Topoisomerase I is an Evolutionarily Conserved Key Regulator for Satellite DNA Transcription.

Repetitive satellite DNAs, divergent in nucleic-acid sequence and size across eukaryotes, provide a physical site for centromere assembly to orchestrate chromosome segregation during the cell cycle. These non-coding DNAs are transcribed by RNA polymerase (RNAP) II and the transcription has been shown to play a role in chromosome segregation, but a little is known about the regulation of centromeric transcription, especially in higher organisms with tandemly-repeated-DNA-sequence centromeres. Using RNA interference knockdown, chemical inhibition and AID/IAA degradation, we show that Topoisomerase I (TopI), not TopII, promotes the transcription of α-satellite DNAs, the main type of satellite on centromeres in human cells. Mechanistically, TopI localizes to centromeres, binds RNAP II and facilitates RNAP II elongation on centromeres. Interestingly, in response to DNA double-stranded breaks (DSBs) induced by chemotherapy drugs or CRSPR/Cas9, α-satellite transcription is dramatically stimulated in a DNA damage checkpoint-independent but TopI-dependent manner. These DSB-induced α-satellite RNAs were predominantly derived from the α-satellite high-order repeats of human centromeres and forms into strong speckles in the nucleus. Remarkably, TopI-dependent satellite transcription also exists in mouse 3T3 and Drosophila S2 cells and in Drosophila larval imaginal wing discs and tumor tissues. Altogether, our findings herein reveal an evolutionally conserved mechanism with TopI as a key player for the regulation of satellite transcription at both cellular and animal levels.

CDK11 facilitates centromeric transcription to maintain centromeric cohesion during mitosis.

Actively-transcribing RNA polymerase (RNAP)II is remained on centromeres to maintain centromeric cohesion during mitosis, although it is largely released from chromosome arms. This pool of RNAPII plays an important role in centromere functions. However, the mechanism of RNAPII retention on mitotic centromeres is poorly understood. We here demonstrate that Cyclin-dependent kinase (Cdk)11 is involved in RNAPII regulation on mitotic centromeres. Consistently, we show that Cdk11 knockdown induces centromeric cohesion defects and decreases Bub1 on kinetochores, but the centromeric cohesion defects are partially attributed to Bub1. Furthermore, Cdk11 knockdown and the expression of its kinase-dead version significantly reduce both RNAPII and elongating RNAPII (pSer2) levels on centromeres and decrease centromeric transcription. Importantly, the overexpression of centromeric α-satellite RNAs fully rescues Cdk11-knockdown defects. These results suggest that the maintenance of centromeric cohesion requires Cdk11-facilitated centromeric transcription. Mechanistically, Cdk11 localizes on centromeres where it binds and phosphorylates RNAPII to promote transcription. Remarkably, mitosis-specific degradation of G2/M Cdk11-p58 recapitulates Cdk11-knockdown defects. Altogether, our findings establish Cdk11 as an important regulator of centromeric transcription and as part of the mechanism for retaining RNAPII on centromeres during mitosis.

Changes of Serum D-Dimer, NT-proBNP, and Troponin I Levels in Patients with Acute Aortic Dissection and the Clinical Significance.

Objective: To investigate the changes in blood D-dimer (D-D), high-sensitivity troponin I (hs-cTnI), and N-terminal B-type brain natriuretic peptide (NT-proBNP) levels in patients with acute aortic dissection (AAD) and its clinical significance. Methods: Forty patients with AAD diagnosed in our hospital from January 2018 to December 2019 were selected as the observation group, and 40 patients with chest pain and non-AAD treated in our hospital during the same period were included in the control group. The patients were subdivided into a death group and a survival group as per the prognosis. The clinical symptoms and signs of the two groups of patients upon admission were observed, and the levels of D-D, hs-cTnI, and NT-proBNP were determined. The differences in clinical data, plasma D-D, hs-cTnI, and NT-proBNP levels between the two groups of patients were analyzed. Results: The clinical data and physical signs were homogeneous between the two groups (P > 0.05), while a significant elevation in the level of hs-cTnI in the control group was observed 24 h after admission (P < 0.05). The observation group showed significantly higher levels of D-D, NT-proBNP, and hs-cTnI than the control group (P < 0.05). The prevalence and surgical cure rate of Stanford A in the survival group were significantly lower in contrast with the death group, with an obvious higher intervention cure rate in the survival group. Higher D-dimer and NT-proBNP levels were identified at 24 h after admission versus upon admission, and the death group had a greater increase of D-dimer and NT-proBNP levels. Conclusion: Clinical symptoms and signs are insufficient to constitute a diagnosis of AAD, whereas the elevated expression levels of D-D, hs-cTnI, and NT-proBNP demonstrated great potential for the diagnosis and prognosis of AAD.

