Identification and Quantification of Locus-Specific 8-Oxo-7,8-dihydroguanine in DNA at Ultrahigh Resolution Based on G-Triplex-Assisted Rolling Circle Amplification.

Damage of reactive oxygen species to various molecules such as DNA has been related to many chronic and degenerative human diseases, aging, and even cancer. 8-Oxo-7,8-dihydroguanine (OG), the most significant oxidation product of guanine (G), has become a biomarker of oxidative stress as well as gene regulation. The positive effect of OG in activating transcription and the negative effect in inducing mutation are a double-edged sword; thus, site-specific quantification is helpful to quickly reveal the functional mechanism of OG at hotspots. Due to the possible biological effects of OG at extremely low abundance in the genome, the monitoring of OG is vulnerable to signal interference from a large amount of G. Herein, based on rolling circle amplification-induced G-triplex formation and Thioflavin T fluorescence enhancement, an ultrasensitive strategy for locus-specific OG quantification was constructed. Owing to the difference in the hydrogen-bonding pattern between OG and G, the nonspecific background signal of G sites was completely suppressed through enzymatic ligation of DNA probes and the triggered specificity of rolling circle amplification. After the signal amplification strategy was optimized, the high detection sensitivity of OG sites with an ultralow detection limit of 0.18 amol was achieved. Under the interference of G sites, as little as 0.05% of OG-containing DNA was first distinguished. This method was further used for qualitative and quantitative monitoring of locus-specific OG in genomic DNA under oxidative stress and identification of key OG sites with biological function.

New G-Triplex DNA Dramatically Activates the Fluorescence of Thioflavin T and Acts as a Turn-On Fluorescent Sensor for Uracil-DNA Glycosylase Activity Detection.

G-triplexes are G-rich oligonucleotides composed of three G-tracts and have absorbed much attention due to their potential biological functions and attractive performance in biosensing. Through the optimization of loop compositions, DNA lengths, and 5'-flanking bases of G-rich sequences, a new stable G-triplex sequence with 14 bases (G3-F15) was discovered to dramatically activate the fluorescence of Thioflavin T (ThT), a water-soluble fluorogenic dye. The fluorescence enhancement of ThT after binding with G3-F15 reached 3200 times, which was the strongest one by far among all of the G-rich sequences. The conformations of G3-F15 and G3-F15/ThT were studied by circular dichroism. The thermal stability measurements indicated that G3-F15 was a highly stable G-triplex structure. The conformations of G3-F15 and G3-F15/ThT in the presence of different metal cations were studied thoroughly by fluorescent spectroscopy, circular dichroism, and nuclear magnetic resonance. Furthermore, using the G3-F15/ThT complex as a fluorescent probe, a robust and simple turn-on fluorescent sensor for uracil-DNA glycosylase activity was developed. This study proposes a new systematic strategy to explore new functional G-rich sequences and their ligands, which will promote their applications in diagnosis, therapy, and biosensing.

Hypertension in non-obese children and BMI in adulthood: the Bogalusa heart study.

OBJECTIVE: This study explored the association between hypertension(HTN) in non-obese children body mass index (BMI) in adulthood. METHODS: A retrospective analysis of 1111 participants from the Bogalusa Heart Study was conducted, in which data on hypertension history during childhood in non-obese children, anthropometric and cardiovascular risk factors and other indicators from cross-sectional examinations in adulthood were collected. BMI was used as both a continuous and a categorical variable, and multivariate linear regression modelling and logistic regression modelling were used. RESULTS: Of the 1111 participants finally enrolled, 40 (3.60%) had HTN during childhood. After adjusting for demographic characteristics, lipid, glucose and insulin levels in childhood, and smoking status, alcohol intake, and disease history as adults, HTN among non-obese children was positively associated with BMI in adulthood (ß = 2.64 kg/m2, 95% CI: 0.88-4.40, P = 0.0033), and the odds of being overweight or obese was 3.71 times higher in the group with a history of hypertension in childhood than those without a history of HTN(95% CI: 1.11-12.46, P = 0.0337). CONCLUSION: Among non-obese children, hypertension is at risk for higher levels of BMI in adulthood. Identifying and controlling blood pressure and childhood may aid in the prevention of adult obesity.

