ZNF554 Inhibits Endometrial Cancer Progression via Regulating RBM5 and Inactivating WNT/ß-Catenin Signaling Pathway.

OBJECTIVE: Uterine corpus endometrial carcinoma (UCEC), a kind of gynecologic malignancy, poses a significant risk to women's health. The precise mechanism underlying the development of UCEC remains elusive. Zinc finger protein 554 (ZNF554), a member of the Krüppel-associated box domain zinc finger protein superfamily, was reported to be dysregulated in various illnesses, including malignant tumors. This study aimed to examine the involvement of ZNF554 in the development of UCEC. METHODS: The expression of ZNF554 in UCEC tissues and cell lines were examined by qRT-PCR and Western blot assay. Cells with stably overexpressed or knocked-down ZNF554 were established through lentivirus infection. CCK-8, wound healing, and Transwell invasion assays were employed to assess cell proliferation, migration, and invasion. Propidium iodide (PI) staining combined with fluorescence-activated cell sorting (FACS) flow cytometer was utilized to detect cell cycle distribution. qRT-PCR and Western blotting were conducted to examine relative mRNA and protein levels. Chromatin immunoprecipitation assay and luciferase reporter assay were used to explore the regulatory role of ZNF554 in RNA binding motif 5 (RBM5). RESULTS: The expression of ZNF554 was found to be reduced in both UCEC samples and cell lines. Decreased expression of ZNF554 was associated with higher tumor stage, decreased overall survival, and reduced disease-free survival in UCEC. ZNF554 overexpression suppressed cell proliferation, migration, and invasion, while also inducing cell cycle arrest. In contrast, a decrease in ZNF554 expression resulted in the opposite effect. Mechanistically, ZNF554 transcriptionally regulated RBM5, leading to the deactivation of the Wingless (WNT)/ß-catenin signaling pathway. Moreover, the findings from rescue studies demonstrated that the inhibition of RBM5 negated the impact of ZNF554 overexpression on ß-catenin and p-glycogen synthase kinase-3ß (p-GSK-3ß). Similarly, the deliberate activation of RBM5 reduced the increase in ß-catenin and p-GSK-3ß caused by the suppression of ZNF554. In vitro experiments showed that ZNF554 overexpression-induced decreases in cell proliferation and migration were counteracted by RBM5 knockdown. Additionally, when RBM5 was overexpressed, it hindered the improvements in cell proliferation and migration caused by reducing the ZNF554 levels. CONCLUSION: ZNF554 functions as a tumor suppressor in UCEC. Furthermore, ZNF554 regulates UCEC progression through the RBM5/WNT/ß-catenin signaling pathway. ZNF554 shows a promise as both a prognostic biomarker and a therapeutic target for UCEC.

Metabolomics-based study of chemical compositions in cellulase additives derived from a tobacco-origin Bacillus subtilis and their impact on tobacco sensory attributes.

To enhance the quality of tobacco leaves and optimize the smoking experience, diverse strains of functional bacteria and their associated metabolites have been used in tobacco aging. Exogenous cellulase additives are frequently employed to facilitate the degradation of cellulose and other macromolecular matrices and enhance the quality of the tobacco product. However, little is known about how microbial metabolites present in exogenous enzyme additives affect tobacco quality. In this study, crude cellulase solutions, produced by a tobacco-originating bacterium Bacillus subtilis FX-1 were employed on flue-cured tobacco. The incorporation of cellulase solutions resulted in the reduction of cellulose crystallinity in tobacco and the enhancement of the overall sensory quality of tobacco. Notably, tobacco treated with cellulase obtained from laboratory flask fermentation demonstrated superior scent and flavor attributes in comparison to tobacco treated with enzymes derived from industrial bioreactor fermentation. The targeted and untargeted metabolomic analysis revealed the presence of diverse flavor-related precursors and components in the cellulase additives, encompassing sugars, alcohols, amino acids, organic acids, and others. The majority of these metabolites exhibited significantly higher levels in the flask group compared to the bioreactor group, probably contributing to a pronounced enhancement in the sensory quality of tobacco. Our findings suggest that the utilization of metabolic products derived from B. subtilis FX-1 as additives in flue-cured tobacco holds promise as a viable approach for enhancing sensory attributes, establishing a solid theoretical foundation for the potential development of innovative tobacco aging additives.

