Rab2A regulates the progression of nonalcoholic fatty liver disease downstream of AMPK-TBC1D1 axis by stabilizing PPARγ.

Nonalcoholic fatty liver disease (NAFLD) affects approximately a quarter of the population worldwide, and persistent overnutrition is one of the major causes. However, the underlying molecular basis has not been fully elucidated, and no specific drug has been approved for this disease. Here, we identify a regulatory mechanism that reveals a novel function of Rab2A in the progression of NAFLD based on energy status and PPARγ. The mechanistic analysis shows that nutrition repletion suppresses the phosphorylation of AMPK-TBC1D1 signaling, augments the level of GTP-bound Rab2A, and then increases the protein stability of PPARγ, which ultimately promotes the hepatic accumulation of lipids in vitro and in vivo. Furthermore, we found that blocking the AMPK-TBC1D1 pathway in TBC1D1S231A-knock-in (KI) mice led to a markedly increased GTP-bound Rab2A and subsequent fatty liver in aged mice. Our studies also showed that inhibition of Rab2A expression alleviated hepatic lipid deposition in western diet-induced obesity (DIO) mice by reducing the protein level of PPARγ and the expression of PPARγ target genes. Our findings not only reveal a new molecular mechanism regulating the progression of NAFLD during persistent overnutrition but also have potential implications for drug discovery to combat this disease.

Loss of growth differentiation factor 9 causes an arrest of early folliculogenesis in zebrafish-A novel insight into its action mechanism.

Growth differentiation factor 9 (GDF9) was the first oocyte-specific growth factor identified; however, most information about GDF9 functions comes from studies in the mouse model. In this study, we created a mutant for Gdf9 gene (gdf9-/-) in zebrafish using TALEN approach. The loss of Gdf9 caused a complete arrest of follicle development at primary growth (PG) stage. These follicles eventually degenerated, and all mutant females gradually changed to males through sex reversal, which could be prevented by mutation of the male-promoting gene dmrt1. Interestingly, the phenotypes of gdf9-/- could be rescued by simultaneous mutation of inhibin α (inha-/-) but not estradiol treatment, suggesting a potential role for the activin-inhibin system or its signaling pathway in Gdf9 actions. In gdf9-null follicles, the expression of activin ßAa (inhbaa), but not ßAb (inhbab) and ßB (inhbb), decreased dramatically; however, its expression rebounded in the double mutant (gdf9-/-;inha-/-). These results indicate clearly that the activation of PG follicles to enter the secondary growth (SG) requires intrinsic factors from the oocyte, such as Gdf9, which in turn works on the neighboring follicle cells to trigger follicle activation, probably involving activins. In addition, our data also support the view that estrogens are not involved in follicle activation as recently reported.

Melatonin ameliorates PM2.5-induced spermatogenesis disorder by preserving H3K9 methylation and SIRT3.

There was a link between exposure to PM2.5 and male infertility. Melatonin has beneficial effects on the male reproductive processes. How PM2.5 caused spermatogenesis disturbance and whether melatonin could prevent PM2.5-induced reproductive toxicity have remained unclear. The results showed that PM2.5 could inhibit the Nrf2-mediated antioxidant pathway and distinctly increase the cell apoptosis in testes. Moreover, PM2.5 also perturbed the process of meiosis by modulating meiosis-associated proteins such as γ-H2AX and Stra8. Mechanistically, PM2.5 inhibited G9a-dependent H3K9 methylation and SIRT3-mediated p53 deacetylation, which consistent with decreased sperm count and motility rate in ApoE-/- mice. Further investigation revealed melatonin effectively alleviated PM2.5-induced meiosis inhibition by preserving H3K9 methylation. Melatonin also alleviated PM2.5-induced apoptosis by regulating SIRT3-mediated p53 deacetylation. Overall, our study revealed PM2.5 resulted in spermatogenesis disorder by perturbing meiosis via G9a-dependent H3K9 di-methylation and causing cell apoptosis via SIRT3/p53 deacetylation pathway and provided promising insights into the protective role of melatonin in air pollution associated with male infertility.