Tfh Exosomes Derived from Allergic Rhinitis Promote DC Maturation Through miR-142-5p/CDK5/STAT3 Pathway.

Background: Dendritic cells (DCs) play an important role in allergen signal presentation. Many studies showed that follicular helper T cells (Tfhs) are related to allergic rhinitis (AR). However, the relationship between Tfhs and DCs and the mechanism of their interaction with AR remain unclear. Purpose: To explore the mechanism of Tfhs on DC maturation in AR. Methods: Tfhs were isolated from OVA-sensitized mice and co-cultured with DCs derived from mouse bone marrow. DCs maturity was monitored using flow cytometry and immunofluorescence staining. Exosomes of Tfhs were extracted, and miRNAs inside exosomes were analyzed using RNA-seq to identify differentially expressed genes. Using the TargetScan algorithm, it was predicted that CDK5 is a direct target gene, which is validated in a dual luciferase assay. DCs were treated with miR-142-5p mimics or inhibitors or transfected with CDK5 small interfering RNAs to verify the regulatory effects of miR-142-5p and CDK5 on DC maturation. How CDK5 regulates STAT3 signaling pathway was investigated to elucidate the molecular mechanism of DC maturation. Finally, in an in vivo experiment, the exosomes of AR-derived Tfhs were injected intravenously to detect their promotion of AR. Results: Tfh exosomes derived from AR mice contributed to DC maturation. RNA-seq results showed that miR-142-5p was the differentially decreased gene. Using the TargetScan algorithm, it was predicted that CDK5 was the target gene for the direct action of miR-142-5p. By detecting the effects of changes in the expression levels of miR-142-5p and CDK5 on DC maturation, it was demonstrated that miR-142-5p inhibits DC maturation by inhibiting CDK5 expression. CDK5-regulated STAT3 signaling pathway during DC maturation, and inhibition of the STAT3 signaling pathway can reverse the regulation of miR-142-5p/CDK5 on DC maturation. Finally, in vivo experiment indicated that the injection of AR-derived Tfhs promoted AR in mice. Conclusion: Tfh-derived exosomes induce DC maturation by regulating miR-142-5p/CDK5/STAT3 signaling pathway, thereby promoting the occurrence of AR.

Physicochemical, Oxidative Stability and Sensory Properties of Frankfurter-Type Sausage as Influenced by the Addition of Carrot (Daucus carota) Paste.

This study examined the addition of carrot paste (CP) at levels of 3%, 5%, and 10% as a potential antioxidant in frankfurter-type sausages, denoted as F1, F2, and F3. F0, was a control sample with no addition of CP. All formulated samples were stored for 14 days during which their physicochemical, oxidative stability, and sensory properties were evaluated. Results showed that the pH of frankfurter-type sausages was not affected by the addition of CP, however, higher pH values were observed in CP-enriched samples on the first day of production and subsequent storage days. Cooking loss (CL) in frankfurter-type sausages was in the range of 2.20% to 2.87%, with the CP-enriched samples having a lower CL percentage, particularly F3 samples, compared to the control. Protein and fat content were lower in CP-enriched samples, but ash content increased. CP-enriched frankfurter-type sausages recorded significantly higher polyphenol contents compared to the control. Total polyphenol content in CP-enriched samples F1, F2, and F3 was higher throughout storage compared to the control. Lower peroxide values were also recorded in CP-enriched samples F1 (2.5 meq/kg), F2 (2.4 meq/kg), and F3 (2.2 meq/kg) compared to the control (2.9 meq/kg), demonstrating greater 2,2-Diphenyl-1-picrylhydrazyl (DPPH) antioxidant activity than the control samples. Formulations treated with 10% CP gained significantly higher scores for color, texture, and overall acceptability. Principal component analysis showed that higher inclusion levels of CP in formulation improved the sensory quality and oxidative stability. In conclusion, CP could be used to enhance the oxidative stability of frankfurter-type sausage without negatively influencing the sensory quality.

