Discovery of Cytotoxic Nitric Oxide-Releasing Piperlongumine Derivatives Targeting Wnt/ß-Catenin in Colon Cancer Cells.

Piperlongumine (1) increases reactive oxygen species (ROS) levels and induces apoptosis in cancer cells through various pathways. Nitric oxide (NO) donors have demonstrated potent anticancer activities with exogenous NO being oxidized by ROS in the tumor microenvironment to form highly reactive N-oxides (RNOS). This amplifies oxidative stress cascade reactions, ultimately inducing cancer cell apoptosis. To exploit this synergy, a series of NO-releasing piperlongumine derivatives (2-5) were designed and synthesized. These compounds were expected to release NO in cancer cells, simultaneously generating piperlongumine derivative fragments to enhance the anticancer effects. Compound 6, structurally similar to compounds 2-5 but not releasing NO, served as a control. Among these derivatives, compound 5 exhibited the most potent antiproliferative activity against HCT-116 cells and efficiently released NO in this cell line. Further investigation revealed that compound 5 inhibited colon cancer cell proliferation by modulating ß-catenin expression, which is a pivotal protein in the Wnt/ß-catenin signaling pathway. These findings highlight compound 5 as a promising candidate for colon cancer treatment targeting the Wnt/ß-catenin pathway.

Characterization of tumor endothelial cells (TEC) in gastric cancer and development of a TEC-based risk signature using single-cell RNA-seq and bulk RNA-seq data.

BACKGROUND: Tumor endothelial cells (TECs) are essential participants in tumorigenesis. This study is focused on elucidating the TEC traits in gastric cancer (GC) and constructing a prognostic risk model to predict the clinical outcome of GC patients. METHODS: Single-cell RNA sequencing (scRNA-seq) data were obtained from the GEO database. Using specific markers, the Seurat R package aided in processing scRNA-seq data and identifying TEC clusters. Based on TEC cluster-associated genes identified by Pearson correlation analysis, TEC-related prognostic genes were screened by lasso-Cox regression analysis, thereby constructing a risk signature. A nomogram was created by combining the risk signature with clinicopathological features. RESULTS: Based on the scRNA-seq data, 5 TEC clusters were discovered in GC, with 3 of them showing prognostic associations in GC. A total of 163 genes were pinpointed among 3302 DEGs as significantly linked to TEC clusters, leading to the formulation of a risk signature comprising 8 genes. Furthermore, there was a notable correlation between the risk signature and the immune cell infiltration. Multivariate analysis findings indicated that the risk signature served as an independent prognostic factor for GC. Moreover, its efficacy in forecasting immune response was validated. CONCLUSION: TEC-based risk model is highly effective in predicting the survival outcomes of GC patients and can forecast the immune response. Targeting TECs may significantly inhibit tumor progression and enhance the efficacy of immunotherapy.

FishTEDB 2.0: an update fish transposable element (TE) database with new functions to facilitate TE research.

We launched the initial version of FishTEDB in 2018, which aimed to establish an open-source, user-friendly, data-rich transposable element (TE) database. Over the past 5 years, FishTEDB 1.0 has gained approximately 10 000 users, accumulating more than 450 000 interactions. With the unveiling of extensive fish genome data and the increasing emphasis on TE research, FishTEDB needs to extend the richness of data and functions. To achieve the above goals, we introduced 33 new fish species to FishTEDB 2.0, encompassing a wide array of fish belonging to 48 orders. To make the updated database more functional, we added a genome browser to visualize the positional relationship between TEs and genes and the estimated TE insertion time in different species. In conclusion, we released a new version of the fish TE database, FishTEDB 2.0, designed to assist researchers in the future study of TE functions and promote the progress of biological theories related to TEs. Database URL: https://www.fishtedb.com/.

Neuroprotective effect of marrubiin against MPTP-induced experimental Parkinson's disease in male wistar rats.

