Dietary bamboo charcoal powder ameliorates high-fat diet-induced hyperlipidemia by enhancing fecal lipid excretions in Sprague-Dawley rats.

Introduction: Bamboo charcoal powder (BCP) is increasingly used as a food colorant. This study aims to evaluate the effects of BCP consumption on improving high-fat diet-induced hyperlipidemia. Methods: Fifty male SD rats were randomly assigned into five groups, with 10 rats in each group: the control group was fed a low-fat diet (LFD); the model control group was fed a high-fat diet (HFD); the low-BCP dose group was fed a HFD and given 2.81 g of BCP/kg of body weight (BCP-L) by gavage; the medium-BCP dose group was fed a HFD and given 5.62 g of BCP/kg of body weight (BCP-M) by gavage; the high-BCP dose group was fed a HFD and given 11.24 g of BCP/kg of body weight (BCP-H) by gavage. Results: After 90 days, the consumption of BCP caused a decrease in body weight, plasma lipids (triglyceride, cholesterol, and low-density lipoprotein (LDL)), liver triglyceride, and cholesterol levels, and liver histopathological scores. BCP caused a significant increase in superoxide dismutase (SOD) activity and total antioxidant capacity (T-AOC) in liver tissues. BCP also led to an increase in 72-h fecal dry weight and crude fat in a rat metabolic cage. The analysis of fecal samples with liquid chromatography time-of-flight mass spectrometry (LC-Q-TOF-MS) showed that the biomarkers associated with BCP consumption were mainly related to fatty and amino acid metabolism. Notably, BCP treatment significantly promoted linoleic acid metabolism. Discussion: These results suggest that BCP may have a preventive effect against diet-induced hyperlipidemia through the promotion of fecal fat excretion. BCP may potentially be used as an alternative functional food component for people with diet-induced hyperlipidemia.

Mode of action exploration for prostate epithelial cell injury caused by bisphenol A.

Bisphenol A (BPA) is a typical food chemical contaminant with various detrimental effects, especially on reproductive system. Male prostate damage is also one of its major adverse health effects, of which mode of action (MOA) remains unclear. This study aims to explore the MOA for prostate toxicity of BPA using human normal prostate epithelial cell RWPE-1 for 28-day human-relevant-level exposure. A physiological based pharmacokinetic model was used to determine the concentration of BPA based on the actual oral exposure in China. The possible key events were identified by high-throughput transcriptome sequencing and validated by qPCR, Western blot and cell cycle assay, and the benchmark concentration analysis were conducted. The enriched KEGG pathways include the endocytosis, cell cycle, cellular senescence, MAPK and TNF signaling pathways. With increasing BPA concentrations, the increased mRNA and/or protein expressions of MAPKAPK2, c-JUN and c-fos in the MAPK signaling pathway, the increased mRNA expressions of CCND1 and CDKN1A, the decreased mRNA expression of CDC25C, the increased proportion of G0/G1 phase and S phase, as well as the decreased proportion of G2/M phase, were observed. The lowest value of benchmark concentration lower confidence limit (BMCL) was retrieved from G2/M phase ratio, with 110.580 and 175.862 nM for BMCL5 and BMCL10, respectively, much higher than the male gonad maximum concentration of 0.019 nM of BPA at the current exposure level of adult Chinese males. In conclusion, the MOA of BPA induced male prostatic toxicity at human-relevant levels may include: key event (KE)1-MAPK signaling pathway activation, KE2-disorder of cell cycle regulatory gene expression (increased expression of CCND1 and CDKN1A, decreased expression of CDC25C), and KE3-disturbance of cell cycle (increased proportion of G0/G1 and S phases, decreased proportion of G2/M phases). However, more studies are needed to validate and complete the MOA.

Construction of an adverse outcome pathway for the cardiac toxicity of bisphenol a by using bioinformatics analysis.

