Resting State Brain Networks under Inverse Agonist versus Complete Knockout of the Cannabinoid Receptor 1.

The cannabinoid receptor 1 (CB1) is famous as the target of Δ9-tetrahydrocannabinol (THC), which is the active ingredient of marijuana. Suppression of CB1 is frequently suggested as a drug target or gene therapy for many conditions (e.g., obesity, Parkinson's disease). However, brain networks affected by CB1 remain elusive, and unanticipated psychological effects in a clinical trial had dire consequences. To better understand the whole brain effects of CB1 suppression we performed in vivo imaging on mice under complete knockout of the gene for CB1 (cnr1-/-) and also under the CB1 inverse agonist rimonabant. We examined white matter structural changes and brain function (network activity and directional uniformity) in cnr1-/- mice. In cnr1-/- mice, white matter (in both sexes) and functional directional uniformity (in male mice) were altered across the brain but network activity was largely unaltered. Conversely, under rimonabant, functional directional uniformity was not altered but network activity was altered in cortical regions, primarily in networks known to be altered by THC (e.g., neocortex, hippocampal formation). However, rimonabant did not alter many brain regions found in both our cnr1-/- results and previous behavioral studies of cnr1-/- mice (e.g., thalamus, infralimbic area). This suggests that chronic loss of cnr1 is substantially different from short-term suppression, subtly rewiring the brain but largely maintaining the network activity. Our results help explain why pathological mutations in CB1 (e.g., chronic pain) do not always provide insight into the side effects of CB1 suppression (e.g., clinical depression), and thus urge more preclinical studies for any drugs that suppress CB1.

The impact of the digital economy on high-quality agricultural development--Based on the regulatory effects of financial development.

The digital economy, as a new economic form with high information density, provides a new driving force for the realization of high-quality agricultural development. Panel data of 31 provinces in China from 2011 to 2020 were selected for analysis. The static panel data interaction effect model and panel threshold model were used to verify the nonlinear influence mechanism and heterogeneity of financial development in the process of the digital economy affecting high-quality agricultural development. The findings are as follows. (1) During the study period, the high-quality development of China's agriculture showed a steady upward trend; however, the regional differences were significant, and the eastern part was larger than the central and western part. (2) The digital economy can promote high-quality agricultural development. (3) The digital economy has a double threshold effect in the process of affecting high-quality agricultural development, which depends on the level of financial development. When the threshold is exceeded, the digital economy has a more significant promoting effect on high-quality agricultural development. (4) The impact of the digital economy on high-quality agricultural development is heterogeneous. From the perspective of different regions, the impact effect is greatest in the eastern region, while the effect is smaller in the central and western regions. From different resource endowments, the positive impact effect is greatest in the major grain-selling areas, followed by the major grain producing areas, but the positive digital economy driving effect is not significant in the balance of production and sales areas. Finally, three policy suggestions are proposed. First, the Chinese government should increase investments in and support for digital technology to promote the integration of the digital economy and agriculture. Second, the Chinese government should promote the development of digital inclusive finance in areas with financial development below the threshold. Third, different regions should implement differentiated digital economies to promote high-quality agricultural development.

Bioinspired Selenium-Nitrogen Exchange (SeNEx) Click Chemistry Suitable for Nanomole-Scale Medicinal Chemistry and Bioconjugation.

Click chemistry is a powerful molecular assembly strategy for rapid functional discovery. The development of click reactions with new connecting linkage is of great importance for expanding the click chemistry toolbox. We report the first selenium-nitrogen exchange (SeNEx) click reaction between benzoselenazolones and terminal alkynes (Se-N to Se-C), which is inspired by the biochemical SeNEx between Ebselen and cysteine (Cys) residue (Se-N to Se-S). The formed selenoalkyne connection is readily elaborated, thus endowing this chemistry with multidimensional molecular diversity. Besides, this reaction is modular, predictable, and high-yielding, features fast kinetics (k2≥14.43 M-1 s-1), excellent functional group compatibility, and works well at miniaturization (nanomole-scale), opening up many interesting opportunities for organo-Se synthesis and bioconjugation, as exemplified by sequential click chemistry (coupled with ruthenium-catalyzed azide-alkyne cycloaddition (RuAAC) and sulfur-fluoride exchange (SuFEx)), selenomacrocycle synthesis, nanomole-scale synthesis of Se-containing natural product library and DNA-encoded library (DEL), late-stage peptide modification and ligation, and multiple functionalization of proteins. These results indicated that SeNEx is a useful strategy for new click chemistry developments, and the established SeNEx chemistry will serve as a transformative platform in multidisciplinary fields such as synthetic chemistry, material science, chemical biology, medical chemistry, and drug discovery.

