Natural Occurrence and Co-Occurrence of Beauvericin and Enniatins in Wheat Kernels from China.

A total of 769 wheat kernels collected from six provinces in China were analyzed for beauvericin (BEA) and four enniatins (ENNs), namely, ENA, ENA1, ENB and ENB1, using a solid phase extraction (SPE) technique with ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The results show that the predominant toxin was BEA, which had a maximum of 387.67 µg/kg and an average of 37.69 µg/kg. With regard to ENNs, the prevalence and average concentrations of ENB and ENB1 were higher than those of ENA and ENA1. The geographical distribution of BEA and ENNs varied. Hubei and Shandong exhibited the highest and lowest positive rates of BEA and ENNs (13.46% and 87.5%, respectively). However, no significant difference was observed among these six provinces. There was a co-occurrence of BEA and ENNs, and 42.26% of samples were simultaneously detected with two or more toxins. Moreover, a significant linear correlation in concentrations was observed between the four ENN analogs (r range: 0.75~0.96, p < 0.05). This survey reveals that the contamination and co-contamination of BEA and ENNs in Chinese wheat kernels were very common.

Macrophage polarization as a novel endpoint for assessing combined risk of phthalate esters.

Combined exposure to phthalate esters (PAEs) has garnered increasing attention due to potential synergistic effects on human health. This study aimed to develop an in vitro model using human macrophages to evaluate the combined toxicity of PAEs and explore the underlying mechanisms. A high-throughput screening system was engineered by expressing a PPRE-eGFP reporter in THP-1 monocytes to monitor macrophage polarization upon PAEs exposure. Individual PAEs exhibited varied inhibitory effects on M2 macrophage polarization, with mono(2-ethylhexyl) phthalate (MEHP) being the most potent. Isobologram analysis revealed additive interactions when MEHP was combined with other PAEs, resulting in more pronounced suppression of M2 markers compared to individual compounds. Mechanistic studies suggested PAEs may exert effects by modulating PPARγ activity to inhibit M2 polarization. Notably, an equimolar mixture of six PAEs showed additive inhibition of M2 markers. In vivo experiments corroborated the combined hepatotoxic effects, with mice exposed to a PAEs mixture exhibiting reduced liver weight, dyslipidemia, and decreased hepatic M2 macrophages compared to DEHP alone. Transcriptome analysis highlighted disruptions in PPAR signaling, and distinct pathway alterations on cholesterol metabolism in the mixture group. Collectively, these findings underscore the importance of evaluating mixture effects and provide a novel approach for hazard assessment of combined PAEs exposure with implications for environmental health risk assessment.

Enhancing Phosphorus Release from Sewage Sludge in Anaerobic Digestion via Thermal Hydrolysis Pretreatment: Insights from Phosphorus Speciation and Molecular Biological Pathways.

This study explores the mechanisms enhancing phosphorus (P) release from sludge in anaerobic digestion (AD) with thermal hydrolysis pretreatment (THP) using sequential chemical extraction, X-ray absorption near-edge structure spectroscopy (XANES), 31P NMR, and multiomics. THP-treated sludge notably increased liquid-phase P by 53.8% over 3 days compared to sewage sludge (SS), identifying solid-phase Fe-P as the primary P source. The THP+AD also provided a higher abundance of bacteria that contributed to P release through multiple pathways (MPRPB), whereas SS+AD enriched some microbial species with single P release pathway. Moreover, species co-occurrence network analysis underlined the pivotal role of P-releasing bacteria in THP+AD, with 8 out of 16 keystones being P-releasers. Among the 63 screened genes that were related to P transformations and release, the poly beta-hydroxybutyrate (PHB) synthesis genes associated with polyphosphate bacteria-mediated P release were more abundant in THP+AD than in SS+AD. Furthermore, the upregulation of genes involved in methyl phosphonate metabolism in the THP-treated sludge enhanced the methane production potential of the AD process. These findings suggested that MPRPB were indeed the main contributors to P release, and enrichment in the THP+AD process enhanced their capability for P liberation.

