Circadian clock genes REV-ERBα regulates the secretion of IL-1ß in deciduous tooth pulp stem cells by regulating autophagy in the process of physiological root resorption of deciduous teeth.

Physiological root resorption is a common occurrence during the development of deciduous teeth in children. Previous research has shown that the regulation of the inflammatory microenvironment through autophagy in DDPSCs is a significant factor in this process. However, it remains unclear why there are variations in the autophagic status of DDPSCs at different stages of physiological root resorption. To address this gap in knowledge, this study examines the relationship between the circadian clock of DDPSCs, the autophagic status, and the periodicity of masticatory behavior. Samples were collected from deciduous teeth at various stages of physiological root resorption, and DDPSCs were isolated and cultured for analysis. The results indicate that the circadian rhythm of important autophagy genes, such as Beclin-1 and LC3, and the clock gene REV-ERBα in DDPSCs, disappears under mechanical stress. Additionally, the study found that REV-ERBα can regulate Beclin-1 and LC3. Evidence suggests that mechanical stress is a trigger for the regulation of autophagy via REV-ERBα. Overall, this study highlights the importance of mechanical stress in regulating autophagy of DDPSCs via REV-ERBα, which affects the formation of the inflammatory microenvironment and plays a critical role in physiological root resorption in deciduous teeth.

Single-cell RNA sequencing reveals vascularization-associated cell subpopulations in dental pulp: PDGFRß+ DPSCs with activated PI3K/AKT pathway.

BACKGROUND: This study aims to address challenges in dental pulp regeneration therapy. The heterogeneity of DPSCs poses challenges, especially in stem cell transplantation for clinical use, particularly when sourced from donors of different ages and conditions. METHODS: Pseudotime analysis was employed to analyze single-cell sequencing data, and immunohistochemical studies were conducted to investigate the expression of fibronectin 1 (FN1). We performed in vitro sorting of PDGFRß+ DPSCs using flow cytometry. A series of functional assays, including cell proliferation, scratch, and tube formation assays, were performed to experimentally validate the vasculogenic capabilities of the identified PDGFRß+ DPSC subset. Furthermore, gene-edited mouse models were utilized to demonstrate the importance of PDGFRß+ DPSCs. Transcriptomic sequencing was conducted to compare the differences between PDGFRß+ DPSCs and P1-DPSCs. RESULTS: Single-cell sequencing analysis unveiled a distinct subset, PDGFRß+ DPSCs, characterized by significantly elevated FN1 expression during dental pulp development. Subsequent cell experiments demonstrated that this subset possesses remarkable abilities to promote HUVEC proliferation, migration, and tube formation. Gene-edited mouse models confirmed the vital role of PDGFRß+ DPSCs in dental pulp development. Transcriptomic sequencing and in vitro experiments demonstrated that the PDGFR/PI3K/AKT signaling pathway is a crucial factor mediating the proliferation rate and pro-angiogenic properties of PDGFRß+ DPSCs. CONCLUSION: We defined a new subset, PDGFRß+ DPSCs, characterized by strong proliferative activity and pro-angiogenic capabilities, demonstrating significant clinical translational potential.

Age and light damage influence Fzd5 regulation of ocular growth-related genes.

Genetic and environmental factors can independently or coordinatively drive ocular axis growth. Mutations in FRIZZLED5 (FZD5) have been associated with microphthalmia, coloboma, and, more recently, high myopia. The molecular mechanism of how Fzd5 participates in ocular growth remains unknown. In this study, we compiled a list of human genes associated with ocular growth abnormalities based on public databases and a literature search. We identified a set of ocular growth-related genes from the list that was altered in the Fzd5 mutant mice by RNAseq analysis at different time points. The Fzd5 regulation of this set of genes appeared to be impacted by age and light damage. Further bioinformatical analysis indicated that these genes are extracellular matrix (ECM)-related; and meanwhile an altered Wnt signaling was detected. Altogether, the data suggest that Fzd5 may regulate ocular growth through regulating ECM remodeling, hinting at a genetic-environmental interaction in gene regulation of ocular axis control.

Triclosan exposure causes abnormal bile acid metabolism through IL-1ß-NF-κB-Fxr signaling pathway.