Bisphenol A (BPA), a common endocrine disruptor, has shown cardiovascular toxicity in several epidemiological studies, as well as in vivo and in vitro experimental studies. However, the related adverse outcome pathway (AOP) of BPA toxicity remains unraveled. This study aimed to develop an AOP for the cardiac toxicity of BPA through bioinformatics analysis. The interactions among BPA, genes, phenotypes, and cardiac toxicity were retrieved from several databases, including the Comparative Toxicogenomics Database, Computational Toxicology, DisGeNet, and MalaCards. The target genes and part of target phenotypes were obtained by Venn analysis and literature screening. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were performed for target genes by using the DAVID online analysis tool to obtain other target phenotypes. AOP hypotheses from BPA exposure to heart disease were established and evaluated comprehensively by a quantitative weight of evidence (QWOE) method. The target genes included ESR2, MAPK1, TGFB1, and ESR1, and the target phenotypes included heart contraction, cardiac muscle contraction, cellular Ca2+ homeostasis, cellular metabolic process, heart development, etc. Overall, the AOP of BPA cardiac toxicity was deduced to be as follows. Initially, BPA bound with ERα/ß and then activated the MAPK, AKT, and IL-17 signaling pathways, leading to Ca2+ homeostasis disorder and increased inflammatory response. Subsequently, cardiac function was impaired, causing coronary heart disease, arrhythmia, cardiac dysplasia, and other heart diseases. According to the Bradford-Hill causal considerations, the score of AOP by QWOE was 69, demonstrating a moderate confidence and providing clues on cardiotoxicity-assessment procedure and further studies on BPA.

Association between calcification and risk stratification in gastric gastrointestinal stromal tumors.

BACKGROUND: Risk assessment of gastric gastrointestinal stromal tumors (GISTs), particularly those with a diameter ≤ 5 cm, remains a clinical challenge. Previous research has primarily focused on tumor size, ulceration, necrosis, and enhancement patterns, with less emphasis on the role of tumor calcification, which remains controversial regarding its correlation with malignancy risk. OBJECTIVE: This study aims to explore the characteristics of calcification in gastric GISTs and its correlation with risk stratification as defined by the National Institutes of Health (NIH), to improve preoperative risk assessment for gastric GISTs ≤ 5 cm. METHODS: A retrospective analysis of 385 pathologically confirmed gastric GIST patients, including 178 with small gastric GISTs (< 2 cm), was conducted. Tumors were categorized into low-risk (very low / low) and high-risk (intermediate / high) groups based on NIH criteria. Variables such as age, gender, tumor long-axis diameter, calcification rates, calcification size, the number and distribution of calcification, calcification to tumor long-axis diameter ratio were analyzed. Logistic regression was used to identify independent predictors of malignancy for gastric GISTs, with predictive values assessed via receiver operating characteristic (ROC) curves. RESULTS: Significant differences were found between high-risk and low-risk groups in treatment methods, tumor long-axis diameter, the ratio of calcification to tumor long-axis, and calcification distribution (P < 0.05). Calcification rates varied across risk categories, with 23.6% in very low-risk, 31.6% in low-risk, 9.8% in intermediate-risk, and 31.7% in high-risk categories (P < 0.05). In GISTs ≤ 5 cm, both tumor long-axis diameter (OR = 3.07, 95% CI: 2.29-4.10) and calcification (OR = 0.36, 95% CI: 0.13-0.97) were independent predictors of malignancy risk (both P < 0.05). ROC curve analysis yielded areas of 0.849 for tumor long-axis diameter, 0.578 for calcification, and 0.862 for their combination. CONCLUSION: The study indicates lower calcification rates in intermediate-risk gastric GISTs and higher rates in other risk categories. Additionally, tumors of different sizes exhibit two distinct calcification patterns, suggesting possible differing mechanisms of calcification in tumors. Calcification in gastric GISTs ≤ 5 cm acts as a protective factor against higher malignancy risk, and when combined with tumor long-axis diameter, significantly enhances predictive accuracy over long-axis diameter alone.

Organophosphate Esters in Raw Cow Milk and Cow's Drinking Water and Feed from China: Occurrence, Regional Distribution, and Dietary Exposure Assessment.

Organophosphate esters (OPEs) have been widely produced and used, while little is known about their occurrence in the food chain and potential sources. In this study, raw cow milk, cow drinking water, and feed were collected from pastures across China, and OPEs were tested to explore the occurrence and transmission of OPEs in the food chain and to further assess daily OPE intakes for cows and humans via certain food consumption. The median level of ∑OPEs (sum of 15 OPEs) in raw milk was 2140 pg/mL, and tris(1-chloro-2-propyl) phosphate (TCIPP) was the most abundant OPE. Levels of OPEs in water were lower than those in raw milk except for triethyl phosphate (TEP), while levels of most OPEs in feed were significantly higher than those in raw milk (adjusted by dry weight). The estimated dietary intake of OPEs via feed for cows was 2530 ng/kg bw/day, which was much higher than that via water (742 ng/kg bw/day), indicating that feed was a more critical exposure source. For liquid milk consumers, the high-exposure (95th) estimated daily intakes (EDIs) of ∑15OPE were 20 and 7.11 ng/kg bw/day for 3-17 years and adults, respectively, and it is obvious that cows had much heavier OPE intake. Finally, the calculated hazard indexes (HIs) suggested that the intake of OPEs via cow milk consumption would not pose significant health risks to the Chinese population.

