RESUMEN

Probiotics serve a very important role in human health. However, probiotics have poor stability during processing, storage, and gastrointestinal digestion. The gellan gum (GG) is less susceptible to enzymatic degradation and resistant to thermal and acidic environments. This study investigated the effect of casein (CS)-GG emulsions to encapsulate Lactiplantibacillus plantarum CICC 6002 (L. plantarum CICC 6002) on its storage stability, thermal stability, and gastrointestinal digestion. L. plantarum CICC 6002 was suspended in palm oil and emulsions were prepared using CS or CS-GG complexes. We found the CS-GG emulsions improved the viability of L. plantarum CICC 6002 after storage, pasteurization, and digestion compared to the CS emulsions. In addition, we investigated the influence of the gellan gum concentration on emulsion stability, and the optimal stability was observed in the emulsion prepared by CS-0.8% GG complex. This study provided a new strategy for the protection of probiotics based on CS-GG delivery system.

Asunto(s)

RESUMEN

Mesoporous ceria nanoparticles featuring ordered pores (O-MCNs) have much greater potential than their counterparts featuring interparticle pores (I-MCNs) due to their uniform pore size and interconnected framework structures. However, current methods can only synthesize I-MCNs and fail to achieve O-MCNs. Understanding the mechanisms underlying the formation of pores in I-MCNs can spark ideas for designing new methods to realize the synthesis of O-MCNs. In this study, the details of an established I-MCN synthetic method using 1-octadecene (ODE) and ethanol as a mixed solvent, Ce(NO3)3·6H2O as a precursor and trioctylphosphine oxide (TOPO) as a ligand were explored. The results revealed that six groups of molecules were generated ahead of ceria crystal nucleation, and these molecules played different roles in the formation of I-MCNs. Four steps, namely, ceria crystal nucleation, small ceria nanoparticle formation, small ceria nanoparticle assembly, and I-MCN growth, were involved in the formation of the I-MCNs. The assembly of small ceria nanoparticles driven by the fusion of the (200) plane leaving behind unoccupied spaces was the major reason for the formation of pores in the I-MCNs. These findings provided very useful information for the future design of new methods to achieve O-MCNs.

RESUMEN

The mechanism for water-saving and high-yield of wide-range precision sowing technology remains unclear. We investigated the impact of wide-range precision sowing on the physiological characteristics of root system, water consumption, and grain yield of wheat 'Jimai 22' during the growing seasons of 2017-2019. We set up two planting modes: wide precision sowing and conventional strip sowing, and three row spacings of 20 cm, 25 cm, and 30 cm under water-saving cultivation with supplemental irrigation to examine the effects of planting modes on root biomass and senescence characteristics of wheat, water utilization characteristics, interplant evaporation, grain yield, and water utilization efficiency. The results showed that the 25 cm treatment (K25) led to an increase in root weight density, root soluble protein content, and root activity by 7.2%-23.9%, 8.7%-25.1%, 10.7%-29.9%, and 7.3%-27.6%, 8.0%-38.5%, 15.2%-32.7%, respectively, compared to the other treatments. At the same row spacing, the wide-range precision sowing treatment showed a significantly higher soil water storage consumption and proportion to total water consumption compared to the conventional strip-tillage treatment. Additionally, irrigation and interplant evaporation were lower in the wide-range precision sowing treatment. The K25 treatment exhibited significantly higher water consumption and modal coefficient of water consumption from flowering to ripening than other treatments. Furthermore, it had significantly higher seed yield, water utilization efficiency, and irrigation utilization efficiency than the other treatments. We found that a 25 cm spacing in the lower rows and density of 180-270 plants·m-2 was the water-saving and high-yielding planting pattern of wide-range precision sowing wheat in Huang-Huai-Hai region.