Towards Superior Aqueous Zinc-Ion Batteries: The Insights of Artificial Protective Interfaces.

Aqueous zinc ion batteries (AZIBs) with metallic Zn anode have the potential for large-scale energy storage application due to their cost-effectiveness, safety, environmental-friendliness, and ease of preparation. However, the concerns regarding dendrite growth and side reactions on Zn anode surface hamper the commercialization of AZIBs. This review aims to give a comprehensive evaluation of the protective interphase construction and provide guidance to further improve the electrochemical performance of AZIBs. The failure behaviors of the Zn metal anode including dendrite growth, corrosion, and hydrogen evolution are analyzed. Then, the applications and mechanisms of the constructed interphases are introduced, which are classified by the material species. The fabrication methods of the artificial interfaces are summarized and evaluated, including the in-situ strategy and ex-situ strategy. Finally, the characterization means are discussed to give a full view for the study of Zn anode protection. Based on the analysis of this review, a stable and high-performance Zn anode could be designed by carefully choosing applied material, corresponding protective mechanism, and appropriate construction technique. Additionally, this review for Zn anode modification and construction techniques for anode protection in AZIBs may be helpful in other aqueous metal batteries with similar problems.

Tunneling Proton Grotthuss Transfer Channels by Hydrophilic-Zincophobic Heterointerface Shielding for High-Performance Zn-MnO2 Batteries.

Hollandite-type manganese dioxide (α-MnO2) is recognized as a promising cathode material upon high-performance aqueous zinc-ion batteries (ZIBs) owing to the high theoretical capacities, high working potentials, unique Zn2+/H+ co-insertion chemistry, and environmental friendliness. However, its practical applications limited by Zn2+ accommodation, where the strong coulombic interaction and sluggish kinetics cause significant lattice deformation, fast capacity degradation, insufficient rate capability, and undesired interface degradation. It remains challenging to accurately modulate H+ intercalation while suppressing Zn2+ insertion for better lattice stability and electrochemical kinetics. Herein, proton Grotthuss transfer channels are first tunneled by shielding MnO2 with hydrophilic-zincophobic heterointerface, fulfilling the H+-dominating diffusion with the state-of-the-art ZIBs performance. Local atomic structure and theoretical simulation confirm that surface-engineered α-MnO2 affords to the synergy of Mn electron t2g-eg activation, oxygen vacancy enrichment, selective H+ Grotthuss transfer, and accelerated desolvation kinetics. Consequently, fortified α-MnO2 achieves prominent low current density cycle stability (≈100% capacity retention at 1 C after 400 cycles), remarkable long-lifespan cycling performance (98% capacity retention at 20 C after 12 000 cycles), and ultrafast rate performance (up to 30 C). The study exemplifies a new approach of heterointerface engineering for regulation of H+-dominating Grotthuss transfer and lattice stabilization in α-MnO2 toward reliable ZIBs.

Na+ Preintercalated MoO3 Microrods for Aqueous Zinc/Sodium Batteries with Enhanced Performance.

Layered molybdenum trioxide (MoO3) is being investigated as a cathode material with high theoretical capacity and holds promise for aqueous secondary batteries. Unfortunately, the severe structural degradation of MoO3 and insufficient intrinsic properties hinder its practical application. Herein, a Na+ preintercalation strategy is reported as an effective method to construct cathodes with high performance for aqueous zinc/sodium batteries (AZSBs). Compared with pristine MoO3, the Na+ preintercalated Na0.25MoO3 cathode delivers a reversible capacity of 251.1 mAh g-1 at 1 A g-1, achieves a capacity retention of 79.2% after 500 cycles, and exhibits a high rate capability (121.5 mAh g-1 at 20 A g-1), which is superior to that in most of the previous reports. Through the experimental measurements and density functional theory (DFT) calculations, the preintercalation method could shorten the forbidden band gap and modulate the electronic structure and hence effectively inhibit the structural collapse of MoO3 microrods, induce reversible Na+ insertion, and enhance the discharge potential. This work is of significance for further research on molybdenum-based compounds as cathode materials for aqueous secondary batteries.