Evolution of chemistry and selection technology for DNA-encoded library.

DNA-encoded chemical library (DEL) links the power of amplifiable genetics and the non-self-replicating chemical phenotypes, generating a diverse chemical world. In analogy with the biological world, the DEL world can evolve by using a chemical central dogma, wherein DNA replicates using the PCR reactions to amplify the genetic codes, DNA sequencing transcripts the genetic information, and DNA-compatible synthesis translates into chemical phenotypes. Importantly, DNA-compatible synthesis is the key to expanding the DEL chemical space. Besides, the evolution-driven selection system pushes the chemicals to evolve under the selective pressure, i.e., desired selection strategies. In this perspective, we summarized recent advances in expanding DEL synthetic toolbox and panning strategies, which will shed light on the drug discovery harnessing in vitro evolution of chemicals via DEL.

Urchin-like multiscale structured fluorinated hydroxyapatite as versatile filler for caries restoration dental resin composites.

Caries is one of the most prevalent human diseases, resulting from demineralization of tooth hard tissue caused by acids produced from bacteria, and can progress to pulpal inflammation. Filling restoration with dental resin composites (DRCs) is currently the most common treatment for caries. However, existing DRCs suffer from low fracture strength and lack comprehensive anti-caries bioactivity including remineralization, pulp protection, and anti-cariogenic bacteria effects. In this study, inspired by plant roots' ability to stabilize and improve soil, fluorinated urchin-like hydroxyapatite (FUHA) with a three-dimensional whisker structure and bioactive components of calcium, phosphorus, and fluorine was designed and synthesized by a dynamic self-assembly method. Furthermore, versatile FUHA particles with different loading fractions were used as functional fillers to fabricate methacrylate-based DRCs, where the urchin-like hydroxyapatite (UHA) filled DRCs and commercial DRCs (Z350XT and BEAUTIFIL II) served as the control groups. The results demonstrated that FUHA with 50 wt% loading in resin matrix endowed DRC (F5) with excellent physicochemical properties, dentin remineralization property, cell viability, promotion of dental pulp stem cells mineralization, and antibacterial properties. Meanwhile, F5 also presented good clinical handling and aesthetic characteristics. Therefore, structure/functional-integrated FUHA filled DRCs have potential as a promising strategy for tooth restoration and anti-caries bioactivity.

Harel-Yoon syndrome caused by a novel variant in ATAD3A: A case report.

Objectives: To describe the clinical feature of a very recently identified phenotype associated with ATAD3A variation. Methods: A neonate with Harel-Yoon syndrome was identified. We describe the proband's clinical and radiological features. The affected newborn and her parents underwent whole-exome sequencing and PCR-Sanger sequencing. Results: Previously reported clinical manifestations were rare in the neonatal period, including unmanageable seizures necessitating the use of multiple drugs, congenital laryngeal stridor, hypotonia, challenges with feeding, corneal opacity, and subsequent demise due to respiratory failure. Molecular investigations have unveiled the presence of a newly identified heterozygous single-base substitution (c.1517A > C; p.Q506P) within the ATAD3A gene. Discussion: This study unveils a novel single-base substitution, thereby expanding the mutation spectrum associated with ATAD3A. Furthermore, the clinical characteristics exhibited during the neonatal phase are comprehensively described, potentially facilitating improved clinical recognition of ATAD3A-associated HAYOS.

Applications of Prolamin-Based Edible Coatings in Food Preservation: A Review.

Foods are susceptible to deterioration and sour due to external environmental influences during production and storage. Coating can form a layer of physical barrier on the surface of foods to achieve the purpose of food preservation. Because of its good barrier properties and biocompatibility, prolamin-based film has been valued as a new green and environment-friendly material in the application of food preservation. Single prolamin-based film has weaknesses of poor toughness and stability, and it is necessary to select appropriate modification methods to improve the performance of film according to the application requirements. The practical application effect of film is not only affected by the raw materials and the properties of the film itself, but also affected by the selection of preparation methods and processing techniques of film-forming liquid. In this review, the properties and selection of prolamins, the forming mechanisms and processes of prolamin-based coatings, the coating techniques, and the modifications of prolamin-based coatings were systematically introduced from the perspective of food coating applications. Moreover, the defects and deficiencies in the research and development of prolamin-based coatings were also reviewed in order to provide a reference for the follow-up research on the application of prolamin-based coatings in food preservation.