Pubertal exposure to Microcystin-LR arrests spermatogonia proliferation by inducing DSB and inhibiting SIRT6 dependent DNA repair in vivo and in vitro.

The reproduction toxicity of pubertal exposure to Microcystin-LR (MC-LR) and the underlying mechanism needs to be further investigated. In the current study, pubertal male ICR mice were intraperitoneally injected with 2 µg/kg MC-LR for four weeks. Pubertal exposure to MC-LR decreased epididymal sperm concentration and blocked spermatogonia proliferation. In-vitro studies found MC-LR inhibited cell proliferation of GC-1 cells and arrested cell cycle in G2/M phase. Mechanistically, MC-LR exposure evoked excessive reactive oxygen species (ROS) and induced DNA double-strand break in GC-1 cells. Besides, MC-LR inhibited DNA repair by reducing PolyADP-ribosylation (PARylation) activity of PARP1. Further study found MC-LR caused proteasomal degradation of SIRT6, a monoADP-ribosylation enzyme which is essential for PARP1 PARylation activity, due to destruction of SIRT6-USP10 interaction. Additionally, MG132 pretreatment alleviated MC-LR-induced SIRT6 degradation and promoted DNA repair, leading to the restoration of cell proliferation inhibition. Correspondingly, N-Acetylcysteine (NAC) pre-treatment mitigated the disturbed SIRT6-USP10 interaction and SIRT6 degradation, causing recovered DNA repair and subsequently restoration of cell proliferation inhibition in MC-LR treated GC-1 cells. Together, pubertal exposure to MC-LR induced spermatogonia cell cycle arrest and sperm count reduction by oxidative DNA damage and simultaneous SIRT6-mediated DNA repair failing. This study reports the effect of pubertal exposure to MC-LR on spermatogenesis and complex mechanism how MC-LR induces spermatogonia cell proliferation inhibition.

1-Nitropyrene disrupts testicular steroidogenesis via oxidative stress-evoked PERK-eIF2α pathway.

Our previous study showed 1-Nitropyrene (1-NP) exposure disrupted testicular testosterone synthesis in mouse, but the exact mechanism needs further investigation. The present research found 4-phenylbutyric acid (4-PBA), an endoplasmic reticulum (ER) stress inhibitor, recovered 1-NP-induced ER stress and testosterone synthases reduction in TM3 cells. GSK2606414, a protein kinase-like ER kinase (PERK) kinase inhibitor, attenuated 1-NP-induced PERK-eukaryotic translation initiation factor 2α (eIF2α) signaling activation and downregulation of steroidogenic proteins in TM3 cells. Both 4-PBA and GSK2606414 attenuated 1-NP-induced steroidogenesis disruption in TM3 cells. Further studies used N-Acetyl-L-cysteine (NAC) as a classical antioxidant to explore whether oxidative stress-activated ER stress mediated 1-NP-induced testosterone synthases reduction and steroidogenesis disruption in TM3 cells and mouse testes. The results showed NAC pretreatment mitigated oxidative stress, and subsequently attenuated ER stress, particularly PERK-eIF2α signaling activation, and downregulation of testosterone synthases in 1-NP-treated TM3 cells. More importantly, NAC extenuated 1-NP-induced testosterone synthesis in vitro and in vivo. The current work indicated that oxidative stress-caused ER stress, particularly PERK-eIF2α pathway activation, mediates 1-NP-downregulated steroidogenic proteins and steroidogenesis disruption in TM3 cells and mouse testes. Significantly, the current study provides a theoretical basis and demonstrates the experimental evidence for the potential application of antioxidant, such as NAC, in public health prevention, particularly in 1-NP-induced endocrine disorder.

An In-Situ Cyanidation Strategy To Access Tetracyanodiacenaphthoanthracene Diimides with High Electron Mobilities Exceeding 10†cm2 †V-1 s-1.