[Toxicity of bisphenol S on human normal ovarian epithelial cells mediated by ERß-MAPK signaling pathway].

OBJECTIVE: To investigate the effects of long-term(7 days and 14 days) bisphenol S(BPS) exposure on the ERß-MAPK signaling pathway, hormone secretion phenotype and cell cycle in human normal ovarian epithelial cells IOSE 80 at actual human exposure level. METHODS: Physiologically based pharmacokinetic model combined with BPS levels in the serum of women along the Yangtze River in China was used to determine the dosing concentrations of BPS, and vehicle control and 17 ß-estradiol(E_2) control were used. Complete medium with corresponding concentrations(0, 6.79×10~(-6), 6.79×10~(-4), 6.79×10~(-2), 6.79 µmol/L BPS and 10 nmol/L E_2) was replaced every 2 days. mRNA expressions of estrogen receptor(ERß and GPR30), key genes in MAPK signaling pathway(P38/JNK/ERK signaling pathway) and gonadotropin-releasing hormone-related genes(GnRH-I, GnRH-II and GnRH-R) were measured by qPCR. The ERß-MAPK signaling pathway inhibitors were employed to detect the effect of long-term exposure to BPS on the cell cycle by flow cytometry. Dose-response relationship analysis was performed to calculate the benchmark does lower confidence limits. RESULTS: Compared to the vehicle control, after 7 days exposure to BPS, the ratio of G_2/M phase was significantly increased(P<0.05), and the mRNA expressions of GnRH-I, GnRH-II and GnRH-R were significantly decreased(P<0.05); after 14 days exposure to BPS, the mRNA expressions of ESR2, MAPK3, and MAPK9 were significantly increased(P<0.05), and the mRNA expressions of GnRH-II and GnRH-R were significantly decreased(P<0.05). The GnRH-II mRNA expression level of BPS treatment for 7 days; the G_0/G_1 phase ratio, MAPK3 and MAPK8 mRNA expression level of BPS exposure for 14 days; and the GnRH-I mRNA expression level after BPS treatment for 7 days and 14 days showed a good dose-response relationship but with poor fit. CONCLUSION: Long-term low-dose exposure to BPS may cause cell cycle arrest by activating the ERß-MAPK signaling pathway, and may lead to changes in the hormone secretion of IOSE 80 cells.

Anthracycline-induced arrhythmias in breast cancer therapy: A meta-analysis of single-arm trials.

INTRODUCTION: As of 2020, breast cancer has emerged as the predominant cause of cancer incidence globally. Anthracycline-based chemotherapy serves as a crucial element in the treatment regimen for breast cancer. However, these anthracycline-based drugs are associated with cardiac toxicity. This study represents the first clinical quantitative analysis aimed at accurately determining the incidences of arrhythmia and abnormal electrocardiogram (ECG) changes, thereby providing valuable data to bolster clinical drug usage and monitoring. METHODS: A systematic search was conducted across multiple databases including CNKI, VIP, Wanfang, PubMed, Embase, Web of Science, and the Cochrane Library. The incidence of combined arrhythmias in breast cancer patients and the associated heterogeneity were calculated using either a random effect model or a fixed effect model. Statistical analysis was performed using STATA16. RESULTS: The study encompassed a total of 37 articles, which included 5705 breast cancer patients undergoing anthracycline treatment. Among these patients, 2257 developed arrhythmias. The meta-analysis revealed that the incidence of anthracycline-associated arrhythmias and abnormal ECG changes in breast cancer patients was 0.41 (0.37, 0.44). Subgroup analysis indicated that the incidence of ST-T segment change was 0.19 (0.15, 0.23), the incidence of conduction block was 0.04 (0.02, 0.05), the incidence of premature beats was 0.09 (0.07, 0.11), and the incidence of atrial fibrillation was 0.04 (0.00, 0.12). Additional results are presented in Table 3. CONCLUSION: This pioneering study accurately assesses the incidence of arrhythmias in breast cancer patients treated with anthracyclines. The findings provide clinicians with valuable insights into understanding and managing the cardiac toxicity associated with such treatment. Moreover, this study lays the foundation for future research exploring the mechanisms underlying these arrhythmias and potential preventative strategies.

Structure and Properties of Epoxy Resin/Graphene Oxide Composites Prepared from Silicon Dioxide-Modified Graphene Oxide.