In this work, we have analyzed the neuroprotective activity of marrubiin against MPTP-induced Parkinson's disease (PD) in rat brains. MPTP (1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine) a neurotoxin was administered intraperitoneally (i.p.,) to rats and then treated using marrubiin. After marrubiin treatment, rats were trained, and tested for behavioral analyses like cognitive performance, open field test, rotarod test, grip strength test, beam walking test, the status of body weight, and striatal levels of neurotransmitters like dopamine, norepinephrine, serotonin, DOPAC, homovanillic acid, 5-hydroxy indole acetic acid, the status of oxidative stress markers like LPO, protein carbonyl content (PCC), Xanthine oxidase (XO), and status of antioxidant enzyme levels like SOD, CAT, GPX in the striatum and hippocampal tissues, status of neuroinflammatory markers like TNF-α, IL1ß, IL-6, and status of histological architecture in brain striatum were also analyzed. All these parameters were significantly (p < 0.05) abnormal in MPTP-induced rats. Marrubiin (MB) treated shows significant (p < 0.05) near normal behavioral restoration in cognitive performance, open field, rotarod, grip strength, and beam walking tests. Furthermore, the status of body weight, and levels of neurotransmitters, were also significantly (p < 0.05) reversed to near normalcy in marrubiin-treated rats. Similarly, oxidative stress, antioxidant enzyme levels in the striatum and hippocampal tissues, TNF-α, IL1ß, IL-6 levels, and histological architecture were noted to be restored to near normalcy in marrubiin-treated rats. Collectively, our preliminary results highlight the neuroprotective ability of marrubiin. However, the cellular and biochemical mechanisms of marrubiin's neuroprotective ability have to be studied in detail.

Promoting Cross-Link Reaction of Polymers by the Matrix-Filler Interface Effect: Role of Coupling Agents and Intermediate Linkers.

The matrix-filler interface effect plays an important role in determining the structural stability and mechanical properties of polymer composite materials, which remain ambiguous and need to be studied. The network-forming dynamics of poly(3,3-bis (azidomethyl) oxetane-tetrahydrofuran) (PBT) at the ammonium perchlorate (AP) surface was studied by using atomistic molecular dynamics simulation, considering the additives of curing agent toluene diisocyanate (TDI), cross-linker trimethylolpropane (TMP), and coupling agent triethanolamine (TEA). The presence of the AP surface promotes chain cross-link reaction, which is attributed to the increased production of intermediate linkers formed by TDI, TMP, and TEA. The intermediate linker has three reactive sites that can react with PBT main chains to form a cross-linked structure. Owing to the strong interaction with the AP surface, the coupling agent TEA plays a dominant role in forming the intermediate linker. At the early stage of network forming (reaction ratio r < 30%), the AP surface adsorbs TEA, which leads to a maximum contact density to PBT. As r increases to 60%, the density of intermediate linkers near the AP surface reaches a maximum value. Consequently, the chain cross-link reactions between the intermediate linker and PBT main chains are enhanced as r > 60%. This work explains the micromechanism of the promotion of chain cross-link reaction by the interface effect and provides important insights on designing polymer materials with high mechanical properties.

Molecular Dynamics Study on the Stress Concentration in Polymer Networks with Dangling Chains.

Owing to structural defects, stress concentration frequently occurs in polymer network materials (PEMs), significantly altering their overall mechanical properties. Here, we investigate the impact of dangling chain defects on the stress concentration in PEMs using coarse-grained molecular dynamics simulation. Stress distributions on the network structure are calculated by using graph theory, with considering the effects of defect ratio (ϕ) and the distance from defects. It is found that the existence of dangling chains can alleviate stress by dissipating more internal energy. When considering the effects of all defects statistically, the stress concentration consistently occurs near the joint segments between dangling chains and the bare network (i.e., removing all of the dangling chains from the network). The stress concentration effect is significant when defects are in the region near the network edges. Stress tends to concentrate more on the dangling chains at low ϕ, while it tends to concentrate more on the bare network at high ϕ because of the enhanced chain motions in bare network. This implies that the stress concentration effect near the joint segment is predominant at low ϕ, and it is slightly weak as ϕ increased.