Decabromodiphenyl ether induces the chromosome association disorders of spermatocytes and deformation failures of spermatids in mice.

The environmental presence of decabromodiphenyl ether (BDE-209), which is toxic to the male reproductive system, is widespread. The current study investigated its mechanism of toxicity in mice. The results showed, that BDE-209 induced DNA damage, decreased the expression of the promoter of meiosis spermatogenesis- and oogenesis-specific basic helix-loop-helix 1 (Sohlh1), meiosis related-factors Lethal (3) malignant brain tumor like 2 (L3MBTL2), PIWI-like protein 2 (MILI), Cyclin-dependent kinase 2 (CDK2), Cyclin A, synaptonemal complex protein 1 (SYCP1) and synaptonemal complex protein 3 (SYCP3), and caused spermatogenic cell apoptosis, resulting in a decrease in sperm quantity and quality. Furthermore, BDE-209 downregulated the levels of anaphase-promoting complex/cyclosome (APC/C), increased the expression of PIWI-like protein 1 (MIWI) in the cytoplasm of elongating spermatids, and decreased the nuclear levels of RING finger protein 8 (RNF8), ubiquitinated (ub)-H2A/ub-H2B, and Protamine 1 (PRM1)/Protamine 2 (PRM2), while increasing H2A/H2B nuclear levels in spermatids. The reproductive toxicity was persistent for 50 days following the withdrawal of BDE-209 exposure. The results suggested that BDE-209 inhibits the initiation of meiosis by decreasing the expression of Sohlh1. Furthermore, the reduced expression of L3MBTL2 inhibited the formation of chromosomal synaptonemal complexes by depressing the expression of meiosis regulators affecting the meiotic progression and also inhibited histone ubiquitination preventing the replacement of histones by protamines, by preventing RNF8 from entering nuclei, which affected the evolution of spermatids into mature sperm.

Silica Nanoparticles Trigger Chaperone HSPB8-Assisted Selective Autophagy via TFEB Activation in Hepatocytes.

Silica nanoparticles (SiNPs) are one of the most common inorganic nanomaterials. Autophagy is the predominant biological response to nanoparticles and transcription factor EB (TFEB) is a master regulator of the autophagy-lysosome pathway. Previous studies show that SiNPs induce autophagosome accumulation, yet the precise underlying mechanisms remain uncertain. The present study investigates the role of TFEB during SiNP-induced autophagy. SiNP-induced TFEB nuclear translocation is verified using immunofluorescence and western blot assay. The regulation of TFEB is proved to be via EIF2AK3 pathway. A TFEB knockout (KO) cell line is constructed to validate the TFEB involvement in SiNP-induced autophagy. The transcriptomes of wild-type and TFEB KO cells are compared using RNA-sequencing to identify genes of the TFEB-mediated autophagy and lysosome pathways affected by SiNPs. Based on these data and the Human Autophagy Database, four candidate autophagic genes are identified, including HSPB8, ATG4D, CTSB and CTSD. Specifically, that the chaperone HSPB8 is upregulated through SiNP-mediated TFEB activation and forms a chaperone-assisted selective autophagy (CASA) complex with BAG3 and HSC70, triggering HSPB8-assisted selective autophagy, is found. Thus, this study characterizes a novel mechanism underlying SiNP-induced autophagy that helps pave the way for further research on the toxicity and risk assessment of SiNPs.

Genetic and Epigenetic Evidence for Nonestrogenic Disruption of Otolith Development by Bisphenol A in Zebrafish.