Asunto(s)

RESUMEN

Myeloid-derived suppressor cells (MDSCs) are reported to be responsible for the negative prognosis of colorectal cancer (CRC) patients due to the mediated immunosuppressive tumor microenvironment (TME). The selective and chronic circumvention of tumor-infiltrated MDSCs has potential clinical significance for CRC treatment, which unluckily remains a technical challenge. Because tumor hypoxia makes a significant contribution to the recruitment of MDSCs in tumor sites, a dual oxygen-supplied immunosuppression-inhibiting nanomedicine (DOIN) is demonstrated for overcoming tumor hypoxia, which achieves selective and long-term inhibition of intratumoral recruitment of MDSCs. The DOIN is constructed by the encasement of perfluorooctyl bromide (PFOB) and 4-methylumbelliferone (4-MU) into a TME-responsive amphiphilic polymer. This nanoplatform directly carries oxygen to the tumor region and simultaneously loosens the condensed tumor extracellular matrix for the normalization of tumor vasculature, which selectively remodels the TME toward one adverse to the intratumoral recruitment of MDSCs. Importantly, this nanoplatform offers a long-acting alleviation of the hypoxic TME, chronically avoiding the comeback of tumor-infiltrated MDSCs. Consequently, the immunosuppressive TME is relieved, and T cells are successfully proliferated and activated into cytotoxic T lymphocytes, which boosts a systemic immune response and contributes to lasting inhibition of tumor growth with a prolonged survival span of xenograft.

RESUMEN

Penicillium species are renowned for their ability to produce a wide range of secondary metabolites with medicinal properties. In this study, compounds 1-10 were isolated from Penicillium sp. Z-16, of which compound 1 is a new benzophenone derivative named methyl 2-(2,6-dihydroxy-4-methylbenzoyl)-4,5-dihydroxy-3-methoxybenzoate. The chemical structure of 1 was determined through comprehensive spectroscopic analysis, including 1D, 2D NMR (HMBC, HSQC) and HRESIMS. In addition, six other known compounds (11-16) were isolated and identified from Penicillium sp. T-5-1. The antimicrobial activity tests demonstrated that compound 1 was moderately active against Candida albicans with a MIC value of 125 µg/mL, while compound 2 showed a MIC value of 62.5 µg/mL against Staphylococcus aureus.

RESUMEN

PURPOSE: The influence of pregnancy on tuberculosis (TB) has not been well studied. This study aimed to investigate the demographics, clinical characteristics and outcomes of pregnant-related TB compared with the general population with TB. METHODS: We retrospectively analysed medical records of women during pregnancy or within six months postpartum with active TB who were admitted to the West China Hospital between 2011 and 2022. According to age, gender and admission time, the general population with active TB was matched at a ratio of 1:2, and the demographics, clinical characteristics and outcomes were compared. RESULTS: All the participants in both the pregnant and non-pregnant groups were females, averaging 26 years old, with a majority of Han nationality (72.4% vs. 69.5%, respectively). The two groups were comparable (p < .05). Pregnant TB cases showed higher rates of fever (61% vs. 35%), dyspnoea (39.9% vs. 18.7%), neurological symptoms (34.4% vs. 11.0%) and miliary TB (24.5% vs. 10.9%) compared to non-pregnant cases (p < .05). Additionally, the pregnant group exhibited lower red blood cell counts (3.62 × 109/L vs. 4.37 × 109/L), lower albumin levels (31.20 g/L vs. 40.40 g/L) and elevated inflammatory markers (p < .05). Pregnant women with TB had severe outcomes, with 16.3% requiring intensive care unit (ICU) care and a 3.3% TB-related mortality rate - higher than local averages. In contrast, the non-pregnant group had lower rates (0.8% for ICU admission, and no TB-related deaths). Moreover, active TB during pregnancies led to a high rate of spontaneous abortion (34.1%), with military pulmonary TB identified as the sole risk factor for severe TB in pregnancies (OR: 3.6; 95% CI: 1.15, 11.34). CONCLUSIONS: Manifestations of TB in pregnant women differ from those in the general population with TB. Pregnancy complicated with active TB greatly harms the mother and foetus and requires special attention in the future.

