Revealing core functional microorganisms in the fermentation process of Qicaipaojiao (Capsicum annuum L.) based on microbial metabolic network.

Paojiao, a typical Chinese traditional fermented pepper, is favored by consumers for its unique flavor profile. Microorganisms, organic acids, amino acids, and volatile compounds are the primary constituents influencing the development of paojiao's flavor. To elucidate the key flavor compounds and core microorganisms of Qicaipaojiao (QCJ), this study conducted a comprehensive analysis of the changes in taste substances (organic acids and amino acids) and volatile flavor compounds during QCJ fermentation. Key flavor substances in QCJ were identified using threshold aroma value and odor activity value and the core microorganisms of QCJ were determined based on the correlation between dominant microorganisms and the key flavor substances. During QCJ fermentation, 16 key taste substances (12 free amino acids and 4 organic acids) and 12 key aroma substances were identified. The fermentation process involved 10 bacteria and 7 fungal genera, including Lactiplantibacillus, Leuconostoc, Klebsiella, Pichia, Wickerhamomyces, and Candida. Correlation analysis revealed that the core functional microorganisms encompassed representatives from 8 genera, including 5 bacterial genera (Lactiplantibacillus, Weissella, Leuconostoc, Klebsiella, and Kluyvera) and 3 fungal genera (Rhodotorula, Phallus, and Pichia). These core functional microorganisms exhibited significant correlations with approximately 70 % of the key flavor substances (P < 0.05). This study contributes to an enhanced understanding of flavor formation mechanisms and offers valuable insight into flavor quality control in food fermentation processes.

Control and surveillance of redox potential for 233Pa dissolution in 2LiF-BeF2 molten salt.

233Pa, the precursor nuclide of 233U in the thorium-uranium conversion is prone to reductive deposition in 2LiF-BeF2 (66 : 34 mol%, FLiBe) molten salt. We explored the adjustment and control of the redox potential of the FLiBe melt to avoid the 233Pa reduction deposition. The experimental data indicated that the deposited 233Pa can be completely dissolved and reentered into the molten salt with the addition of oxidant NiF2, and the distribution and behaviour of uranium, thorium, neptunium, and most fission products did not have any significant change in the NiF2-oxidised FLiBe molten salt, showing the feasibility of this manner to make 233Pa exist stably in the melt. The effects of NiF2-addition on the behaviour of the fission products 95Nb and 131I in the FLiBe molten salt were also investigated. It was found that 131I could be used as a redox indicator to monitor the redox potential of the oxidation-enhanced FLiBe molten salt. All the information drawn from this study could provide significant support for the control and surveillance of the redox potential of the FLiBe molten salt in the upcoming thorium molten salt reactor (TMSR).

Exosomal YB-1 facilitates ovarian restoration by MALAT1/miR-211-5p/FOXO3 axis.

Premature ovarian failure (POF) affects many adult women less than 40 years of age and leads to infertility. Mesenchymal stem cells-derived small extracellular vesicles (MSCs-sEVs) are attractive candidates for ovarian function restoration and folliculogenesis for POF due to their safety and efficacy, however, the key mediator in MSCs-sEVs that modulates this response and underlying mechanisms remains elusive. Herein, we reported that YB-1 protein was markedly downregulated in vitro and in vivo models of POF induced with H2O2 and CTX respectively, accompanied by granulosa cells (GCs) senescence phenotype. Notably, BMSCs-sEVs transplantation upregulated YB-1, attenuated oxidative damage-induced cellular senescence in GCs, and significantly improved the ovarian function of POF rats, but that was reversed by YB-1 depletion. Moreover, YB-1 showed an obvious decline in serum and GCs in POF patients. Mechanistically, YB-1 as an RNA-binding protein (RBP) physically interacted with a long non-coding RNA, MALAT1, and increased its stability, further, MALAT1 acted as a competing endogenous RNA (ceRNA) to elevate FOXO3 levels by sequestering miR-211-5p to prevent its degradation, leading to repair of ovarian function. In summary, we demonstrated that BMSCs-sEVs improve ovarian function by releasing YB-1, which mediates MALAT1/miR-211-5p/FOXO3 axis regulation, providing a possible therapeutic target for patients with POF.

Comprehensive single-cell analysis deciphered microenvironmental dynamics and immune regulator olfactomedin 4 in pathogenesis of gallbladder cancer.