Bisphenol A (BPA) is a well-known endocrine-disrupting chemical (EDC) that has estrogenic activities. In addition to disrupting reproductive development and function via estrogenic signaling pathways, BPA can also interfere with nonreproductive functions through nonestrogenic pathways; however, the mechanisms underlying such nonestrogenic activities are not well understood. In this study, we demonstrated that BPA could disrupt otolith formation during the early development of zebrafish with long-lasting ethological effects. Using multiple mutants of estrogen receptors, we provided strong genetic evidence that the BPA-induced otolith malformation was independent of estrogen signaling. Transcriptome analysis revealed that two genes related to otolith development, otopetrin 1 (otop1) and starmaker (stm), decreased their expression significantly after BPA exposure. Knockout of both otop1 and stm genes could phenocopy the BPA-induced otolith malformation, while microinjection of their mRNAs could rescue the BPA-induced abnormalities of otolith formation. Further experiments showed that BPA inhibited the expression of otop1 and stm by activating the MEK/ERK-EZH2-H3K27me3 signaling pathway. Taken together, our study provided comprehensive genetic and molecular evidence that BPA induced the otolith malformation through nonestrogenic pathway during zebrafish early development and its activities involved epigenetic control of key genes (e.g., otop1 and stm) participating in otolith formation.

Amorphous silica nanoparticles cause abnormal cytokinesis and multinucleation through dysfunction of the centralspindlin complex and microfilaments.

BACKGROUND: With the large-scale production and application of amorphous silica nanoparticles (aSiNPs), its adverse health effects are more worthy of our attention. Our previous research has demonstrated for the first time that aSiNPs induced cytokinesis failure, which resulted in abnormally high incidences of multinucleation in vitro, but the underlying mechanisms remain unclear. Therefore, the purpose of this study was firstly to explore whether aSiNPs induced multinucleation in vivo, and secondly to investigate the underlying mechanism of how aSiNPs caused abnormal cytokinesis and multinucleation. METHODS: Male ICR mice with intratracheal instillation of aSiNPs were used as an experimental model in vivo. Human hepatic cell line (L-02) was introduced for further mechanism study in vitro. RESULTS: In vivo, histopathological results showed that the rate of multinucleation was significantly increased in the liver and lung tissue after aSiNPs treatment. In vitro, immunofluorescence results manifested that aSiNPs directly caused microfilaments aggregation. Following mechanism studies indicated that aSiNPs increased ROS levels. The accumulation of ROS further inhibited the PI3k 110ß/Aurora B pathway, leading to a decrease in the expression of centralspindlin subunits MKLP1 and CYK4 as well as downstream cytokines regulation related proteins Ect2, Cep55, CHMP2A and RhoA. Meanwhile, the particles caused abnormal co-localization of the key mitotic regulatory kinase Aurora B and the centralspindlin complex by inhibiting the PI3k 110ß/Aurora B pathway. PI3K activator IGF increased the phosphorylation level of Aurora B and improved the relative ratio of the centralspindlin cluster. And ROS inhibitors NAC reduced the ratio of multinucleation, alleviated the PI3k 110ß/Aurora B pathway inhibition, and then increased the expression of MKLP1, CYK4 and cytokinesis-related proteins, whilst NAC restored the clustering of the centralspindlin. CONCLUSION: This study demonstrated that aSiNPs led to multinucleation formation both in vivo and in vitro. ASiNPs exposure caused microfilaments aggregation and inhibited the PI3k 110ß/Aurora B pathway through excessive ROS, which then hindered the centralspindlin cluster as well as restrained the expression of centralspindlin subunits and cytokinesis-related proteins, which ultimately resulted in cytokinesis failure and the formation of multinucleation.

Ferroptosis mediates decabromodiphenyl ether-induced liver damage and inflammation.

Decabromodiphenyl ether (BDE-209) is an environmental toxin. Increasing evidence showed that BDE-209 exposure induced liver injury, but the mechanism still remains unknown. The present study explored the effect and mechanism of ferroptosis on hepatotoxicity triggered by BDE-209 in vivo and in vitro. In vivo experiment, ICR mice were exposed to BDE-209 for 50 days, and then recovered for 50 days; HepG2 and L02 cells were treated with BDE-209 or/and ferrostatin-1 (Fer-1) for establishing in vitro model. In vivo, the results showed that BDE-209 accumulated in liver and induced liver damage, increased Fe2+ and MDA contents, and blocked the activation of SLC7A11/GSH/GPX4 pathway in liver; BDE-209 also activated IKK/IκB/NF-κB pathway and elevated inflammatory cytokines levels in liver after exposure for 50 days. After BDE-209 stopping exposure 50 days, the severity of liver damage, ferroptosis and inflammatory response were still higher than the corresponding control group. In vitro, ferroptosis inhibitor Fer-1 rescued ferroptotic damage and attenuated cell death in BDE-209-treated HepG2 and L02 cells. In addition, Fer-1 reversed the activation of IKK/IκB/NF-κB pathway and the increase of pro-inflammatory cytokines levels in BDE-209-treated HepG2 and L02 cells. Together, the above results suggested that BDE-209 induced tissue damage and inflammatory response by activating ferroptosis through increasing iron-dependent lipid peroxidation and blocking the activation of SLC7A11/GSH/GPX4 pathway in liver, indicating that ferroptosis is a potential mechanism for BDE-209-induced hepatotoxicity.