Asunto(s)

RESUMEN

Age-related osteoporosis manifests as a complex pathology that disrupts bone homeostasis and elevates fracture risk, yet the mechanisms facilitating age-related shifts in bone marrow macrophages/osteoclasts (BMMs/OCs) lineage are not fully understood. To decipher these mechanisms, we conducted an investigation into the determinants controlling BMMs/OCs differentiation. We performed single-cell multi-omics profiling on bone marrow samples from mice of different ages (1, 6, and 20 months) to gain a holistic understanding of cellular changes across time. Our analysis revealed that aging significantly instigates OC differentiation. Importantly, we identified Cebpd as a vital gene for osteoclastogenesis and bone resorption during the aging process. Counterbalancing the effects of Cebpd, we found Irf8, Sox4, and Klf4 to play crucial roles. By thoroughly examining the cellular dynamics underpinning bone aging, our study unveils novel insights into the mechanisms of age-related osteoporosis and presents potential therapeutic targets for future exploration.

RESUMEN

Mesenchymal stem cells (MSCs) have demonstrated significant therapeutic potential in heart failure (HF) treatment. However, their clinical application is impeded by low retention rate and low cellular activity of MSCs caused by high inflammatory and reactive oxygen species (ROS) microenvironment. In this study, monascus pigment (MP) nanoparticle (PPM) was proposed for improving adverse microenvironment and assisting in transplantation of bone marrow-derived MSCs (BMSCs). Meanwhile, in order to load PPM and reduce the mechanical damage of BMSCs, injectable hydrogels based on Schiff base cross-linking were prepared. The PPM displays ROS-scavenging and macrophage phenotype-regulating capabilities, significantly enhancing BMSCs survival and activity in HF microenvironment. This hydrogel demonstrates superior biocompatibility, injectability, and tissue adhesion. With the synergistic effects of injectable, adhesive hydrogel and the microenvironment-modulating properties of MP, cardiac function was effectively improved in the pericardial sac of rats. Our results offer insights into advancing BMSCs-based HF therapies and their clinical applications.

RESUMEN

To enhance the mechanical properties of polylactic acid (PLA) material, the PLA-based composite films are prepared by using Pueraria lobata (Willd.) Ohwi root microcrystalline cellulose (PRMCC) treated with 3-aminopropyl triethoxysilane (KH550) silane coupling agent as the dispersed phase through solvent casting method. The effects of the concentrations of PRMCC and KH550 as well as the KH550 pretreating condition (ethanol concentration) on the tensile properties of PLA-based composite films are investigated. The PLA-based composite film treated with 5 wt% PRMCC and 18 wt% KH550 (pretreated by 90 % EtOH) exhibits the greatest performance. Its elongation at break value is detected to be 4.0 %, 1.6 times as large as that of pure PLA film. The water absorption of the as-prepared PLA-based composite film is reduced from 0.49 % of the unmodified PLA/PRMCC film to 0.12 %. Moreover, the modified PLA-based composite film has a hydrophobic surface and exhibits good thermal stability. Compared with pure PLA film, the modified PLA-based composite film exhibits improved UV shielding performance with acceptable transparency. Furthermore, after adding poly(butylene adipate-co-terephthalate) (PBAT) to the composite system, the elongation at break of the PLA-based composite film is up to 7.2 %. This research can provide theoretical guidance for enhancing the performance of PLA products.

RESUMEN

INTRODUCTION: Poststroke shoulder pain is a common complication that severely affects the recovery of upper limb motor function. Acupuncture has positive analgesic effects in treating poststroke shoulder pain, and studies have demonstrated the efficacy of transcranial direct current stimulation (tDCS) in treating patients with this pain. However, whether acupuncture combined with tDCS has a superior rehabilitation effect on poststroke shoulder pain is currently unknown. We aimed to observe the effect of the combined intervention on poststroke shoulder pain and explore its possible central analgesic mechanism. METHODS AND ANALYSIS: This study describes a randomised controlled trial using assessor blinding. A total of 135 poststroke patients with shoulder pain will be randomly assigned in a 1:1:1 ratio to the tDCS group, acupuncture group and combined group (acupuncture plus tDCS). All three groups will undergo conventional rehabilitation treatment. Participants in the tDCS group will receive tDCS stimulation on the M1 area for 20 min, while the acupuncture group will receive 20 min of acupuncture. The combined treatment group will receive both. All treatments will be performed five times per week for 4 weeks. The primary outcome indicator in this study is the Visual Analogue Scale pain score. Secondary outcome indicators include shoulder mobility, Shoulder Pain and Disability Index, Fugl-Meyer Motor Function Scale, Modified Barthel Index Scale, Self-Rating Anxiety and Depression Scale and functional MRI. All scale results will be assessed at baseline and at 2 weeks and 4 weeks, and during follow-up at 1 month, 3 months and 6 months postdischarge. A repeated analysis of variance will be conducted to observe the group×time interaction effects of the combined intervention. Moreover, functional MRI will be applied to explore the central analgesic mechanism. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Ethics Committee of the Affiliated Rehabilitation Hospital of Fujian University of Traditional Chinese Medicine (2023KY-039-001). The results of the study will be published in a peer-reviewed journal and presented at scientific conferences. TRIAL REGISTRATION NUMBER: ChiCTR2300078270.