Gene expression profiles to analyze the anticancer and carcinogenic effects of arsenic in bladder cancer.

OBJECTIVES: Arsenic is one of the greatest hazards as an environmental carcinogen. At the same time it is also a promising anticancer agent, that can be used to treat acute promyelocytic leukemia (APL) and some other tumors. Arsenic trioxide (ATO) exerts its therapeutic effect by promoting degradation of an oncogenic protein that drives the growth of APL cells. However, the molecular mechanisms that govern these paradoxical effects of arsenic in bladder cancer remain unclear. We speculate that they share the common mechanism that arsenic binds to the target proteins and subsequently impacts the expression of downstream genes. METHODS: To address this issue, three Gene Set Enrichments (GSE) were loaded from the Gene Expression Omnibus (GEO) database with four expression matrices. Three of them were mice samples at exposure times of 1, 2, and 12 weeks, and the last was a human urothelial cell (HUC1) sample. Differentially expressed genes (DEGs) from 4 expression groups were identified at iDEP and analyzed at Metascape and Cytoscape for signaling pathway analysis and protein-protein interaction (PPI) analysis. The web-portals UALCAN and GEPIA were used to analyze the role of DEGs in the crosstalk between carcinogenic and anticancer effects. The putative downstream genes of arsenic binding proteins were retrieved using the Cistrome Data Browser. Real-time PCR was used to validate the expression of DEGs. RESULTS: The signaling pathways referred to lipid metabolism. Responses to various stimuli or hormones were overrepresented in 4 expression matrices. The PPI network emphasized the role of KRAS and TNF signaling in different groups. Furthermore, BDKRB2, FOS, NR4A1, PLAU, SH3BGRL, and F10 played an important role in the crosstalk between carcinogenic and anticancer effects in bladder cancer. Arsenic may impact the activity of ACTB, BACH1, NME2, RBBP4, PARP1, and PML by direct binding, and thus influence the expression of downstream genes such as PAX6, MLLT11, LTBP1, PCSK5, ZFP36, COL8A2, and IL1R2. CONCLUSION: Arsenic exerted carcinogenic and anticancer functions by altering the expression of crosstalk genes such as BDKRB2, FOS, NR4A1, PLAU, SH3BGRL, and F10, and these were due to arsenic binding proteins.

Positive associations between different circulating trans fatty acids (TFAs) and urinary albumin excretion among adults in the U.S.: a population-based study.

BACKGROUND: It is well established that the consumption of trans-fatty acids (TFAs) can increase the incidence of total mortality, cardiovascular disease, cancer, and diabetes. However, there are still no demographic studies on the effects of circulating TFA isoforms on the albumin-creatinine ratio (ACR), an early marker of chronic kidney disease. Our goal was to explore the possible relationships between TFAs and ACR. METHODS: In this study, complete TFAs and urinary ACR data were collected from the National Health and Nutrition Examination Survey (NHANES) (2009-2010 and 1999-2000 cycles). The independent linear relationships between different circulating TFA isoforms and the ACR were examined by performing multivariable linear regression models. Machine learning was used to analyze the contribution of the different TFA isoforms to the ACR. To assess the nonlinearity of the relationship, smooth curve fitting and an analysis of threshold effect were performed, and a stratified analysis was conducted to identify possible susceptible populations. RESULTS: Our analysis included a total of 3785 individuals. Elaidic acid, linolelaidic acid, and sum TFAs were shown to be positively associated with the ACR after full adjustment by weighted multivariable regression analysis. In the subgroup analysis, the positive associations were maintained in participants with hypertension and without diabetes. In the XGBoost model of the ACR, Sum TFAs were found to be the most crucial factor. In addition, smooth curve fitting showed that there was a nonlinear relationship between the different TFAs and the ACR, and there was a saturation point. CONCLUSIONS: Our study demonstrated that TFA isoforms were positively and independently correlated with urinary albumin excretion, especially in participants with hypertension and without diabetes. This suggested that reducing trans fatty acid intake may reduce the risk of renal events.