OBJECTIVE: Elucidating complex ecosystems and molecular features of gallbladder cancer (GBC) and benign gallbladder diseases is pivotal to proactive cancer prevention and optimal therapeutic intervention. DESIGN: We performed single-cell transcriptome analysis on 230 737 cells from 15 GBCs, 4 cholecystitis samples, 3 gallbladder polyps, 5 gallbladder adenomas and 16 adjacent normal tissues. Findings were validated through large-scale histological assays, digital spatial profiler multiplexed immunofluorescence (GeoMx), etc. Further molecular mechanism was demonstrated with in vitro and in vivo studies. RESULTS: The cell atlas unveiled an altered immune landscape across different pathological states of gallbladder diseases. GBC featured a more suppressive immune microenvironment with distinct T-cell proliferation patterns and macrophage attributions in different GBC subtypes. Notably, mutual exclusivity between stromal and immune cells was identified and remarkable stromal ecosystem (SC) heterogeneity during GBC progression was unveiled. Specifically, SC1 demonstrated active interaction between Fibro-iCAF and Endo-Tip cells, correlating with poor prognosis. Moreover, epithelium genetic variations within adenocarcinoma (AC) indicated an evolutionary similarity between adenoma and AC. Importantly, our study identified elevated olfactomedin 4 (OLFM4) in epithelial cells as a central player in GBC progression. OLFM4 was related to T-cell malfunction and tumour-associated macrophage infiltration, leading to a worse prognosis in GBC. Further investigations revealed that OLFM4 upregulated programmed death-ligand 1 (PD-L1) expression through the MAPK-AP1 axis, facilitating tumour cell immune evasion. CONCLUSION: These findings offer a valuable resource for understanding the pathogenesis of gallbladder diseases and indicate OLFM4 as a potential biomarker and therapeutic target for GBC.

Differences in archaeal diversity and potential ecological functions between saline and hypersaline lakes on Qinghai-Tibet Plateau were driven by multiple environmental and non-environmental factors beyond the salinity.

BACKGROUND: Saline lakes are home to various archaea that play special and crucial roles in the global biogeochemical cycle. The Qinghai-Tibet Plateau hosts a large number of lakes with diverse salinity ranging from 0.1 to over 400 g/L, harboring complex and diverse archaea. To the best of our knowledge, the formation mechanisms and potential ecological roles of archaea in Qinghai-Tibetan Plateau saline lakes remain largely unknown. RESULTS: Using High-throughput Illumina sequencing, we uncovered the vastly distinct archaea communities between two typical saline lakes with significant salinity differences on the Qinghai Tibet Plateau (Qinghai saline lake and Chaka hypersaline lake) and suggested archaea played different important roles in methanogenesis-related and nitrate reduction-related functions of these two lakes, respectively. Rather than the individual effect of salinity, the composite effect of salinity with diverse environmental parameters (e.g., temperature, chlorophyll a, total nitrogen, and total phosphorus) dominated the explanation of the variations in archaeal community structure in different habitats. Based on the network analysis, we further found the correlations between dominant archaeal OTUs were tight but significantly different between the two habitats, implying that archaeal interactions may also largely determine the shape of archaeal communities. CONCLUSION: The present study improved our understanding of the structure and function of archaea in different saline lakes on the Qinghai-Tibet Plateau and provided a new perspective on the mechanisms underlying shaping their communities.

Changes in physio-biochemical metabolism, phenolics and antioxidant capacity during germination of different wheat varieties.

Changes in physio-biochemical metabolism, phenolics and antioxidant capacity during germination were studied in eight different wheat varieties. Results showed that germination enhanced sprout growth, and caused oxidative damage, but enhanced phenolics accumulation. Ferulic acid and p-coumaric acid were the main phenolic acids in wheat sprouts, and dihydroquercetin, quercetin and vitexin were the main flavonoids. The phenolic acid content of Jimai 44 was the highest on the 2th and 4th day of germination, and that of Bainong 307 was the highest on the 6th day. The flavonoid content of Hei jingang was the highest during whole germination. The enzymes activities of phenylalanine ammonia lyase (PAL), cinnamic acid 4-hydroxylase (C4H) and 4-coumarate coenzyme A ligase (4CL) were up-regulated. The activities of catalase, polyphenol oxidase and peroxidase were also activated. Antioxidant capacity of wheat sprouts was enhanced. The results provided new ideas for the production of naturally sourced phenolic rich foods.

Circ_0006949 as a potential non-invasive diagnosis biomarker promotes the proliferation of NSCLC cells via miR-4673/GLUL axis.