TPR is a prognostic biomarker and potential therapeutic target associated with immune infiltration in hepatocellular carcinoma.

Liver cancer is the fourth leading cause of cancer-related mortality worldwide and hepatocellular carcinoma (HCC) is the most common primary liver cancer. In the present study, it was demonstrated that translocated promoter region (TPR) was upregulated in tumor tissues and associated with prognosis and immune infiltration in HCC. The clinical outcome of patients with HCC with aberrant expression of TPR was examined using multiple databases, including Gene Expression Omnibus, The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression, Kaplan-Meier (KM) Plotter and Xiantao tool. The clinicopathologic characteristics of patients from TCGA database that were associated with overall survival were assessed using Cox regression and KM analysis. The potential hallmarks associated with TPR expression were further predicted by Metascape and Gene Set Enrichment Analysis, and the relationship between TPR and immune infiltration was explored using the Tumor-Immune System Interactions Database and the Tumor Immune Estimation Resource. The results demonstrated that TPR expression was higher in HCC and its overexpression was associated with a worse prognosis, alongside a correlation with several clinical features. Furthermore, cell differentiation, a prospective new hallmark of cancer, was differentially enriched in the high TPR expression phenotype pathway. Moreover, TPR may also modulate the tumor immune microenvironment as it was significantly associated with immunoregulators and chemokines, as well as different tumor infiltration immune cells. According to the in vitro experiments, TPR silencing inhibited the phosphorylation of AKT and the proliferation of HCC cells. In summary, TPR may be a new marker and target for HCC therapy.

Complete genome sequence analysis of Bacillus velezensis A5, a promising biocontrol agent from the Pacific Ocean.

Tobacco bacterial wilt (TBW) caused by Ralstonia solanacearum is a serious soil-borne disease, which seriously damages the growth of tobacco crops. Bacillus velezensis A5 was isolated from 3000 m deep-sea sediments of the Pacific Ocean, and was found to be antagonistic to TBW. Here, we report the complete genome sequence of strain A5, which has a 4,000,699-bp single circular chromosome with 3827 genes and a G + C content of 46.44%, 87 tRNAs, and 27 rRNAs. A total of 12 gene clusters were identified in the genome of strain A5, which were responsible for the biosynthesis of antibacterial compounds, including surfactin, bacillaene, fengycin, difficidin, bacillibactin, and bacilysin. Additionally, strain A5 was found to contain a series of genes related to the biosynthesis of carbohydrate-active enzymes and secreted proteins. Our results indicate that strain A5 can be considered a promising biocontrol agent against TBW in agricultural fields.

Nickel-Catalyzed Three-Component Alkylarylation of Alkenyl N-Heteroarenes.

A nickel-catalyzed three-component alkylarylation of alkenyl N-heteroarenes with α-bromocarboxylates and aryl boronic acids is reported. The protocol provides a new method to access a variety of N-heteroarene substituted diarylalkanes in moderate to good yields. It features mild reaction conditions, cheap nickel catalyst, readily available substrates, and broad substrate scope.

Comparable Clinical Outcomes Between Transarterial Chemoembolization or Hepatic Arterial Infusion Chemotherapy Combined with Tyrosine Kinase Inhibitors and PD-1 Inhibitors in Unresectable Hepatocellular Carcinoma.