Robotic-assisted double lingual mucosal graft ureteroplasty for multifocal ureteral strictures: Case report and technical description.

BACKGROUND: Ureteroplasty with a single onlay graft for proximal ureter stricture has been widely used in the clinic. However, robotic ureteroplasty with a double lingual mucosal graft (RU-DLMG) has not been reported. METHODS: The intraoperative measured ureteral stricture lengths of patient 1 were 1.8, 2.5, and 4.6 cm, and those of patient 2 were 2.5 and 3.5 cm. We performed a RU-DLMG in which the diseased ureter was incised longitudinally from the ventral side and repaired with a double lingual mucosal graft to widen the ureteral lumen. Because of the presence of a distal ureter stricture, RU-DLMG combined with ureteral reimplantation was performed in patient 1. RESULTS: Antegrade urography showed no obstruction of the reconstructed ureteral segment after removing the ureteral stent. The patients had no complaints about the donor site and flank pain during the 12-month follow-up. CONCLUSIONS: RU-DLMG appears to be a suitable option for multifocal ureteral strictures.

Natural Occurrence of Alternaria Toxins in Citrus-Based Products Collected from China in 2021.

A total of 181 citrus-based products, including dried fruits, canned fruits, and fruit juices, collected from China and from abroad in 2021 were analyzed for the four Alternaria toxins (ALTs): alternariol (AOH), alternariol monomethyl ether (AME), tentoxin (TEN), and tenuazonic acid (TeA) via ultra-high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS). Although the concentrations of the four ALTs varied by product and geographically, TeA was the predominant toxin followed by AOH, AME, and TEN. Products made in China showed higher levels of ALTs than those made abroad. Maximum levels of TeA, AOH, and AME in analyzed domestic samples were 4.9-fold, 1.3-fold, and 1.2-fold, respectively, higher than those in imported products. Furthermore, 83.4% (151/181) of the analyzed citrus-based products were contaminated with at least two or more ALTs. There were significant positive correlations between AOH and AME, AME and TeA, and TeA and TEN in all analyzed samples. More importantly, the solid and the condensed liquid products had higher concentrations of ALTs than the semi-solid product samples, as well as tangerines, pummelos, and grapefruits compared to the other kinds of citrus-based products. In conclusion, co-contamination with ALTs in commercially available Chinese citrus-based products was universal. Extensive and systematic surveillance of ALTs in citrus-based products, both domestic and imported, is required to obtain more scientific data for the determination of the maximum allowable concentrations of ALTs in China.

Small molecules targeting Pin1 as potent anticancer drugs.

Background: Pin1 is a member of the evolutionarily conserved peptidyl-prolyl isomerase (PPIase) family of proteins. Following phosphorylation, Pin1-catalyzed prolyl-isomerization induces conformational changes, which serve to regulate the function of many phosphorylated proteins that play important roles during oncogenesis. Thus, the inhibition of Pin1 provides a unique means of disrupting oncogenic pathways and therefore represents an appealing target for novel anticancer therapies. Methods: As Pin1 is conserved between yeast and humans, we employed budding yeast to establish a high-throughput screening method for the primary screening of Pin1 inhibitors. This effort culminated in the identification of the compounds HWH8-33 and HWH8-36. Multifaceted approaches were taken to determine the inhibition profiles of these compounds against Pin1 activity in vitro and in vivo, including an isomerization assay, surface plasmon resonance (SPR) technology, virtual docking, MTT proliferation assay, western blotting, cell cycle analysis, apoptosis analysis, immunofluorescence analysis, wound healing, migration assay, and nude mouse assay. Results: In vitro, HWH8-33 and HWH8-36 could bind to purified Pin1 and inhibited its enzyme activity; showed inhibitory effects on cancer cell proliferation; led to G2/M phase arrest, dysregulated downstream protein expression, and apoptosis; and suppressed cancer cell migration. In vivo, HWH8-33 suppressed tumor growth in the xenograft mice after oral administration for 4 weeks, with no noticeable toxicity. Together, these results show the anticancer activity of HWH8-33 and HWH8-36 against Pin1 for the first time. Conclusion: In summary, we identified two hit compounds HWH8-33 and HWH8-36, which after further structure optimization have the potential to be developed as antitumor drugs.