Loss of Nobox prevents ovarian differentiation from juvenile ovaries in zebrafish.

As a species without master sex-determining genes, zebrafish displays high plasticity in sex differentiation, making it an excellent model for studying the regulatory mechanisms underlying gonadal differentiation and gametogenesis. Despite being a gonochorist, zebrafish is a juvenile hermaphrodite that undergoes a special phase of juvenile ovary before further differentiation into functional testis and ovary. The mechanisms underlying juvenile ovary formation and subsequent gonadal differentiation remain largely unknown. In this study, we explored the role of Nobox/nobox (new born ovary homeobox protein), another oocyte-specific transcription factor in females, in early zebrafish gonadogenesis using CRISPR/Cas9 technology. As in mammals, nobox is specifically expressed in zebrafish gonads with a dimorphic pattern at juvenile stage. In contrast to the mutant of figla (factor in the germline alpha, another oocyte-specific transcription factor), the nobox mutants showed formation of typical perinucleolar (PN) follicles at primary growth (PG) stage in juvenile gonads, suggesting occurrence of follicle assembly from cystic oocytes (chromatin nucleolar stage, CN). These follicles, however, failed to develop further to form functional ovaries, resulting in all-male phenotype. Despite its expression in adult testis, the loss of nobox did not seem to affect testis development, spermatogenesis and male spawning. In summary, our results indicate an important role for Nobox in zebrafish ovarian differentiation and early folliculogenesis.

MADS-box transcription factors MADS11 and DAL1 interact to mediate the vegetative-to-reproductive transition in pine.

The reproductive transition is an important event that is crucial for plant survival and reproduction. Relative to the thorough understanding of the vegetative phase transition in angiosperms, a little is known about this process in perennial conifers. To gain insight into the molecular basis of the regulatory mechanism in conifers, we used temporal dynamic transcriptome analysis with samples from seven different ages of Pinus tabuliformis to identify a gene module substantially associated with aging. The results first demonstrated that the phase change in P. tabuliformis occurred as an unexpectedly rapid transition rather than a slow, gradual progression. The age-related gene module contains 33 transcription factors and was enriched in genes that belong to the MADS (MCMl, AGAMOUS, DEFICIENS, SRF)-box family, including six SOC1-like genes and DAL1 and DAL10. Expression analysis in P. tabuliformis and a late-cone-setting P. bungeana mutant showed a tight association between PtMADS11 and reproductive competence. We then confirmed that MADS11 and DAL1 coordinate the aging pathway through physical interaction. Overexpression of PtMADS11 and PtDAL1 partially rescued the flowering of 35S::miR156A and spl1,2,3,4,5,6 mutants in Arabidopsis (Arabidopsis thaliana), but only PtMADS11 could rescue the flowering of the ft-10 mutant, suggesting PtMADS11 and PtDAL1 play different roles in flowering regulatory networks in Arabidopsis. The PtMADS11 could not alter the flowering phenotype of soc1-1-2, indicating it may function differently from AtSOC1 in Arabidopsis. In this study, we identified the MADS11 gene in pine as a regulatory mediator of the juvenile-to-adult transition with functions differentiated from the angiosperm SOC1.

Maternal exposure to PM2.5 disrupting offspring spermatogenesis through induced sertoli cells apoptosis via inhibin B hypermethylation in mice.

