Long-term exposure to the mixture of phthalates induced male reproductive toxicity in rats and the alleviative effects of quercetin.

Phthalates (PEs), such as di(2-ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP) and butyl benzyl phthalate (BBP) could cause reproductive and developmental toxicities, while human beings are increasingly exposed to them at low-doses. Phytochemical quercetin (Que) is a flavonoid that has estrogenic effect, anti-inflammatory and anti-oxidant effects. This study was conducted to assess the alleviative effect of Que. on male reproductive toxicity induced by the mixture of three commonly used PEs (MPEs) at low-dose in rats, and explore the underlying mechanism. Male rats were treated with MPEs (16 mg/kg/day) and/or Que. (50 mg/kg/d) for 91 days. The results showed that MPEs exposure caused male reproductive injuries, such as decreased serum sex hormones levels, abnormal testicular pathological structure, increased abnormal sperm rate and changed expressions of PIWIL1 and PIWIL2. Furthermore, MPEs also changed the expression of steroidogenic proteins in steroid hormone metabolism, including StAR, CYP11A1, CYP17A1, 17ß-HSD, CYP19A1. However, the alterations of these parameters were reversed by Que. MPEs caused male reproductive injuries in rats; Que. inhibited MPEs' male reproductive toxicity, which might relate to the improvement of testosterone biosynthesis.

Alleviative effect of quercetin against reproductive toxicity induced by chronic exposure to the mixture of phthalates in male rats.

Phthalates (PEs) are widely used plasticizers in polymer products, and humans are increasingly exposed to them. This study was designed to investigate the alleviative effect of phytochemicals quercetin (Que) against male reproductive toxicity caused by the mixture of three commonly used PEs (MPEs), and further to explore the underlying mechanism. Forty-eight male SD rats were randomly and evenly divided into control group, Que group, MPEs group and MPEs+Que group (n = 12); The oral exposure doses of MPEs and Que were 450 mg/kg/d and 50 mg/kg/d, respectively. After 91 days of continuous intervention, compared with control group, the testes weight, epididymis weight, serum sex hormones, and anogenital distance were significantly decreased in MPEs group (P < 0.05); Testicular histopathological observation showed that all seminiferous tubules were atrophy, leydig cells were hyperplasia, spermatogenic cells growth were arrested in MPEs group. Ultrastructural observation of testicular germ cells showed that the edges of the nuclear membranes were indistinct, and the mitochondria were severely damaged with the cristae disrupted, decreased or even disappeared in MPEs group. Immunohistochemistry and Western blot analysis showed that testicular CYP11A1, CYP17A1 and 17ß-HSD were up-regulated, while StAR, PIWIL1 and PIWIL2 were down-regulated in MPEs group (P < 0.05); However, the alterations of these parameters were restored in MPEs+Que group. The results indicated MPEs disturbed steroid hormone metabolism, and caused male reproductive injuries; whereas, Que could inhibit MPEs' male reproductive toxicity, which might relate to the restored regulation of steroid hormone metabolism.

Ameliorative effects of zinc and vitamin E against phthalates-induced reproductive toxicity in male rats.

OBJECTIVE: Phthalates (PEs) could cause reproductive harm to males. A mixture of three widely used PEs (MPEs) was used to investigate the ameliorative effects of zinc (Zn) and vitamin E (VE) against male reproductive toxicity. METHODS: Fifty male SD rats were randomly divided into five groups (n = 10). Rats in MPEs group were orally treated with 160 mg/kg/d MPEs, while rats in MPEs combined Zn and/or VE groups were treated with 160 mg/kg/d MPEs plus 25 mg/kg/d Zn and/or 25 mg/kg/d VE. After intervention for 70 days, it's was measured of male reproductive organs' weight, histopathological observation of sperms and testes, serum hormones, PIWI proteins and steroidogenic proteins. RESULTS: Compared with control, anogenital distance, testes weight, epididymides weight, and sex hormones were significantly decreased, while the sperm malformation rate was markedly increased in MPEs group (p < .05); the testicular tissues were injured in MPEs group with disordered and decreased spermatids, and arrested spermatogenesis. PIWIL1, PIWIL2, StAR, CYP11A1 and CYP19A1 were down-regulated in MPEs group (p < .05). However, the alterations of these parameters were restored in MPEs combined Zn and/or VE groups (p < .05). CONCLUSION: Zn and/or VE improved steroid hormone metabolism, and inhibited MPEs' male reproductive toxicity.