Boosting Salinity Energy Extraction Efficiency in Capacitive Mixing by Polyelectrolyte Surface Coating.

The extraction of salinity gradient energy in the capacitive mixing (CapMix) technique can be enhanced by using polyelectrolyte-coated electrodes. The micromechanism of polyelectrolyte (PE) coating enhancing the salinity energy extraction is studied by using a statistical thermodynamic theory. When PE takes same charge sign as the coated electrodes, the extraction efficiency can be boosted owing to the enhanced response of electrical double layer (EDL) to external cell voltage (V0). For the optimal case studied, the extraction efficiency was boosted from 0.25 to 1.25% by PE coatings. Owing to counterion adsorption and the enhanced response of EDL, the extraction energy density presented a local maximum at V0 = 0, which is higher than another local maximum value when V0 ≠ 0. This provides important guidance on the two approaches of CapMix in terms of capacitive Donnan potential (CDP, V0 = 0) and capacitive double-layer expansion (CDLE, V0 ≠ 0). Under the effects of PE coating, the extraction efficiency by CDLE can be improved to about 11% by CDP for the optimal studied case. The synergistic effect of grafting conditions can significantly elevate the energy density and extraction efficiency of the CDP process.

Excellent coagulation performance of polysilicate aluminum ferric for treating oily wastewater from Daqing gasfield: Responses to polymer properties and coagulation mechanism.

The polysilicate aluminum ferric (PSAF) was synthesized via copolymerization of polysilicic acid (PSi), AlCl3 and FeCl3 for treating oily wastewater from Daqing gas field. This study investigated the effects of key preparation factors such as the degree of PSi's preactivation and the ratio of (Fe + Al)/Si and Al/Fe on both polymerization and coagulation performance exhibited by PSAF. To determine the optimal timing for introducing Al3+ and Fe3+, zeta potential, viscosity and particle size were investigated. Additionally, infrared spectroscopy, X-ray powder diffraction, polarizing microscopy and scanning electron microscope analysis were employed to investigate the structure and morphology of PSAF. The results indicate that under conditions characterized by a SiO2 mass fraction of 2.5% and pH = 4.5, an optimal timing for introducing Al3+ and Fe3+ is at 100 min when PSi exhibits moderate polymerization along with sufficient stability. When considering molar ratios such as (Al + Fe)/Si being 6:4 and Al/Fe being 5:5, respectively, PSAF falls within a "stable zone" enabling storage period up to 32 days. Moreover, Jar test results demonstrate that at a dosage of 200 mg/L PSAF for oily wastewater treatment in gas fields could reach the maximum turbidity removal efficiency up to 99.5% while oil removal efficiency reach 88.6% without pH adjustment. The copolymerization facilitates the formation of larger PSAF aggregates with positive potential, thereby augmenting the coagulants' adsorption bridging and charge neutralization capabilities. As a result, PSAF has great potential as a practical coagulant for treating oil-containing wastewater in industrial settings.

Unraveling Flow Effect on Capacitive Energy Extraction from Salinity Gradients.

The harvesting of salinity gradient energy through a capacitive double-layer expansion (CDLE) technique is directly associated with ion adsorption and desorption in electrodes. Herein, we show that energy extraction can be modulated by regulating ion adsorption/desorption through water flow. The flow effects on the output energy, capacitance, and energy density under practical conditions are systematically investigated from a theoretical perspective, upon which the optimal operating condition is identified for energy extraction. We demonstrate that the net charge accumulation displays a negative correlation with the water flow velocity and so does the surface charge density, and this causes a nontrivial variation in the magnitude of output energy when water flows are introduced. When high water flows are introduced in both the charging and discharging processes, the energy extraction can be significantly reduced by 47.69-49.32%. However, when a high flow is solely exerted in the discharging process, the energy extraction can be enhanced by 12.94-14.49% even at low operation voltages. This study not only offers a comprehensive understanding of the microscopic mechanisms of surface-engineered energy extraction with water flows but also provides a novel direction for energy extraction enhancement.