The 5-year survival for non-small cell lung cancer (NSCLC) remains <20 %, primarily due to the early symptoms of lung cancer are inconspicuous. Prompt identification and medical intervention could serve as effective strategies for mitigating the death rate. We therefore set out to identify biomarkers to help diagnose NSCLC. CircRNA microarray and qRT-PCR reveal that sputum circ_0006949 is a potential biomarker for the early diagnosis and therapy of NSCLC, which can enhance the proliferation and clone formation, regulate the cell cycle, and accelerate the migration and invasion of NSCLC cells. Circ_0006949 and miR-4673 are predominantly co-localized in the cytoplasm of NSCLC cell lines and tissues; it upregulates GLUL by adsorption of miR-4673 through competing endogenous RNAs mechanism. The circ_0006949/miR-4673/GLUL axis exerts pro-cancer effects in vitro and in vivo. Circ_0006949 can boost GLUL catalytic activity, and they are highly expressed in NSCLC tissues and correlate with poor prognosis. In summary, circ_0006949 is a potential biomarker for the early diagnosis and therapy of NSCLC. This novel sputum circRNA is statistically more predictive than conventional serum markers for NSCLC diagnosis. Non-invasive detection of patients with early-stage NSCLC using sputum has shown good potential for routine diagnosis and possible screening.

Measuring high-speed train delay severity: Static and dynamic analysis.

This paper focuses on optimizing the management of delayed trains in operational scenarios by scientifically categorizing train delay levels. It employs static and dynamic models grounded in real-world train delay data from high-speed railways. This classification aids dispatchers in swiftly identifying and predicting delay extents, thus enhancing mitigation strategies' efficiency. Key indicators, encompassing initial delay duration, station impacts, average station delay, delayed trains' cascading effects, and average delay per affected train, inform the classification. Applying the K-means clustering algorithm to standardized delay indicators yields an optimized categorization of delayed trains into four levels, reflecting varying risk levels. This static classification offers a comprehensive overview of delay dynamics. Furthermore, utilizing Markov chains, the study delves into sequential dynamic analyses, accounting for China's railway context and specifically addressing fluctuations during the Spring Festival travel rush. This research, combining static and dynamic approaches, provides valuable insights for bolstering railway operational efficiency and resilience amidst diverse delay scenarios.

Case report: detection of multiple sporadic gastrointestinal stromal tumors by dual-time 18 F-FDG PET/CT.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors affecting the gastrointestinal tract. Typically, GISTs are solitary; however, in rare cases, they may be multiple and appear in one or more organs. Multiple GISTs can appear in familial GISTs, children, or certain tumor syndromes such as neurofibromatosis type 1, Carney syndrome, and Carney-Stratakis syndrome. However, the diagnosis of primary multiple sporadic GISTs is often more difficult than that of these diseases. Herein, we report a case of multiple primary sporadic GISTs in a 64-year-old man, affecting the abdominal cavity and retroperitoneum, as identified through dual-time point positron emission tomography (PET) with 18F-labeled fluoro-2-deoxyglucose (18F-FDG) and computed tomography (18F-FDG PET/CT). Notably, the dual-time-point PET/CT revealed the migration of masses near the lower abdomen into the abdominal cavity. Furthermore, a significant increase in radioactive uptake of the mass 3 h after 18F-FDG injection compared with that 1 h after injection may be an important cue for its diagnosis.

STAM2 negatively regulates the MyD88-mediated NF-κB signaling pathway in miiuy croaker, Miichthys miiuy.

Signal transducing adapter molecule 2 (STAM2), a member of the Signal Transducing Adapter Molecule (STAM) family, is a protein with significant implications in diverse signaling pathways and endocytic membrane trafficking. However, the role of the STAM2, especially in fish, remains largely unknown. In this study, we discovered that STAM2 negatively regulates the NF-κB signaling pathway, and its inhibitory effect is enhanced upon LPS induction. Our study confirmed that STAM2 can enhance the degradation of myeloid differentiation primary-response protein 88 (MyD88), an upstream regulator of NF-κB pathway. Furthermore, the UIM domain of STAM2 is important for the inhibition of MyD88. Mechanistically, STAM2 inhibits the NF-κB signaling pathway by targeting the MyD88 autophagy pathway. In addition, we showed that STAM2 promotes the proliferation of Vibrio harveyi. In summary, our study reveals that STAM2 inhibits NF-κB signaling activation and mediates innate immunity in teleost via the autophagy pathway.