Techniques for Dealcoholization of Wines: Their Impact on Wine Phenolic Composition, Volatile Composition, and Sensory Characteristics.

The attention of some winemakers and researchers over the past years has been drawn towards the partial or total dealcoholization of wines and alcoholic beverages due to trends in wine styles, and the effect of climate change on wine alcohol content. To achieve this, different techniques have been used at the various stages of winemaking, among which the physical dealcoholization techniques, particularly membrane separation (nanofiltration, reverse osmosis, evaporative perstraction, and pervaporation) and thermal distillation (vacuum distillation and spinning cone column), have shown promising results and hence are being used for commercial production. However, the removal of alcohol by these techniques can cause changes in color and losses of desirable volatile aroma compounds, which can subsequently affect the sensory quality and acceptability of the wine by consumers. Aside from the removal of ethanol, other factors such as the ethanol concentration, the kind of alcohol removal technique, the retention properties of the wine non-volatile matrix, and the chemical-physical properties of the aroma compounds can influence changes in the wine sensory quality during dealcoholization. This review highlights and summarizes some of the techniques for wine dealcoholization and their impact on wine quality to help winemakers in choosing the best technique to limit adverse effects in dealcoholized wines and to help meet the needs and acceptance among different targeted consumers such as younger people, pregnant women, drivers, and teetotalers.

Correlation between serum 25-hydroxyvitamin D level and coronary heart disease.

OBJECTIVE: To test the relationship between serum 25-hydroxyvitamin D[25(OH)D], interleukin-6 (IL-6), and the severity of coronary heart disease (CHD). METHODS: A total of 150 patients with suspected myocardial ischemia presenting to our hospital from January 2018 to January 2020 were recruited. All patients underwent percutaneous coronary angiography (CAG). According to CAG results, they were divided into normal group (n=40) and CHD group (n=110). According to the coronary Gensini score, CHD patients were divided into 62 cases in the low-risk group (< 20 points), 31 cases in the moderate-risk group (20-40 points), and 17 cases in the high-risk group (> 40 points). The Gensini scores and serum 25(OH)D and IL-6 levels in each group were recorded, and the correlation between the serum 25(OH)D and IL-6 levels and the severity of the disease was analyzed. The Essen Stroke Risk Scale (ESRS) was evaluated and compared between the two groups. RESULTS: The serum 25(OH)D, IL-6 level, and ESRS score in the CHD group and the normal group statistically differed (P < 0.05). In the CHD group, Gensini score, serum IL-6 level and ESRS score increased with the increase of coronary artery stenosis, and 25(OH)D level decreased with the increase of coronary artery stenosis, and all the differences were significant (P < 0.05). Pearson correlation analysis demonstrated that serum IL-6 levels in patients with CHD are positively correlated with the severity of the disease (r=0.724, P < 0.001), and 25(OH)D levels are in a negative relation (r=-0.522, P < 0.001). CONCLUSION: A decrease of serum 25(OH)D level and increase in IL-6 level in patients with CHD are associated with the severity of CHD. This may provide a reference for clinical diagnosis, treatment, and prognosis.

Centromeric transcription maintains centromeric cohesion in human cells.

Centromeric transcription has been shown to play an important role in centromere functions. However, lack of approaches to specifically manipulate centromeric transcription calls into question that the proposed functions are a direct consequence of centromeric transcription. By monitoring nascent RNAs, we found that several transcriptional inhibitors exhibited distinct, even opposing, efficacies on the suppression of ongoing gene and centromeric transcription in human cells, whereas under the same conditions, total centromeric RNAs were changed to a lesser extent. The inhibitor suppressing ongoing centromeric transcription weakened centromeric cohesion, whereas the inhibitor increasing ongoing centromeric transcription strengthened centromeric cohesion. Furthermore, expression of CENP-B DNA-binding domain or CENP-B knockdown moderately increased centromeric transcription without altering gene transcription; as a result, centromeric cohesion was accordingly strengthened. Targeting of the Kox1-KRAB domain with CENP-B DB to centromeres specifically decreased centromeric transcription and weakened centromeric cohesion. Thus, based on these findings, we propose that a major function of centromeric transcription is to maintain centromeric cohesion in human cells.

Adsorption and desorption behaviors of antibiotics by tire wear particles and polyethylene microplastics with or without aging processes.