Particulate Matter 2.5 (PM2.5) disrupts endocrine functions and may negatively affect sperm quality and quantity in males; however, the long-term effects and potential mechanisms of this effect are unknown. This study aimed to investigate the epigenetic mechanism of maternal exposure to PM2.5-induced inhibin B hypermethylation in male offspring. In this experiment design, pregnant C57BL/6 mice were treated with two doses of PM2.5 (4.8 and 43.2 mg/kg bw). The membrane control group was given a sampling membrane and the control group received nothing. Following the formation of the vaginal plug, intratracheal instillation of PM2.5 was administered every three days until delivery of the pups. To assess the effect of PM2.5 in vitro, TM4 cells, a Sertoli-like cell line, was treated with different concentrations (0, 25, 50, 100 µg/mL) of PM2.5 for 24 h. The results displayed that Sperm motility, as well as the number of adult offspring, was decreased in the PM2.5 exposed group relative to the untreated controls. Increased vacuolization was observed in the Sertoli cells of mice that were exposed to PM2.5 in utero. The levels of inhibin and testosterone were reduced and the levels of LH and FSH increased in the PM2.5 groups relative to the untreated controls. In vitro, PM2.5 resulted in cell cycle inhibition as well as increased apoptosis in TM4 cells. Moreover, PM2.5-induced inhibin B hypermethylation and activation of the p21/Cleaved Caspase-3 pathway resulted in TM4 cell apoptosis that was rescued through the use of a DNA methylation inhibitor. Together, our data suggest that prenatal exposure to PM2.5 results in inhibin B hypermethylation and can activate the p21/Cleaved Caspase-3 pathway, resulting in Sertoli cell apoptosis, aberrant secretion of androgen binding protein, and decreased testosterone, thus resulting in the inhibition of spermatogenesis.

Decabromodiphenyl ethane induces male reproductive toxicity by glycolipid metabolism imbalance and meiotic failure.

Decabromodiphenyl ethane (DBDPE) is a typical flame retardant found in various electrical and textile items. DBDPE is abundantly available in the surrounding environment and wild animals based on its persistence and bioaccumulation. DBDPE has been shown to cause apoptosis in rat spermatogenic cells, resulting in reproductive toxicity. However, the toxicity of DBDPE on the male reproductive system and the potential mechanisms are still unclear. This study evaluated the effect of DBDPE on the reproductive system in male SD rats and demonstrated the potential mechanisms of reproductive toxicity. DBDPE (0, 5, 50, and 500 mg/kg/day) was administered via gavage to male SD rats for 28 days. DBDPE caused histopathological changes in the testis, reduced sperm quantity and motility, and raised the malformation rate in rats, according to the findings. Furthermore, it caused DNA damage to rat testicular cells. It inhibited the expressions of spermatogenesis-and oogenesis-specific helix-loop-helix transcription factor 1 (Sohlh1), piwi-like RNA-mediated gene silencing 2 (MILI), cyclin-dependent kinase 2 (CDK2), and CyclinA, resulting in meiotic failure, as well as the expressions of synaptonemal complex proteins 1 and 3 (SYCP1 and SYCP3), leading to chromosomal association disorder in meiosis and spermatocyte cycle arrest. Moreover, DBDPE induced glycolipid metabolism disorder and activated mitochondria-mediated apoptosis pathways in the testes of SD rats. The quantity and quality of sperm might be declining due to these factors. Our findings offer further evidence of the harmful impact of DBDPE on the male reproductive system.

Fat mass and obesity-associated gene (FTO) hypermethylation induced by decabromodiphenyl ethane causing cardiac dysfunction via glucolipid metabolism disorder.