Research on factor analysis and method for evaluating grouting effects using machine learning.

The evaluation of grouting effects constitutes a critical aspect of grouting engineering. With the maturity of the grouting project, the workload and empirical characteristics of grouting effect evaluation are gradually revealed. In the context of the Qiuji coal mine's directional drilling and grouting to limestone aquifer reformation, this study thoroughly analyzes the influencing factors of grouting effects from geological and engineering perspectives, comparing these with various engineering indices associated with drilling and grouting. This led to the establishment of a "dual-process, multi-parameter, and multi-factor" system, employing correlation analysis to validate the selected indices' reasonableness and scientific merit. Utilizing the chosen indices, eight high-performing machine learning models and three parameter optimization algorithms were employed to develop a model for assessing the effectiveness of directional grouting in limestone aquifers. The model's efficacy was evaluated based on accuracy, recall, precision, and F-score metrics, followed by practical engineering validation. Results indicate that the "dual-process, multi-parameter, multi-factor" system elucidates the relationship between influencing factors and engineering parameters, demonstrating the intricacy of evaluating grouting effects. Analysis revealed that the correlation among the eight selected indicators-including the proportion of boreholes in the target rock strata, drilling length, leakage, water level, pressure of grouting, mass of slurry injected, permeability properties of limestone aquifers before being grouted, permeability properties of limestone aquifers after being grouted-is not substantial, underscoring their viability as independent indicators for grouting effect evaluation. Comparative analysis showed that the Adaboost machine learning model, optimized via a genetic algorithm, demonstrated superior performance and more accurate evaluation results. Engineering validation confirmed that this model provides a more precise and realistic assessment of grouting effects compared to traditional methods.

Collaborative optimization of depot location, capacity and rolling stock scheduling considering maintenance requirements.

Generally, when optimizing a rolling stock schedule, the locations of the depots, or places in the network where the composition changes and maintenance occurs, are assumed known. The locations where maintenance is performed naturally influence the quality of any resulting rolling stock schedules. In this paper, the problem of selecting new depot locations and their corresponding capacities is considered. A two-stage mixed integer programming approach for rolling stock scheduling with maintenance requirements is extended to account for depot selection. First, a conventional flow-based model is solved, ignoring maintenance requirements, to obtain a variety of rolling stock schedules with multiple depot locations and capacity options. Then, a maintenance feasible rolling stock schedule can be obtained by solving a series of assignment problems by using the schedules found in the first stage. The proposed methodology is tested on real-life instances, and the numerical experiments of different operational scenarios are discussed.

Sodium-alginate-based indicator film containing a hydrophobic nanosilica layer for monitoring fish freshness.

In this study, hydrophobic sodium alginate/anthocyanin/cellulose nanocrystal indicator films were fabricated by incorporating nanosilica (NS) as a waterproofing layer. The concentrations and formation methods (spraying (S), coating (C), and impregnation (I)) of the NS layer (denoted as NSS, NSC, NSI, respectively) were optimized. The results indicated that the optimum concentration of the NS layer was 5 % at a water contact angle (WCA) 110.5°. Further, Fourier transform infrared spectra showed the presence of SiOSi and SiCH3 groups in the NSS, NSC, and NSI films, and X-ray diffraction spectra indicated that original structures of these films were disordered. Moreover, the surface morphology, mechanical properties, and light transmission were affected by the NS layer, and the optimal layer was found to be NSI. After 10 days of storage at 100 % humidity, the NSI film exhibited low water vapor adsorption (37.22 g) and permeability (0.1484 g/m·s·Pa·10-11) and a high WCA (110.2°). In addition, the NSI film exhibited a visible color shift with an increasing pH of the buffer solution. A monitoring test of fish freshness showed that the NSI film displayed a distinctive color change corresponding to fish spoilage during 14 days of storage. This indicates that NSI has high potential in indicator film applications.

High KRT17 expression in tumour budding indicates immunologically 'hot' tumour budding and predicts good survival in patients with colorectal cancer.