Tire wear particles (TWP), as the significant proportion of microplastics (MPs), has adsorbed much attention due to its widespread presence in aquatic ecosystem. However, compared with traditional MPs, few studies have investigated the interaction between TWP and coexisting contaminants. The adsorption-desorption behavior of chlortetracycline (CTC) and amoxicillin (AMX) by original and aged TWP was studied, and polyethylene (PE) was studied for comparison. After aging, small holes and cracks were produced on the surfaces of the TWP and PE. Meanwhile, the specific surface areas (SBET) of TWP and PE increased, but the aged TWP had a larger SBET than the aged PE, which indicated that TWP was more likely to degrade than PE. The adsorption kinetics results showed that the adsorption of CTC and AMX by TWP and PE conformed to the pseudo-second-order model. The adsorption isotherm results showed that the Freundlich model could describe the adsorption isotherm data of TWP and PE. The adsorption capacity of antibiotics by TWP increased by 1.13-23.40 times, and by 1.08-14.24 times on PE, after aging. Desorption experiments showed that the desorption amount of antibiotics on TWP and PE in simulated gastric fluid was greater than that in ultrapure water. The desorption amount and rate of CTC and AMX from TWP were higher than those of PE, indicating that TWP might be more harmful to the aquatic environment and organisms. These findings indicated that, compared with PE, TWP might have stronger carrier effects on antibiotics, which might pose more serious potential risks to the aquatic environment and organisms, especially considering the effects of the aging process. This study would expand the research on environmental risk of MPs and contribute to providing new insights into the evaluation of tire material particles.

[Correlation of B-type Natriuretic Peptide Level with Hemodynamic Parameters and Inflammatory Cytokines in Patients with Gram-negative Sepsis].

Objective To study the correlation of B-type natriuretic peptide(BNP)level with hemodynamic parameters and inflammatory cytokines in patients with Gram-negative sepsis,and further determine the main factors for the significant increase of BNP level. Methods The prospective study method was applied,and septic patients infected with Gram-negative bacteria from May 2017 to October 2019 were enrolled.The patients were divided into the BNP<2400 ng/L group and the BNP≥2400 ng/L group by taking the average value of BNP as the dividing point.The independent predictors of BNP≥2400 ng/L were analyzed by Logistic regression.Pearson correlation analysis was used to analyze the correlation between BNP and various indicators. Results A total of 106 patients with Gram-negative sepsis were included,among which 60 cases present with higher serum BNP levels than the average of(2398.45 ± 421.45)ng/L.Thus BNP≥2400 ng/L was considered as a significantly increased BNP level.Multiple logistic regression analysis showed that cardiac index(CI)[odds ratio (OR)=0.428,95% confidence interval (95%CI)=0.743-0.965,P=0.011],left ventricular ejection fraction(LVEF) (OR=0.394,95%CI=0.182-0.549,P=0.013),lactic acid (OR=1.983,95%CI=1.264-3.420,P=0.023),endotoxin (OR=6.146,95%CI=4.091-8.226,P=0.001),procalcitonin(PCT) (OR=6.513,95%CI=4.365-8.210,P=0.005) and cardiac troponin I(cTnI) (OR=1.144,95%CI=1.001-2.150,P=0.047) were independent predictors of BNP≥2400 ng/L in patients with Gram-negative sepsis.Pearson correlation analysis showed that BNP was negatively correlated with CI(R=-0.514,P<0.001)and LVEF (R=-0.552,P<0.001),whereas positively correlated with lactic acid (R=0.265,P=0.032),cTnI (R=0.204, P=0.036),PCT(R=0.801,P<0.001),and endotoxin(R=0.765,P<0.001). Conclusions In septic patients with Gram-negative bacterial infection,LVEF,CI,lactic acid,cTnI,endotoxin and PCT are all independent risk factors for the significant increase of BNP,and endotoxin and PCT were more significantly correlated with BNP increase.Endotoxin and inflammatory reaction may be the more important stimulators of BNP increase in septic patients with Gram-negative bacterial infection.

High-Entropy Pyrochlore A2B2O7 with Both Heavy and Light Rare-Earth Elements at the A Site.