Hydrogel dressings with intrinsic antibiofilm and antioxidative dual functionalities accelerate infected diabetic wound healing.

Chronic wounds are often infected with biofilm bacteria and characterized by high oxidative stress. Current dressings that promote chronic wound healing either require additional processes such as photothermal irradiation or leave behind gross amounts of undesirable residues. We report a dual-functionality hydrogel dressing with intrinsic antibiofilm and antioxidative properties that are synergistic and low-leaching. The hydrogel is a crosslinked network with tethered antibacterial cationic polyimidazolium and antioxidative N-acetylcysteine. In a murine diabetic wound model, the hydrogel accelerates the closure of wounds infected with methicillin-resistant Staphylococcus aureus or carbapenem-resistant Pseudomonas aeruginosa biofilm. Furthermore, a three-dimensional ex vivo human skin equivalent model shows that N-acetylcysteine promotes the keratinocyte differentiation and accelerates the re-epithelialization process. Our hydrogel dressing can be made into different formats for the healing of both flat and deep infected chronic wounds without contamination of the wound or needing other modalities such as photothermal irradiation.

Quantitative thresholds for variant enrichment in 13,845 cases: improving pathogenicity classification in genetic hearing loss.

BACKGROUND: The American College of Medical Genetics and Genomics (ACMG)/Association for Molecular Pathology (AMP) guidelines recommend using variant enrichment among cases as "strong" evidence for pathogenicity per the PS4 criterion. However, quantitative support for PS4 thresholds from real-world Mendelian case-control cohorts is lacking. METHODS: To address this gap, we evaluated and established PS4 thresholds using data from the Chinese Deafness Genetics Consortium. A total of 9,050 variants from 13,845 patients with hearing loss (HL) and 6,570 ancestry-matched controls were analyzed. Positive likelihood ratio and local positive likelihood ratio values were calculated to determine the thresholds corresponding to each strength of evidence across three variant subsets. RESULTS: In subset 1, consisting of variants present in both cases and controls with an allele frequency (AF) in cases ≥ 0.0005, an odds ratio (OR) ≥ 6 achieved strong evidence, while OR ≥ 3 represented moderate evidence. For subset 2, which encompassed variants present in both cases and controls with a case AF < 0.0005, and subset 3, comprising variants found only in cases and absent from controls, we defined the PS4_Supporting threshold (OR > 2.27 or allele count ≥ 3) and the PS4_Moderate threshold (allele count ≥ 6), respectively. Reanalysis applying the adjusted PS4 criteria changed the classification of 15 variants and enabled diagnosis of an additional four patients. CONCLUSIONS: Our study quantified evidence strength thresholds for variant enrichment in genetic HL cases, highlighting the importance of defining disease/gene-specific thresholds to improve the precision and accuracy of clinical genetic testing.

Effect of postoperative radiotherapy on survival in patients with completely resected and pathologically confirmed stage N2 non-small-cell lung cancer: a systematic review and meta-analysis.

