Flurbiprofen Inhibits Androgen Productions in Rat Immature Leydig Cells.

Flurbiprofen is one of the nonsteroidal anti-inflammatory drugs. Whether flurbiprofen affects androgen biosynthesis in Leydig cells is still unknown. Immature Leydig cells (ILCs) isolated from 35-day-old male Sprague-Dawley rats were cultured with 0-100 µM flurbiprofen for 24 h and medium androgen levels and Leydig cell mRNA levels were measured. Immature Leydig cells were also incubated with 100 µM flurbiprofen for 3 h in combination with luteinizing hormone (LH), 8bromo-cAMP, 22R-OH-cholesterol, pregnenolone, progesterone, androstenedione, testosterone, and dihydrotestosterone, respectively, and medium androgen levels were measured. The ROS generation and apoptosis rate were also investigated. The direct effects of flurbiprofen on androgen biosynthetic and metabolizing enzyme activities were measured. Flurbiprofen significantly inhibited basal, LH, and 8bromo-cAMP stimulated androgen production at 10 and 100 µM. Further study demonstrated that flurbiprofen competitively inhibited rat and human testis 3ß-hydroxysteroid dehydrogenase (HSD3B) activity with the half maximal inhibitory concentration (IC50) values of 0.95 µM for rat enzyme and 6.31 µM for human enzyme. In addition, flurbiprofen down-regulated the expression of Srd5a1 and Akr1c14 at 1, 10, and 100 µM. Flurbiprofen also down-regulated Lhcgr expression at 100 µM. Flurbiprofen at 10 and 100 µM increased ROS production and apoptosis rate of rat Leydig cells. In conclusion, flurbiprofen directly inhibits HSD3B activity and the expression levels of Srd5a1 and Akr1c14 in rat Leydig cells, thus leading to the reduction of androgen secretion.

Effects of ketoconazole, voriconazole, and itraconazole on the pharmacokinetics of apatinib in rats.

We investigated the effect of azole antifungal drugs (ketoconazole, voriconazole, and itraconazole) on the pharmacokinetics of apatinib in rats. The rats in ketoconazole, voriconazole, and itraconazole groups received single-dose apatinib 30 mg/kg after the oral administration of ketoconazole, voriconazole, and itraconazole, respectively. Co-administration of ketoconazole or voriconazole significantly increased the apatinib Cmax and AUC(0-t) and decreased the clearance. Co-administration of itraconazole did not significantly affect the pharmacokinetics parameters of apatinib. It could be concluded that both ketoconazole and voriconazole significantly increase the exposure of apatinib, and affect the pharmacokinetics of apatinib in rat. Apatinib can be co-administered with itraconazole, but ketoconazole and voriconazole should be avoided if possible or be underwent therapeutic drug monitoring of apatinib. A further clinical study should be conducted to investigate the inhibitory effect of azole antifungal drugs on the apatinib plasma concentration.

Effects of Ziram on Rat and Human 11ß-Hydroxysteroid Dehydrogenase Isoforms.

Ziram is a widely used fungicide for crops. Its endocrine disrupting action is largely unknown. 11ß-Hydroxysteroid dehydrogenases, isoforms 1 (HSD11B1) and 2 (HSD11B2), have been demonstrated to be the regulators of the local levels of active glucocorticoids, which have broad physiological actions. In the present study, the potency of ziram was tested for its inhibition of rat and human HSD11B1 and HSD11B2. Ziram showed the inhibition of rat HSD11B1 reductase with IC50 of 87.07 µM but no inhibition of human enzyme at 100 µM. Ziram showed the inhibition of both rat and human HSD11B2 with IC50 of 90.26 and 34.93 µM, respectively. Ziram exerted competitive inhibition of rat HSD11B1 when 11-dehydrocorticosterone was used and mixed inhibition when NADPH was supplied. Ziram exerted a noncompetitive inhibition of both rat and human HSD11B2 when steroid substrates were used and an uncompetitive inhibition when NAD(+) was supplied. Increased DTT concentrations antagonized rat and human HSD11B2 activities, suggesting that the cysteine residues are associated with the inhibition of ziram. In conclusion, for humans, ziram is a selective inhibitor of HSD11B2, implying that this agent may cause excessive glucocorticoid action in local tissues such as the kidney, brain, and placenta.

Effects of Polybrominated Diphenyl Ethers on Rat and Human 11ß-Hydroxysteroid Dehydrogenase 1 and 2 Activities.

Polybrominated diphenyl ethers (PBDEs) are a class of brominated flame retardants. PBDEs have been widely used in textiles, flexible polyurethane foams, electronic components, electrical components, and plastics. 11ß-Hydroxysteroid dehydrogenases, isoform 1 (HSD11B1) and isoform 2 (HSD11B2), have been demonstrated to be the regulators of local glucocorticoid levels. In this study, the potencies of 4 different PBDEs (BDE-3, BDE-47, BDE-100, and BDE-153) with 1-6 bromine atoms attached in inhibition of rat and human HSD11B1 and HSD11B2 activities were compared to 4-bromobiphenyl (BBP), a structurally similar compound. All 4 PBDEs and BBP did not inhibit rat and human HSD11B1. BDE-3 and BDE-47 potently inhibited rat HSD11B2, and BDE-47 and BDE-153 potently inhibited human HSD11B2, with the half maximal inhibitory concentration values of 12.42, 5.95, 11.97, and 4.41 µmol/l, respectively. All PBDEs noncompetitively inhibited HSD11B2 when a steroid substrate was used. However, PBDEs exerted uncompetitive inhibition when the cofactor NAD+ was used. In conclusion, some PBDEs are selective inhibitors of HSD11B2, possibly causing excessive glucocorticoid action in local tissues.