Triclosan (TCS) is an eminent antibacterial agent. However, extensive usage causes potential health risks like hepatotoxicity, intestinal damage, kidney injury, etc. Existing studies suggested that TCS would disrupt bile acid (BA) enterohepatic circulation, but its toxic mechanism remains unclear. Hence, the current study established an 8-week TCS exposure model to explore its potential toxic mechanism. The results discovered 8 weeks consecutive administration of TCS induced distinct programmed cell death, inflammatory cell activation and recruitment, and excessive BA accumulation in liver. Furthermore, the expression of BA synthesis and transport associated genes were significantly dysregulated upon TCS treatment. Additional mechanism exploration revealed that Fxr inhibition induced by TCS would be the leading cause for unusual BA biosynthesis and transport. Subsequent Fxr up-stream investigation uncovered TCS exposure caused pyroptosis and its associated IL-1ß would be the reason for Fxr reduction mediated by NF-κB. NF-κB blocking by dimethylaminoparthenolide ameliorated TCS induced BA disorder which confirmed the contribution of NF-κB in Fxr repression. To sum up, our findings conclud TCS-caused BA disorder is attributed to Fxr inhibition, which is regulated by the IL-1ß-NF-κB signaling pathway. Hence, we suggest Fxr would be a potential target for abnormal BA stimulated by TCS and its analogs.

Root Abscisic Acid Contributes to Defending Photoinibition in Jerusalem Artichoke (Helianthus tuberosus L.) under Salt Stress.

The aim of the study was to examine the role of root abscisic acid (ABA) in protecting photosystems and photosynthesis in Jerusalem artichoke against salt stress. Potted plants were pretreated by a specific ABA synthesis inhibitor sodium tungstate and then subjected to salt stress (150 mM NaCl). Tungstate did not directly affect root ABA content and photosynthetic parameters, whereas it inhibited root ABA accumulation and induced a greater decrease in photosynthetic rate under salt stress. The maximal photochemical efficiency of PSII (Fv/Fm) significantly declined in tungstate-pretreated plants under salt stress, suggesting photosystem II (PSII) photoinhibition appeared. PSII photoinhibition did not prevent PSI photoinhibition by restricting electron donation, as the maximal photochemical efficiency of PSI (ΔMR/MR0) was lowered. In line with photoinhibition, elevated H2O2 concentration and lipid peroxidation corroborated salt-induced oxidative stress in tungstate-pretreated plants. Less decrease in ΔMR/MR0 and Fv/Fm indicated that PSII and PSI in non-pretreated plants could maintain better performance than tungstate-pretreated plants under salt stress. Consistently, greater reduction in PSII and PSI reaction center protein abundance confirmed the elevated vulnerability of photosystems to salt stress in tungstate-pretreated plants. Overall, the root ABA signal participated in defending the photosystem's photoinhibition and protecting photosynthesis in Jerusalem artichoke under salt stress.

Influence of fermentation conditions on polysaccharide production and the activities of enzymes involved in the polysaccharide synthesis of Cordyceps militaris.

The influence of different fermentation conditions on intracellular polysaccharide (IPS) production and activities of the phosphoglucomutase (PGM), UDPG-pyrophosphorylase (UGP), phosphoglucose isomerase (PGI), UDPG-dehydrogenase (UGD), and glucokinase (GK) implicated in metabolite synthesis in Cordyceps militaris was evaluated. The highest IPS production (327.57 ± 6.27 mg/100 mL) was obtained when the strain was grown in the optimal medium containing glucose (40 g · L(-1)), beef extract (10 g · L(-1)), and CaCO3 (0.5 g · L(-1)), and the initial pH and temperature were 7 and 25 °C, respectively. The activities of PGM, UGP, and PGI were proved to be influenced by the fermentation conditions. A strong correlation between the activities of these enzymes and the production of IPS was found. The transcription level of the pgm gene (encoding PGM) was 1.049 times and 1.467 times compared to the ugp gene and pgi gene (encoding UGP and PGI), respectively, in the optimal culture medium. This result indicated that PGM might be the highly key enzyme to regulate the biosynthesis of IPS of C. militaris in a liquid-submerged culture. Our study might be helpful for further research on the pathway of polysaccharide biosynthesis aimed to improve the IPS production of C. militaris.