A novel class of high-entropy pyrochlore ceramics (HEPCs) with multiple heavy and light rare-earth elements at the A site were successfully synthesized via solid-state reaction. Both the XRD patterns and Raman spectroscopy demonstrated the single pyrochlore structure feature of seven kinds of HEPCs. Electron microscopic images revealed the typical morphology and the homogeneous distribution of all rare-earth elements. It can be concluded that the significance of configuration entropy in the HEPC system has promoted the tervalent lanthanide nuclides to form a single pyrochlore structure. This work is expected to provide guidance for the further design of high-entropy pyrochlore/fluorite ceramics.

Effect of Different Clarification Treatments on the Volatile Composition and Aromatic Attributes of 'Italian Riesling' Icewine.

The aim of this study was to evaluate the influence of clarification treatments on volatile composition and aromatic attributes of wine samples. 'Italian Riesling' icewines from the Hexi Corridor Region of China were clarified by fining agents (bentonite (BT) and soybean protein (SP)), membrane filtration (MF), and centrifugation (CF) methods. The clarity, physicochemical indexes, volatile components, and aromatic attributes of treated wines were investigated. Both the fining agents and mechanical clarification treatments increased the transmittance and decreased the color intensity of icewine samples. Bentonite fining significantly influenced the total sugar content, total acidity and volatile acidity. Total acidity decreased 2-3.5% and volatile acidity 2-12%. MF showed the greatest influence on total phenol content, decreasing the initial content by 12%, while other treatments by less than 8%. Volatile analysis indicated that both the categories and contents of volatile compounds of wine samples decreased. MF treatment showed the most significant influence, while SP fining showed much lower impact. Odor activity values indicated the compound with the highest odor activity in Italian Riesling icewines was ß-damascenone. For this compound, BT and SP did not show significant differences, however, in MF and CF it decreased by 20% and 63%, respectively. Furthermore, with high impact on aroma were: ethyl hexanoate which reduced by 20-80% especially in MF; rose oxide which extremely reduced in MF and undetected in BT, SP, and CF; isoamyl acetate which reduced by 3-33% and linalool decreased by 10-20% and undetected for BT. Principle component analysis indicated that icewine clarified by different methods could be distinguished and positively correlated with odor-active compounds. Floral and fruity were the dominant aroma series in icewine samples followed by fatty, earthy, spicy, vegetative and pungent flavor. The total odor active value of these series significantly (p < 0.5) decreased in different clarification treatments. Sensory evaluation showed similar results, but the SP and CF wine samples achieved better sensory quality. This study provides information that could help to optimize the clarification of ice wines.

Carbon Nanofibers Propped Hierarchical Porous SiOC Ceramics Toward Efficient Microwave Absorption.

The hierarchical porous SiOC ceramics (HPSCs) have been prepared by the pyrolysis of precursors (the mixture of dimethicone and KH-570) and polyacrylonitrile nanofibers (porous template). The HPSCs possess hierarchical porous structure with a BET surface area of 51.4 m2/g and have a good anti-oxidation property (only 5.1 wt.% weight loss). Owing to the porous structure, the HPSCs deliver an optimal reflection loss value of - 47.9 dB at 12.24 GHz and an effective absorption bandwidth of 4.56 GHz with a thickness of 2.3 mm. The amorphous SiOC, SiOx, and free carbon components within SiOC make contributions to enhancing dipolar polarization. Besides, the abundant interfaces between SiOC and carbon nanofibers (CNFs) are favorable for improving interfacial polarization. The conductive loss arisen from cross-linked CNFs can also boost the microwave absorption performance.

SP1 governs primordial folliculogenesis by regulating pregranulosa cell development in mice.

Establishment of the primordial follicle (PF) pool is pivotal for the female reproductive lifespan; however, the mechanism of primordial folliculogenesis is poorly understood. Here, the transcription factor SP1 was shown to be essential for PF formation in mice. Our results showed that SP1 is present in both oocytes and somatic cells during PF formation in the ovary. Knockdown of Sp1 expression, especially in pregranulosa cells, significantly suppressed nest breakdown, oocyte apoptosis, and PF formation, suggesting that SP1 expressed by somatic cells functions in the process of primordial folliculogenesis. We further demonstrated that SP1 governs the recruitment and maintenance of Forkhead box L2-positive (FOXL2+) pregranulosa cells using an Lgr5-EGFP-IRES-CreERT2 (Lgr5-KI) reporter mouse model and a FOXL2+ cell-specific knockdown model. At the molecular level, SP1 functioned mainly through manipulation of NOTCH2 expression by binding directly to the promoter of the Notch2 gene. Finally, consistent with the critical role of granulosa cells in follicle survival in vitro, massive loss of oocytes in Sp1 knockdown ovaries was evidenced before puberty after the ovaries were transplanted under the renal capsules. Conclusively, our results reveal that SP1 controls the establishment of the ovarian reserve by regulating pregranulosa cell development in the mammalian ovary.