Factors influencing TCM syndrome types of acute cerebral infarction: A binomial logistic regression analysis.

BACKGROUND: Acute cerebral infarction, characterized by a rapid onset and high fatality rate, presents a significant global challenge in terms of timely and effective treatment. In recent years, research focusing on the combined approach of traditional Chinese medicine (TCM) and Western medicine has demonstrated promising results in improving therapeutic outcomes in patients with acute cerebral infarction. DIAGNOSIS: This study adhered to the latest edition of Internal Medicine of Traditional Chinese Medicine, published by the China Press of Traditional Chinese Medicine, as a reference. It selects eight commonly encountered TCM syndrome differentiations for accurate diagnosis. METHODS: This study included 151 patients admitted to the hospital between 2019 and 2022 with acute cerebral infarction. Data on various diagnostic indicators were meticulously collected and subjected to single-factor analysis. RESULTS: Among the multiple factors analyzed, those exhibiting a significance level of P < 0.05 included blood pressure, uric acid, glucose level, triglyceride level, total cholesterol level, homocysteine level, duration of disease, and cerebral infarction site. Subsequently, a binary logistic regression analysis was performed to assess the impact of these factors on different TCM syndrome types. CONCLUSION: The findings of this study indicate that Wind Phlegm Obstruction syndrome, triglyceride levels, location of cerebral infarction, uric acid levels, and disease duration significantly influence the development and progression of acute cerebral infarction. Additionally, blood pressure and cerebral infarction site were found to have a statistically significant impact on the Wind Yang Disturbance syndrome. Uric acid level and blood pressure were also identified as statistically significant factors. Moreover, total cholesterol and homocysteine levels were found to significantly affect phlegm stasis-blocking collateral syndrome. The insights gained from this study will contribute to the advancement of integrated treatment approaches, combining traditional Chinese and Western medicine, for acute cerebral infarction. Furthermore, these findings can serve as a valuable reference for the general population in terms of preventive measures against this condition.

Triglyceride-glucose index is associated with severe obstructive coronary artery disease and atherosclerotic target lesion failure among young adults.

BACKGROUND: Early diagnosis and treatment effectiveness of early-onset coronary artery disease (EOCAD) are crucial, and non-invasive predictive biomarkers are needed for young adults. We aimed to evaluate the usefulness of the triglyceride-glucose (TyG) index, a novel marker of insulin resistance, in identifying young CAD patients and predicting their risk of developing target lesion failure (TLF). METHODS: We recruited EOCAD patients (luminal narrowing ≥ 70%) and controls free from CAD (luminal narrowing < 30%), both aged 45 years or younger, from 38 hospitals in China between 2017 and 2020. EOCAD patients who underwent successful percutaneous coronary intervention were followed for incident TLF. TyG index was defined as Ln [fasting triglyceride (mg/dL) × fasting blood glucose (mg/dL)/2]. We used logistic regression and Cox proportional hazards modeling to evaluate the association of TyG index with prevalent EOCAD and incident TLF, respectively. The discriminatory ability of TyG index was assessed by the area under the receiver-operating characteristic curve (AUC). RESULTS: Among the included 1513 EOCAD patients (39.6 ± 4.4 years, 95.4% male) and 1513 age-matched controls (39.0 ± 4.4 years, 46.4% male), TyG index was positively associated with the prevalence of EOCAD (adjusted odds ratio: 1.40, 95% confidence interval [CI] 1.23-1.60, per standard deviation [SD] increase in TyG index). The addition of TyG index to an empirical risk model provided an improvement in diagnostic ability for EOCAD, with a net reclassification improvement of 0.10 (95% CI 0.03-0.17, p = 0.005). During a medium of 33 month (IQR: 31-34 months) follow-up, 43 (3.3%) patients experienced TLF. Multivariate Cox regression model revealed that TyG index was an independent risk factor for TLF (adjusted hazard ratio [HR]: 2.410, 95% CI 1.07-5.42 comparing the top to bottom TyG index tertile groups; HR: 1.30, 95% CI 1.01-1.73, per SD increase in TyG index). Compared with a model of conventional risk factors alone, the addition of the TyG index modestly improved the AUC (0.722-0.734, p = 0.04) to predict TLF. CONCLUSIONS: TyG index is positively associated with prevalent EOCAD and incident TLF. TyG index appeared to be a valuable component of future efforts to improve CAD risk stratification and TLF outcome prediction among young adults.