Effect of Ball-Milling Treatment Combined with Glycosylation on the Structure and Functional Properties of Litopenaeus vannamei Protein.

Litopenaeus vannamei protein (LVP) is a high-quality protein. However, its functional properties do not fully meet the needs of food processing. In this study, LVP-xylose conjugates were prepared by conventional wet heat method (GLVP) and ball-milling-assisted wet heat method (GBLVP), respectively. The changes in structure and functional properties of the glycosylated LVP were explored. The findings revealed that ball-milling pretreatment increased the grafting degree to 35.21%. GBLVP had a sparser surface structure and lower particle size than GLVP. FTIR spectra showed that xylose was grafted onto LVP successfully and GBLVP had the lowest α-helix content. Compared with GLVP, GBLVP had a decrease in intrinsic fluorescence intensity and surface hydrophobicity, and an increase in UV absorption intensity. Moreover, GBLVP had higher foaming capacity, solubility and water-holding capacity, and lower allergenicity than GLVP. However, ball-milling pretreatment had a negative impact on the vitro digestibility and oil-holding capacity of GBLVP. In conclusion, ball-milling-assisted treatment of glycosylation could effectively improve the functional properties of LVP, benefiting the broader application of LVP in the food industry.

Nasal instillation of polystyrene nanoplastics induce lung injury via mitochondrial DNA release and activation of the cyclic GMP-AMP synthase-stimulator of interferon genes-signaling cascade.

Nanoplastics (NPs) are a common type of degraded plastic material associated with adverse health effects such as pulmonary injury. However, the molecular mechanism(s) underlying lung injury as caused by NPs remains uncertain. Thus, we herein investigated the pulmonary toxicity of NPs on RAW264.7 cells and C57BL/6 mice. Our in vitro study indicated that NPs induced oxidative stress, cell death, inflammation, and the activation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING)-signaling pathway. Mice in our in vivo study displayed significant pulmonary fibrosis, inflammation, apoptosis, necrosis, and excessive double-stranded DNA release into serum and bronchoalveolar lavage fluid. Our mechanistic exploration uncovered cGAS-STING-signaling activation as the leading cause of NPs-induced pulmonary fibrosis. The current study opens an avenue toward elucidating the role of the cGAS-STING-signaling pathway in NPs-induced pulmonary injury.

The structural characterization of a novel Chinese yam polysaccharide and its hypolipidemic activity in HFD-induced obese C57BL/6J mice.

Obesity was considered as a rapidly growing chronic disease that influences human health worldwide. In this study, we investigated the primary structure characteristics of Chinese yam polysaccharide (CYP) and its role in regulating lipid metabolism in a high-fat diet (HFD)-fed obese mice. The molecular weight of CYP was determined to be 3.16 × 103 kDa. Periodic acid oxidation & smith degradation and nuclear magnetic resonance results suggested that CYP consists of 1 → 2, 1 â†’ 2, 6, 1 â†’ 4, 1 â†’ 4, 6, 1→, or 1 â†’ 6 glycoside bonds. The in vivo experiment results suggested that the biochemical indices, tissue sections, and protein regulation associated with lipid metabolism were changed after administering CYP in obese mice. In addition, the abundances of short-chain fatty acid (SCFA)-producing bacteria Lachnospiraceae, Lachnospiraceae_NK4A136_group, and Ruminococcaceae_UCG-014 were increased, and the abundances of bacteria Desulfovibrionaceae and Ruminococcus and metabolites of arginine, propionylcarnitine, and alloisoleucine were decreased after CYP intervention in obese mice. Spearman's correlation analysis of intestinal flora, metabolites, and lipid metabolism parameters showed that CYP may affect lipid metabolism in obese mice by regulating the intestinal environment. Therefore, CYP may be used as a promising nutritional intervention agent for lipid metabolism.

A comprehensive literature mining and analysis of nitrous oxide emissions from different innovative mainstream anammox-based biological nitrogen removal processes.