Asunto(s)

RESUMEN

Hepatocellular carcinoma (HCC) is a typical highly heterogeneous solid tumor with high morbidity and mortality worldwide, especially in China; however, the immune microenvironment of HCC has not been clarified so far. Here, we employed single-cell RNA sequencing (scRNA-seq) on diethylnitrosamine (DEN)-induced mouse HCC model to dissect the immune cell dynamics during tumorigenesis. Our findings reveal distinct immune profiles in both precancerous and cancerous lesions, indicating early tumor-associated immunological alterations. Notably, specific T and B cell subpopulations are preferentially enriched in the HCC tumor microenvironment (TME). Furthermore, we identified a subpopulation of naïve B cells with high CD83 expression, correlating with improved prognosis in human HCC. These signature genes were validated in The Cancer Genome Atlas HCC RNA-seq dataset. Moreover, cell interaction analysis revealed that subpopulations of B cells in both mouse and human samples are activated and may potentially contribute to oncogenic processes. In summary, our study provides insights into the dynamic immune microenvironment and cellular networks in HCC pathogenesis, with a specific emphasis on naïve B cells. These findings emphasize the significance of targeting TME in HCC patients to prevent HCC pathological progression, which may give a new perspective on the therapeutics for HCC.

RESUMEN

Gastrointestinal digestibility behavior, structural and functional characteristics of bovine ß-casein (ß-CN) were studied in vitro under infant and adult conditions. This direct comparison helps reveal the effects of different physiological stages on the digestive behavior of ß-CN. Not only was the degree of hydrolysis (DH) of ß-CN analyzed, but also the changes in its digestive morphology, microstructure, and secondary structure during digestion were explored in depth. Meanwhile, we focused on the physicochemical properties of ß-CN digesta, including solubility, emulsifying and foaming properties, as well as their functional properties, such as antimicrobial and antioxidant activities. Key results showed that ß-CN underwent more extensive hydrolysis in the adult digestion model, with approximately twice the DH compared to the infant model. The adult model exhibited faster digestion kinetics, less protein flocculation, and a more loosened secondary structure, indicating a more efficient digestion process. Notably, the digesta from the adult model displayed significantly improved solubility and emulsifying properties, and also enhanced antioxidant capacities, with significantly better inhibition of two common pathogenic bacteria than the infant model, and an average increase in the diameter of the inhibition zone of approximately 2 mm. These findings underscore the differential digestive behavior and functional potential of ß-CN across physiological stages. This comprehensive assessment approach contributes to a more comprehensive insight into the digestive behavior of ß-CN. Therefore, we conclude that producing products from unmodified ß-CN may be more suitable for the adult population, and that the digesta in the adult model exhibit higher functional properties.