In this study, graphene oxide (GO) was modified via electrostatic interactions and chemical grafting by silica (SiO2), and two SiO2@GO hybrids (GO-A and GO-B, respectively) with different structures were obtained and carefully characterized. Results confirmed the successful grafting of SiO2 onto the GO surface using both strategies. The distribution of SiO2 particles on the surface of GO-A was denser and more agglomerated, while it was more uniform on the surface of GO-B. Then, epoxy resin (EP)/GO composites were prepared. The curing mechanism of EP/GO composites was studied by differential scanning calorimetry and in situ infrared spectra spectroscopy. Results of tensile tests, hardness tests, dynamic mechanical analysis, and dielectric measurement revealed that EP/GO-B exhibited the highest tensile properties, with a tensile strength of 79 MPa, a 43% increase compared to raw EP. Furthermore, the addition of fillers improved the hardness of EP, and EP/GO-B showed the highest energy storage modulus of 1900 MPa. The inclusion of SiO2@GO hybrid fillers enhanced the dielectric constant, volume resistivity, and breakdown voltage of EP/GO composites. Among these, EP/GO-B displayed the lowest dielectric loss, relatively good insulation, and relatively high volume resistivity and breakdown voltage. A related mechanism was proposed.

[Protective effects of galacto-oligosaccharide and polydextrose on Caco-2 intestinal cell barrier injury model].

OBJECTIVE: To explore the protective effect of different ratios of galactose oligosaccharide(GOS) and polydextrose(PDX) on intestinal cell barrier damage model of Caco-2. METHODS: The same batch of Caco-2 cells were cultured to form a cell barrier model and randomly divided into damaged model group without calcium, calcium-containing blank control group(1.8 mmol/L Ca~(2+)), low-ratio/low-dose group(1.8 mmol/L Ca~(2+)+2 mg/mL GOS+2 mg/mL PDX) and low-ratio/medium-dose group(1.8 mmol/L Ca~(2+)+4 mg/mL GOS+4 mg/mL PDX), low-ratio/high-dose group(1.8 mmol/L Ca~(2+)+8 mg/mL GOS+8 mg/mL PDX) and high-ratio/low-dose group(1.8 mmol/L Ca~(2+)+0.8 mg/mL GOS+3.2mg/mL PDX), high-ratio/medium-dose group(1.8 mmol/L Ca~(2+)+1.6 mg/mL GOS+6.4 mg/mL PDX), high-ratio/high-dose group(1.8 mmol/L Ca~(2+)+3.2mg/mL GOS+12.8 mg/mL PDX), a total of 8 groups, three parallel groups were performed in each group. The Trans Epithelial Electrical Resistance value and apparent permeability coefficient value of each group were determined after 4 d culture, and the morphology of tight junction proteins ZO-1, Occludin and Claudin-1 were observed by immunofluorescence method, and the expression levels of inflammatory related factors in each group were determined by protein microarray method. RESULTS: Compared with damaged model group, TEER ratio in calcium-containing blank control group was significantly increased(P<0.05), while Papp value was significantly decreased(P<0.05);Compared with calcium-containing blank control group, TEER ratio in low-ratio/medium-dose group and high-ratio/high-dose group was significantly increased(P<0.05) while Papp value was significantly decreased(P<0.05), and they could significantly down-regulate some inflammatory response related cytokines. The cell barrier was intact in all groups except for the compact junction protein structure in the model group. CONCLUSION: Compared with Ca~(2+) alone, the combination of two prebiotics can enhance the density of Caco-2 cell barrier and reduced the permeability of cell bypass. And it can significantly reduce the expression level of some inflammatory cytokines and effectively protect the intestinal cell barrier.

Mode of action exploration of reproductive toxicity induced by bisphenol S using human normal ovarian epithelial cells through ERß-MAPK signaling pathway.