Background: The role of postoperative radiotherapy (PORT) for patients with completely resected stage N2 non-small-cell lung cancer (NSCLC) has been controversial. This study aimed to investigate the efficacy of PORT and prognosis in these patients. Objectives: An updated meta-analysis was conducted in this study to investigate the efficacy of PORT and prognosis in patients with completely resected and pathologically confirmed stage N2 NSCLC. Design: This study is a systematic review and meta-analysis. Data source and methods: Databases were searched up to 2 March 2022. All trials on patients with completely resected and pathologically confirmed stage N2 NSCLC undergoing PORT were screened, and data indicators in the PORT and non-PORT groups were extracted, respectively. The effect of PORT on overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) was estimated. Subgroup and sensitivity analyses were performed. Results: In all, 20 studies involving 6340 patients were finally included. The PORT significantly increased OS [hazard ratio (HR) = 0.77, 95% CI: 0.71-0.84, p < 0.001), LRFS (HR = 0.63, 95% CI: 0.52-0.76, p < 0.001), and DFS (HR = 0.72, 95% CI: 0.63-0.82, p < 0.001) while it showed no significant difference in improving DMFS (HR = 0.86, 95% CI: 0.71-1.05, p = 0.14). Conclusion: Our results suggest that in the postoperative treatment of patients with completely resected and pathologically confirmed stage N2 NSCLC, the addition of PORT provides better local recurrence control and survival benefit, but no benefit for distant metastases. The PORT may be incorporated into the postoperative treatment options for some patients with high-risk factors. However, it needs to be validated by more prospective studies in the future. Trail registration: CRD42022314095.

Synergistic Effect of Salt and Anionic Surfactants on Interfacial Tension Reduction: Insights from Molecular Dynamics Simulations.

Surfactants are commonly utilized in chemical flooding processes alongside salt to effectively decrease interfacial tension (IFT). However, the underlying microscopic mechanism for the synergistic effect of salt and surfactants on oil displacement remains ambiguous. Herein, the structure and properties of the interface between water and n-dodecane are studied by means of molecular dynamics simulations, considering three types of anionic surfactants and two types of salts. As the salt concentration (ρsalt) increases, the IFT first decreases to a minimum value, followed by a subsequent increase to higher values. The salt ions reduce the IFT only at low ρsalt due to the salt screening effect and ion bridging effect, both of which contribute to a decrease in the nearest head-to-head distance of surfactants. By incorporating salt doping, the IFTs can be reduced by at most 5%. Notably, the IFTs of different surfactants are mainly determined by the hydrogen bond interactions between oxygen atoms in the headgroup and water molecules. The presence of a greater number of oxygen atoms corresponds to lower IFT values. Specifically, for alkyl ethoxylate sulfate, the ethoxy groups play a crucial role in reducing the IFTs. This study provides valuable insights into formulating anionic surfactants that are applicable to oil recovery processes in petroleum reservoirs using saline water.

Exogenous BR delayed peach fruit softening by inhibiting pectin degradation enzyme genes.

Peach fruit deteriorates and senesces rapidly when stored at room temperature. Brassinosteroids (BRs) play an important role in regulating plant growth and development and maintaining fruit quality. However, little information is available on the effect of BRs on the senescence of harvested peach fruit. In this study, different concentrations of BR were used to treat 'Hongniang' peach fruit, and the results showed that 10 µM BR was the most beneficial concentration to delay the senescence of peach fruits. BR treatment delayed the decrease of fruit firmness, the release of ethylene, the increase in water-soluble pectin (WSP) and ionic-soluble pectin (ISP) content and the decrease in covalently bound pectin (CBP) content, inhibited the activities of pectin degradation enzymes, and inhibited the gene expression of PpPME1/3, PpPG, PpARF2, and PpGAL2/16. In addition, BR treatment also inhibited the expression of PpBES1-5/6. Cis-acting regulatory element analysis of pectin degradation enzyme promoters showed that many of them contained BES1 binding elements. All the above results showed that BR treatment had a positive effect on delaying the senescence of peach fruit and prolonging its storage period.

Using the Multidimensional Health Locus of Control Scale Form C to Investigate Health Beliefs About Bladder Cancer Prevention and Treatment Among Male Patients: Cross-Sectional Study.