Decabromodiphenyl ethane (DBDPE) is a major alternative to BDE-209 owing to its lower toxicity. However, the mass production and increased consumption of DBDPE in recent years have raised concerns related to its adverse health effects. However, the effect and mechanism of DBDPE on cardiotoxicity have rarely been studied. In the present study, we investigated the impacts of DBDPE on the cardiovascular system in male SD rats and then explored the underlying mechanisms to explain the cardiotoxicity of DBDPE using AC16 cells. Under in vivo conditions, male rats were administered with an oral dosage of DBDPE at 0, 5, 50, and 500 mg/kg/day for 28 days, respectively. Histopathological analysis demonstrated that DBDPE induced cardiomyocyte injury and fibrosis, and ultrastructural observation revealed that DBDPE could induce mitochondria damage and dissolution. DBDPE could thus decrease the level of MYH6 and increase the level of SERCA2, which are the two key proteins involved in the maintenance of homeostasis during myocardial contractile and diastolic processes. Furthermore, DBDPE could increase the serum levels of glucose and low-density lipoprotein but decrease the content of high-density lipoprotein. In addition, DBDPE could activate the PI3K/AKT/GLUT2 and PPARγ/RXRα signaling pathways in AC16 cells. In addition, DBDPE decreased the UCP2 level and ATP synthesis in mitochondria both under in vitro and in vivo conditions, consequently leading to apoptosis via the Cytochrome C/Caspase-9/Caspase-3 pathway. Bisulfite sequencing PCR (BSP) identified the hypermethylation status of fat mass and obesity-associated gene (FTO). 5-aza exerted the opposite effects on the PI3K/AKT/GLUT2, PPARγ/RXRα, and Cytochrome C/Caspase-9/Caspase-3 signaling pathways induced by DBDPE in AC16 cells. In addition, the DBDPE-treated altered levels of UCP2, ATP, and apoptosis were also found to be significantly reversed by 5-aza in AC16 cells. These results suggested that FTO hypermethylation played a regulative role in the pathological process of DBDPE-induced glycolipid metabolism disorder, thereby contributing to the dysfunction of myocardial contraction and relaxation through cardiomyocytes fibrosis and apoptosis via the mitochondrial-mediated apoptotic pathway resulting from mitochondrial dysfunction.

Non-Destructive Hyperspectral Imaging for Rapid Determination of Catalase Activity and Ageing Visualization of Wheat Stored for Different Durations.

(1) In order to accurately judge the new maturity of wheat and better serve the collection, storage, processing and utilization of wheat, it is urgent to explore a fast, convenient and non-destructively technology. (2) Methods: Catalase activity (CAT) is an important index to evaluate the ageing of wheat. In this study, hyperspectral imaging technology (850-1700 nm) combined with a BP neural network (BPNN) and a support vector machine (SVM) were used to establish a quantitative prediction model for the CAT of wheat with the classification of the ageing of wheat based on different storage durations. (3) Results: The results showed that the model of 1ST-SVM based on the full-band spectral data had the best prediction performance (R2 = 0.9689). The SPA extracted eleven characteristic bands as the optimal wavelengths, and the established model of MSC-SPA-SVM showed the best prediction result with R2 = 0.9664. (4) Conclusions: The model of MSC-SPA-SVM was used to visualize the CAT distribution of wheat ageing. In conclusion, hyperspectral imaging technology can be used to determine the CAT content and evaluate wheat ageing, rapidly and non-destructively.

Study on sampling scheme for detecting mycotoxin during wheat storage.

BACKGROUND: Mycotoxin produced by mould is one of the most serious contamination sources in food security. Safe storage of grain has become more important to control food security. Currently, there is no officially approved or standardized sampling scheme for detecting mycotoxin in grain storage worldwide. RESULTS: In this study, deoxynivalenol (DON) was taken as a typical mycotoxin in stored wheat to be detected. Population density of corn weevil could not significantly increase wheat moisture, but wheat moisture was highly significantly and positively correlated with DON content (P < 0.01). Corn weevil density significantly increased the DON content in wheat. DON contamination degree was mainly distributed in the region of 14-20 cm below the surface layer of wheat. In the process of ventilation and dehumidification during the storage period, moisture of wheat decreased slightly with the extension of ventilation, but the DON content in wheat increased significantly. Combined with the analysis of ventilation, DON content in the upper layer and H1 position, where the wind direction is not easy to reach, increased significantly. CONCLUSION: Areas with high insect population density (14-20 cm below the surface layer of stored wheat) and low ventilation and high humidification (H1 position in the upper layer) should be taken as the key cutting sample areas for detecting mycotoxin during the period of grain storage. This study provides for the first time a scientific basis for the standardization of the wheat sampling scheme to monitor mycotoxin contamination during wheat storage. © 2022 Society of Chemical Industry.