BACKGROUND: In the plastics production sector, bisphenol S (BPS) has gained popularity as a replacement for bisphenol A (BPA). However, the mode of action (MOA) of female reproductive toxicity caused by BPS remains unclear and the safety of BPS is controversial. METHODS: Human normal ovarian epithelial cell line, IOSE80, were exposed to BPS at human-relevant levels for short-term exposure at 24 h or 48 h, or for long-term exposure at 28 days, either alone or together with five signaling pathway inhibitors: ICI 18,2780 (estrogen receptor [ER] antagonist), G15 (GPR30 specific inhibitor), U0126 (extracellular regulated protein kinase [ERK] 1/2 inhibitor), SP600125 (c-Jun N-terminal kinase [JNK] inhibitor) or SB203580 (p38 mitogen­activated protein kinase [p38MAPK] inhibitor). MOA through ERß-MAPK signaling pathway interruption was explored, and potential thresholds were estimated by the benchmark dose method. RESULTS: For short-term exposure, BPS exposure at human-relevant levels elevated the ESR2 and MAPK8 mRNA levels, along with the percentage of the G0/G1 phase. For long-term exposure, BPS raised the MAPK1 and EGFR mRNA levels, the ERß, p-ERK, and p-JNK protein levels, and the percentage of the G0/G1 phase, which was partly suppressed by U0126. The benchmark dose lower confidence limit (BMDL) of the percentage of the S phase after 24 h exposure was the lowest among all the BMDLs of a good fit, with BMDL5 of 9.55 µM. CONCLUSIONS: The MOA of female reproductive toxicity caused by BPS at human-relevant levels might involve: molecular initiating event (MIE)-BPS binding to ERß receptor, key event (KE)1-the interrupted expression of GnRH, KE2-the activation of JNK (for short-term exposure) and ERK pathway (for long-term exposure), KE3-cell cycle arrest (the increased percentage of the G0/G1 phase), and KE4-interruption of cell proliferation (only for short-term exposure). The BMDL of the percentage of the S phase after 24 h exposure was the lowest among all the BMDLs of a good fit, with BMDL5 of 9.55 µM.

Genotoxic mode of action and threshold exploration of 2-methyl furan under 120-day sub-chronic exposure in male Sprague-Dawley rats.

2-Methylfuran (2-MF) is an important member of the furan family generated during food thermal processing. An in-vivo multiple endpoint genotoxicity assessment system was applied to explore the genotoxic mode of action and threshold of 2-MF. Male Sprague-Dawley rats received 2-MF by oral gavage at doses of 0.16, 0.625, 2.5, and 10 mg/kg.bw/day for 120 days. An additional 15 days were granted for recovery. The Pig-a gene mutation frequency of RET and RBC showed significant increases among the 2-MF groups on day 120. After a 15-day recovery period, the Pig-a gene mutation frequency returned to levels similar to those in the vehicle control. The tail intensity (TI) values of peripheral blood cells at a dose of 10 mg/kg.bw/day significantly increased from day 4 and remained at a high level after the recovery period. No statistical difference was found in the micronucleus frequency of peripheral blood between any 2-MF dose group and the corn oil group at any timepoint. 2-MF may not induce the production of micronuclei, but it could cause DNA breakage. It could not be ruled out that 2-MF may accumulate in vivo and cause gene mutations. Hence, DNA, other than the spindle, may be directly targeted. The mode of action of 2-MF may be that it was metabolized by EPHX1 to more DNA-active metabolites, thus leading to oxidative and direct DNA damage. The point of departure (PoD) of 2-MF-induced genotoxicity was derived as 0.506 mg/kg bw/day.

Genotoxicity of bisphenol AF in rats: Detrimental to male reproductive system and probable stronger micronucleus induction potency than BPA.

Bisphenol AF (BPAF), as one of structural analogs of BPA, has been increasingly used in recent years. However, limited studies have suggested its adverse effects similar to or higher than BPA. In order to explore the general toxicity and genotoxicity of subacute exposure to BPAF, the novel 28-day multi-endpoint (Pig-a assay + micronucleus [MN] test + comet assay) genotoxicity evaluation platform was applied. Male rats were randomly distributed into seven main experimental groups and four satellite groups. The main experimental groups included BPAF-treated groups (0.5, 5, and 50 µg/kg·bw/d), BPA group (10 µg/kg·bw/d), two solvent control groups (PBS and 0.1% ethanol/99.9% oil), and one positive control group (N-ethyl-N-nitrosourea, 40 mg/kg bw). The satellite groups included BPAF high-dose recovery group (BPAF-HR), oil recovery group (oil-R), ENU recovery group (ENU-R), and PBS recovery group (PBS-R). All groups received the agents orally via gavage for 28 consecutive days, and satellite groups were given a recovery period of 35 days. Among all histopathologically examined organs, testis and epididymis damage was noticed, which was further manifested as blood-testis barrier (BTB) junction protein (Connexin 43 and Occludin) destruction. BPAF can induce micronucleus production and DNA damage, but the genotoxic injury can be repaired after the recovery period. The expression of DNA repair gene OGG1 was downregulated by BPAF. To summarize, under the design of this experiment, male reproductive toxicity of BPAF was noticed, which is similar to that of BPA, but its ability to induce micronucleus production may be stronger than that of BPA.