BACKGROUND: Bladder cancer is a leading cause of death among Chinese male populations in recent years. The health locus of control construct can mediate health status and outcomes, and it has proven helpful in predicting and explaining specific health-related behaviors. However, it has never been used to investigate health beliefs about bladder cancer prevention and treatment. OBJECTIVE: This study aimed to classify male patients into different latent groups according to their beliefs about bladder cancer prevention and treatment and to identify associated factors to provide implications for the delivery of tailored education and interventions and the administration of targeted prevention and treatment. METHODS: First, we designed a four-section questionnaire to solicit data: section 1-age, gender, and education; section 2-the communicative subscale of the All Aspects of Health Literacy Scale; section 3-the eHealth Literacy Scale; and section 4-health beliefs about bladder cancer prevention and treatment measured by the Multidimensional Health Locus of Control Scale Form C. We hypothesized that the participants' health beliefs about bladder cancer prevention and treatment measured in section 4 could be closely associated with information collected through sections 1 to 3. We recruited 718 Chinese male patients from Qilu Hospital of Shandong University, China, and invited them to participate in a web-based questionnaire survey. Finally, we used latent class analysis to identify subgroups of men based on their categorical responses to the items on the Multidimensional Health Locus of Control Scale Form C and ascertained factors contributing to the low self-efficacy group identified. RESULTS: We identified 2 subgroups defined as low and moderate self-efficacy groups representing 75.8% (544/718) and 24.2% (174/718) of the total sample, respectively. Men in the low self-efficacy cluster (cluster 1: 544/718, 75.8%) were less likely to believe in their own capability or doctors' advice to achieve optimal outcomes in bladder cancer prevention and treatment. Men in the moderate self-efficacy cluster (cluster 2: 174/718, 24.2%) had distinct psychological traits. They had stronger beliefs in their own capability to manage their health with regard to bladder cancer prevention and treatment and moderate to high levels of trust in health and medical professionals and their advice to achieve better prevention and treatment outcomes. Four factors contributing to low self-efficacy were identified, including limited education (Year 6 to Year 12), aged ≥44 years, limited communicative health literacy, and limited digital health literacy. CONCLUSIONS: This was the first study investigating beliefs about bladder cancer prevention and treatment among Chinese male patients. Given that bladder cancer represents a leading cause of death among Chinese male populations in recent years, the low self-efficacy cluster and associated contributing factors identified in this study can provide implications for clinical practice, health education, medical research, and health policy-making.

Who Should I Engage With at What Time? A Missing Event-Aware Temporal Graph Neural Network.

Temporal graph neural network (GNN) has recently received significant attention due to its wide application scenarios, such as bioinformatics, knowledge graphs, and social networks. There are some temporal GNNs that achieve remarkable results. However, these works focus on future event prediction and are performed under the assumption that all historical events are observable. In real-world applications, events are not always observable, and estimating event time is as important as predicting future events. In this article, we propose, a missing event-aware temporal GNN, which uniformly models evolving graph structure and timing of events to support predicting what will happen in the future and when it will happen. models the dynamic of both observed and missing events as two coupled temporal point processes (TPPs), thereby incorporating the effects of missing events into the network. Experimental results on several real-world temporal graphs demonstrate that significantly outperforms the existing methods with up to 89% and 112% more accurate time and link prediction. Code can be found on https://github.com/HIT-ICES/TNNLS-MTGN.

Synthetic Phenolic Antioxidants and Their Metabolites in Follicular Fluid and Association with Diminished Ovarian Reserve: A Case-Control Study.