Quantitative proteomics analysis of lysine 2-hydroxyisobutyrylation in IgA nephropathy.

BACKGROUND: Protein posttranslational modification is an indispensable regulatory element that can fine-tune protein functions and regulate diverse cellular processes. Lysine 2-hydroxyisobutyrylation (Khib) is a protein posttranslational modification that was recently identified and is thought to play a role in a wide variety of active cellular functions. METHODS: In this report, for the first time, we comparatively studied the 2-hydroxyisobutyrylation proteome in peripheral blood mononuclear cells from a biopsy-proven immunoglobulin A nephropathy (IgAN) group and a normal control group based on liquid chromatography-tandem mass spectrometry. RESULTS: Altogether, 7405 proteins were identified and added to a Khib library. Of these proteins, we identified 111 with upregulated expression and 83 with downregulated expression. Furthermore, we identified 428 Khib modification sites on 290 Khib-modified proteins, including 171 sites with increased modification on 122 Khib-modified proteins and 257 specific sites with reduced modification on 168 Khib-modified proteins. CONCLUSIONS: Importantly, the abundance of lipocalin 2 was increased in the differentially expressed proteins, and a KEGG-based functional enrichment analysis showed that Khib proteins clustered in the IL-17 signaling pathway and phagosome category, which may have important associations with IgAN. Our data enlighten our understanding of Khib in IgAN and indicate that Khib may have important regulatory roles in IgAN.

Primary research on sampling scheme for analyzing mycotoxin distribution in wheat and rice fields.

BACKGROUND: Mycotoxins are among the most severe food contaminants. Deoxynivalenol and aflatoxin contamination are predominant in wheat and rice, respectively. Nowadays, there are no standardized and approved grain-sampling schemes worldwide. This study aimed to develop a scientific grain-sampling scheme to investigate the regularity of mycotoxin distributed in wheat and rice fields. The data were analyzed with analysis of variance and cluster analysis to select a better sampling scheme. RESULTS: Considering the influences of the weather before harvest (temperature, humidity, wind direction, and other conditions), we sampled grains from different places in different farmlands and detected the mycotoxin content of the sampled grains. The mycotoxin content had extremely significant differences in the area of rice fields (P<0.01) and significant differences in the area of wheat fields (P<0.05). The filtering effect existed peripheral the field areas, especially peripheral the humid areas, where the fungi were filtered and the toxin were easily produced. Furthermore, the upwind direction peripheral the field areas cause more filterature effect than other wind direction. Although 97% of mycotoxins in wheat can be removed through the shelling process, the toxin content were not obviously affected by rice lodging in the field. According to the cluster analysis, the peripheral and middle areas were divided into the same group with higher mycotoxin content. CONCLUSION: This paper developed a sampling scheme to detect the mycotoxin content of wheat and rice in the field, considering the temperature and humidity of the weather, locations, and other grain contamination conditions before harvest. Meanwhile, the sampling rule of lodging and wind direction in the field was also assayed. © 2021 Society of Chemical Industry.

DNA methylation changes induced by BDE-209 are related to DNA damage response and germ cell development in GC-2spd.