A family of novel highly π-extended tetracyano-substituted acene diimides, named as tetracyanodiacenaphthoanthracene diimides (TCDADIs), have been synthesized using a facile four-fold Knoevenagel condensation strategy. Unlike conventional cyano substitution reactions, our approach enables access to a large π-conjugated backbone with the in-situ formation of four cyano substitutents at room temperature while avoiding extra cyano-functionalization reactions. TCDADIs decorated with different N-alkyl substituents present good solubility, near-coplanar backbones, good crystallinity, and low-lying lowest unoccupied molecular orbital energies of -4.33 eV, all of which contribute to desirable electron-transport performance when applied in organic field-effect transistors (OFET). The highest electron mobility of an OFET based on a 2-hexyldecyl-substituted TCDADI single crystal reaches 12.6 cm2  V-1 s-1 , which is not only among the highest values for the reported n-type organic semiconductor materials (OSMs) but also exceeds that of most n-type OSMs decorated with imide units.

A sulfamethoxazole molecularly imprinted two-dimensional photonic crystal hydrogel sensor.

In this paper, a molecularly imprinted two-dimensional photonic crystal hydrogel sensor (SMZ-MIPCH) for the sensitive and label-free recognition of sulfamethoxazole (SMZ) was prepared. The SMZ-MIPCH sensor response performance was investigated via measuring the diameter of the Debye ring (D). When the SMZ-MIPCH sensor recognized SMZ, the diameter of the Debye ring gradually decreased and the particle spacing (d) of the photonic crystals gradually increased. As the SMZ concentration increased from 0 to 10-4 mol L-1, the diameter decreased by 15.2 mm and the corresponding particle spacing increased by 131 nm. As the diffraction peak wavelength of the sensor gradually red-shifted, the color changed from blue to green and finally to orange-red. A good linear relationship was found between the variation of the particle spacing (Δd) and the value of the logarithm of the SMZ concentration (lg c) in the range from 10-16 mol L-1 to 10-10 mol L-1. The limit of detection of the SMZ-MIPCH sensor is 10-16 mol L-1. In the presence of analogues of SMZ, such as sulfisoxazole, sulfadiazine, and sulfamethazine, the diameter changed only slightly, indicating that the SMZ-MIPCH sensor had specific recognition abilities for SMZ. The SMZ-MIPCH sensor has the advantages of high sensitivity, specific recognition, and naked eye detection, and it can be used for the detection of SMZ in water samples.

The Exploration of a New Stable G-Triplex DNA and Its Novel Function in Electrochemical Biosensing.

A G-triplex, a new kind of DNA structure, has been identified as an intermediate in the folding of G-quadruplexes. However, the studies on G-triplexes are still very limited, and the functions and applications of G-triplexes need to be further developed. In this paper, a new G-triplex sequence (5'-CTGGGAGGGAGGGA-3', G3), obtained by truncating four bases (GGGA) from the 3' end of an 18-base G-quadruplex sequence (G4), was found to significantly decrease the diffusion current of methylene blue (MB). In particular, we proved that (a) MB stabilized the structure of G3 and increased the Tm of G3 considerably based on circular dichroism; and (b) MB formed a 1:1 noncovalent complex with G3 based on electrospray ionization mass spectrometry. Moreover, molecular dynamics simulations established reliable speculation in the folding topology of G3 and interaction sites between G3 and MB. Based on the strong affinity of G3 with MB, we further developed a novel function of G3 as an electrochemical signal read-out and applied it in the fabrication of a sensitive homogeneous electrochemical aptasensor for cocaine. The features we observed in the G3/MB complex will serve as a new inspiring guideline for developing functional short G-rich ligands.

High-throughput ultra-sensitive discrimination of single nucleotide polymorphism via click chemical ligation.