Carotenoids in maternal and cord blood, breast milk and their association with maternal dietary intake: a longitudinal study in Shanghai, China.

Carotenoids are important bioactive substances in breast milk, the profile of which is seldom studied. This study aimed to explore the profile of carotenoids in breast milk and maternal/cord plasma of healthy mother-neonate pairs in Shanghai, China, and their correlation with dietary intake. Maternal blood, umbilical cord blood and breast milk samples from five lactation stages (colostrum, transitional milk and early-, mid- and late-term mature milk) were collected. Carotenoid levels were analysed by HPLC. Carotenoid levels in breast milk changed as lactation progressed (P < 0·001). ß-Carotene was the primary carotenoid in colostrum. Lutein accounted for approximately 50 % of total carotenoids in transitional milk, mature milk and cord blood. Positive correlations were observed between five carotenoids in umbilical cord blood and maternal blood (P all < 0·001). ß-Carotene levels were also correlated between maternal plasma and three stages of breast milk (r = 0·605, P < 0·001; r = 0·456, P = 0·011, r = 0·446; P = 0·013, respectively). Dietary carotenoid intakes of lactating mothers also differed across lactation stages, although no correlation with breast milk concentrations was found. These findings suggest the importance of exploring the transport mechanism of carotenoids between mothers and infants and help guide the development of formulas for Chinese infants as well as the nutritional diets of lactating mothers.

Deep Learning Radiomics Model of Dynamic Contrast-Enhanced MRI for Evaluating Vessels Encapsulating Tumor Clusters and Prognosis in Hepatocellular Carcinoma.

BACKGROUND: Vessels encapsulating tumor cluster (VETC) is a critical prognostic factor and therapeutic predictor of hepatocellular carcinoma (HCC). However, noninvasive evaluation of VETC remains challenging. PURPOSE: To develop and validate a deep learning radiomic (DLR) model of dynamic contrast-enhanced MRI (DCE-MRI) for the preoperative discrimination of VETC and prognosis of HCC. STUDY TYPE: Retrospective. POPULATION: A total of 221 patients with histologically confirmed HCC and stratified this cohort into training set (n = 154) and time-independent validation set (n = 67). FIELD STRENGTH/SEQUENCE: A 1.5 T and 3.0 T; DCE imaging with T1-weighted three-dimensional fast spoiled gradient echo. ASSESSMENT: Histological specimens were used to evaluate VETC status. VETC+ cases had a visible pattern (≥5% tumor area), while cases without any pattern were VETC-. The regions of intratumor and peritumor were segmented manually in the arterial, portal-venous and delayed phase (AP, PP, and DP, respectively) of DCE-MRI and reproducibility of segmentation was evaluated. Deep neural network and machine learning (ML) classifiers (logistic regression, decision tree, random forest, SVM, KNN, and Bayes) were used to develop nine DLR, 54 ML and clinical-radiological (CR) models based on AP, PP, and DP of DCE-MRI for evaluating VETC status and association with recurrence. STATISTICAL TESTS: The Fleiss kappa, intraclass correlation coefficient, receiver operating characteristic curve, area under the curve (AUC), Delong test and Kaplan-Meier survival analysis. P value <0.05 was considered as statistical significance. RESULTS: Pathological VETC+ were confirmed in 68 patients (training set: 46, validation set: 22). In the validation set, DLR model based on peritumor PP (peri-PP) phase had the best performance (AUC: 0.844) in comparison to CR (AUC: 0.591) and ML (AUC: 0.672) models. Significant differences in recurrence rates between peri-PP DLR model-predicted VETC+ and VETC- status were found. DATA CONCLUSIONS: The DLR model provides a noninvasive method to discriminate VETC status and prognosis of HCC patients preoperatively. EVIDENCE LEVEL: 4. TECHNICAL EFFICACY: Stage 2.

Effect of Crosslinking Conditions on the Transport of Protons and Methanol in Crosslinked Polyvinyl Alcohol Membranes Containing the Phosphoric Acid Group.