The biological nitrogen removal (BNR) process in wastewater treatment plants generates a substantial volume of nitrous oxide (N2O), which possesses a potent greenhouse gas effect. A limited number of studies have systematically investigated the N2O emissions of anammox-based systems with different BNR processes under mainstream conditions. Based on extensive big data statistical analysis, it had been revealed that simultaneous nitritation, anammox and denitrification (SNAD), partial nitritation anammox (PNA) and partial denitrification anammox (PDA), exhibit significantly lower N2O emission factors when compared to traditional BNR processes. The median values for N2O emission factors were determined to be 1.01 %, 1.15 % and 1.43 % for SNAD, PNA and PDA, respectively. Based on nitrogen removal data and N2O emission factors, the N2O emissions from PNA, SNAD and PDA processes were calculated to be 0.016 g·d-1, 0.037 g·d-1 and 0.008 g·d-1, respectively. Furthermore, the machine learning models (SVM and ANN) exhibited excellent predictive performance for N2O emissions in the BNR processes. However, after removing environmental factors, the R2 value of the SVM model sharply decreased. The SHAP feature analysis demonstrated the significant impact of environmental factors on the accuracy of predictive performance in machine learning models. Spearman correlation analysis was employed to investigate the relationship between N2O emissions and operational factors as well as microbial communities. The results demonstrated a negative correlation between HRT, temperature and C/N with N2O emissions. Moreover, strong associations were observed between Nitrosomonas, Nitrospira, Denitratisoma, Thauera species and N2O emissions. The contribution of N2O production via AOB pathways played a key role that was quantitatively calculated to be 93 %, 80 % and 48 % in the PNA, SNAD and PDA processes, respectively. These findings highlight the potential of these innovative BNR processes in mitigating N2O emissions.

Inhibitory effects of Stevioside on Streptococcus mutans and Candida albicans dual-species biofilm.

Introduction: Streptococcus mutans is the most prevalent biofilm-forming pathogen in dental caries, while Candida albicans is often detected in the presence of S. mutans. Methods: We aimed to evaluate the anti-caries effect of stevioside in medium trypticase soy broth (TSB) with or without sucrose supplementation compared with the same sweetness sucrose and xylitol in a dual-species model of S. mutans and C. albicans, based on planktonic growth, crystal violet assay, acid production, biofilm structural imaging, confocal laser scanning microscopy, and RNA sequencing. Results: Our results showed that compared with sucrose, stevioside significantly inhibited planktonic growth and acid production, changed the structure of the mixed biofilm, and reduced the viability of biofilm and the production of extracellular polysaccharides in dual-species biofilm. Through RNA-seq, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway impact analysis showed that stevioside decreased sucrose metabolism and increased galactose and intracellular polysaccharide metabolism in S. mutans, and decreased genes related to GPI-modified proteins and secreted aspartyl proteinase (SAP) family in C. albicans. In contrast to xylitol, stevioside also inhibited the transformation of fungal morphology of C. albicans, which did not form mycelia and thus had reduced pathogenicity. Stevioside revealed a superior suppression of dual-species biofilm formation compared to sucrose and a similar anti-caries effect with xylitol. However, sucrose supplementation diminished the suppression of stevioside on S. mutans and C. albicans. Conclusions: Our study is the first to confirm that stevioside has anticariogenic effects on S. mutans and C. albicans in a dual-species biofilm. As a substitute for sucrose, it may help reduce the risk of developing dental caries.

Enhancing the compost maturation of deer manure and corn straw by supplementation via black liquor.

In this paper, the relationship between black liquor and microbial growth, enzymatic secretion and humus formation in composting was studied. The results showed that black liquor inoculation is an effective way to promote fermentation process. After black liquor inoculation, the abundance of Corynebacterium, Aequorivita, and Pedobacter, which have the catalase and oxidase activity, has been significantly increased. The enzymatic activity of alkaline phosphatase, catalase, peroxidase and invertase was 40 mg/(g·24h), 6.5 mg/(g·20 min), 13 100 mg/(g·24h), and 6100 mg/(g·24h) respectively at day 18. Humic acid and fulvic acid concentration was 12 g/kg and 11 g/kg which is higher than that of the treatments of no black liquor inoculation. The results suggested that black liquor inoculation was beneficial to indigenous microorganisms reproduce efficiently, then the secretion of enzymes related to cellulose, hemicellulose, and lipid hydrolysis, and the formation of humic substances.