Primary Cutaneous Aspergillosis Due to Aspergillus fumigatus in an Immunocompetent Patient with Diabetes Mellitus After Tattooing: A Case Report and Review of Literature.

Background: Aspergillosis is an uncommon fungal infection in which primary cutaneous sites are very rare, and most cases occur in patients with immunocompromised status. Although primary cutaneous aspergillosis is usually encountered in immunocompromised patients, it also occurs in immunocompetent individuals. Case Presentation: We report a case of primary cutaneous aspergillosis in a 46-year-old immunocompetent woman with diabetes mellitus after tattooing. She presented with erythematous papules, papulopustules and a plaque on the right lower limb of more than two years duration which had failed to respond to antihistamine treatment. Histological examination of a skin biopsy sample showed oval spores in the corneous layer, a slightly thickened epidermis, and infiltrating lymphocytes and neutrophils around the blood vessels in the superficial dermis. Aspergillus fumigatus was isolated and identified in cultures. Clinical and biological examinations did not reveal any systemic localization of aspergillosis, ruling out a hypothesis of blood dissemination. Lesions resolved completely after systemic antifungal treatment with itraconazole. Conclusion: Clinical lesions of primary cutaneous aspergillosis are nonspecific and usually present as a variety of lesions, including macules, papules, nodules, plaques, purpura, blood blisters, and pustules. The nonspecific features and variety of lesions can lead to misdiagnosis and delayed treatment. Direct microscopy, microbiological culture, and histopathological examination are helpful for diagnosing primary cutaneous aspergillosis. Moreover, the physicians should be aware of the possibility of Aspergillus infection in tattooed cases.

Tremella-like Vanadium Tetrasulfide as a High-Performance Cathode Material for Rechargeable Aluminum Batteries.

Rechargeable aluminum batteries (RABs) are gaining widespread attention for large-scale energy storage applications as a result of their high energy densities, high security, and abundance. The key to sustain the progress of RABs lies in the quest for the proper cathode materials with prominent capacity and reversible cycle life. Herein, we propose a tremella-like VS4 as a cathode material aiming to tackle this problem. Obtained from a morphology modification process, VS4 with a unique nanosheet structure provides sufficient active sites for intercalation and conversion reactions, shortens the transport paths for charge carrier ions, and facilitates the infiltration process for electrolyte. The RAB with the VS4 cathode exhibits excellent electrochemical performance, including outstanding specific capacity (407.9 mAh g-1) and stable cycling performance (∼300 cycles at a high current density). The energy storage mechanism has been comprehensively investigated and is confirmed to be a combination of the intercalation/deintercalation of Al3+ and AlCl4- ions and conversion reaction by various techniques and DFT calculation. Our study not only provides a peculiar and simple strategy for the rational design of metal sulfide cathode materials with high capacity and long-term stability but also proposes a specific energy storage mechanism that guides the development of cathode materials of RABs in the future.

Nutrient dynamics and microbial community response in macrophyte-dominated lakes: Implications for improved restoration strategies.