Quercetin inhibits testicular toxicity induced by the mixture of three commonly used phthalates in rats.

BACKGROUND: Phthalates (PEs), such as butyl benzyl phthalate, dibutyl phthalate and di(2-ethylhexyl) phthalate, are one of the most widely used plasticizers, and humans are increasingly exposed to them. Phytochemical quercetin (Que) is a typical flavonoid with several biological effects, such as antioxidative and anti-inflammatory. The present study was designed to explore the effect of Que on testicular toxicity caused by the mixture of three commonly used PEs (MPEs), and the underlying mechanism. Forty male Sprague-Dawley rats were randomly and equally divided into five groups (n = 8). Rats in control the group were orally treated with the excipient. Rats in the MPEs group were orally administered with 900 mg kg-1 day-1 MPEs, whereas rats in the MPEs+L-Que, MPEs+M-Que and MPEs+H-Que groups were simultaneously treated with 900 mg kg-1 day-1 MPEs and, respectively, 10, 30 and 90 mg kg-1 day-1 Que for 30 days. RESULTS: Compared with the control group, the testes weight, epididymides weight, serum testosterone, luteinizing hormone, follicle-stimulating hormone and estradiol levels, and anogenital distance in the MPEs group were significantly decreased (P < 0.05). The testicular tissues were injured with atrophy of seminiferous tubules, hyperplasia of Leydig cells and arrest of spermatogenesis in the MPEs group. Testicular steroidogenic proteins (StAR, P450scc, CYP17A1 and 17ß-HSD, P450arom) were up-regulated, whereas P-element-induced wimpy testis proteins (PIWIL1 and PIWIL2) were down-regulated in the MPEs group (P < 0.05). However, the alterations of these parameters were inhibited in the MPEs+M-Que and MPEs+H-Que groups. CONCLUSION: MPEs disturbed steroid hormone metabolism and caused testicular injuries. Que could inhibit testicular toxicity of MPEs, which might relate to the improved regulation of steroid hormone metabolism. © 2022 Society of Chemical Industry.

Combined effects of simultaneous exposure to six phthalates and emulsifier glycerol monosterate on male reproductive system in rats.

Human beings are inevitably exposed to ubiquitous phthalate esters (PEs), and simultaneously ingesting high quantities of food emulsifiers via daily diet. Glycerin monostearate (GMS) is a widely used food emulsifier. The purposes of this study were to investigate the combined effects between the mixture of six frequently used PEs (MIXPs) and GMS on male rat reproductive system, and further to explore the underlying mechanisms. Male rats were orally administered either sodium carboxymethyl cellulose as controls or MIXPs at three different low-doses with or without GMS (200mg/kg/d) by gavage. The 15-week exposure of MIXPs caused male reproductive toxicity in a dose- and time-dependent manner, including the decrease of serum testosterone and morphological damage of testis. Metabonomics analyses of urine and Western blotting analyses of steroidogenic proteins (StAR, P450scc, CYP17A1, 17ß-HSD and P450arom) indicated that MIXPs exposure down-regulated the expression of steroidogenic proteins, and might alter androgen metabolism. The results also showed that the presence of GMS exacerbated the toxicities of MIXPs to male rat reproductive system. These findings suggest that food emulsifier GMS could enhance the toxic effects of MIXPs on male hormone biosynthesis.

Total synthesis of (+)-iresin.

The first asymmetric total synthesis of (+)-iresin (4), an historically important ent-Drimane sesquiterpene lactone, was realized from aldehyde 3 via cyclic orthoester 6 in 5 steps. Notable transformations in this synthesis include a tandem trifluoroperacetic acid (TFPAA)-mediated Baeyer-Villiger oxidation-olefin epoxidation-epoxy ester cyclization, regioselective Burgess dehydration, and regioselective Fétizon oxidative lactonization.

