding proteins, except for neomycin. Surface plasmon resonance experiments demonstrated that berberine and sanguinarine display relatively quick association and dissociation binding profiles. Treating human colorectal carcinoma cells with each of the TBMs reduced MALAT1 levels by ~20–60%. This study demonstrates that TBMs broadly recognize the premature and mature MALAT1 triple helix but exhibit subtle sensitivities, suggesting that TBMs can be designed to selectively bind triple helices based on nucleotide composition, length, and structural context. Full article

Bursera microphylla A. Gray (Burseraceae) is a medicinal plant native to Sonora, Mexico, with antioxidant, anti-inflammatory, and antiproliferative properties. However, the pharmacological potential of its ecotypes remains underexplored. This study evaluated the biological activity and chemical composition of ethanolic extracts from the fruit and stem of the Magdalena ecotype. Total phenolic content was quantified using the Folin–Ciocalteu method, and phenolic profiles were characterized by ESI-IT-MS. Antioxidant activity was assessed by DPPH and FRAP assays; anti-inflammatory activity was evaluated by measuring nitric oxide (NO) and tumor necrosis factor-alpha (TNF-α) levels in LPS-activated RAW 264.7 macrophages. Antiproliferative activity was tested against LS180, C-33 A, and ARPE-19 cell lines using the MTT assay. Fruit extract exhibited higher phenolic content (180.6 ± 22.0 mg GAE/g) and ferric-reducing power (FRAP = 2034.3 ± 89.7 μM Fe(II)/g), whereas the stem extract showed stronger DPPH scavenging capacity (IC₅₀ = 52.9 ± 0.02 μg/mL). For the first time, gallic acid glucoside, kaempferol rhamnoside, quercetin rhamnoside, and isorhamentin xyloside were identified in B. microphylla fruit extract. Furthermore, the fruit extract significantly reduced NO production (93.6 ± 4.6 μg/mL) and TNF-α levels (IC₅₀ = 101.5 ± 9.1 μg/mL). It also showed strong cytotoxicity against C-33 A (IC₅₀ = 0.6 ± 0.07 μg/mL) and LS180 (0.7 ± 0.01 μg/mL), with lower cytotoxicity in ARPE-19 cells (77.9 ± 4.3 μg/mL). These findings highlight the therapeutic potential of the Magdalena ecotype, likely associated with its phenolic and other bioactive metabolites that require further investigation. Full article

Fermentation possesses intriguing and promising potential as a bioprocess for enhancing and/or transforming bioactive compounds derived from agricultural processing by-products. This study aimed to enhance the phenolic compounds and antioxidant properties of coffee cherry husks through the sustainable methodology of solid-state fermentation (SSF) using various Trichoderma fungi, specifically Trichoderma asperellum CB-Pin-01 and two Trichoderma isolates (NTY211 and PSUT001). The coffee cherry husks underwent fermentation at a controlled temperature of 28 ± 1 °C over a duration of 7 days. Both fermented and unfermented extracts, prepared using different solvents (water, ethanol, and acetone), were systematically evaluated concerning total phenolic content (TPC), total flavonoid content (TFC), and antioxidant capacities measured via DPPH and ABTS radical scavenging assays, as well as ferric reducing antioxidant power (FRAP). The findings indicated that SSF involving Trichoderma fungi significantly augmented the phenolic content and antioxidant activities in comparison to the unfermented samples (p < 0.05). Notably, the acetonic extract obtained from fermentation with the isolate NTY211 exhibited the highest contents of phenolic (191.48 ± 3.94 mg GAE/g extract) and flavonoid (106.61 ± 3.09 mg QE/g extract). The identification of phenolic compounds by UHPLC-QqQ-MS/MS analysis revealed a predominant increase in chlorogenic acid and quercetin through SSF. Consequently, SSF utilizing Trichoderma fungi may represent a viable strategy for enhancing the value of coffee cherry husks, rendering them into bioactive ingredients with potential applications in the cosmetic and food industries. Full article