Although lakes dominated by macrophytes are conducive to ecological balance, this balance is easily disrupted by excessive nutrients flowing into the lake. However, knowledge of whether excessive nutrients lead to different microbial environmental vulnerabilities in the lake sediment between macrophyte-dominated areas and macrophyte-free areas is a prerequisite for the implementation of targeted protection measures. In this study, we investigated bacterial communities in sediments using high-throughput sequencing of 16S rRNA genes. Our results showed that the sources of total nitrogen (TN) and organic matter (OM) were related to the macrophytes. The structure, drivers, and interspecific associations of bacterial community, which were more susceptible to increased changes in TN and OM, differed significantly between macrophyte-dominated areas and macrophyte-free areas. More precisely, the lake edge, where was occupied by macrophytes, had a higher proportion of deterministic phylogenetic turnover (88.89%) than other sites, as well as a wider ecological niche and a tighter network structure. Further, as the difference in TN increased, the main assembly processes in surface sediments changed from stochastic to deterministic. However, the majority of phyla from the lake edge showed a greater correlation with excessive nutrients, and the selection of the community by excessive nutrients was more obvious at the edge of the lake. In addition, our results demonstrated that the stability of the bacterial community in macrophyte-free areas is greater than in macrophyte-dominated areas, while an excessively high deterministic process ratio and nutrient (TN and OM) concentration significantly reduced bacterial community stability at macrophyte-dominated areas. Taken together, these results provide a better understanding of the effects of excessive nutrients derived from macrophytes on bacterial community patterns, and highlight the importance of avoiding the accumulation of TN and OM in macrophyte-dominated areas to enhance the sustainability of the ecosystem after restoration of lakes with macrophytes.

The locoweed endophyte Alternaria oxytropis affects root development in Arabidopsis in vitro through auxin signaling and polar transport.

Locoweeds are leguminous forbs known for their toxicity to livestock caused by the endophytic fungi Alternaria sect. Undifilum. Unlike the defensive mutualisms reported in many toxin-producing endophytes and their plant hosts, the benefits that A. sect. Undifilum can confer to it host plants remains unclear. Here, we conducted physiological and genetic analyses to show that A. (sect. Undifilum) oxytropis influences growth, especially root development, in its locoweed host Oxytropis ochrocephala and Arabidopsis. The presence of A. oxytropis significantly decreased primary root length while increasing the numbers of lateral roots and root hairs, and increasing plant leaf area and fresh weight. The fungus also increased the concentrations of plant endogenous auxin, and the expression of key genes for auxin biosynthesis, signaling, and transport. These effects on root development were abolished in mutants deficient in auxin signaling and polar transport. Alternaria oxytropis down-regulated expression of PIN1 but increased expression of PIN2, PIN7, and AUX1, which might reflect alterations in the spatial accumulation of auxin responsible for the changes in root architecture. Plant growth was insensitive to A. oxytropis when naphthylphthalamic acid was applied. Our findings indicate a function of A. oxytropis in promoting the growth and development of Arabidopsis via the regulation of auxin, which in turn suggests a possible role in benefiting its locoweed hosts via a process independent of its toxin production.

Characterization of the Composition Variation of Healthy Human Gut Microbiome in Correlation with Antibiotic Usage and Yogurt Consumption.

Antibiotic usage and yogurt consumption are the major interventions for gut microbiota, yet their shared characteristics and disparities in healthy human gut microbiome remain unclear. This study aimed to decipher the composition changes among healthy humans, comparing antibiotic usage and yogurt consumption. The relative bacterial abundances of 1113 fecal samples were collected from an ongoing, population-based longitudinal cohort study in China that covered lifestyle, diet, disease status and physical measurements, and biological indicators of participants were obtained by the sequencing of 16S rRNA. The samples were divided into three groups, which were antibiotic users (122), yogurt consumers (497) and controls (494), where data visualization, alpha diversity, beta diversity and LEfSe analysis were conducted. At the family level, the relative abundances of Streptococcaceae, Enterobacteriaceae and Enterococcaceae families in antibiotic users increased almost 50%, 70% and 200%, respectively, while yogurt consumption also increased relative abundances of Streptococcaceae and Enterococcaceae, but not Enterobacteriaceae. Alpha diversity analyses suggested that the microbiome of the antibiotic usage and yogurt consumption groups exhibited an alpha diversity lower than that of the control. LEfSe analysis showed that, at the family level, the number of biomarkers in the yogurt consumption and antibiotic usage group were respectively 5 and 7, lower than that of the control (13). This study demonstrated the importance in considering the potential assistance of yogurt consumption on ARG gene transfer from commensal bacteria to pathogens in the human gut, which may pose a risk for human health. Antibiotic usage and yogurt consumption share more identical changes on healthy human gut flora than disparities. Therefore, in order to understand the potential risks of antibiotic usage and yogurt consumption on antibiotic resistance transmission in human gut microbiota, further research needs to be undertaken.