Single nucleotide polymorphisms (SNPs) have been proven to be important biomarkers for disease diagnosis, prognosis and disease pathogenesis. Here, taking the advantages of a self-assembled oligonucleotide sandwich structure and robust chemical reactions, we have developed a simple, high-throughput and effective colorimetric analytical technique termed CuAAC-based ligation-assisted assays (CuAAC-LA) for SNP detection using a DNA-BIND 96-well plate. With the 5'-azide and 3'-alkyne groups labelled on two oligonucleotide probes, the target DNA can direct a Cu(i)-catalyzed alkyne-azide cycloaddition (CuAAC) click reaction. Since the small difference in duplex stability caused by a single-nucleotide mismatch was amplified by the steric effects of these reactive groups for the ligation reaction of an unstable duplex, CuAAC-LA exhibited an ultra-sensitive discrimination ability for a mutant type target in the presence of large amounts of wild type targets. As low as 0.05% SNP could be clearly detected, which was better than most previously reported methods by various DNA ligases, indicating that a simple and rapid synthetic method i.e., the DNA template-directed click reaction held the potential to replace the ligase for SNP detection.

Methods of Population Spatialization Based on the Classification Information of Buildings from China's First National Geoinformation Survey in Urban Area: A Case Study of Wuchang District, Wuhan City, China.

Most of the currently mature methods that are used globally for population spatialization are researched on a single level, and are dependent on the spatial relationship between population and land covers (city, road, water area, etc.), resulting in difficulties in data acquisition and an inability to identify precise features on the different levels. This paper proposes a multi-level population spatialization method on the different administrative levels with the support of China's first national geoinformation survey, and then considers several approaches to verify the results of the multi-level method. This paper aims to establish a multi-level population spatialization method that is suitable for the administrative division of districts and streets. It is assumed that the same residential house has the same population density on the district level. Based on this assumption, the least squares regression model is used to obtain the optimized prediction model and accurate population space prediction results by dynamically segmenting and aggregating house categories.In addition, it is assumed that the distribution of the population is relatively regular in communities that are spatially close to each other, and that the population densities on the street level are similar, so the average population density is assessed by optimizing the community and surrounding residential houses on the street level. Finally, the scientificalness and rationality of the proposed method is proved by spatial autocorrelation analysis, overlay analysis, cross-validation analysis and accuracy assessment methods.

Polarimetric Calibration and Quality Assessment of the GF-3 Satellite Images.

The GaoFen-3 (GF-3) satellite is the first fully polarimetric synthetic aperture radar (SAR) satellite designed for civil use in China. The satellite operates in the C-band and has 12 imaging modes for various applications. Three fully polarimetric SAR (PolSAR) imaging modes are provided with a resolution of up to 8 m. Although polarimetric calibration (PolCAL) of the SAR system is periodically undertaken, there is still some residual distortion in the images. In order to assess the polarimetric accuracy of this satellite and improve the image quality, we analyzed the polarimetric distortion errors and performed a PolCAL experiment based on scattering properties and corner reflectors. The experiment indicates that the GF-3 images can meet the satellite's polarimetric accuracy requirements, i.e., a channel imbalance of 0.5 dB in amplitude and ±10 degrees in phase and a crosstalk accuracy of -35 dB. However, some images still contain residual polarimetric distortion. The experiment also shows that the residual errors of the GF-3 standard images can be diminished after further PolCAL, with a channel imbalance of 0.26 dB in amplitude and ±0.2 degrees in phase and a crosstalk accuracy of -42 dB.

Associations between urinary level of bisphenol A, phthalates, 8-iso-prostaglandin-F2α, and emotional and behavioral problems among Chinese adolescents.

BACKGROUND: Emotional and behavioral problems (EBPs) of adolescents is a worldwide public health problem. Bisphenol A (BPA) and phthalate (PAEs) are prevalent and potentially toxic to human health. Therefore, this study aimed to investigate the associations between urinary level of BPA, PAEs, 8-iso-prostaglandin-F2α (8-iso-PGF2α), and EBPs. METHODS: A total of 865 Chinese adolescents were included in this study and EBPs was assessed using the Strengths and Difficulties Questionnaire (SDQ). Urinary concentrations of BPA and seven PAEs metabolites in adolescents were determined by high performance liquid chromatography-tandem mass spectrometry. Urinary 8-iso-PGF2α concentration was detected by enzyme-linked immunosorbent assay (ELISA). Spearman rank correlation analysis, multivariate logistic regression analysis, restricted cubic spline functions were used to explore the relationship between the levels of BPA, PAEs, 8-iso-PGF2α and EBPs. RESULTS: BPA and PAEs metabolites were positively associated with EBPs in Chinese adolescents. And the 8-iso-PGF2α was significantly non-linearly correlated with emotional symptoms, conduct problems, peer problems and total difficulties. Furthermore, 8-iso-PGF2α may partially mediate the association between BPA and PAEs exposure and EBPs. LIMITATIONS: This study was a cross-sectional study, the cause-effect relationship between BPA, PAEs exposure and EBPs could not be determined. A single spot urine sample for BPA and PAEs exposure characterization maybe could not represent their long-term exposure level. CONCLUSIONS: High exposure of BPA and PAEs are associated with EBPs, which may be partly mediated by oxidative stress among adolescents. The results of this study could provide certain ideas for subsequent related research.