Purpose: To compare the treatment efficacy and safety of transarterial chemoembolization (TACE) or hepatic arterial infusion chemotherapy (HAIC) combined with tyrosine kinase inhibitors (TKIs) and programmed cell death protein-1 (PD-1) inhibitors for patients with unresectable hepatocellular carcinoma (HCC). Patients and Methods: 81 unresectable HCC patients were retrospectively analyzed, including 30 or 51 patients treated with either TKIs and PD-1 inhibitors combined with TACE (TTP) or HAIC (HTP), respectively. Tumor response and survival outcomes were compared. Results: The median overall survival (mOS) was 21.0 months in the TTP group and 15.0 months in the HTP group (P = 0.525; HR = 1.23; 95% CI 0.66-2.29). The median progression-free survival (mPFS) was 6.7 months in the TTP group and 9.9 months in the HTP group (P = 0.160; HR = 0.70; 95% CI 0.42-1.16). After Propensity Score Matching (PSM), the mOS was 21.0 months in the TTP group and 18.0 months in the HTP group (P = 0.644; HR = 1.20; 95% CI 0.56-2.58). The mPFS was 6.4 months in the TTP group and 15.0 months in the HTP group (P = 0.028; HR = 0.49; 95% CI 0.26-0.93). The disease control rate in overall response (90.2% vs 76.7%, P = 0.116, before PSM; 91.7% vs 75.0%, P = 0.121, after PSM) and intrahepatic response (94.1% vs 80.0%, P = 0.070, before PSM; 91.7% vs 79.2%, P = 0.220, after PSM) were higher in the HTP group than in the TTP group. Conclusion: Though including more advanced tumors, the clinical outcomes of HAIC combined with TKIs and PD-1 inhibitors are comparable to TACE-based combination therapy for unresectable HCC. Nevertheless, HTP significantly improved the PFS benefits in HCC patients with with large tumor burden or vascular invasion.

Application of starch degrading bacteria from tobacco leaves in improving the flavor of flue-cured tobacco.

Starch is an essential factor affecting the quality of flue-cured tobacco, and high starch content can affect the sensory quality and safety. Recently, the degradation of macromolecules in tobacco raw materials by using additional microorganisms to improve their intrinsic quality and safety has become a new research hotspot in the tobacco industry. However, the technical maturity and application scale are limited. Our study analyzed the correlation between microbial community composition and volatile components on the surface of tobacco leaves from 14 different grades in Fujian tobacco-producing areas. The PICRUSt software was utilized to predict the function of the microbial community present in tobacco leaves. Furthermore, dominant strains that produced amylase were screened out, and an enzyme solution was prepared to enhance the flue-cured tobacco flavor. Changes in the content of macromolecules and volatile components were determined, and sensory evaluations were conducted to assess the overall quality of the tobacco leaves. The results showed that the dominant bacterial genera on the surface of Fujian tobacco leaves were Variovorax, Sphingomonas, Bacillus, etc. Bacillus was positively correlated with various volatile components, which contributed to the sweet and aromatic flavors of Fujian flue-cured tobacco. The main genetic functions of Fujian flue-cured tobacco surface bacteria were carbohydrate metabolism and amino acid metabolism. After treating flue-cured tobacco with an enzyme preparation prepared by the fermentation of Paenibacillus amylolyticus A17 #, the content of starch, pectin, and cellulose in flue-cured tobacco decreased significantly compared with the control group. Meanwhile, the content of total soluble sugar and reducing sugar was significantly increased, and the volatile aroma components, such as 3-hydroxy--damascone, 2,3-dihydro-3,5-dihydroxy-6-methyl-4 H-Pyran-4-one, ethyl palmitate, ethyl linolenic acid, etc., were significantly increased. The aroma quality and quantity of flue-cured tobacco were enhanced, while impurities were reduced. The smoke characteristics were improved, with increased fineness, concentration, and moderate strength. The taste characteristics were also improved, with reduced irritation and a better aftertaste. In conclusion, Bacillus, as the dominant genus in the abundance of bacterial communities on tobacco surfaces in Fujian, had an essential impact on the flavor of tobacco leaves by participating in carbohydrate metabolism and finally forming the unique flavor style of flue-cured tobacco in Fujian tobacco-producing areas. Paenibacillus amylolyticus A17 #, a target strain with amylase-producing ability, was screened from the surface of Fujian flue-cured tobacco. The enzyme preparation, produced by the fermentation of Paenibacillus amylolyticus A17 #, was utilized to reduce the content of macromolecules, increase the content of water-soluble total sugar and reducing sugar, and produce a variety of crucial volatile aroma components, which had a significant improvement on the quality of tobacco leaves.