Monitoring of 49 Pesticides and 17 Mycotoxins in Wine by QuEChERS and UHPLC-MS/MS Analysis.

An effective method for the determination of 49 pesticide residues and 17 mycotoxins in wine by a modified QuEChERS (quick, easy, cheap, effective, rugged, and safe) method and ultrahigh-performance liquid chromatography-tandem mass spectrometry was developed. The target compounds were extracted with 1% (v/v) formic acid-acetonitrile, and no cleanup steps were required. The extracts were separated on a C18 chromatographic column (2.1 mm × 50 mm, 1.7 µm) with acetonitrile and water with 0.2% formic acid solution and ammonium acetate (10 mM) as the mobile phases under gradient elution at a flow rate of 0.2 mL/min. The determination was conducted using electrospray ionization in positive ion mode with multiple reaction monitoring. The analytes were quantified by comparison with matrix-matched standard solutions. The good linearities were obtained in the range of 0.05 to 500.0 µg/kg, and the correlation coefficients were all greater than 0.9935. The average recoveries of the 66 target compounds ranged from 69% to 119%, and the RSDs were in the range of 1% to 10%. The limits of detection were in the range of 0.05 to 20.0 µg/kg. The method was proved to be rapid, selective, sensitive, and stable, and it has been applied to analysis of 64 wine samples.

Dual-functional SiOC ceramics coating modified carbon fibers with enhanced microwave absorption performance.

Multi-functional carbon fiber (CF) based composites have great potential as new-type microwave absorption materials (MAMs). However, it was still a huge challenge to integrate antioxidation and MA properties into CF based composites. Herein, the SiOC ceramics coating modified carbon fibers (SiOC/CFs) were prepared by a polymer precursor pyrolysis method. The X-ray photoelectron spectroscopy (XPS) revealed that the SiOC coating was composed of SiOC, SiO2, and amorphous carbon phases. The SiOC ceramics as dual-functional coating not only heightened the oxidation temperature from 415 °C to 890 °C, but also highly improved the microwave absorbing ability from -12.60 dB to -47.50 dB. The enhanced MA performance could be attributed to multiple reflections in the cross-linked structure, various polarization relaxation processes, and the favorable impedance matching effect. The SiOC ceramics coating as a semiconductor could suppress the skin effect originating from the cross-linked CF network, thus leading to a favorable impedance matching behavior.

Simultaneous Analysis of 20 Mycotoxins in Grapes and Wines from Hexi Corridor Region (China): Based on a QuEChERS⁻UHPLC⁻MS/MS Method.

The aim of this study is to develop and validate an improved analytical method for the simultaneous quantification of 20 types of mycotoxins in grapes and wines. In this research, the optimization of tandem mass spectrometer (MS/MS) parameter, ultra-high pressure liquid chromatography (UHPLC) separation, and QuEChERS procedure, which includes wine/water ratio, the amount and type of salt, clean-up sorbent, were performed, and the whole separation of mycotoxins was accomplished within 7 min analyzing time. Under optimum conditions, recoveries ranged from 85.6% to 117.8%, while relative standard deviation (RSD) remained between 6.0% and 17.5%. The limit of detection (LOD, 0.06⁻10 µg/L) and the limit of quantification (LOQ, 0.18⁻30 µg/L) were lower than those permitted by legislation in food matrices, which demonstrated the high sensitivity and applicability of this efficient method. Finally, 36 grapes and 42 wine samples from the Hexi Corridor region were analyzed. Penicillic acid (PCA), mycophenolic acid (MPA), cyclopiazonic acid (CPA), fumonisin B1 (FB1) and zearalenone (ZEN) were detected in a small number of grape samples with lower concentrations between 0.10 µg/L and 81.26 µg/L. Meanwhile, ochratoxin A (OTA), aflatoxin B2 (AFB2), MPA, CPA, and ZEN were detected in some wine counterparts with concentrations ranged from 0.10 µg/L to 4.62 µg/L. However, the concentrations of the detected mycotoxins were much lower than the maximum legal limits set of other products.