Comprehensive analysis of lower mitochondrial complex I expression is associated with cell metastasis of clear cell renal cell carcinoma.

Background: Clear cell renal cell carcinoma (ccRCC) is characterized by high metastasis potential. It is of great importance to explore the mechanisms underlying ccRCC metastasis and to enable development of potent therapeutics. The mitochondrial complex I (CI) had been considered to play an important role in the development of cancers, but less known in ccRCC. Methods: We utilized available public databases of ccRCC, including single-cell RNA sequencing (scRNA-seq) data GSE73121 and The Cancer Genome Atlas-kidney renal clear cell carcinoma (TCGA-KIRC). Principal component analysis (PCA) and t-Distributed Stochastic Neighbor Embedding (tSNE) analysis were evaluated the heterogeneity of metastatic renal cell carcinoma (mRCC) and primary renal cell carcinoma (pRCC). Protein-protein interaction (PPI) network identified critical gene. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) performed to explore the potential biologic pathways. Results: Our study revealed a significant gene expression heterogeneity between pRCC and mRCC. A PPI network based on differentially expressed genes (DEGs) identified electron transport chain (ETC), especially mitochondrial CI, as the key network hub. Further analysis revealed that the role of mitochondrial CI is associated with tumor metastasis and immune responds of ccRCC. Although CI had low frequency mutations in ccRCC, CI expression is associated with the high frequency mutated genes. A prognosis model included 7 CI genes, and these had a significant effect on overall survival (OS). The area under the curve at 1, 3, and 5 years was 0.717, 0.685, and 0.728, respectively. Transcription factor analysis predicted that PPARG possibly is a potential transcription activator of CI genes in ccRCC. Conclusions: Overall, we found that CI expression is associated with ccRCC progress. CI and PPARG may be potential biomarkers for metastatic ccRCC.

The effects of modified RNA-binding proteins HuR on the biological behavior of the bladder cancer T24 cell line.

Background: In tumors, the role of human antigen R (HuR) includes regulating tumor cell proliferation, differentiation, apoptosis, angiogenesis, and lymphangiogenesis. Previous studies have revealed that the expression of HuR can be detected in bladder cancer, and is related to the biological behavior of malignancy. Methods: T24 cells were transfected by HuR overexpression and HuR knockdown vectors, and divided into the control group, the overexpression-HuR group, and the cas9-HuR group. Cell viability was detected after 48 h by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay, apoptosis was detected by Annexin V-allophycocyanin (APC)/7-aminoactinomycin D (7-AAD) double staining, cell migration was detected by Transwell assays, and the expression levels of HuR, cyclin D1, and apoptosis-related factors [i.e., B-cell lymphoma 2 (Bcl-2)] were detected by fluorescence quantitative polymerase chain reaction (PCR) and Western blot. Results: Compared to the control group, cell viability after 48 h increased significantly in the overexpression-HuR group, and decreased significantly in the cas9-HuR group (P<0.05). The number of migrating cells increased significantly in the overexpression-HuR group, and decreased significantly in the cas9-HuR group (P<0.05). The apoptosis rate was significantly decreased in the overexpression-HuR group, and significantly increased in the cas9-HuR group (P<0.05). The messenger ribonucleic acid and protein expression levels of HuR, cyclin D1, and Bcl-2 were significantly increased in the overexpression-HuR group, and significantly decreased in the cas9-HuR group (P<0.05). Conclusions: HuR promotes the proliferation and migration of T24 cells, and inhibits cell apoptosis. The mechanism may be related to the expression of cyclin D and the apoptosis-related protein, Bcl-2.