Decabrominated diphenyl ether (BDE-209) is generally utilized in multiple polymer materials as common brominated flame retardant. BDE-209 has been listed as persistent organic pollutants (POPs), which was considered to be reproductive toxin in the environment. But it still remains unclear about the effects of BDE-209 on DNA methylation and the induced-male reproductive toxicity. Due to the extensive epigenetic regulation in germ line development, we hypothesize that BDE-209 exposure impacts the statue of DNA methylation in spermatocytes in vitro. Therefore, the mouse GC-2spd (GC-2) cells were used for the genome wide DNA methylation analysis after treated with 32 µg/mL BDE-209 for 24 hr. The results showed that BDE-209 caused genomic methylation changes with 32,083 differentially methylated CpGs in GC-2 cells, including 16,164 (50.38%) hypermethylated and 15,919 (49.62%) hypomethylated sites. With integrated analysis of DNA methylation data and functional enrichment, we found that BDE-209 might affect the functional transcription in cell growth and sperm development by differential gene methylation. qRT-PCR validation demonstrated the involvement of p53-dependent DNA damage response in the GC-2 cells after BDE-209 exposure. In general, our findings indicated that BDE-209-induced genome wide methylation changes could be interrelated with reproductive dysfunction. This study might provide new insights into the mechanisms of male reproductive toxicity under the environmental exposure to BDE-209.

Maternal exposure to fine particle matters cause autophagy via UPR-mediated PI3K-mTOR pathway in testicular tissue of adult male mice in offspring.

Epidemiological studies have shown that particulate matters are closely related to human infertility. However, the long-term risk of particulate matters exposure in early life is rarely considered. For the first time this study is designed to explore and elucidate the mechanism of maternal exposure to fine particle matters (PM2.5) on autophagy in spermatogenic cells of adult offspring. Pregnant C57BL/6 mice were randomly divided into four groups. The 4.8 mg/kg.b.w group and the 43.2 mg/kg.b.w group were administered with different doses of PM2.5. The membrane control group was administered with PM2.5 sampling membrane and the control group received no treatment. The exposure was performed every three days from the day after vaginal plug was checked until delivery for a total of 6 times. The results showed that sperms motility and sperms concentration decreased, and sperm deformity increased in adult male offspring. The expression of SOD decreased and MDA increased. Moreover, the level of GRP78/ATF6 and P62 was upregulated, and the expression of PI3K/Akt/mTOR/p-mTOR was down-regulated. This suggests that early-life exposure to PM2.5 can induce autophagy through the PI3K/Akt/mTOR pathway mediated by unfolded protein response in adult testicular tissue. PM2.5 may pose a significant role and long-term threat to adult after early-life exposure.

A comparison of the thyroid disruption induced by decabrominated diphenyl ethers (BDE-209) and decabromodiphenyl ethane (DBDPE) in rats.

In recent years, decabromodiphenyl ethane (DBDPE), a new alternative flame retardant to the decabrominated diphenyl ethers (BDE-209), is widely used in a variety of products. Previous studies have indicated that DBDPE, like BDE-209, could disrupt thyroid function. However, compared with BDE-209, the degrees of thyrotoxicosis induced by DBDPE were not clear. In addition, the mechanism of thyrotoxicosis induced by DBDPE or BDE-209 was still under further investigation. In this study, male rats as a model were orally exposed to DBDPE or BDE-209 by 5, 50, 500 mg/kg bw/day for 28 days. Then, we assessed the thyrotoxicosis of DBDPE versus BDE-209 and explored the mechanisms of DBDPE and BDE-209-induced thyrotoxicosis. Results showed that decreased free triiodothyronine (FT3) and increased thyroid-stimulating hormone (TSH) and thyrotropin-releasing hormone (TRH) in serum were observed in both 500 mg/kg bw/day BDE-209 and DBDPE group. Decreased total thyroxine (TT4), total T3 (TT3), and free T4 (FT4) were only observed in BDE-209 group but not in DBDPE group. Histological examination and transmission electron microscope examination showed that high level exposure to BDE-209 and DBDPE both caused significant changes in histological structure and ultrastructure of the thyroid gland. Additionally, oxidative damages of thyroid gland (decreased SOD and GSH activities, and increased MDA content) were also observed in both BDE-209 and DBDPE groups. TG contents in the thyroid gland was reduced in BDE-209 group but not in DBDPE group. Both BDE-209 and DBDPE affected the expression of hypothalamic-pituitary-thyroid (HPT) axis related genes. These findings suggested that both BDE-209 and DBDPE exposure could disrupt thyroid function in the direction of hypothyroidism and the underlying mechanism was likely to be oxidative stress and perturbations of HPT axis. However, DBDPE was found to be less toxic than BDE-209.