BACKGROUND: Diminished/decreased ovarian reserve (DOR) is a disorder of ovarian function, which severely affects women's reproductive health. Accumulating evidence has found that adverse environmental factors can affect ovarian function. However, whether synthetic phenolic antioxidants (SPAs) exposure is associated with DOR is still unknown. OBJECTIVES: We explored whether concentrations of SPAs and their metabolites are associated with DOR. METHODS: A case-control study was conducted from January 2019 to January 2020 in China. One hundred eighty-one women 20-44 years of age, with (case group, n=63) and without DOR (control group, n=118) were included in our study. The follicular fluid concentrations of typical SPAs and their metabolites were measured, including butylated hydroxyanisole (BHA), tert-butylhydroquinone (TBHQ), butylated hydroxytoluene (BHT), and five BHT metabolites [3,5-di-tert-butyl-4-hydroxy-benzylalcohol (BHT-OH), 3,5-di-tert-butyl-4-hydroxybenzaldehyde (BHT-CHO), 3,5-di-tert-butyl-4-hydroxybenzoic acid (BHT-COOH), 2,6-di-tert-butyl-1,4-benzoquinone (BHT-Q), and 2,6-di-tert-butyl-4-hydroxy-4-methylcyclohexa-2,5-dien-1-one (BHT-quinol)]. Information about serum basal concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and anti-Müllerian hormone (AMH) and the basal antral follicle count (AFC) was collected. RESULTS: The measured frequencies of BHA, TBHQ, BHT, BHT-OH, BHT-CHO, BHT-COOH, BHT-Q, and BHT-quinol in follicular fluid were 1.7%, 2.2%, 40.3%, 46.4%, 57.5%, 100%, 64.6%, and 49.2%, respectively. The concentrations of BHT-CHO (0.49 ng/mL vs. 0.12 ng/mL, p=0.041), BHT-COOH (0.45 ng/mL vs. 0.28 ng/mL, p<0.001), BHT-Q (0.70 ng/mL vs. 0.13 ng/mL, p<0.001), and the sum of five BHT metabolites (Σ5metabolites; 1.79 ng/mL vs. 1.0 ng/mL, p<0.001) in the case group were significantly higher than those in the control group. The risk of DOR was further analyzed according to the tertiles of chemical concentration. Compared with the low levels of BHT metabolites, the adjusted odds ratios (ORs) for DOR were significantly increased in the high levels of BHT-CHO [OR=3.19, 95% confidence interval (CI): 1.22, 8.31, p=0.018], BHT-COOH [OR=4.73 (95% CI: 1.63, 13.71), p=0.004], and BHT-Q [OR=4.48 (95% CI: 1.69, 11.86), p=0.003] after adjusting for age, body mass index, education, infertility type, triglycerides, and total cholesterol. Moreover, compared with the low level of Σ5metabolites, increased adjusted ORs for DOR were found both in the middle level [OR=4.11 (95% CI: 1.44, 11.75), p=0.008] and high level [OR=5.51 (95% CI: 1.81, 16.77), p=0.003], showing an obvious dose-response relationship (pTrend=0.003). CONCLUSION: In this study, we report the measured frequency and concentrations of BHA, TBHQ, BHT, and their metabolites in follicular fluid. Moreover, we found the concentrations of BHT metabolites, especially BHT-CHO, BHT-COOH, and BHT-Q, are positively associated with the increased risk of DOR. https://doi.org/10.1289/EHP11309.

Low temperatures inhibit the pectin degradation of 'Docteur Jules Guyot' pear (Pyrus communis L.).

The most remarkable characteristic of European pears is extremely perishable and difficult to store after postharvest softening. Low-temperature storage is one of the most commonly used methods to prolong the shelf life of European pears. However, the regulatory mechanism of the low-temperature delay of the softening of European pears is still unclear. In this study, the fruit firmness, pectin polysaccharide content, pectin-degrading enzyme activity, and pectin degradation gene expression of 'Docteur Jules Guyot' pears under low temperature (LT) and room temperature (RT) were analyzed. It was found that water-soluble pectin (WSP) was significantly negatively correlated with fruit flesh firmness, and the activities of several pectin-degrading enzymes were inhibited under LT storage conditions. In addition, it was also found that the gene expression patterns of PcPME2, PcPME3, PcPG1, PcPG2, PcPL, PcGAL1, PcGAL2, PcGAL4, and PcARF1 were inhibited by LT. The C-repeat binding factors PcCBF1 and PcCBF2 were also inhibited by long-term LT storage. Correlation analysis showed that the expression of PcCBFs was positively correlated with pectin-degradation enzyme genes, and we found that the promoters of many pectin-degradation enzyme genes contain the CRT/DRE motif, which CBF can directly bind. Therefore, it is speculated that long-term low-temperature conditions inhibit pectin degradation through PcCBFs.