Natural flavonoids disrupt bacterial iron homeostasis to potentiate colistin efficacy.

In the face of the alarming rise in global antimicrobial resistance, only a handful of novel antibiotics have been developed in recent decades, necessitating innovations in therapeutic strategies to fill the void of antibiotic discovery. Here, we established a screening platform mimicking the host milieu to select antibiotic adjuvants and found three catechol-type flavonoids-7,8-dihydroxyflavone, myricetin, and luteolin-prominently potentiating the efficacy of colistin. Further mechanistic analysis demonstrated that these flavonoids are able to disrupt bacterial iron homeostasis through converting ferric iron to ferrous form. The excessive intracellular ferrous iron modulated the membrane charge of bacteria via interfering the two-component system pmrA/pmrB, thereby promoting the colistin binding and subsequent membrane damage. The potentiation of these flavonoids was further confirmed in an in vivo infection model. Collectively, the current study provided three flavonoids as colistin adjuvant to replenish our arsenals for combating bacterial infections and shed the light on the bacterial iron signaling as a promising target for antibacterial therapies.

Effect of surgical treatment on patients with stage T3 or T4 triple-negative breast cancer: a SEER-based retrospective observational study.

Background: The use of surgery is controversial in patients with stage T3 or T4 triple-negative breast cancer (TNBC). We aimed to explore the effect of surgical treatment on overall survival (OS) of these patients. Methods: A total of 2,041 patients were selected and divided into the surgical and non-surgical groups based on the Surveillance, Epidemiology, and End Results database from 2010 to 2018. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were applied to balance covariates between different groups. The OS of the two groups were assessed by Kaplan-Meier survival curves and Cox proportional hazards regression models. Results: A total of 2,041 patients were included in the study. After PSM and IPTW, baseline characteristics of the matched variables were fully balanced. Kaplan-Meier survival curves showed that the median survival time and OS of TNBC patients with stage T3 or T4 in the surgical group were significantly improved compared with those in the non-surgical group. Multivariate Cox proportional hazards regression analysis showed that surgery was a protective factor for prognosis. Conclusion: Our study found that surgery prolonged the median survival and improved OS compared with the non-surgical group of TNBC patients with stage T3 or T4.

Experiments and hyperelastic modeling of porcine meniscus show heterogeneity at high strains.

Constitutive modeling of the meniscus is critical in areas like knee surgery and tissue engineering. At low strain rates, the meniscus can be described using a hyperelastic model. Calibration of hyperelastic material models of the meniscus is challenging on many fronts due to material variability and friction. In this study, we present a framework to determine the hyperelastic material parameters of porcine meniscus (and similar soft tissues) using no-slip uniaxial compression experiments. Because of the nonhomogeneous deformation in the specimens, a finite element solution is required at each step of the iterative calibration process. We employ a Bayesian calibration approach to account for the inherent material variability and a Bayesian optimization approach to minimize the resulting cost function in the material parameter space. Cylindrical specimens of porcine meniscus from the anterior, middle and posterior regions are tested up to 30% compressive strain and the Yeoh form of hyperelastic strain energy density function is used to describe the material response. The results show that the Yeoh form is able to accurately describe the compressive response of porcine meniscus and that the Bayesian calibration and optimization approaches are able to calibrate the model in a computationally efficient manner while taking into account the inherent material variability. The results also show that the shear modulus or the initial stiffness is roughly uniform across the different areas of the meniscus, but there is significant spatial heterogeneity in the response at high strains. In particular, the middle region is considerably stiffer at high strains. This heterogeneity is important to consider in modeling the response of the meniscus for clinical applications.

Metagenomic insight into the microbial degradation of organic compounds in fermented plant leaves.