Diet composition affects long-term zearalenone exposure on the gut-blood-liver axis metabolic dysfunction in mice.

Zearalenone (ZEN), one of the most contaminated Fusarium toxins worldwide, is very common in contaminating wheat, corn oil and other foods. People are more vulnerable to ZEN exposure with more daily caloric intake, yet little is known about the combined effect of different dietary patterns with mycotoxins. This study aimed to compare the effects of long-term ZEN exposure on the overall biochemical landscape of the "gut-blood-liver axis" under normal diet and high-fat diet (HFD) using a combined multi-omics approach. The results indicated that ZEN exposure, possibly via the phenylalanine metabolic pathway, led to dysbiosis of mouse flora, suppression of short-chain fatty acids (SCFAS) metabolism, systemic inflammatory responses, and disturbances in serum and liver metabolism, which were exacerbated in synergy with HFD and ultimately led to a more severe state of lipid metabolism in the liver. We further found that ZEN exposure attenuated the indole-3-propionic acid (IPA) metabolic pathway, enhanced 2-hydroxybutyric acid metabolism in serum, and attenuated ß-alanine metabolism in liver which was positively correlated with the abundance of Prevotellaceae UCG-004, Prevotellaceae UCG-001, and Prevotellaceae NK3B31 groups. The results highlighted the damaging effects of ZEN on the gut-blood-liver axis under different dietary patterns, which might serve as a reference for future studies exploring the combined effects of fungal toxins and multiple dietary patterns.

Role of Hepatocyte- and Macrophage-Specific PPARγ in Hepatotoxicity Induced by Diethylhexyl Phthalate in Mice.

BACKGROUND: Phthalates may disturb metabolic homeostasis in the liver by interfering with the peroxisome proliferator-activated receptors (PPARs). However, the role of hepatic macrophages in the lipid metabolic dysregulation induced by diethylhexyl phthalate (DEHP) remains unclear. OBJECTIVES: We aimed to evaluate the respective role of hepatocyte- and macrophage-specific PPARγ in the hepatotoxicity induced by DEHP. METHODS: Wild-type (WT), hepatocyte-specific PPARγ knockout (Hep-KO), and macrophage-specific PPAR knockout (Mac-KO) mice were administered DEHP (625mg/kg body weight) by daily gavage for 28 d, followed by hepatotoxicity examination and macrophage analysis. RNA sequencing and lipid metabolomic analysis were used to characterize the molecular changes in mouse liver. Mouse bone marrow-derived macrophages (BMDMs) and human monocytic THP-1 cell-derived macrophages were used to investigate the mechanistic regulation of macrophages' polarization by DEHP and mono(2-ethylhexyl) phthalate (MEHP). RESULTS: The levels of hepatic steatosis and triglyceride were significantly higher in the mice treated with DEHP compared with the control mice in the WT and Hep-KO model. Lipid accumulation induced by DEHP was notably attenuated in the Mac-KO mice, but M2-polarization of hepatic macrophages in the Mac-KO mice was significantly higher compared with the WT mice under DEHP treatment. The M2-polarization of BMDMs and human macrophages was suppressed by DEHP and MEHP. Transcriptomic and lipidomic data suggested lower levels of lipid biosynthesis, fatty acid oxidation, and oxidative phosphorylation in the Mac-KO mice compared with the WT and Hep-KO mice under DEHP treatment. CONCLUSIONS: Our data suggested that the orchestrated activation of PPARα and PPARγ by MEHP may reprogram hepatic macrophages' polarization, thereby affecting lipid homeostasis in the mouse liver. Although this conclusion was based on studies conducted in mice and in vitro, these findings may aid in elucidating the health effect of environmental phthalate exposure. https://doi.org/10.1289/EHP9373.