Enzymatic fermentation of rapeseed cake significantly improved the soil environment of tea rhizosphere.

BACKGROUND: Rapeseed cake is an important agricultural waste. After enzymatic fermentation, rapeseed cake not only has specific microbial diversity but also contains a lot of fatty acids, organic acids, amino acids and their derivatives, which has potential value as a high-quality organic fertilizer. However, the effects of fermented rapeseed cake on tea rhizosphere microorganisms and soil metabolites have not been reported. In this study, we aimed to elucidate the effect of enzymatic rapeseed cake fertilizer on the soil of tea tree, and to reveal the correlation between rhizosphere soil microorganisms and nutrients/metabolites. RESULTS: The results showed that: (1) The application of enzymatic rapeseed cake increased the contents of soil organic matter (OM), total nitrogen (TN), total phosphorus (TP), available nitrogen (AN), and available phosphorus (AP); increased the activities of soil urease (S-UE), soil catalase (S-CAT), soil acid phosphatase (S-ACP) and soil sucrase (S-SC); (2) The application of enzymatic rapeseed cake increased the relative abundance of beneficial rhizosphere microorganisms such as Chaetomium, Inocybe, Pseudoxanthomonas, Pseudomonas, Sphingomonas, and Stenotrophomonas; (3) The application of enzymatic rapeseed cake increased the contents of sugar, organic acid, and fatty acid in soil, and the key metabolic pathways were concentrated in sugar and fatty acid metabolisms; (4) The application of enzymatic rapeseed cake promoted the metabolism of sugar, organic acid, and fatty acid in soil by key rhizosphere microorganisms; enzymes and microorganisms jointly regulated the metabolic pathways of sugar and fatty acids in soil. CONCLUSIONS: Enzymatic rapeseed cake fertilizer improved the nutrient status and microbial structure of tea rhizosphere soil, which was beneficial for enhancing soil productivity in tea plantations. These findings provide new insights into the use of enzymatic rapeseed cake as an efficient organic fertilizer and expand its potential for application in tea plantations.

CDC42-mediated Wnt signaling facilitates odontogenic differentiation of DPCs during tooth root elongation.

BACKGROUND: CDC42 is a member of Rho GTPase family, acting as a molecular switch to regulate cytoskeleton organization and junction maturation of epithelium in organ development. Tooth root pattern is a highly complicated and dynamic process that dependens on interaction of epithelium and mesenchyme. However, there is a lack of understanding of the role of CDC42 during tooth root elongation. METHODS: The dynamic expression of CDC42 was traced during tooth development through immunofluorescence staining. Then we constructed a model of lentivirus or inhibitor mediated Cdc42 knockdown in Herwig's epithelial root sheath (HERS) cells and dental papilla cells (DPCs), respectively. Long-term influence of CDC42 abnormality was assessed via renal capsule transplantation and in situ injection of alveolar socket. RESULTS: CDC42 displayed a dynamic spatiotemporal pattern, with abundant expression in HERS cells and apical DPCs in developing root. Lentivirus-mediated Cdc42 knockdown in HERS cells didn't disrupt cell junctions as well as epithelium-mesenchyme transition. However, inhibition of CDC42 in DPCs undermined cell proliferation, migration and odontogenic differentiation. Wnt/ß-catenin signaling as the downstream target of CDC42 modulated DPCs' odontogenic differentiation. The transplantation and in situ injection experiments verified that loss of CDC42 impeded root extension via inhibiting the proliferation and differentiation of DPCs. CONCLUSIONS: We innovatively revealed that CDC42 was responsible for guiding root elongation in a mesenchyme-specific manner. Furthermore, CDC42-mediated canonical Wnt signaling regulated odontogenic differentiation of DPCs during root formation.

Enolate-Azide [3 + 2]-Cycloaddition Reaction Suitable for DNA-Encoded Library Synthesis.

The DNA-encoded chemical library (DEL) is a powerful hit selection technique in either basic science or innovative drug discovery. With the aim to circumvent the issue concerning DNA barcode damage in a conventional on-DNA copper-catalyzed azide-alkyne cycloaddition reaction (CuAAC), we have successfully developed the first DNA-compatible enolate-azide [3 + 2] cycloaddition reaction. The merits of this DEL chemistry include metal-free reaction and high DNA fidelity, high conversions and easy operation, broad substrate scope, and ready access to the highly substituted 1,4,5-trisubstituted triazoles. Thus, it will not only further enrich the DEL chemistry toolbox but also will have great potential in practical DEL synthesis.