Objectives: Emerging evidence has demonstrated that tumour budding (TB) is negatively associated with T-lymphocyte infiltration in CRC. Despite extensive research, the molecular characteristics of immunologically 'hot' TB remain poorly understood. Methods: We quantified the number of TB by haematoxylin-eosin (H&E) sections and the densities of CD3+ and CD8+ T-lymphocytes by immunohistochemistry in a CRC cohort of 351 cases who underwent curative resection. We analysed the differential expression and T-lymphocyte infiltration score of 37 human epithelial keratins in CRC using RNA sequencing from the TCGA dataset. In 278 TB-positive cases, KRT17 expression was evaluated in tumour centre (TC) and TB with a staining score. Patient demographic, clinicopathological features and survival rates were analysed. Results: In a CRC cohort of 351 cases, low-grade TB was associated with high CD3+ and CD8+ T-cell densities in the invasive margin (IM) but not in the TC. Of 37 human epithelial keratins, only KRT17 expression in TB had an apparent association with TB-grade and T-lymphocyte infiltration. In 278 TB-positive cases, high KRT17 expression in TB (KRT17TB) was negatively associated with low-grade TB and positively associated with high CD3+ and CD8+ T-cell densities in IM. High KRT17TB predicted early tumour grade, absence of lymph node metastasis and absence of tumour deposits. Additionally, patients with high KRT17TB had good overall survival and disease-free survival. Notably, low KRT17TB can specifically identify those patients with a poor prognosis among colorectal cancer patients with low TB and high T-lymphocyte infiltration. Conclusions: KRT17 can be employed as a new indicator for distinguishing different immunological TBs.

A Case of Nasal Extranodal NK/T-cell Lymphoma of Lower Limb Muscle Revealed by 18F-FDG PET/CT.

BACKGROUND: Extranodal NK/T-cell lymphoma (ENKTCL) is a type of malignant non-Hodgkin's lymphoma originating from mature T cells and NK cells, mainly involving the upper aerodigestive tract, including the nasal cavity, nasopharynx, oropharynx, oral cavity, hypopharynx, larynx, and occasionally the skin, salivary glands, testes, and gastrointestinal tract, but rarely the skeletal muscle. CASE PRESENTATION: An 82-year-old man presented with redness, swelling, and pain in his right lower limb for 3 months. He was initially diagnosed with cellulitis at another hospital and was treated conservatively for two weeks without improvement. He underwent a biopsy of the lesioned muscle and histopathology revealed nasal type ENKTCL. 18F-FDG PET/CT was recommended for the staging of the lymphoma, and the results showed that except for the muscles of the right lower extremity, no other organs and tissues were involved. CONCLUSION: ENKTCL confined to the muscle of the lower extremity is rare and often initially misdiagnosed as myositis because of red, swollen, heat, and painful symptoms that resemble inflammation, and in it, higher radiotracer uptake in 18F-FDG PET/CT helps to distinguish it from myositis.

Anaphylactic deaths: A retrospective study of forensic autopsy cases from 2009 to 2019 in Shanghai, China.

Anaphylaxis is a rare but well-known cause of sudden unexpected death, although data from forensic autopsies in anaphylactic deaths are limited. Herein, a retrospective study of a series of allergic deaths from 2009 through 2019 in Shanghai, China, was conducted to investigate the demographic, medical, and forensic pathological characteristics of fatal anaphylaxis to improve medicolegal understanding on anaphylactic death. Sixty-two autopsy cases of anaphylactic death were registered in this study. Males dominated the cases (74.2%) against females (25.8%), with an average age of 38.8 years. Medications (98.4%), particularly antibiotics (72.6%), were the most frequent cause of anaphylaxis, and 44 cases (71.0%) occurred in clinics administered illegally by unlicensed clinicians. The anaphylactic symptoms began within a few minutes to less than 1 h in 53 cases, with dyspnea (56.5%) and sudden shock (46.8%) being the most common clinical signs. Thirty cases (48.4%) of anaphylaxis resulted in death within 1 h. Laryngeal edema and multiple tissue eosinophil infiltration (85.5%) were the most prevalent autopsy findings, followed by pulmonary edema and congestion (24.2%), which were considered to be non-specific but suggestive. The comorbidities were mainly cardiovascular disease (33.9%), pneumonia (8.1%) and asthma (8.1%). Serum IgE were measured in 11 of 62 cases, ranging from 43.3 to 591 IU/ml, severed as a helpful marker. Therefore, we suggested a thorough analysis of allergen exposure, clinical history and autopsy findings is required for the diagnosis of anaphylactic death currently.

Targeting ABCA1 via Extracellular Vesicle-Encapsulated Staurosporine as a Therapeutic Strategy to Enhance Radiosensitivity.