Extraction and immunomodulatory activity of the polysaccharide obtained from Craterellus cornucopioides.

In this study, we investigated the structural features of the polysaccharide obtained from Craterellus cornucopioides (CCP2) by high-performance liquid chromatography, Fourier transform infrared spectroscopy and ion chromatography. The results showed that CCP2 was a catenarian pyranose that principally comprised of mannose, galactose, glucose, and xylose in the ratio of 1.86: 1.57: 1.00: 1.14, with a molecular weight of 8.28 × 104 Da. Moreover, the immunoregulation effect of CCP2 was evaluated both in vitro and in vivo. It displayed a remarkable immunological activity and activation in RAW264.7 cells by enhancing the phagocytosis of macrophages in a dose-dependent manner without showing cytotoxicity at the concentrations of 10-200 µg/mL in vitro. Additionally, Histopathological analysis indicated the protective function of CCP2 against immunosuppression induced by cyclophosphamide (Cy). Meanwhile, the intake of CCP2 had better immunoregulatory activity for immunosuppression BALB/c mice model. After prevention by CCP2, the spleen and thymus weight indexes of BALB/c mice model were significantly increased. The RT-qPCR and Western Blot results provided comprehensive evidence that the CCP2 could activate macrophages by enhancing the production of cytokines (IL-2, IL-6, and IL-8) and upregulating the protein expression of cell membrane receptor TLR4 and its downstream protein kinase (TRAF6, TRIF, and NF-κB p65) production of immunosuppressive mice through TLR4-NFκB p65 pathway. The results demonstrated that CCP2 could be a potential prebiotic and might provide meaningful information for further research on the immune mechanism.

Alloying nickel and cobalt with iron on ZSM-5 for tuning competitive hydrogenation reactions for selective one-pot conversion of furfural to gamma-valerolactone.

One-pot conversion of furfural, a biomass-derived platform chemical, to gamma-valerolactone (GVL), a fuel additive and green solvent, involves multiple steps of hydrogenation. Among these reactions, the deep hydrogenation of the furan ring in furfural interrupts GVL formation over Ni or Co-based catalysts. In this study, a method of alloying Ni and Co with Fe over a ZSM-5 support was proposed for tackling excessive activity of the catalyst for hydrogenation. The results indicated that the formation of binary NiFe and CoFe alloys in Ni-Co-Fe/ZSM-5 enhanced the dispersion of metallic species, reduction of metal oxides, formation of more Lewis acidic sites, and the adsorption of the C-O functionality of the furan ring, while lowering the capability for adsorption/activation of H2 and the adsorption of the CC group of the furan ring. These factors together reduced the activity for the hydrogenation of the furan ring in furfural, but enhanced the hydrogenation of the CO in ethyl levulinate (EL). The kinetic study confirmed that the hydrogenation of EL was the rate-determining step. The coordination of the dual alloys, NiFe and CoFe, in the bifunctional Ni-Co-Fe/ZSM-5 catalyst rendered superior activity for selective one-pot conversion of furfural to GVL with a yield of 85.7%.

Regulatory effect of non-starch polysaccharides from purple sweet potato on intestinal microbiota of mice with antibiotic-associated diarrhea.

Antibiotic treatment causes antibiotic-associated diarrhea (AAD), which is usually accompanied by disorders of the intestinal flora, aggravating the patient's condition. Recently, more attention has been devoted to the ability of plant polysaccharides to improve the body's flora and enhance immunity. However, reports on whether purple sweet potato polysaccharides (PSPPs) can improve AAD are scarce. This study aimed to extract a non-starch polysaccharide from purple sweet potato and analyze its structure and ability to regulate the intestinal flora of mice with AAD. The diarrhea model was established via intragastric administration of lincomycin and different concentrations of PSPPs (0.1 g kg-1, 0.2 g kg-1, and 0.4 g kg-1) to Balb/C mice. The results showed that PSPP was a pyran polysaccharide with 1 → 2, 1 → 2, 6, 1 → 4, 1 → 4, 6 glycosidic bonds in an α-configuration. In vivo experiments showed that PSPP could relieve diarrhea and improve the structural damage in the ileum caused by lincomycin hydrochloride. In addition, treatment with PSPPs decreased the levels of IL-1ß, IL-6 and TNF-α but increased the level of IL-10 in the intestines of mice (p < 0.01). The results of 16S rRNA sequencing showed that PSPPs changed the composition and diversity of the intestinal flora of mice with AAD. In addition, PSPP treatment increased the content of short-chain fatty acids (p < 0.01). These results revealed that PSPPs regulated the intestinal flora, balanced fatty acid metabolism, and relieved the symptoms of diarrhea to a certain extent in mice.