Background/Objective: Eclipta prostrata (L.) L. is a traditional medicinal herb utilized throughout Asia that is widely used for hepatoprotective activity, wound healing, and blood cooling/bleeding disorders. This work aimed to identify bioactive constituents from E. prostrata collected in Vietnam, and clarify their anti-inflammatory capacity of the extract and active fraction. Method: Extraction and isolation of compounds from the extract of E. prostrata were performed. The extract, fractions, and isolated compounds were evaluated for inflammatory cytokines in LPS-stimulated RAW264.7 cells. Isolates showed inflammatory potential by in silico approaches. Results: Thirteen compounds, comprising a first isolated compound (diosmin), flavonoids, and phenolic derivatives, were separated and identified. The protein–protein interaction (PPI) network demonstrated TNF, IL6, AKT1, NFKB1, EGFR, and PTGS2 as central targets, highlighting their significance in inflammatory signaling. Gene Ontology and KEGG pathway enrichment underscored substantial participation in TNF and IL-17 cytokine signaling pathways. Molecular docking demonstrated robust interactions between several flavonoids and core targets, indicating their function as essential regulators. Experimental validation in LPS-stimulated RAW264.7 macrophages revealed that wedelolactone, luteolin, apigenin, and quercetin significantly inhibited TNF-α and IL-6 production. Conclusions: The results proposed that E. prostrata demonstrates its anti-inflammatory efficacy via a multi-target, poly-pharmacological strategy that encompasses central cytokine pathways and upstream receptor-mediated signaling. Our findings offer new mechanistic evidence that supports the ethnomedicinal application of E. prostrata and indicates its potential as a valuable natural resource for treating anti-inflammatory diseases. Full article

Procyanidins are oligomeric flavonoids with several bioactive properties. Their antidiabetic potential is related to their capacity to inhibit enzymes responsible for the absorption of dietary carbohydrates, such as pancreatic α-amylase. Procyanidins possess great structural diversity, including types of monomers and interflavanic bonds (A- or B-), and the degree of polymerization. However, there is a lack of evidence that systematically analyzes the effect of these structural features on their α-amylase inhibitory activity. In this paper, the activity of a mammalian pancreatic α-amylase was assessed using two different substrates, and the inhibitory activity of five commercially available procyanidins and three monomeric flavonoids was compared. The enzyme-binding sites of the eight compounds were predicted by in silico analysis to help explain the different enzyme-inhibitory activities. The inhibitory activity of procyanidins and monomeric flavonoids depended on the substrate used. A-type dimers presented the best activity against a polymeric substrate, while a B-type dimer was the best inhibitor for an oligomeric substrate. The predicted binding site for dimers and monomers was close to the active site. For the B-type trimer, the binding site was on the back side (approximately 180°) of the catalytic triad. In silico predictions suggested that dimeric procyanidins, especially A-type, could better enter the active site cavity, which could explain their superior inhibitory activity. We may conclude that inhibition of pancreatic α-amylase by procyanidins is mainly related to the type of interflavanic bond and the degree of polymerization. Dimers could be the most effective procyanidins to mildly inhibit this enzyme and present antidiabetic potential. Full article

While sweet cherries (Prunus avium L.) are globally recognized for their numerous potential health benefits, yet limited data exist on New Zealand-grown cultivars. This study examined the nutritional and bioactive profiles of six commercial cultivars—Kordia^®, ‘Lapins’, Sweetheart^®, Staccato^®, ‘Bing’, and ‘Rainier’—in both fresh and processed (washed and packaged) forms. All cultivars contained notable levels of minerals, phenolics, and essential nutrients. Fresh cherries had higher mineral content (0.3–0.5 g/100 g) than processed ones (0.2–0.3 g/100 g). Carbohydrates ranged from 16.8 to 18.6 g/100 g in fresh and 15.1–17.5 g/100 g in processed cherries. Dietary fiber was slightly higher in processed samples (0.5–0.6 g/100 g) than fresh (0.2–0.5 g/100 g). Potassium, calcium, and phosphorus were more concentrated in fresh cherries. Major phenolic metabolites included neochlorogenic acid (up to 44.26 mg/100 g), (-)-epicatechin (7.89 mg/100 g), quercetin 3-rutinoside (4.34 mg/100 g), and cyanidin 3-rutinoside (80.42 mg/100 g). Processed ‘Lapins’ and ‘Bing’ retained high levels of neochlorogenic acid (40.98 and 44.26 mg/100 g), indicating minimal loss during processing. This study offers insights into the nutritional and bioactive composition of New Zealand-grown cherries, emphasizing their dietary value and health-promoting compounds such as polyphenols. Full article