Microbial degradation of organic compounds is an environmentally benign and energy efficient part in product processing. Fermentation of plant leaves involves enzymatic actions of many microorganisms. However, microbes and enzymes discovered from natural degradation communities were still limited by cultural methods. In this study, we used a metagenomics sequence-guided strategy to identify the microbes and enzymes involved in compound degradation and explore the potential synergy among community members in fermented tobacco leaves. The results showed that contents of protein, starch, pectin, lignin, and cellulose varied in fermented leaves from different growing sites. The different compound contents were closely related to taxonomic composition and functional profiles of foliar microbial communities. Microbial communities showed significant correlations with protein, lignin, and cellulose. Vital species for degradations of protein (Bacillus cereus and Terribacillus aidingensis), lignin (Klebsiella pneumoniae and Pantoea ananatis) and cellulose (Pseudomonas putida and Sphingomonas sp. Leaf20) were identified and relating hydrolytic enzymes were annotated. Further, twenty-two metagenome-assembled genomes (MAGs) were assembled from metagenomes and six potential cellulolytic genomes were used to reconstruct the cellulose-degrading process, revealing the potential metabolic cooperation related to cellulose degradation. Our work should deepen the understanding of microbial roles in plant fermentation and provide a new viewpoint for applying microbial consortia to convert plant organic components to small molecules.

The Effect of Endoscopy on Patients with Malignant Esophageal Cancer after Medical Treatment and Chemotherapy.

The esophagus is one of the most commonly used parts in a person's life, and its importance is self-evident. With the unhealthy food diet, people are more and more likely to suffer from esophageal cancer, and there is an urgent need for breakthroughs in the treatment of esophageal cancer. This article is aimed at studying the effects of medical treatment and chemotherapy for patients with malignant esophageal cancer. To this end, this article proposes a treatment method based on endoscopy and improves the image imaging of the endoscopy and the image quality of the image and the edge processing of the image. At the same time, this article designs an experiment to conduct statistical analysis of the situation during the treatment process. The experimental results in this article show that the improved treatment method has a 21% increase in success rate compared with the existing treatment method. And the optimized image quality has increased by 27%. It can very well help the attending doctor to improve the efficiency of treatment in the actual treatment process. Its most important contribution is that through the edge optimization and image enhancement processing technology, the success rate of endoscopic treatment has been better improved, and the treatment efficiency has also been improved.

Preliminary Study on Immediate Postoperative CT Images and Values of the Modular Polyetheretherketone Based Total Knee Arthroplasty: An Observational First-in-Human Trial.

BACKGROUND: Total knee arthroplasty (TKA) is now frequently performed and is highly successful. However, patient satisfaction after TKA is often difficult to achieve. Because of the presence of metallic prosthetic knee joints, there is a lack of imaging tools that can accurately assess the patient's postoperative prosthetic position, soft tissue impingement, and periprosthetic bone density after TKA. We conducted a clinical trial of the world's first totally modular polyetheretherketone (PEEK) TKA and determined the bone density values in the stress concentration area around the prosthesis based on postoperative computed tomography data to reconstruct a three-dimensional model of the PEEK prosthetic knee joint after implantation. Based on the model, the overhang of the prosthesis was measured at various locations on the prosthesis. METHODS: All patients who underwent PEEK-based TKA were postoperatively assessed with radiography and computed tomography (CT). Hounsfield units (HUs) for the different components of the quantitative CT assessment were measured separately. RESULTS: Ten patients (nine female and one male) aged 59-74 (mean 66.9, median 67) years were included. The HU values were as follows: PEEK prosthesis mean 182.95, standard deviation (SD) 4.90, coefficient of variation (CV) 2.68; polyethylene mean -89.41, SD 4.14, CV -4.63; lateral femoral osteochondral mean 192.19, SD 55.05, CV 28.64; lateral tibial osteochondral mean 122.94, SD 62.14, CV 42.86; medial femoral osteophyte mean 180.76, SD 43.48, CV 24.05; and medial tibial osteophyte mean 282.59, SD 69.28, CV 24.52. Analysis of the data at 1, 3, and 6 months showed that the mean PE (p = 0.598) and PEEK (p = 0.916) measurements did not change with the time of measurement. There was a decrease in bone mineral density in the lateral tibia at 3 months (p = 0.044). Otherwise, there was no significant change in bone density in other regions (p = 0.124-0.803). There was no overhang in all femoral prostheses, whereas there were two cases of overhang in tibial prostheses. Overhang measurements do not differ significantly across time points. The overhang measurements were not significantly different at all time points (p = 0.186-0.967). CONCLUSION: PEEK knee joint prosthesis has excellent CT compatibility. The change in periprosthetic bone volume during the follow-up period can be determined using the HU value after CT scan, while the prosthesis position can be assessed. This assessment may potentially guide future improvements in knee prosthesis alignment techniques and artificial knee prosthesis designs.