[Essential oil from Artemisia lavandulaefolia induces apoptosis and necrosis of HeLa cells].

OBJECTIVE: To investigate the effects of Artemisia lavandulaefolia essential oil on apoptosis and necrosis of HeLa cells. METHODS: Cell viability was assayed using MTT method. The morphological and structure alterations in HeLa cells were observed by microscopy. Furthermore, cell apoptosis was measured by DNA Ladder and flow cytometry. DNA damage was measured by comet assay, and the protein expression was examined by Western blot analysis. RESULTS: MTT assay displayed essential oil from Artemisia lavandulaefolia could inhibit the proliferation of HeLa cells in a dose-dependent manner. After treated with essential oil of Artemisia lavadulaefolia for 24 h, HeLa cells in 100 and 200 microg/mL experiment groups exhibited the typical morphology changes of undergoing apoptosis, such as cell shrinkage and nucleus chromatin condensed. However, the cells in the 400 microg/mL group showed the necrotic morphology changes including cytomembrane rupture and cytoplasm spillover. In addition, DNA Ladder could be demonstrated by DNA electrophoresis in each experiment group. Apoptosis peak was also evident in flow cytometry in each experiment group. After treating the HeLa cells with essential oil of Artemisia lavadulaefolia for 6 h, comet tail was detected by comet assay. Moreover, western blotting analysis showed that caspase-3 was activated and the cleavage of PARP was inactivated. CONCLUSION: Essential oil from Artemisia lavadulaefolia can inhibit the proliferation of HeLa cells in vitro. Low concentration of essential oil from Artemisia lavadulaefolia can induce apoptosis, whereas high concentration of the compounds result in necrosis of HeLa cells. And,the mechanism may be related to the caspase-3-mediated-PARP apoptotic signal pathway.

TREM2 as an independent predictor of poor prognosis promotes the migration via the PI3K/AKT axis in prostate cancer.

OBJECTIVE: Prostate adenocarcinoma (PRAD) is one of the most common cancers, with high morbidity and mortality. Triggering receptors expressed on myeloid cells 2 (TREM2) is upregulated in various malignancies, however its effect on PRAD remains unknown. This study aimed to investigate the prognostic value of TREM2 in PRAD. METHODS: PRAD samples were collected from The Cancer Genome Atlas (TCGA), the Gene Expression Omnibus (GEO), Oncomine, and the Human Protein Atlas (HPA) to analyze the differences in TREM2 expression between normal and tumor tissues. The influence of TREM2 on the clinicopathological characteristics and its prognostic value were evaluated using the Kaplan-Meier curve, Cox regression analysis, ROC (receiver operating characteristic) plot, and nomogram. Gene Ontology (GO), gene set enrichment analysis (GSEA), and protein-protein interaction (PPI) were conducted to screen biological functions and pathways. The relationship between TREM2 and tumor microenvironment (TME) characteristics was explored. The TREM2 expression in PRAD specimens and cell lines was assessed by immunohistochemistry staining and western blot. TREM2-specific siRNAs were used to evaluate the effects of TREM2 on cell function. RESULTS: TREM2 was upregulated and positively associated with poor clinicopathologic characteristics. Overexpression of TREM2 is an independent biomarker for the prognosis of PFI (progression-free interval). Moreover, TREM2 expression was positively correlated with various TME characteristics. Knockdown of TREM2 inhibited the migration of PRAD cell lines via the PI3K/AKT axis. CONCLUSION: High TREM2 expression may represent a novel diagnostic and prognostic biomarker and serve as a potential target gene for PRAD therapy.

SF3B4 promotes Twist1 expression and clear cell renal cell carcinoma progression by facilitating the export of KLF 16 mRNA from the nucleus to the cytoplasm.