Cancer stem cells (CSCs) are essential for tumor initiation, recurrence, metastasis, and resistance. However, targeting CSCs as a therapeutic approach remains challenging. Here, a stemness signature based on 22-gene is developed to predict prognosis in esophageal squamous cell carcinoma (ESCC). Staurosporine (STS) is identified as a radioresistance suppressor by high-throughput screening of a library of 2131 natural compounds, leading to dramatically improved radiotherapy efficacy in subcutaneous tumor models. Mechanistically, STS inhibits cell proliferation through the mTOR/AKT signaling pathway and suppressed stemness by targeting ATP-binding cassette A1 (ABCA1), which is transcriptionally regulated by liver X receptor alpha (LXRα). STS can selectively bind to the nucleotide-binding domain (NBD) of ABCA1 and compete for ATP, blocking ABCA1-mediated drug efflux and facilitating intracellular accumulation of STS. Considering the cytotoxicity of STS, an extracellular vesicle-encapsulated STS system (EV-STS) is established for effective STS delivery. EV-STS shows remarkable tumor growth inhibition, even at half the dose of STS, with superior safety and efficacy. These findings indicate that ABCA1 may serve as a predictor of response to neoadjuvant chemotherapy and/or radiotherapy in ESCC patients. EV-STS has shown improved antitumor efficacy and low systemic toxicity, offering a promising therapeutic approach for ESCC.

Liraglutide induced browning of visceral white adipose through regulation of miRNAs in high-fat-diet-induced obese mice.

OBJECTIVE: Obesity is characterized by excessive accumulation of white adipose tissue (WAT). Conversely, brown adipose tissue is protective against obesity. We recently reported liraglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), could inhibit high-fat-diet-induced obesity by browning of WAT. However, the molecular mechanism involved is not well defined. Hence, we aimed to explore whether GLP-1RA could promote brown remodeling in WAT by regulating miRNAs. METHODS: After the obesity model was successfully constructed, C57BL/6J mice were treated with liraglutide (200 µg/kg/d) or equivoluminal saline subcutaneously for 12 weeks. Then, the deposition of abdominal fat was measured by CT scanning. At the end of the treatments, glucose and insulin tolerance in mice were assessed. Serum lipid levels were monitored and epididymal WAT (eWAT) were collected for analysis. Quantitative real-time PCR and western blot analyses were conducted to evaluate the expression of genes and miRNAs associated with white fat browning. RESULTS: Liraglutide significantly reduced body weight and visceral fat mass. Levels of lipid profile were also improved. Liraglutide upregulated the expression of browning-related genes in eWAT. Meanwhile, the expression level of miRNAs (miR-196a and miR-378a) positively associated with the browning of WAT were increased, while the expression of miR-155, miR-199a, and miR-382 negatively related with browning of WAT were decreased. CONCLUSION: Our findings suggest that liraglutide could promote brown remodeling of visceral WAT by bi-regulating miRNAs; this might be one of the mechanisms underlying its effect on weight loss.

JunD-miR494-CUL3 axis promotes radioresistance and metastasis by facilitating EMT and restraining PD-L1 degradation in esophageal squamous cell carcinoma.

Therapy resistance and metastatic progression jointly determine the fatal outcome of cancer, therefore, elucidating their crosstalk may provide new opportunities to improve therapeutic efficacy and prevent recurrence and metastasis in esophageal squamous cell carcinoma (ESCC). Here, we have established radioresistant ESCC cells with the remarkable metastatic capacity, and identified miR-494-3p (miR494) as a radioresistant activator. Mechanistically, we demonstrated that cullin 3 (CUL3) is a direct target of miR494, which is transcriptionally regulated by JunD, and highlighted that JunD-miR494-CUL3 axis promotes radioresistance and metastasis by facilitating epithelial-mesenchymal transition (EMT) and restraining programmed cell death 1 ligand 1 (PD-L1) degradation. In clinical specimens, miR494 is significantly up-regulated and positively associated with T stage and lymph node metastasis in ESCC tissues and serum. Notably, patients with higher serum miR494 expression have poor prognosis, and patients with higher CUL3 expression have more conventional dendritic cells (cDCs) and plasmacytoid DCs (pDCs), less cancer-associated fibroblasts (CAF2/4), and tumor endothelial cells (TEC2/3) infiltration than patients with lower CUL3 expression, suggesting that CUL3 may be involved in tumor microenvironment (TME). Overall, miR494 may serve as a potential prognostic predictor and therapeutic target, providing a promising strategy for ESCC treatment.