Non-human primate papillomavirus E6-mediated p53 degradation reveals ancient evolutionary adaptation of carcinogenic phenotype to host niche.

Non-human primates (NHPs) are infected with papillomaviruses (PVs) closely related to their human counterparts, but there are few studies on the carcinogenicity of NHP-PVs. Using an in vitro cell co-transfection assay, we systematically screened the biochemical activity of E6 proteins encoded by macaque PVs for their ability to bind and promote degradation of host p53 proteins. A host species barrier exists between HPV16 and MfPV3 with respect to E6-mediated p53 degradation that is reversed when p53 residue 129 is swapped between human and macaque hosts. Systematic investigation found that E6 proteins encoded by most macaque PV types in the high-risk species α12, but not other Alpha-PV clades or Beta-/Gamma-PV genera, can effectively promote monkey p53 degradation. Interestingly, two macaque PV types (MfPV10 and MmPV1) can simultaneously inhibit the expression of human and monkey p53 proteins, revealing complex cross-host interactions between PV oncogenes and host proteomes. Single point-mutant experiments revealed that E6 residue 47 directly interacts with p53 residue 129 for host-specific degradation. These findings suggest an ancient host niche adaptation toward a carcinogenic phenotype in high-risk primate PV ancestors. Following periods of primate host speciation, a loss-of-function mutation model could be responsible for the formation of a host species barrier to E6-mediated p53 degradation between HPVs and NHP-PVs. Our work lays a genetic and functional basis for PV carcinogenicity, which provides important insights into the origin and evolution of specific pathogens in host pathogenesis.

Lignans from Euphorbia hirta L.

Five new lignans, euphorhirtins A-D (1-4), 5-methoxyvirgatusin (5), three artefacts, 7S-ethoxyisolintetralin (6), 7R-ethoxyisolintetralin (7), and 7R-ethoxy-3-methoxyisolintetralin (8), together with 13 known ones (9-21) were isolated from the medicinal plant Euphorbia hirta L. The structures of the compounds were elucidated by means of extensive spectroscopic analysis, including 1D and 2D NMR and HR-ESI-MS experiments. The absolute configurations of compound 1 was determined by ECD calculation. The isolates were evaluated for their inhibitory effects against the proliferation of the cancer cell lines (Hep G2, A549, and DU145) and compounds 14 and 18 showed inhibitory activity against the Hep G2 cells with IC50 values 7.2 ± 0.17 and 8.5 ± 0.36 µM.

The structure and flavor of low sodium seasoning salts in combination with different sesame seed meal protein hydrolysate derived Maillard reaction products.

In recent years, Maillard peptides have attracted considerable attention of food researchers due to their distinct flavor properties in food processing. We investigated the structure and flavor properties of the newly developed low-sodium seasoning salt with sesame seed hydrolysate Maillard products (SSH-MRPs), cysteine Maillard products (Cys-MRPs), methionine Maillard products (Met-MRPs), and thiamine Maillard products (Thi-MRPs). Compared to the control group, the Cys-MRPs salt (CMS) had the smallest angle of repose, the highest bulk density, and the highest sensory score. The seasoning salt with SSH-MRPs (SMS) had appreciable hygroscopicity and thermal stability. The seasoning salt with Thi-MRPs (TMS) had the highest solubility. These MRPs seasoning salts showed better flavor characteristics and physicochemical properties, suggesting that MRPs can replace part of NaCl to develop new low sodium seasoning salts and promote their application in food flavoring systems.