Splicing factor 3B subunit 4 (SF3B4) plays important functional roles not only in pre-mRNA splicing, but also in the regulation of transcription, translation, and cell signaling, and its dysregulation contributes to various diseases including Nager syndrome and tumorigenesis. However, the role of SF3B4 and underlying mechanisms in clear cell renal cell carcinoma (ccRCC) remain obscure. In the present study, we found that the expression of SF3B4 was significantly elevated in ccRCC tissues and negatively correlated with the overall survival of ccRCC patients. Upregulation of SF3B4 promotes migration and invasion of ccRCC cells in vitro and in vivo. The promoting effect of SF3B4 on cell migration and invasion is mediated by Twist1, a key transcription factor to mediate EMT. Interestingly, SF3B4, a component of the pre-mRNA spliceosome, is able to promote KLF16 expression by facilitating the transport of KLF16 mRNA into the cytoplasm. Mechanistically, SF3B4 promotes the export of KLF16 mRNA from the nucleus to the cytoplasm and thus enhances KLF16 expression, and in turn elevated KLF16 directly binds to the Twist1 promoter to activate its transcription, leading to EMT and ccRCC progression. Our findings provide evidence that the SF3B4-KLF16-Twist1 axis plays important functional roles in the development and progression of ccRCC, and manipulating this pathway may be a novel therapeutic target for the treatment of ccRCC.

Modulation of gut microbiota alleviates cerebral ischemia/reperfusion injury in rats by inhibiting M1 polarization of microglia.

Gut microbiota affects the gut-brain axis; hence, the modulation of the microbiota has been proposed as a potential therapeutic strategy for cerebral ischemia/reperfusion injury (CIRI). However, the role and mechanism of the gut microbiota in regulating microglial polarization during CIRI remain poorly understood. Herein, using a middle cerebral artery occlusion and reperfusion (MCAO/R) rat model, we evaluated changes in the gut microbiota after CIRI and the potential effects of fecal microbiota transplant (FMT) on the brain. Rats underwent either MCAO/R or sham surgery, and then they received FMT (started 3 days later; continued for 10 days). 2,3,5-Triphenyltetrazolium chloride staining, neurological outcome scale, and Fluoro-Jade C staining showed that MCAO/R induced cerebral infarction, neurological deficits, and neuronal degeneration. In addition, immunohistochemistry or real-time PCR assay showed increased expression levels of M1-macrophage markers-TNF-α, IL-1ß, IL-6, and iNOS-in the rats following MCAO/R. Our finding suggests that microglial M1 polarization is involved in CIRI. 16 S ribosomal RNA gene sequencing data revealed an imbalance in the gut microbiota of MCAO/R animals. In contrast, FMT reversed this MCAO/R-induced imbalance in the gut microbiota and ameliorated nerve injury. In addition, FMT prevented the upregulation in the ERK and NF-κB pathways, which reversed the M2-to-M1 microglial shift 10 days after MCAO/R injury in rats. Our primary data showed that the modulation of the gut microbiota can attenuate CIRI in rats by inhibiting microglial M1 polarization through the ERK and NF-κB pathways. However, an understanding of the underlying mechanism requires further study.

CDK13 promotes lipid deposition and prostate cancer progression by stimulating NSUN5-mediated m5C modification of ACC1 mRNA.

Cyclin-dependent kinases (CDKs) regulate cell cycle progression and the transcription of a number of genes, including lipid metabolism-related genes, and aberrant lipid metabolism is involved in prostate carcinogenesis. Previous studies have shown that CDK13 expression is upregulated and fatty acid synthesis is increased in prostate cancer (PCa). However, the molecular mechanisms linking CDK13 upregulation and aberrant lipid metabolism in PCa cells remain largely unknown. Here, we showed that upregulation of CDK13 in PCa cells increases the fatty acyl chains and lipid classes, leading to lipid deposition in the cells, which is positively correlated with the expression of acetyl-CoA carboxylase (ACC1), the first rate-limiting enzyme in fatty acid synthesis. Gain- and loss-of-function studies showed that ACC1 mediates CDK13-induced lipid accumulation and PCa progression by enhancing lipid synthesis. Mechanistically, CDK13 interacts with RNA-methyltransferase NSUN5 to promote its phosphorylation at Ser327. In turn, phosphorylated NSUN5 catalyzes the m5C modification of ACC1 mRNA, and then the m5C-modified ACC1 mRNA binds to ALYREF to enhance its stability and nuclear export, thereby contributing to an increase in ACC1 expression and lipid deposition in PCa cells. Overall, our results disclose a novel function of CDK13 in regulating the ACC1 expression and identify a previously unrecognized CDK13/NSUN5/ACC1 pathway that mediates fatty acid synthesis and lipid accumulation in PCa cells, and targeting this newly identified pathway may be a novel therapeutic option for the treatment of PCa.