In this investigation, we systematically explored the intricate relationship between the structural attributes of polyvinyl alcohol (PVA) membranes and their multifaceted properties relevant to fuel cell applications, encompassing diverse crosslinking conditions. Employing the solution casting technique, we fabricated crosslinked PVA membranes by utilizing phosphoric acid (PA) as the crosslinking agent, modulating the crosslinking temperature across a range of values. This comprehensive approach aimed to optimize the selection of crosslinking parameters for the advancement of crosslinked polymer materials tailored for fuel cell contexts. A series of meticulously tailored crosslinked PVA membranes were synthesized, each varying in PBTCA content (5-30 wt.%) to establish a systematic framework for elucidating chemical interactions, morphological transformations, and physicochemical attributes pertinent to fuel cell utilization. The manipulation of crosslinking agent concentration and crosslinking temperature engendered a discernible impact on the crosslinking degree, leading to a concomitant reduction in crystallinity. Time-resolved attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) was harnessed to evaluate the dynamics of liquid water adsorption and ionomer swelling kinetics within the array of fabricated PVA films. Notably, the diffusion of water within the PVA membranes adhered faithfully to Fick's law, with discernible sensitivity to the crosslinking conditions being implemented. Within the evaluated membranes, proton conductivities exhibited a span of between 10-3 and 10-2 S/cm, while methanol permeabilities ranged from 10-8 to 10-7 cm2/s. A remarkable revelation surfaced during the course of this study, as it became evident that the structural attributes and properties of the PVA films, under the influence of distinct crosslinking conditions, underwent coherent modifications. These changes were intrinsically linked to alterations in crosslinking degree and crystallinity, reinforcing the interdependence of these parameters in shaping the characteristics of PVA films intended for diverse fuel cell applications.

Genotoxicity Evaluation of Titanium Dioxide Nanoparticles In Vivo and In Vitro: A Meta-Analysis.

BACKGROUND: Recent studies have raised concerns about genotoxic effects associated with titanium dioxide nanoparticles (TiO2 NPs), which are commonly used. This meta-analysis aims to investigate the potential genotoxicity of TiO2 NPs and explore influencing factors. METHODS: This study systematically searched Chinese and English literature. The literature underwent quality evaluation, including reliability evaluation using the toxicological data reliability assessment method and relevance evaluation using routine evaluation forms. Meta-analysis and subgroup analyses were performed using R software, with the standardized mean difference (SMD) as the combined effect value. RESULTS: A total of 26 studies met the inclusion criteria and passed the quality assessment. Meta-analysis results indicated that the SMD for each genotoxic endpoint was greater than 0. This finding implies a significant association between TiO2 NP treatment and DNA damage and chromosome damage both in vivo and in vitro and gene mutation in vitro. Subgroup analysis revealed that short-term exposure to TiO2 NPs increased DNA damage. Rats and cancer cells exhibited heightened susceptibility to DNA damage triggered by TiO2 NPs (p < 0.05). CONCLUSIONS: TiO2 NPs could induce genotoxicity, including DNA damage, chromosomal damage, and in vitro gene mutations. The mechanism of DNA damage response plays a key role in the genotoxicity induced by TiO2 NPs.

Adverse outcome pathway exploration of furan-induced liver fibrosis in rats: Genotoxicity pathway or oxidative stress pathway through CYP2E1 activation?

Furan is a widespread endogenous contaminant in heat-processed foods that can accumulate rapidly in the food chain and has been widely detected in foods, such as wheat, bread, coffee, canned meat products, and baby food. Dietary exposure to this chemical may bring health risk. Furan is classified as a possible category 2B human carcinogen by the International Agency for Research on Cancer, with the liver as its primary target organ. Hepatic fibrosis is the most important nontumoral harmful effect of furan and also an important event in the carcinogenesis of furan. Although the specific mechanism of furan-induced liver fibrosis is still unclear, it may involve oxidative stress and genetic toxicity, in which the activation of cytochrome P450 2E1 (CYP2E1) may be the key event. Thus, we conducted a study using an integrating multi-endpoint genotoxicity platform in 120-day in vivo subchronic toxicity test in rats. Results showed that the rats with activated CYP2E1 exhibited DNA double-strand breaks in D4, gene mutations in D60, and increased expression of reactive oxygen species and nuclear factor erythroid 2-related factor 2 in D120. Necrosis, apoptosis, hepatic stellate cell activation, and fibrosis also occurred in the liver, suggesting that furan can independently affect liver fibrosis through oxidative stress and genotoxicity pathways. Point of Departure (PoD) was obtained by benchmark-dose (BMD) method to establish health-based guidance values. The human equivalent dose of PoD derived from BMDL05 was 2.26 µg/kg bw/d. The findings laid a foundation for the safety evaluation and risk assessment of furan and provided data for the further construction and improvement of the adverse outcome pathway network in liver fibrosis.

Investigation on Nanocomposites of Polysulfone and Different Ratios of Graphene Oxide with Structural Defects Repaired by Cellulose Nanocrystals.