CCL2 promotes lymphatic metastasis via activating RhoA and Rac1 pathway and predict prognosis to some extent in tongue cancer.

BACKGROUND: Oral tongue cancer is an extremely malignant tumor with high rate of lymphatic metastasis. Little is known about its invasion and metastasis mechanisms so far. METHODS: To clarify the main role of CCL2 in tongue cancer progression, we performed Transwell migration assay to confirm the effects of different concentrations of CCL2 on the migration and invasion of tongue cancer cells. Next, by siRNA interference of RhoA and Rac1 in LNMTca8113 cells, we are able to observe that these two molecules block the effect of CCL2 on cell migration and cytoskeleton reorganization by laser confocal microscopy. Moreover, the AKT phosphorylation level of PI3K downstream molecule under the action of CCL2 also be detected by qRT-PCR and western blot, so as to determine whether CCL2 affects the proliferation of LNMTca8113 cells through PI3K/AKT pathway. Finally, we analyzed the relationship between plasma CCL2 level and various clinicopathological parameters in patients with tongue cancer. Results: We found that tongue cancer cells treated with CCL2 migrate faster at first. CCL2 may enhance the invasion and migration of LNMTca8113 cells by activating RhoA and Rac1 to promote cytoskeleton reorganization. Promotion of LNMTca8113 migration induced by CCL2 was inhibited by silence of RhoA and Rac1. CCL2 could increase the phosphorylation of downstream Akt/PI3K signal and promoted the proliferation. Plasma concentration confirmed that the CCL2 level was closely related to the clinical stage of tongue cancer. Patients with lower CCL2 levels had a relatively longer progression-free survival and total survival time. RESULTS: After adding CCL2, the number of proliferation and migration of tongue cancer cells increased and the expression of RhoA and Rac1 rose up in LNMTca8113 cell line. The cytoskeleton reorganization was notable. Patients with higher serum levels of CCL2 had shorter progression-free survival than those with lower levels of CCL2 (P < 0.0001). CONCLUSIONS: CCL2 promotes the invasion and metastasis of tongue cancer by PI3K/Akt pathway. The plasma level of CCL2 may predict prognosis of tongue cancer patients. CCL2 can serve as a potential therapeutic target for tongue cancer treatment.

Increased CCL2 concentration is associated with short- term progress-free survival.CCL2 levels predict patient prognosis are similar to TNM staging.CCL2 levels may be a preferable biomarker for predicting the prognosis of patients with tongue cancer.

Priority conservation area of Larix gmelinii under climate change: application of an ensemble modeling.

Larix gmelinii (Rupr.) Kuzen is a major tree species with high economic and ecological value in the Greater Khingan Mountains coniferous forest of Northeast China. Reconstructing the priority Conservation Area of Larix gmelinii under Climate could provide a scientific basis for its germplasm conservation and management. The present study used ensemble and Marxan model simulations to predict species distribution areas and delineate priority conservation areas for Larix gmelinii in relation to productivity characteristics, understory plant diversity characteristics, and climate change impacts. The study revealed that the Greater Khingan Mountains and the Xiaoxing'an Mountains, with an area of approximately 300 974.2 km2, were the most suitable for L. gmelinii. The stand productivity of L. gmelinii in the most suitable area was significantly higher than that in the less suitable and marginally suitable areas, but understory plant diversity was not dominant. The increase in temperature under future climate change scenarios will reduce the potential distribution and area under L. gmelinii; the species will migrate to higher latitudes of the Greater Khingan Mountains, while the degree of niche migration will gradually increase. Under the 2090s-SSP585 climate scenario, the most suitable area for L. gmelinii will completely disappear, and the climate model niche will be completely separated. Therefore, the protected area of L. gmelinii was demarcated with a target of the productivity characteristics, understory plant diversity characteristics and climate change sensitive area, and the current key protected area was 8.38 × 104 km2. Overall, the study's findings will lay a foundation for the protection and rational development and utilization of cold temperate coniferous forests dominated by L. gmelinii in the northern forested region of the Greater Khingan Mountains.

Micromechanical interlocking structure at the filler/resin interface for dental composites: a review.