Ethyl 2-diethyl-amino-4-oxo-3,5-diphenyl-4,5-dihydro-3H-pyrrolo-[3,2-d]pyrimidine-7-carboxyl-ate.

In the title compound, C(25)H(26)N(4)O(3), the two fused pyrrolo-[3,2-d]pyrimidine rings form a dihedral angle of 3.7 (2)°. The two substituent phenyl rings are twisted with respect to the pyrrole and pyrimidine rings, making dihedral angles of 57.2 (2) and 69.0 (2)°, respectively. The ethyl and eth-oxy groups are disordered over two positions; the site occupancies are 0.53 (1) and 0.47 (1) for ethyl, and 0.63 (1) and 0.37 (1) for eth-oxy. The crystal packing features C-H⋯O hydrogen bonds.

Protective effect of quercetin against phthalates induced hepatotoxicity in rats.

Humans are increasingly exposed to ubiquitous phthalates (PEs), e.g. butyl benzyl phthalate (BBP), dibutyl phthalate (DBP), and di(2-ethylhexyl) phthalate (DEHP), which are widely used plasticizers in polymer products. This study was aimed to investigate the effect of phytochemical quercetin (Que) on hepatotoxicity caused by the mixture of the 3 commonly used PEs (MPEs), and further to explore the underlying mechanism. Forty male Sprague-Dawley rats were randomly divided into control group, MPEs group, and MPEs combined Que at Low-, Median-, and High-dose groups; rats in MPEs group were orally administered with 900 mg/kg/d MPEs, whereas rats in MPEs combined Que groups were simultaneously treated with 900 mg/kg/d MPEs and respectively 10, 30, and 90 mg/kg/d Que. The intervention last 30 days. Compared with control group, serum ALT, AST, LDH and AKP, and hepatic MDA, SOD, CAT and GPx were significantly increased, whereas, serum albumin and total protein were significantly decreased in MPEs group (P < 0.05); hepatic histopathological observation showed numerous inflammatory cells infiltration, hepatocyte ballooning degeneration, and numerous residual erythrocytes in the central vein in MPEs group. Western-blot analysis showed that hepatic Keap1 was downregulated, whereas Nrf2 and HO-1 were upregulated in MPEs group (P < 0.05). However, the alterations of these parameters were alleviated in MPEs combined Que at Median- and High-dose groups. The results indicated that MPEs-induced hepatic oxidative stress, and caused hepatic injuries; whereas, Que inhibited MPEs' hepatotoxicity, which might relate to Que's ability of quenching free radicals directly, and restored the regulation of Nrf2 signaling pathway.

6-Benzyl-3-[(6-chloro-pyridin-3-yl)meth-yl]-6,7-dihydro-3H-1,2,3-triazolo[4,5-d]pyrimidin-7-imine.

The title compound, C(17)H(14)ClN(7), crystallizes with two independent mol-ecules in the asymmetric unit. Inter-molecular N-H⋯N and C-H⋯N hydrogen bonds contribute to the stability of the crystal structure. In addition, weak C-H⋯π and π-π stacking [centroid-centroid distances of 3.699 (8) and 3.699 (6) Å] interactions are observed.

Study on the Shale Gas Reservoir-Forming Characteristics of the Taiyuan Formation in the Eastern Qinshui Basin, China.