Research on the structural characteristics of a novel Chinese Iron Yam polysaccharide and its gastroprotection mechanism against ethanol-induced gastric mucosal lesion in a BALB/c mouse model.

In this study, a triple-helix Chinese Iron Yam polysaccharide (CIYP) with a molecular weight of 1.67 × 103 kDa was obtained. The CIYP was extracted with deionized water followed by deproteination, decoloration and purification using anion-exchange chromatography and size exclusion chromatography. Its structural characteristics and micromorphology were investigated by GC-MS, periodate oxidation and Smith degradation, FT-IR, NMR spectroscopy, SEM and AFM. The results showed that CIYP is a catenarian polysaccharide composed of rhamnose, arabinose, mannose, glucose, galactose and galacturonic acid in the ratio of 1 : 1.33 : 8.31 : 2.83 : 1.12 : 2.62. Meanwhile, the gastric mucosa protective effect of CIYP on an ethanol-injured BALB/c mouse model was investigated. It was found that the preventive CIYP-treatment groups (200 and 400 mg kg-1 d-1) showed gastric mucosa protective effects on the BALB/c mouse model. The lesion index and lesion inhibition rate of the CIYP and cimetidine treatment groups were significantly altered compared with the ethanol-induced gastric mucosal lesion (GML) group. Moreover, the administration of CIYP showed definite effects of increasing the NO, PGE2 and EGF levels, and SOD activities, and reducing the MDA levels of gastric mucosa tissues to prevent gastric oxidative stress. Histopathological analysis indicated that the microscopic morphology of gastric mucosal tissues was changed after being damaged by ethanol and the damage was significantly reduced after CIYP administration. Finally, the western blot and quantitative real-time polymerase chain reaction (qRT-PCR) results provided comprehensive evidence that the CIYP could repress gastric inflammation through the reduction of IL-1ß, TNF-α and IL-6, prevent gastric oxidative stress through the inhibition of lipid peroxides, and favor cell survival via downregulating the TAK1, MKK3, P-p38 and Bax levels and upregulating the protein expression levels, compared with the CIM group.

Application of Machine Learning in Developing a Novelty Five-Pseudogene Signature to Predict Prognosis of Head and Neck Squamous Cell Carcinoma: A New Aspect of "Junk Genes" in Biomedical Practice.

Head and neck squamous cell carcinoma (HNSCC) is the sixth malignancy, which is characterized by poor prognosis or high mortality because of the lack of predicting markers. Aberrant cancer pseudogenes have been found predictive for prognosis. We aim to identify a pseudogene-based prognosis signature for HNSCC by machine learning. RNA-seq data were downloaded from The Cancer Genome Atlas, and 700 differentially-expressed pseudogenes were identified. The survival-related pseudogenes were screened through COX-regression analysis, which includes univariate regression, least absolute shrinkage and selection operator regression, and multivariate regression, and a five-pseudogene signature was constructed. The value of prediction for the signature was validated in multiple subgroups in terms of survival. Gene set enrichment analysis (GSEA) and coexpression analysis were used to determine the underlying biological functions. Seven hundred dysregulated pseudogenes were identified, and the five-pseudogene signature can distinguish the low-risk and high-risk patients for both training and testing sets and predicted prognosis with high sensitivity and specificity. Furthermore, the signature was applicable to patients of different genders, ages, stages, and grades. Coexpression analysis revealed that the five-pseudogene is associated with immune system. GSEA showed cancer-related biological process and pathways the five-pseudogene involved in. The five-pseudogene signature is not only a novel marker for prognosis but also a promising signature for monitoring therapeutic schedule. Therefore, our findings may have potential clinical significance.