Asunto(s)

RESUMEN

Acetochlor residues can contaminate anoxic habitats where anaerobic microbial transformation dominates. Herein, a highly efficient anaerobic acetochlor-degrading consortium ACT6 was enriched using sulfate and acetochlor as selection pressures. The acclimated consortium ACT6 showed an 8.7-fold increase in its ability to degrade acetochlor compared with the initial consortium ACT1. Two degradation pathways of acetochlor were found: reductive dechlorination and thiol-substitution dechlorination in the chloroacetyl group, in which the latter dominated. Acclimation enhanced the abundances of Desulfovibrio, Proteiniclasticum, and Lacrimispora from 0.7 to 28.0% (40-fold), 4.7 to 18.1% (4-fold), and 2.3 to 12.3% (5-fold), respectively, which were positively correlated with sulfate concentrations and acetochlor degradation ability. Three acetochlor-degrading anaerobes were isolated from the acclimated consortium ACT6, namely Cupidesulfovibrio sp. SRB-5, Proteiniclasticum sp. BAD-10, and Lacrimispora sp. BAD-7. This study provides new insights into the anaerobic catabolism of acetochlor and the anaerobic treatment of acetochlor in wastewater.

RESUMEN

3,6-Dichlorosalicylic acid (3,6-DCSA) is the demethylation metabolite of herbicide 3,6-dichloro-2-methoxy benzoic acid (dicamba). Previous studies have shown that anaerobic sludge further transformed 3,6-DCSA through decarboxylation and dechlorination. However, the anaerobe, enzyme, and gene involved in the anaerobic degradation of 3,6-DCSA are still unknown. In this study, an anaerobic sludge that efficiently degraded dicamba was enriched, and a 3,6-DCSA decarboxylase, designated chlorosalicylic acid decarboxylase (CsaD), was partially purified and identified from the anaerobic sludge. Metagenomic analysis showed that the csaD gene was located in a gene cluster of metagenome-assembled genome 8 (MAG8). MAG8 belonged to an uncultured order, OPB41, in the class Coriobacteriia of the phylum Actinobacteria, and its abundance increased approximately once during the enrichment process. CsaD was a non-oxidative decarboxylase in the amidohydrolase 2 family catalyzing the decarboxylation of 3,6-DCSA and 6-chlorosalicylic acid (6-CSA). Its affinity and catalytic efficiency for 3,6-DCSA were significantly higher than those for 6-CSA. This study provides new insights into the anaerobic catabolism of herbicide dicamba.IMPORTANCEDicamba, an important hormone herbicide, easily migrates to anoxic habitats such as sediment, ground water, and deep soil. Thus, the anaerobic catabolism of dicamba is of importance. Anaerobic bacteria or sludge demethylated dicamba to 3,6-DCSA, and in a previous study, based on metabolite identification, it was proposed that 3,6-DCSA be further degraded via two pathways: decarboxylation to 2,5-dichlorophenol, then dechlorination to 3-chlorophenol (3-CP); or dechlorination to 6-CSA, then decarboxylation to 3-CP. However, there was no physiological and genetic validation for the pathway. In this study, CsaD catalyzed the decarboxylation of both 3,6-DCSA and 6-CSA, providing enzyme-level evidence for the anaerobic catabolism of 3,6-DCSA through the two pathways. CsaD was located in MAG8, which belonged to an uncultured anaerobic actinomycetes order, OPB41, indicating that anaerobic actinomycetes in OPB41 was involved in the decarboxylation of 3,6-DCSA. This study provides a basis for understanding the anaerobic catabolism of dicamba and the demethylation product, 3,6-DCSA.

RESUMEN

Mechanical metamaterials with integrated functionalities can simultaneously fulfill multiple design requirements through design consolidation, which is highly desirable for weight-sensitive and space-constrained applications. Despite the extensive research on multistable metamaterials, their integration with other functionalities, such as vibration isolation, sensing, and hierarchical energy absorption, remains largely untapped. Here, we report a novel class of mechanical metamaterial featuring programmable multistability and function-oriented multitransition behaviors. This integration is realized through a novel assembly-based design concept that incorporates interchangeable contact block (CB) units into a classical bistable structure. By varying the position, number, and shape of CB units, we can obtain a spectrum of function-oriented transition behaviors, offering reconfigurability through unit replacement. To ensure the rational design of CB, we employ a comprehensive approach that combines theoretical analysis, numerical simulations, and experimental validation to investigate the nonlinear behaviors of these assembled metamaterials, including snap-through instability and contact behaviors. Additionally, we explore design strategies such as 2D arraying and 3D extension to achieve programmable multistability. Furthermore, we demonstrate the versatility of these assembled mechanical metamaterials by constructing digital materials with scalability, reconfigurability, and multidirectionality. The proposed assembly-based design concept breaks new ground in engineering multistable structures with integrated functionalities for deployable structures, robotics, and beyond.