CDC42 controls the activation of primordial follicles by regulating PI3K signaling in mouse oocytes.

BACKGROUND: In mammalian females, progressive activation of dormant primordial follicles in adulthood is crucial for the maintenance of the reproductive lifespan. Misregulated activation of primordial follicles leads to various ovarian diseases, such as premature ovarian insufficiency (POI). Although recent studies have revealed that several functional genes and pathways, such as phosphoinositide 3-kinase (PI3K) signaling, play roles in controlling the activation of primordial follicles, our understanding of the molecular networks regulating the activation progress is still incomplete. RESULTS: Here, we identify a new role for cell division cycle 42 (CDC42) in regulating the activation of primordial follicles in mice. Our results show that CDC42 expression increases in oocytes during the activation of primordial follicles in the ovary. Disruption of CDC42 activity with specific inhibitors or knockdown of Cdc42 expression significantly suppresses primordial follicle activation in cultured mouse ovaries. Conversely, the follicle activation ratio is remarkably increased by overexpression of CDC42 in ovaries. We further demonstrate that CDC42 governs the process of primordial follicle activation by binding to phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta (p110ß) and regulating the expression levels of PTEN in oocytes. Finally, we extend our study to potential clinical applications and show that a short-term in vitro treatment with CDC42 activators could significantly increase the activation rates of primordial follicles in both neonatal and adult mouse ovaries. CONCLUSION: Our results reveal that CDC42 controls the activation of primordial follicles in the mammalian ovary and that increasing the activity of CDC42 with specific activators might improve the efficiency of in vitro activation approaches, opening avenues for infertility treatments.

Bacterial magnetic particles improve testes-mediated transgene efficiency in mice.

Nano-scaled materials have been proved to be ideal DNA carriers for transgene. Bacterial magnetic particles (BMPs) help to reduce the toxicity of polyethylenimine (PEI), an efficient gene-transferring agent, and assist tissue transgene ex vivo. Here, the effectiveness of the BMP-PEI complex-conjugated foreign DNAs (BPDs) in promoting testes-mediated gene transfer (TMGT) in mouse was compared with that of liposome-conjugated foreign DNAs. The results proved that through testes injection, the clusters of BPDs successfully reached the cytoplasm and the nuclear of spermatogenesis cell, and expressed in testes of transgene founder mice. Additionally, the ratio of founder mice obtained from BPDs (88%) is about 3 times higher than the control (25%) (p < 0.05). Interestingly, the motility of sperms recovered from epididymis of the founder mice from BPD group were significantly improved, as compared with the control (p < 0.01). Based on classic breeding, the ratio of transgene mice within the first filial was significantly higher in BPDs compared with the control (73.8% versus 11.6%, p < 0.05). TMGT in this study did not produce visible histological changes in the testis. In conclusion, nano-scaled BPDs could be an alternative strategy for efficiently producing transgene mice in vivo.

Rac1 modulates the formation of primordial follicles by facilitating STAT3-directed Jagged1, GDF9 and BMP15 transcription in mice.

The size of the primordial follicle pool determines the reproductive potential of mammalian females, and establishment of the pool is highly dependent on specific genes expression. However, the molecular mechanisms by which the essential genes are regulated coordinately to ensure primordial follicle assembly remain a mystery. Here, we show that the small GTPase Rac1 plays an indispensable role in controlling the formation of primordial follicles in mouse ovary. Employing fetal mouse ovary organ culture system, we demonstrate that disruption of Rac1 retarded the breakdown of germline cell cysts while Rac1 overexpression accelerated the formation of primordial follicles. In addition, in vivo inhibitor injection resulted in the formation of multi-oocyte follicles. Subsequent investigation showed that Rac1 induced nuclear import of STAT3 by physical binding. In turn, nuclear STAT3 directly activated the transcription of essential oocyte-specific genes, including Jagged1, GDF9, BMP15 and Nobox. Further, GDF9 and BMP15 regulated the translation of Notch2 via mTORC1 activation in pregranulosa cells. Overexression or addition of Jagged1, GDF9 and BMP15 not only reversed the effect of Rac1 disruption, but also accelerated primordial follicle formation via Notch2 signaling activation. Collectively, these results indicate that Rac1 plays important roles as a key regulator in follicular assembly.