Shales are widely developed in the strata of the Carboniferous-Permian coal measures in the Qinshui Basin, and these shales have great potential for shale gas exploration. In this paper, the shales of the Taiyuan Formation in the eastern Qinshui Basin are studied. The shales of the Taiyuan Formation in the study area are investigated through field investigation, organic geochemical testing, X-ray diffraction, scanning electron microscopy, high pressure mercury injection, low temperature liquid nitrogen adsorption and PetroMod simulation and through other tests to study the reservoir characteristics, such as organic geochemistry, mineralogy, petrology, pore permeability, and gas burial history. The results show that the shales of the Taiyuan Formation are well developed over the whole area with a thickness of more than 60 m. The average organic matter content is 2.95%, and the kerogen type is type III. The shale maturity (average value is 2.45%) corresponds to the stage of high maturity evolution, indicating that a large amount of shale gas has been generated in this area. A high content of quartz and clay minerals indicates a high fracturability. The nanopores in the shale reservoir are well developed at pore sizes between 2˜10 nm and greater than 1000 nm; however, the pores at the other pore sizes are poorly developed, resulting in weak pore connectivity in the reservoir. According to the results of the PetroMod simulation, the shale of the Taiyuan Formation has undergone two subsidence and two uplift processes. The Yanshanian magmatic intrusion is the key factor for the rapid increase in gas production. In addition, the geological structure of the area is relatively simple, and the burial history and caprock thickness are also the main controlling factors of gas generation and preservation. The shale-sandstone-shale combination and shale-coal-shale combination are the main models of shale gas preservation. This comprehensive study suggests that the shale gas of the Taiyuan Formation in the eastern Qinshui Bain has good potential for exploration and development.

Analysis of Developmental Characteristics and Dominant Factors of Pore-Fracture Systems in Lower Cambrian Marine Shale Reservoirs: A Case Study of the Niutitang Formation, Fenggang Block, Southern China.

Due to breakthroughs in the Lower Silurian Longmaxi Formation in the Sichuan Basin and multiple strata around the basin, the northern part of Guizhou adjacent to the Sichuan Basin has become a key area for shale gas exploration. Compared with the Longmaxi Formation, the Niutitang Formation displays greater TOC (total organic carbon) content, depositional thickness and distribution area, but the details remain undetermined. In the study area, the Lower Cambrian Niutitang Formation typically has high TOC content, maturity and brittle mineral content. The study area has experienced multiple periods of tectonic movement, which have great influence on the fracture and pore characteristics. The fractures are mainly structural fractures and have obvious zoning. The primary types of pores are intraparticle pores, organic matter pores, and interparticle pores. Further, macropores and mesopores less than 50 nm contribute most of the pore volume, while pores less than 2 nm contribute most of the specific surface area. Many factors affect the pore-fracture system, such as tectonism, TOC content, mineral composition, and sedimentary environment. Tectonic movements produce fractures based on the changing stress field, but the degree of fracture development does not agree well with the degree of pore development. The TOC content has good positive correlations with the development of fractures and micropores, especially for nanoporosity, while clay minerals show a negative correlation with the development of fractures but a strong positive correlation with the growth of micropores. Quartz displays a positive correlation with the development of fractures but no good correlation with pore development. Finally, the lithofacies, lithologies and mineral compositions under the control of sedimentary environments are internal factors that can impact the development of pore-fracture systems.

Ethyl 3-{[(3-methyl-anilino)(1H-1,2,4-triazol-1-yl)methyl-idene]amino}-1-benzofuran-2-carboxyl-ate.

The crystal structure of the title compound, C(21)H(19)N(5)O(3), is stabilized by inter-molecular N-H⋯N and C-H⋯O hydrogen bonds. The mol-ecule contains a planar [maximum deviations = -0.026 (1) and 0.027 (2) Å] benzofuran ring system, which forms dihedral angles of 78.75 (8) and 39.78 (7)° with the benzene and triazole rings, respectively.