RESUMEN

A combined model was developed using contrast-enhanced CT-based radiomics features and clinical characteristics to predict liver fibrosis stages in patients with chronic liver disease (CLD). We retrospectively analyzed multiphase CT scans and biopsy-confirmed liver fibrosis. 160 CLD patients were randomly divided into 7:3 training/validation ratio. Clinical laboratory indicators associated with liver fibrosis were identified using Spearman's correlation and multivariate logistic regression correlation. Radiomic features were extracted after segmenting the entire liver from multiphase CT images. Feature dimensionality reduction was performed using RF-RFE, LASSO, and mRMR methods. Six radiomics-based models were developed in the training cohort of 112 patients. Internal validation was conducted on 48 randomly assigned patients. Receptor Operating Characteristic (ROC) curves and confusion matrices were constructed to evaluate model performance. The radiomics model exhibited robust performance, with AUC values of 0.810 to 1.000 for significant fibrosis, advanced fibrosis, and cirrhosis. The integrated clinical-radiomics model had superior diagnostic efficacy in the validation cohort, with AUC values of 0.836 to 0.997. Moreover, these models outperformed established biomarkers such as the aspartate aminotransferase to platelet ratio index (APRI) and the fibrosis 4 score (FIB-4), as well as the gamma glutamyl transpeptidase to platelet ratio (GPR), in predicting the fibrotic stages. The clinical-radiomics model holds considerable promise as a non-invasive diagnostic tool for the assessment and staging of liver fibrosis in the patients with CLD, potentially leading to better patient management and outcomes.

Asunto(s)

RESUMEN

In cross-country skiing, ski poles play a crucial role in technique, propulsion, and overall performance. The kinematic parameters of ski poles can provide valuable information about the skier's technique, which is of great significance for coaches and athletes seeking to improve their skiing performance. In this work, a new smart ski pole is proposed, which combines the uniaxial load cell and the inertial measurement unit (IMU), aiming to provide comprehensive data measurement functions more easily and to play an auxiliary role in training. The ski pole can collect data directly related to skiing technical actions, such as the skier's pole force, pole angle, inertia data, etc., and the system's design, based on wireless transmission, makes the system more convenient to provide comprehensive data acquisition functions, in order to achieve a more simple and efficient use experience. In this experiment, the characteristic data obtained from the ski poles during the Double Poling of three skiers were extracted and the sample t-test was conducted. The results showed that the three skiers had significant differences in pole force, pole angle, and pole time. Spearman correlation analysis was used to analyze the sports data of the people with good performance, and the results showed that the pole force and speed (r = 0.71) and pole support angle (r = 0.76) were significantly correlated. In addition, this study adopted the commonly used inertial sensor data for action recognition, combined with the load cell data as the input of the ski technical action recognition algorithm, and the recognition accuracy of five kinds of cross-country skiing technical actions (Diagonal Stride (DS), Double Poling (DP), Kick Double Poling (KDP), Two-stroke Glide (G2) and Five-stroke Glide (G5)) reached 99.5%, and the accuracy was significantly improved compared with similar recognition systems. Therefore, the equipment is expected to be a valuable training tool for coaches and athletes, helping them to better understand and improve their ski maneuver technique.