In this manuscript, nanofillers of graphene oxide (GO) and cellulose nanocrystal (CNC) with different weight ratios (G/C ratios), named GC 2:1, GC 4:1, GC 8:1, GC 16:1, and GC 32:1, were successfully prepared. Characterization methods such as Raman spectroscopy, X-ray photoelectron spectrometry (XPS), and thermogravimetric analysis (TGA) were performed. Additionally, the effects of these samples on the thermal stability, mechanical properties, and gas barrier properties of polysulfone (PSF) nanocomposites were investigated. A hydrophilic interaction took place between CNC and GO; as a consequence, CNCs were modified on the surface of GO, thus repairing the structural defects of GO. With the increase in G/C ratios, the repair effect of insufficient CNCs on the defects of GO decreased. The G/C ratio had a great influence on the improvement of mechanical properties, thermal stability, and gas barrier properties of nanocomposites. Compared with PSF/GC 2:1 and PSF/GC 32:1, the differences in the growth rates of tensile strength, elongation at break, and Young's modulus were 30.0%, 39.4%, and 15.9%, respectively; the difference in Td 3% was 7 °C; the difference in decline rate of O2 permeability was 40.0%.

The mediation role of blood lipids on the path from air pollution exposure to MAFLD: A longitudinal cohort study.

BACKGROUND & AIMS: Recent cross-sectional studies found that exposure to ambient air pollution (AP) was associated with an increased risk of metabolic dysfunction-associated fatty liver disease (MAFLD). The alternation of blood lipids may explain the association, but epidemiological evidence is lacking. We aimed to examine whether and to what extent the association between long-term exposure to AP and incident MAFLD is mediated by blood lipids and dyslipidemia in a prospective cohort. METHODS: We included 6350 participants from the China Multi-Ethnic Cohort (CMEC, baseline 2018-2019, follow-up 2020-2021). Three-year average (2016-2018) of AP (PM1, PM2.5, PM10, NO2), blood lipids (TC, LDL-C, HDL-C, TG with their combinations) and incident MAFLD for each individual were assessed chronologically. Linear and logistic regression was used to assess the associations among AP, blood lipids, and MAFLD, and the potential mediation effects of blood lipids were evaluated using causal mediation analysis. RESULTS: A total of 744 participants were newly diagnosed with MAFLD at follow-up. The odds ratios of MAFLD associated with a 10 µm increase in PM1, PM2.5, and NO2 were 1.35 (95 % CI: 1.14, 1.58), 1.34 (1.10, 1.65) and 1.28 (1.14, 1.44), respectively. Blood lipids are important mediators between AP and incident MAFLD. LDL-C (Proportion Mediated: 6.9 %), non-HDL (13.4 %), HDL-C (20.7 %), LDL/HDL (30.1 %), and dyslipidemia (6.5 %) significantly mediated the association between PM2.5 and MAFLD. For PM1, the indirect effects were similar to those for PM2.5, with a larger value for the direct effect, and the mediation proportion by blood lipids was less for NO2. CONCLUSION: Blood lipids are important mediators between AP and MAFLD, and can explain 5 %-30 % of the association between AP and incident MAFLD, particularly cholesterol-related variables, indicating that AP could lead to MAFLD through the alternation of blood lipids. These findings provided mechanical evidence of AP leading to MAFLD in epidemiological studies.

Effects of Menaquinone-7 on the Bone Health of Growing Rats under Calcium Restriction: New Insights from Microbiome-Metabolomics.

Insufficient calcium intake during growth is a global public health concern. The aim of this study was to investigate the effects of dietary menaquinone-7 (MK-7) on bone accrual in growing Sprague-Dawley rats under calcium restriction. Following 13 weeks of treatment, various bone quality parameters, including microarchitecture, were measured. Fecal and cecal samples were subjected to microbiome (16S rRNA gene sequencing) analyses, while metabolomics analysis of the cecum and humerus samples was analyzed based on UHPLC-Q/TOF-MS. We found that calcium deficiency diminished the richness of the microbiome and disrupted microbiome composition, accompanied by an elevation in the relative abundance of Parasutterella. Furthermore, calcium insufficiency escalated the level of isovaleric acid and modified the metabolic profiles. MK-7 supplementation significantly increased the cortical thickness, cortical bone area, and the calcium content of the femur. Apart from improving bone calcium deposition and diminishing bone resorption, the mechanisms underlying the beneficial effects of MK on bone quality also involve the modulation of the host's metabolic pathways and the composition of gut microbiota. The gut-bone axis holds promise as an efficacious target for ameliorating calcium deficiency in children's bone quality, and MK-7 is a promising dietary supplement from this perspective.