Trends in gut-heart axis and heart failure research (1993-2023): A bibliometric and visual analysis.

Background: The incidence of heart failure, the terminal stage of several cardiovascular diseases, is increasing owing to population growth and aging. Bidirectional crosstalk between the gut and heart plays a significant role in heart failure. This study aimed to analyze the gut-heart axis and heart failure from a bibliometric perspective. Methods: We extracted literature regarding the gut-heart axis and heart failure from the Web of Science Core Collection database (January 1, 1993, to June 30, 2023) and conducted bibliometric and visualization analyses using Microsoft Excel, CiteSpace, VOSviewer, and the R package "bibliometrix." Results: The final analysis included 1646 articles with an average of 35.38 citations per article. Despite some fluctuations, the number of articles published per year has steadily increased over the past 31 years, particularly since 2018. A total of 9412 authors from 2287 institutions in 86 countries have contributed to this field. The USA and China have been the most productive countries, with the Cleveland Clinic in the USA and Charité-Universitätsmedizin Berlin in Germany being the most active institutions. The cooperation between countries/regions and institutions was relatively close. Professor Tang WHW was the most productive author in the field and the journal Shocks published the highest number of articles. "Heart failure," "gut microbiota," "trimethylamine N-oxide," and "inflammation" were the most common keywords, representing the current research hotspots. The keyword burst analysis indicated that "gut microbiota" and "short-chain fatty acids" are the current frontier research topics in this field. Conclusion: Research on the gut-heart axis and heart failure is increasing. This bibliometric analysis indicated that the mechanisms associated with the gut-heart axis and heart failure, particularly the gut microbiota, trimethylamine N-oxide, inflammation, and short-chain fatty acids, will become hotspots and emerging trends in research in this field. These findings provide valuable insights into current research and future directions.

CoP/Co heterojunction on porous g-C3N4 nanosheets as a highly efficient catalyst for hydrogen generation.

Designing non-precious catalysts to synergistically achieve a facilitated exposure of abundant active sites is highly desired but remains a significant challenge. Herein, a hetero-structured catalyst CoP-Co supported on porous g-C3N4 nanosheets (CoP-Co/CN-I) was prepared by pyrolysis and P-inducing strategy. The optimal catalyst achieves a turnover frequency (TOF) of 26 min-1 at room temperature and the apparent activation energy (Ea) is 35.5 kJ·mol-1. The catalytic activity is ranked top among the non-precious metal phosphides or the other supports. Meanwhile, the catalytic activity has no significant decrease even after 5 cycles. The CoP/Co interfaces provide richly exposed active sites, optimize hydrogen/water absorption free energy via electronic coupling, and thus improve the catalytic activity. The experimental results reveal that the CoP/Co heterojunction improves the catalytic activity due to the construction of dual-active sites. This research facilitates the innovative construction of non-noble metal catalysts to meet industrial demand for heterogeneous catalysis.

Role of sleep in asthenospermia induced by di (2-ethyl-hexyl) phthalate.