Functional Health Literacy Among Chinese Populations and Associated Factors: Latent Class Analysis.

BACKGROUND: Poor functional health literacy has been found to be independently associated with poor self-assessed health, poor understanding of one's health condition and its management, and higher use of health services. Given the importance of functional health literacy, it is necessary to assess the overall status of functional health literacy in the general public. However, the literature review shows that no studies of functional health literacy have been conducted among the Chinese population in China. OBJECTIVE: This study aimed to classify Chinese populations into different functional health literacy clusters and ascertain significant factors closely associated with low functional health literacy to provide some implications for health education, medical research, and public health policy making. METHODS: We hypothesized that the participants' functional health literacy levels were associated with various demographic characteristics. Therefore, we designed a four-section questionnaire including the following information: (1) age, gender, and education; (2) self-assessed disease knowledge; (3) 3 validated health literacy assessment tools (ie, the All Aspects of Health Literacy Scale, the eHealth Literacy Scale, and the 6-item General Health Numeracy Test); and (4) health beliefs and self-confidence measured by the Multidimensional Health Locus of Control Scales Form B. Using randomized sampling, we recruited survey participants from Qilu Hospital affiliated to Shandong University, China. The questionnaire was administered via wenjuanxing. A returned questionnaire was valid only when all question items included were answered, according to our predefined validation criterion. All valid data were coded according to the predefined coding schemes of Likert scales with different point (score) ranges. Finally, we used latent class analysis to classify Chinese populations into clusters of different functional health literacy and identify significant factors closely associated with low functional health literacy. RESULTS: All data in the 800 returned questionnaires proved valid according to the predefined validation criterion. Applying latent class analysis, we classified Chinese populations into low (n=292, 36.5%), moderate-to-adequate (n=286, 35.7%), and low-to-moderate (n=222, 27.8%) functional health literacy groups and identified five factors associated with low communicative health literacy: (1) male gender (aged 40-49 years), (2) lower educational attainment (below diploma), (3) age between 38 and 68 years, (4) lower self-efficacy, and (5) belief that staying healthy was a matter of luck. CONCLUSIONS: We classified Chinese populations into 3 functional health literacy groups and identified 5 factors associated with low functional health literacy. These associated factors can provide some implications for health education, medical research, and health policy making.

1H NMR-based urinary metabolic analysis of high-dose cyclophosphamide-induced toxicity in mice.

Cyclophosphamide (CP) is widely used in clinical fields. Beside its therapeutic effects, CP shows toxicity depending on dose and administration schedule. In this study, the urinary metabolic profiles were investigated in mice intraperitoneally injected with high-dose CP (150 mg/kg body weight) once a week over four weeks using nuclear magnetic resonance (NMR)-based metabolomics. Twenty-six metabolites were identified as potential biomarkers by multivariate statistical analysis. A decrease in isoleucine, alanine, N-acetylglutamic acid, proline, methionine, valine, phenylacetylglulamine, dimethylamine, hippurate, acetic acid, lactate, α-oxoglutarate, citrate, malonic acid, creatinine, niacin, ß-hydroxybutyrate, and betaine, whereas an increase in leucine, glutamate, glycine, taurine, phenylacetylglycine, glucose, creatine, and choline were observed in the urine of high-dose CP-treated mice. Metabolites related to amino acid metabolism, energy metabolism, and gut microbial metabolism were changed markedly in the urine. Further metabolic pathway analysis suggested that seven metabolic pathways, including alanine, aspartate, and glutamate metabolism, arginine biosynthesis, glyoxylate, and dicarboxylate metabolism, glycine, serine and threonine metabolism, d-glutamine and d-glutamate metabolism, arginine, and proline metabolism, citrate cycle, as well as the gut microbiota metabolism, were significantly involved in response to high-dose CP treatment. These findings help to predict the toxicity of CP and understand the biological mechanism of the toxicity of CP.