Asunto(s)

RESUMEN

OBJECTIVE: To explore whether Resveratrol (RSV) can inhibit the spontaneous senescence of human bone marrow-derived mesenchymal stem cells (MSC). METHODS: MSC were serially cultured to passage 13 and passage 15 to establish model groups exhibiting spontaneous senescence, respectively. MSC at passage 13 and passage 15 were treated with 5 nmol/L RSV for 48 h to establish the RSV-treated groups. SA-ß-Gal staining was used to detect cell senescence. MTT assay was used to detect cell proliferation. RT-PCR method was used to detect senescenceassociated telomerase activity. Western blot was used to detect the senescence-associated protein level of the phosphorylated-mTOR. RESULTS: SA-ß-Gal staining showed that the senescent cells of MSC in RSV-treated group was significantly less than those in the model group (RSV group compared with model group at passage 13, P < 0.05; RSV group compared with model group at passage 15, P < 0.01). The cell proliferation ability of MSC in RSV-treated group was significantly higher than those in model group, at 72 h in passage 13, there was significant difference between RSV-treated group and model group (P < 0.05). RT-PCR results showed that the hTERT mRNA expression of MSC in RSV-treated group was higher than that in model group, which was significantly different between RSV-treated group and model group at passage 13 (P < 0.05). Western blot results showed that the phosphorylated (Ser2448)-mTOR level of MSC in RSV-treated group was lower than that in model group, which was significantly different between RSV-treated group and model group at passage 13 (P < 0.05). CONCLUSION: RSV can inhibit the spontaneous senescence of human MSC by mediating mTOR activity.

Asunto(s)

RESUMEN

Background: The associations between blood heavy metal levels and latent tuberculosis infection (LTBI) have not been fully elucidated. The aim of this study was to investigate the potential association between blood heavy metal levels and LTBI in adults using National Health and Nutrition Examination Survey data from 2011 to 2012. Methods: We enrolled 1710 participants in this study, and compared the baseline characteristics of participants involved. Multivariate logistic regression analysis, restricted cubic splines (RCS) analysis, along with subgroup analysis and interaction tests were utilized to explore the association between blood manganese (Mn) level and LTBI risk. Results: Participants with LTBI had higher blood Mn level compared to non-LTBI individuals (p < 0.05), while the levels of lead, cadmium, total mercury, selenium, copper, and zinc did not differ significantly between the two groups (p > 0.05). In the fully adjusted model, a slight increase in LTBI risk was observed with each 1-unit increase in blood Mn level (OR = 1.00, 95% CI: 1.00-1.01, p = 0.02). Participants in the highest quartile of blood Mn level had a threefold increase in LTBI risk compared to those in the lowest quartile (OR = 4.01, 95% CI: 1.22-11.33, p = 0.02). RCS analysis did not show a non-linear relationship between blood Mn level and LTBI (non-linear p-value = 0.0826). Subgroup analyses and interaction tests indicated that age, alcohol consumption, and income-to-poverty ratio significantly influenced LTBI risk (interaction p-values<0.05). Conclusion: Individuals with LTBI had higher blood Mn level compared to non-LTBI individuals, and higher blood Mn level associated with increased LTBI risk.

Asunto(s)

RESUMEN

The von Hippel-Lindau tumor suppressor protein (VHL), an E3 ubiquitin ligase, functions as a critical regulator of the oxygen-sensing pathway for targeting hypoxia-inducible factors. Recent evidence suggests that mammalian VHL may also be critical to the NF-κB signaling pathway, although the specific molecular mechanisms remain unclear. Herein, the roles of mandarin fish ( Siniperca chuatsi) VHL ( scVHL) in the NF-κB signaling pathway and mandarin fish ranavirus (MRV) replication were explored. The transcription of scVHL was induced by immune stimulation and MRV infection, indicating a potential role in innate immunity. Dual-luciferase reporter gene assays and reverse transcription quantitative PCR (RT-qPCR) results demonstrated that scVHL evoked and positively regulated the NF-κB signaling pathway. Treatment with NF-κB signaling pathway inhibitors indicated that the role of scVHL may be mediated through scIKKα, scIKKß, scIκBα, or scp65. Co-immunoprecipitation (Co-IP) analysis identified scIκBα as a novel target protein of scVHL. Moreover, scVHL targeted scIκBα to catalyze the formation of K63-linked polyubiquitin chains to activate the NF-κB signaling pathway. Following MRV infection, NF-κB signaling remained activated, which, in turn, promoted MRV replication. These findings suggest that scVHL not only positively regulates NF-κB but also significantly enhances MRV replication. This study reveals a novel function of scVHL in NF-κB signaling and viral infection in fish.

Asunto(s)