Di (2-ethyl-hexyl) phthalate (DEHP) mainly enters the human body through the digestive tract, respiratory tract, and skin. At the same time, it has reproductive and developmental toxicity, neurotoxicity, and so on, which can cause the decrease of sperm motility. Asthenospermia is also known as low sperm motility, and the semen quality of men in some areas of China is declining year by year. Interestingly, previous studies have shown that sleep disorders can also lead to asthenospermia. However, the relationship between sleep, DEHP, and asthenospermia is still unclear. Analysis of the National Health and Nutrition Examination Survey (NHANES) population database showed that DEHP was associated with sleep disorders, and subsequent experiments in mice and Drosophila indicated that DEHP exposure had certain effects on sleep and asthenospermia. Furthermore, we analyzed the Comparative Toxicogenomics Database (CTD) to find out the common signaling pathway among the three: hypoxia-inducible factor 1(HIF-1). Then Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) was used to screen out the proteins that DEHP affected the HIF-1 pathway: glyceraldehyde-3-phosphate dehydrogenase (GAPDH), serine/threonine-protein kinase (AKT1), epidermal growth factor receptor (EGFR), and finally Western blot analysis was used to detect the expression levels of the three proteins. Compared with the control group, DEHP decreased the protein expression levels of GAPDH and AKT1 in the HIF-1 pathway, and caused sleep disorders and decreased sperm motility. This study provides preliminary evidence for exploring the mechanism among DEHP, sleep disorders, and asthenospermia.

Single-Incision Plus One Port Laparoscopic Surgery for Myomectomy: A Retrospective Study.

BACKGROUND: The purpose of this study was to evaluate the effect of single-incision plus one port laparoscopic surgery (SILS + 1) for myomectomy. METHODS: We retrospectively analyzed data from patients who underwent laparoendoscopic single-site myomectomy (LESS-M group, n = 40) and SILS + 1 (SILS + 1-M group, n = 40) for myomectomy at our hospital from October 2018 through December 2020. The patients' baseline demographic information and clinical data were compared between the two groups. RESULTS: The results showed that no significant difference in basic characteristics or between the number, size, and location of uterine myomas between the two groups (p < 0.05). However, the surgery was more difficult and the total operating time was significantly longer in the LESS-M group compared to the SILS + 1-M group (83.5 ± 14.2 vs. 108.2 ± 18.1 min, p = 0.001). Moreover, the estimated intraoperative blood loss (113.4 ± 46.5 vs. 211.4 ± 60.3 ml, p = 0.001) and changes in hemoglobin level (13.1 ± 7.6 vs. 18.2 ± 6.0, p = 0.001) were significantly lower in the SILS + 1-M group compared to the LESS-M group. In addition, no serious intraoperative or postoperative complications occurred after surgery in either group. The clinical outcomes in the SILS + 1-M group were associated with a significant reduction in total surgical time compared to the LESS-M group (p < 0.05). CONCLUSION: SILS + 1 for myomectomy is popular in clinics, with a satisfactory clinical effect.

Preparation and application of cinnamon-Litsea cubeba compound essential oil microcapsules for peanut kernel postharvest storage.

This research developed a novel, efficient and safe antimildew for peanut kernel postharvest storage. The antimildew, cinnamon-Litsea cubeba compound essential oil (CLCEO) microcapsule (CLCEOM), was synthesized with CLCEO as core materials and ß-cyclodextrin as wall materials. Fourier transform infrared spectroscopy and gas chromatography-mass spectrometry analyses indicated that major antifungal compounds of CLCEO were encapsulated in the cavity of ß-cyclodextrin. The inhibition zone experiment showed that CLCEOM retained antifungal effect on Aspergillus spp. strains even after storage for 2 months at 4 â„ƒ. Besides, CLCEOM reduced total number of fungal colonies, relative abundance of Aspergillus spp., and aflatoxin B1 content of peanut kernels, and had positive effect on slowing down the increase in acid value of peanut oil without causing any adverse effect on the viability and sensory properties during storage process. Overall, CLCEOM presented good preservative effects on peanut kernels, providing evidence for its potential use as antimildew for peanut storage.

Penpulimab and anlotinib in an elderly patient with recurrent cervical cancer: a case report and literature review.