Dental resin composites (DRCs) are popular materials for repairing caries or dental defect, requiring excellent properties to cope with the complex oral environment. Filler/resin interface interaction has a significant impact on the physicochemical/biological properties and service life of DRCs. Various chemical and physical modification methods on filler/resin interface have been introduced and studied, and the physical micromechanical interlocking caused by the modification of fillers morphology and structure is a promising method. This paper firstly introduces the composition and development of DRCs, then reviews the chemical and physical modification methods of the filler/resin interface, mainly discusses the interface micromechanical interlocking structures and their enhancement mechanism for DRCs, finally give a summary on the existing problems and development potential.

CXCL1 promoted the migration and invasion abilities of oral cancer cells and might serve as a promising marker of prognosis in tongue cancer.

BACKGROUND: Oral tongue squamous cell carcinoma tends to metastasize to cervical lymphatic nodes early which leads to a 50% drop of survival rate. CXCL1 could be secreted by LNMTca8113 cell induced lymphatic endothelial cells and promoted LNMTca8113 cell migration. The current study aimed to further explore the effect of CXCL1 on the proliferation and migration abilities of tongue cancer cells and the prognostic value of serum CXCL1 in oral tongue squamous cell carcinoma. METHODS: Cell proliferation and migration ability were analysed by CCK8 assays and transwell migration assays. Immunofluorescence technique was used to show cytoskeleton. GST pull-down assay was applied to quantify the activation of GTPases. Blood samples of patients were collected and clinicopathological characteristics were analysed. RESULTS: CXCL1 could promote cancer cell proliferation in appropriate concentration by PI3K/AKT pathway. It also regulated the activation of Rho GTPases to mediate the rearrangements of cytoskeleton to promote tumour cell migration. Level of plasma CXCL1 could predict the possibility of early lymphatic metastasis and had a predictive value in progression-free survival and overall survival. CONCLUSIONS: CXCL1 could promote oral cancer cell proliferation, migration and invasion in vitro and contributed theoretical knowledge for the target selection in molecular targeted therapy. Level of plasma CXCL1 might serve as a biomarker for prognosis in oral tongue squamous cell carcinoma patients.

Comparative transcriptome analysis reveals the immune response of turbot (Scophthalmus maximus) induced by inactivated bivalent vaccine.

Vibrio species are important pathogens that affect a wide range of farmed fish. Vaccination is regarded as the most efficacious strategy for fighting bacterial infections. However, the underlying mechanisms remain to be elucidated. In the present study, a comparative transcriptome analysis was performed on the spleens from turbot (Scophthalmus maximus) induced by an inactivated bivalent vaccine (Vibrio anguillarum and Vibrio harveyi, IVVah1) at 4 week and 1 day post further challenge. Strong immune responses were induced by the bivalent vaccine, besides differentially expressed genes (DEGs) associated with adaptive immunity, more innate immunity-related DEGs were detected. At the late stage of vaccination, immune-related molecules associated with pattern recognition receptors, inflammatory factors, complement and coagulation cascade-related components, and antigen processing and presentation were significantly regulated, and some of them were even further up-regulated after the bacterial challenge, indicating the cooperation of multiple immune processes during the vaccine immunization process. In addition to the terms or pathways associated with the immune response, enrichment analysis revealed multiple significantly enriched terms/pathways associated with the response to stimulus/stress, homeostasis, metabolism, and biosynthesis, suggesting that a defensive status was established by the bivalent vaccine. This study furnishes new insights into the internal mechanism of immunity upon a combined vaccine administrating in turbot and lays a foundation for developing highly immunogenic vaccines in teleost.

Innovation and authenticity: Constructing tourists' subjective well-being in festival tourism.

Although festival tourism is an excellent fertile ground for improving individual emotions, few studies have been conducted on the influencing factors and formation mechanisms of festival tourists' subjective well-being. To address the current research gap, this paper draws on Arnold' s theory of emotion to examine a comprehensive formation model of tourists' subjective well-being. The findings from 581 samples indicate that event design innovation, cultural innovation and aesthetic innovation of festival tourism are positive stimulus factors of tourists' subjective well-being. Both experience quality and perceived festival value mediate the effects of cultural innovation and aesthetic innovation on subjective well-being, yet have no mediating effect on the relationship between event design innovation and well-being. However, it can only be achieved when festival authenticity contributes to a positive moderating effect. This study provides new ideas for the collaborative advancement of innovative development and authentic inheritance in festival tourism destinations.