Background: Heart failure (HF) is a leading cause of mortality and represents the final stage of various cardiovascular disorders. Although traditional Chinese herbs have been extensively applied in HF treatment and their clinical efficacy has been investigated, the underlying molecular mechanisms remain insufficiently understood. To address this gap, systematic approaches are required to elucidate the therapeutic basis of herbal interventions. Methods: In this study, we systematically analyzed the bioactive compounds from seven traditional Chinese herbs, Baiguo (Ginkgo biloba), Chishao (Radix Paeoniae Rubra), Biba (Piper longum), Aidicha (Ilex latifolia), Bajiaolian (Dysosma spp.), Beiwuweizi (Schisandra chinensis), and Baiqucai (Sedum sarmentosum) and explored their potential mechanisms in HF by integrating network pharmacology, molecular docking, and molecular dynamics simulations. Result: We identified key targets and pathways implicated in HF pathogenesis and herbal interventions. A total of 63 active compounds were found to regulate 1947 genes. Through integrative analysis of the GSE57338 heart failure dataset from the GEO database, we further identified 265 intersecting targets shared between herb-associated genes and HF-related genes, highlighting their potential involvement in HF progression. Network analysis prioritized three hub proteins, STAT3, SRC, and TP53, which were subsequently subjected to molecular docking with the top bioactive compounds (quercetin, kaempferol, and epigallocatechin-3-gallate). Docking studies revealed strong binding affinities, and molecular dynamics (MD) simulations further validated the stability of these protein compound interactions. Conclusions: This study elucidates key bioactive components and targets involved in HF treatment, with kaempferol and epigallocatechin-3-gallate emerging as promising therapeutic candidates. These results provide a foundation for future experimental validation and the development of targeted HF therapies derived from traditional Chinese medicine. Full article

The Ericaceae family encompasses several berries with recognized health-promoting properties; however, Macleania rupestris, a neotropical species endemic to the Andean region, remains poorly characterized. Background/Objectives: This study aimed to identify the chemical composition of M. rupestris ethanolic extracts and evaluate their biological activities, including antitumoral, hemolytic, anti-inflammatory, and leishmanicidal effects. Methods: The M. rupestris ethanolic extracts were obtained from lyophilized fruits and analyzed by HPLC-MS/MS for phytochemical profiling. Bioactivities were assessed in vitro using tumor and non-tumor cell lines (MTT assay), erythrocyte hemolysis assays, RAW 264.7 macrophage inflammation models, and Leishmania mexicana promastigotes. Results: The chemical analysis revealed anthocyanins (cyanidin-3-glucoside, malvidin-3-glucoside, petunidin-3-glucoside, delphinidin-3-arabinoside), flavonols (quercetin and myricetin derivatives), and coumaroyl iridoids. The extract showed modest antiproliferative activity (IC₅₀ 10.4–22.5 mg/mL) across tumor cell lines with low therapeutic indices, indicating limited selectivity. In contrast, hemolytic activity was negligible (<5% at all tested concentrations), suggesting high biocompatibility. Anti-inflammatory assays indicated a dose-dependent reduction in nitric oxide (NO) production, while no significant leishmanicidal activity was detected. Conclusions: This study provides the first comprehensive evaluation of the previously listed M. rupestris bioactivities. While its antitumoral effects appear limited, its strong hemocompatibility and presence of antioxidant metabolites highlight its potential for biomedical and nutraceutical applications where biocompatibility is critical. Further studies are needed to optimize bioactivity and explore potential synergistic effects. Full article

Non-bagging apple cultivation, which is time-saving, labor-saving, and cost-effective, represents the future direction of apple cultivation in China. However, compared with bagging cultivation, it degrades fruit appearance quality, characterized by rough peels and dull colors, with the underlying physiological and molecular mechanisms remaining unclear. This study used ‘Tianhong 2’ Fuji apples, grafted onto SH dwarfing rootstock, and integrated transcriptomics–metabolomics to explore these mechanisms. Results showed that non-bagging-cultivated apple peels had higher chlorophyll and carotenoid contents but lower anthocyanin content than those of bagging-cultivated ones. Transcriptome sequencing identified 1571 differentially expressed genes (DEGs: 1269 upregulated, 302 downregulated). Functional analysis revealed that the decline in fruit appearance quality was primarily associated with secondary metabolite biosynthesis, lipid metabolism, and carbohydrate metabolism, and 34 candidate genes were identified. Metabolomic analysis detected 394 differentially expressed metabolites (DEMs), 38 of which were closely related to the non-bagging-induced appearance degradation, mainly lipids, organic oxygen compounds, and organic acids and their derivatives. Integrated analysis of DEGs and DEMs indicated the involvement of multiple critical metabolic pathways, including cutin, suberin and wax biosynthesis; starch and sucrose metabolism; cyanoamino acid metabolism; and phenylpropanoid and flavonoid biosynthesis. Compared with bagging-cultivated apples, non-bagging-cultivated apples exhibited faster starch degradation and higher soluble sugar accumulation. Additionally, the accumulation of specific metabolites [e.g., quercetin (HMDB0005794, HMDB03249, LMPK12112097), and suberin components (LMFA01170020, LMFA01050437, HMDB0031885)], along with elevated organic acid levels, contributed to peel roughness and dull coloration. These findings further enrich the theoretical basis for the formation of fruit quality in Fuji apples under non-bagging cultivation and provide valuable theoretical guidance for the practical application of this cultivation mode. Full article