Interplay of m6 A and histone modifications contributes to temozolomide resistance in glioblastoma.

BACKGROUND: Despite the development of new treatment protocols for glioblastoma (GBM), temozolomide (TMZ) resistance remains a primary hindrance. Previous studies, including our study, have shown that aberrant N6-methyladenosine (m6 A) modification is implicated in GBM pathobiology. However, the roles and precise mechanisms of m6 A modification in the regulation of TMZ resistance in GBM remain unclear. METHODS: m6 A individual-nucleotide-resolution cross-linking and immunoprecipitation sequencing (miCLIP-seq) was performed to identify m6 A modification of transcripts in TMZ-resistant and -sensitive tumors. To explore the role of METTL3 in TMZ resistance, TMZ-resistant GBM cells were transfected with METTL3 shRNA or overexpression lentivirus and then assessed by cell viability, tumor sphere formation, and apoptosis assays. An intracranial GBM xenograft model was developed to verify the effect of METTL3 depletion during TMZ treatment in vivo. ATAC-seq, ChIP-qPCR, and dual-luciferase reporter assays were carried out to verify the role of SOX4/EZH2 in the modulation of METTL3 expression upon TMZ treatment. RESULTS: We demonstrated that TMZ treatment upregulated the expression of the m6 A methyltransferase METTL3, thereby increasing m6 A modification of histone modification-related gene transcripts. METTL3 is required to maintain the features of GBM stem cells. When combined with TMZ, METTL3 silencing suppressed orthotopic TMZ-resistant xenograft growth in a cooperative manner. Mechanistically, TMZ induced a SOX4-mediated increase in chromatin accessibility at the METTL3 locus by promoting H3K27ac levels and recruiting RNA polymerase II. Moreover, METTL3 depletion affected the deposition of m6 A on histone modification-related gene transcripts, such as EZH2, leading to nonsense-mediated mRNA decay. We revealed an important role of EZH2 in the regulation of METTL3 expression, which was via an H3K27me3 modification-independent manner. CONCLUSIONS: Our findings uncover the fundamental mechanisms underlying the interplay of m6 A RNA modification and histone modification in TMZ resistance and emphasize the therapeutic potential of targeting the SOX4/EZH2/METTL3 axis in the treatment of TMZ-resistant GBM.

Effects of sugars on the flavor and antioxidant properties of the Maillard reaction products of camellia seed meals.

In the present study, camellia seed meal Maillard reaction products (MRPs) were prepared using camellia seed meal protein as a raw material. The effects of MR on protein structure and volatile components of camellia seed meal were investigated by fluorescence, UV absorption, infrared spectroscopy, and gas chromatography-mass spectrometry. Not only the change of amino acid content in MRPs, but also the antioxidant capacity of MRPs and the antioxidant capacity after in vitro digestion were determined. Our result showed that the ratio of essential amino acids in R-MRPs was increased and the antioxidant activity was the highest. For the potential of MRPs as flavoring, our sensory evaluation results showed improved flavor and antioxidant activity of camellia seed meal after MR which can be used as flavoring agents at industrial level.

Effects of different sulfur-containing substances on the structural and flavor properties of defatted sesame seed meal derived Maillard reaction products.

Lately, plant derived proteins have been used extensively to produce Maillard reaction products (MRPs) for the preparation of various functional food products. We evaluated the effects of cysteine (Cys), methionine (Met), and thiamine (Thi) on the color and flavor development of MRPs derived from sesame seed meal. Compared with the MRPs of sesame seed hydrolysate (SSH), Cys-MRPs had the strongest antioxidant activity and fluorescence intensity, showing the stronger taste and overall acceptability. These MRPs contained the highest sulfur compounds which resulted into stronger meat flavor. Moreover, the content of free amino acids in Met-MRPs was the highest. Compared with MRPs of SSH alone, MRPs with different sulfur content had better flavor characteristics and physicochemical properties, which entail their usage in different food ingredients.