Zinc supplement ameliorates phthalates-induced reproductive toxicity in male rats.

People are inevitably exposed to phthalates (PEs) ubiquitously existing in environment. Our previous studies, simulating the actual situations of people exposure to PEs, have shown that the sub-chronic exposure to low-doses PEs mixture (MIXPs) impaired reproductive function in male rats. Zinc is an important element in maintaining male reproductive functions. However, it is still unknown whether zinc supplement could mitigate PEs-induced male reproductive toxicity or not with sub-chronic low-dose mixture exposure. This study aimed to explore the effect of zinc supplement on the reproductive toxicity caused by sub-chronic MIXPs exposure (160 mg/(kg•body weight)/d, for 90 days) in male rats, and further to reveal the underlying mechanisms. Testosterone (T), FSH and LH in serum, early toxicity indicators in urine, PIWI proteins (PIWIL1 and PIWIL2) expression in testes and pathological examination were performed for toxicity evaluation. Steroidogenic proteins (17ß-HSD, StAR, CYP17A1, P450scc and SRD5A) were measured for mechanisms of exploration. The results indicated that zinc supplement could inhibit the T, LH, FSH level decreases in serum, abolish the effect of 5 early toxicity indicators' levels in urine, restrain the alteration of PIWI proteins expression and improve the constructional injury of testes. These effects might be relevant with the suppressed alteration of the expression of steroidogenic proteins induced by MIXPs in rat testicular cells. This work may offer further insights into reducing health risks of MIXPs exposure.

6-Isopropyl-3-phenyl-5-(p-tol-yloxy)-3H-1,2,3-triazolo[4,5-d]pyrimidin-7(6H)-one: whole-mol-ecule disorder.

The title compound, C(20)H(19)N(5)O(2), exhibits whole-mol-ecule disorder the refined ratios of the two components being 0.57 (2):0.43 (2). In the major component, the essentially planar [maximum deviation 0.033 (17) Å] fused pyrimidine and triazole ring system forms a dihedral angle of 10.5 (3)° with the phenyl ring, while in the minor component of disorder this angle is 27.5 (5)°. The crystal structure is stabilized by π-π stacking inter-actions between symmetry-related triazole and pyrimidine rings, with centroid-centroid distances of 3.594 (10) Å.

Glycerin Monostearate Aggravates Male Reproductive Toxicity Caused by Di(2-ethylhexyl) Phthalate in Rats.

Human beings are increasingly exposed to phthalates, which are a group of chemicals used to make plastics more flexible and harder to break, and simultaneously ingesting abundant food emulsifiers via daily diet. The purpose of this study was to investigate the effect of the food emulsifier glycerin monostearate (GMS) on male reproductive toxicity caused by di(2-ethylhexyl) phthalate (DEHP, one of the phthalates) and explore the underlying mechanism. Thirty male Sprague-Dawley rats were randomly divided into control group, DEHP group and DEHP+GMS group. Rats in the DEHP group and DEHP+GMS group were orally administered with 200 mg/kg/d DEHP with or without 20 mg/kg/d GMS. After 30 days of continuous intervention, it was found that the serum testosterone level was significantly lowered in DEHP group and DEHP+GMS group than that in control group (P<0.01). The serum testosterone level and the relative testis weight were significantly decreased in the DEHP+GMS group as compared with those in the DEHP group and control group (P<0.05). More spermatids were observed to be shed off in DEHP+GMS group than in DEHP group. The expression levels of cell cycle checkpoint kinase 1 (Chk1), cell division cycle gene 2 (Cdc2), and cyclin-dependent kinase 2 (CDK2) were down-regulated in DEHP group, and this tendency was more significant in DEHP+GMS group (P<0.05 or P<0.01). There was no significant difference in the P-glycoprotein (P-gp) expression between DEHP group and control group. However, P-gp was markedly down-regulated in DEHP+GMS group (P<0.01). The results indicated that the food emulsifier GMS aggravated the toxicity of DEHP on male reproduction by inhibiting the cell cycle of testicular cells and the expression of P-gp in testis tissues.