A transcriptional metabolic gene-set based prognostic signature is associated with clinical and mutational features in head and neck squamous cell carcinoma.

PURPOSE: Head and neck squamous cell carcinoma (HNSCC) is a common cancer with high mortality and poor prognosis partially owing to lack of application of predictive markers. Increasing evidence has suggested that metabolic dysregulation plays an important part in tumorigenesis. We aim to identify a prognostic metabolic pathway (MP) signature in HNSCC. METHODS: Single sample gene-set enrichment analysis (ssGSEA) was used in metabolic gene sets to develop a metabolism-based prognostic risk score (MPRS) for HNSCC using Cox regression analysis (univariate, LASSO, and stepwise multiple cox analysis), which was then validated in different subgroups, and association with clinical and mutational features was analyzed. RESULTS: Seventy-two dysregulated metabolic pathways were identified, and a six-MP signature (6MPS) was constructed which can effectively distinguish between the high- and low-risk patients in both training and testing sets, accompanied with high sensitivity and specificity (AUC = 0.7) in prognosis prediction. 6MPS was also applicable to patients of different subgroups. Furthermore, 6MPS is not only an independent prognostic predictor but also associated with clinicopathological and mutational features. Higher tumor stage and tumor mutation burden (TMB) have a higher MPRS. CONCLUSION: 6MPS functions not only as a promising predictor of prognosis and survival but also as potential marker for therapeutic schedule monitoring.

Immunomodulatory effects of the polysaccharide from Craterellus cornucopioides via activating the TLR4-NFκB signaling pathway in peritoneal macrophages of BALB/c mice.

The immunoregulatory effect and immunologic response mechanism of Craterellus cornucopioides (L.) Pers. polysaccharide (CCP) with a triple-helix structure on peritoneal macrophages was investigated in vitro for the first time. These studies demonstrated that treatment of peritoneal macrophages with 80 µg/mL CCP for 48 h significantly strengthened their phagocytic function as well as increases the activities of lysozyme (LZM), acid phosphatase (ACP) and succinodehydrogenase (SDH) when compared with the untreated group. Furthermore, Western Blot and quantitative real-time polymerase chain reaction (qRT-PCR) assays demonstrated that 80 µg/mL CCP activated macrophages, significantly increased mRNA expression of cytokines (IL-8, IL-1ß, IFN-α and TNF-α) and upregulated the protein expression of cell membrane receptor TLR4, as well as its downstream protein kinase products (MyD88, TAK1, P-IKKα/ß and P-MEK) through activation of the TLR4-NFκB pathway in peritoneal macrophages. In conclusion, these results showed that the immunomodulatory mechanism of CCP in peritoneal macrophages was associated with the release of NO, related enzymes and cytokines by stimulating the NF-κB p50 pathway via TLR4-MyD88-TAK1 signaling.

Protective effects of polysaccharides from Cordyceps gunnii mycelia against cyclophosphamide-induced immunosuppression to TLR4/TRAF6/NF-κB signalling in BALB/c mice.

Polysaccharides are closely associated with immune regulation. In this study, the aim was to investigate the effect of polysaccharides from Cordyceps gunnii mycelia (PPS) in cyclophosphamide (CTX)-induced immunodeficient mice. Compared with the CTX-induced immunosuppressed mice, the spleen and thymus indexes in mice with orally administered PPS were significantly increased, body weight loss was alleviated, and the natural killer (NK) cytotoxicity and proliferative activities of the lymphocytes were elevated. The recovery of peripheral white blood cells, red blood cells, hemoglobins and platelets was accelerated. Furthermore, the results from ELISA showed that PPS could up-regulate the serum levels of IL-2, IL-12, IFN-γ and IgG, and reduce the level of TGF-ß. Histopathological analysis of the spleen revealed the protective effect of PPS against CTX-induced immunosuppression. Western blotting results showed that PPS possessed immunomodulatory activity via TLR4/TRAF6/NF-κB signalling pathways. Finally, the intestinal absorption of PPS was poor, as detected in the Caco-2 transwell system. Taken together, these findings suggest that PPS plays a crucial role in protection against immunosuppression in cyclophosphamide-treated mice and could be a potential candidate for use in immune therapy regimens.