We present a case of a 76-year-old patient with recurrent cervical cancer who underwent first-line treatment with penpulimab combined with anlotinib. The patient was diagnosed with poorly differentiated stage III C1r cervical squamous cell carcinoma and received standard cisplatin-sensitized chemoradiotherapy, subsequently achieving a good treatment effect of complete response. Recurrence occurred nearly 14 months after treatment, with multiple metastases including in the brain and lung. Oral anlotinib was less effective, but the treatment of penpulimab combined with anlotinib showed an obvious curative effect. It has been maintained for more than 17 months, and as of April 2023 the patient is still maintaining her response. Our case suggests that penpulimab combined with anlotinib has promising efficacy in the treatment of elderly patients with recurrent cervical cancer.

A 76-year-old female patient was diagnosed with cervical cancer. She received a type of treatment called chemoradiotherapy, which helped her get better. However, after 14 months of treatment, the cancer came back and spread to other parts of the body including the brain and lungs. She was given a medicine called anlotinib, which did not work very well. Then she received two medications at the same time, penpulimab and anlotinib, which worked better. Her cancer went away completely and has stayed this way for 17 months. This case shows that the combination of penpulimab and anlotinib can help treat older people with cervical cancer that comes back.

Newly discovered developmental and ovarian toxicity of 3-monochloro-1,2-propanediol in Drosophila melanogaster and cyanidin-3-O-glucoside's protective effect.

3-Monochloro-1,2-propanediol (3-MCPD) is a pervasive environmental pollutant that is unintentionally produced during industrial production and food processing. Although some studies reported the carcinogenicity and male reproduction toxicity of 3-MCPD thus far, it remains unexplored whether 3-MCPD hazards to female fertility and long-term development. In this study, the model Drosophila melanogaster was employed to evaluate risk assessment of emerging environmental contaminants 3-MCPD at various levels. We found that flies on dietary exposure to 3-MCPD incurred lethality in a concentration- and time-dependent way and interfered with metamorphosis and ovarian development, resulting in developmental retardance, ovarian deformity and female fecundity disorders. Mechanistically, 3-MCPD caused redox imbalance observed as a drastically increased oxidative status in ovaries, confirmed by increased reactive oxygen species (ROS) and decreased antioxidant activities, which is probably responsible for female reproductive impairments and developmental retardance. Intriguingly, these defects can be substantially prevented by a natural antioxidant, cyanidin-3-O-glucoside (C3G), further confirming a critical role of ovarian oxidative damage in the developmental and reproductive toxicity of 3-MCPD. The present study expanded the findings that 3-MCPD acts as a developmental and female reproductive toxicant, and our work provides a theoretical basis for the exploitation of a natural antioxidant resource as a dietary antidote for the reproductive and developmental hazards of environmental toxicants that act via increasing ROS in the target organ.

The activity comparison of six dietary flavonoids identifies that luteolin inhibits 3T3-L1 adipocyte differentiation through reducing ROS generation.

Mitochondrial reactive oxygen species (ROS)generation plays an essential role in the process of adipocyte differentiation and is involved in the development of obesity and associated metabolic diseases. Various dietary flavonoids possess the substantial anti-adipogenic activity. However, it is unclear whether these flavonoids inhibit adipocyte differentiation by reducing ROS generation. In this study, the effects of six common dietary flavonoids on adipocyte differentiation were assessed in 3T3-L1 cells. The flavonoids with the same backbone of 5,7-dihydroxylflavone, including flavones apigenin, chrysin, luteolin and flavonols kaempferol, myricetin, quercetin, dose-dependently inhibited 3T3-L1 adipocyte differentiation, suggesting an associated hierarchy of inhibitory capability: luteolin > quercetin > myricetin > apigenin/kaempferol > chrysin. Meanwhile, six flavonoids were found to inhibit adipogenic gene expression and the early stage of adipocyte differentiation. Among the tested flavonoids, luteolin significantly reduced both intracellular and mitochondrial ROS generation during adipocyte differentiation. Further, luteolin treatment depressed the elevation of H2O2 concentration in the early stage of 3T3-L1 differentiation and reversed the facilitated effects of exogenous H2O2 on 3T3-L1 adipocyte differentiation and ROS generation. Altogether, the activity comparison of six dietary flavonoids identifies that luteolin inhibits 3T3-L1 adipocyte differentiation through reducing ROS generation, elucidating a new mechanism underlying the anti-adipogenic actions of flavonoids.