Effects of methoxychlor and 2,2-bis ( p -hydroxyphenyl)-1,1,1-trichloroethane on cytochrome P450 enzyme activities in human and rat livers.

Cytochrome P450 (CYP) enzymes are involved in the metabolism of endogenous and exogenous compounds. Human and rat liver microsomes were used to investigate the inhibitory effects of methoxychlor (MXC) and its metabolite 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane (HPTE) on the activities of corresponding human and rat CYPs. Probe drugs were used to test the inhibitory effects of MXC and HPTE on human and rat CYPs. The results showed that MXC and HPTE inhibited both human CYP2C9 and rat liver CYP2C11 activity, with half-maximal inhibitory concentration (IC50) values of 15.47 ± 0.36 (MXC) and 8.87 ± 0.53 µmol/l (HPTE) for human CYP2C9, and of 22.45 ± 1.48 (MXC) and 24.63 ± 1.35 µmol/l (HPTE) for rat CYP2C11. MXC and HPTE had no effects on human CYP2C19 activity but inhibited rat CYP2C6 activity with IC50 values of 14.84 ± 0.04 (MXC) and 8.72 ± 0.25 µmol/l (HPTE). With regard to human CYP2D6 and rat CYP2D2 activity, only HPTE potently inhibited human CYP2D6 activity, with an IC50 value of 16.56 ± 0.69 µmol/l. Both chemicals had no effect on human CYP3A4 and rat CYP3A1 activity. In summary, MXC and HPTE are potent inhibitors of some human and rat CYPs.

[Effect of total flavonoids from astragalus complanatus on paraquat poisoning-induced pulmonary fibrosis in rats and its mechanisms].

OBJECTIVE: To investigate the effects of total flavonoids from astragalus complanatus (FAC) on paraquat poisoning-induced pulmonary fibrosis in rats. METHODS: The rats were divided into six groups randomly: control group, paraquat group, prednisolone group and FAC low-dose, middle-dose, high-dose group. Pulmonary fibrosis model was replicated by intratracheal injection of paraquat. In the mext day,the rats were treated by intragastric administration once a day. After 28 days, the rats were sacrificed. The lung index and the levels of HYP and T-AOC were measured, and the pathologic changes of the lung tissue were obtained by HE staining. The levels of TGF-ß, Smad2, α-SMA protein were analyzed by Western blot. RESULTS: FAC improved the activity of T-AOC in serum and reduced pulmonary index and the content of HYP as well (P<0.05 or P<0.01), the alveolitis and fibrosis extent were attenuated. The expression of Smad2 significantly decreased in groups of FAC low-dose, middle-dose and high-dose (0.31±0.11, 0.45±0.12 and 0.30±0.05) as compared with that of the PQ group (0.85±0.34) (P<0.05). The expression of α-SMA significantly decreased in groups of FAC low-dose, middle-dose and high-dose (0.31±0.11, 0.35±0.07 and 0.32±0.10) as compared with that of the PQ group (0.45±0.08) (P<0.05). The expression of TGF-ß significantly decreased in groups of FAC low-dose, middle-dose and high-dose (0.35±0.04, 0.27±0.05 and 0.18±0.04)as compared with that of the PQ group (0.63±0.11) (P<0.05). CONCLUSION: FAC can alleviate PQ-induced pulmonary fibrosis in rats through inhibiting TGF-ß/Smad signaling pathway.

Effects of estradiol and methoxychlor on Leydig cell regeneration in the adult rat testis.

The objective of the present study is to determine whether methoxychlor (MXC) exposure in adulthood affects rat Leydig cell regeneration and to compare its effects with estradiol (E2). Adult 90-day-old male Sprague-Dawley rats received ethane dimethane sulfonate (EDS) to eliminate the adult Leydig cell population. Subsequently, rats were randomly assigned to four groups and gavaged with corn oil (control), 0.25 mg/kg E2 and 10 or 100 mg/kg MXC daily from days 5 to 30 post-EDS treatment. The results showed that MXC and E2 reduced serum testosterone levels on day 58 post-EDS treatment. qPCR showed Hsd17b3 mRNA levels were downregulated 7-15 fold by E2 and MXC, indicating that development of the new population of Leydig cells was arrested at the earlier stage. This observation was supported by the results of histochemical staining, which demonstrated that Leydig cells in MXC-treated testis on day 58 post-EDS treatment were mostly progenitor Leydig cells. However, Pdgfb mRNA levels were downregulated, while Lif transcript levels were increased by MXC. In contrast, E2 did not affect gene expression for these growth factors. In conclusion, our findings indicated that both MXC and E2 delayed rat Leydig cell regeneration in the EDS-treated model, presumably acting by different mechanisms.

Inhibition of soluble epoxide hydrolase relieves adipose inflammation via modulating M1/M2 macrophage polarization to alleviate airway inflammation and hyperresponsiveness in obese asthma.

Obesityincreasestheriskofasthma and tends to enhance the asthma severity, however, its mechanism is not fully elucidated. The expansion of adipose tissue in obesity is accompanied by the accumulation of adiposetissue macrophages (ATMs) that could contribute to alow-gradeinflammationstate. In this study, we researched the regulatory role of soluble epoxide hydrolase (sEH) on ATMs-mediated inflammation in obese asthma. A mouse model of obese asthma that induced by high-fat diet (HFD) feeding and Ovalbumin (OVA) sensitization was employed to investigate the effects of AUDA, a sEH inhibitor (sEHi), on airway inflammation, airway hyperresponsivenesss (AHR) and pulmonary pathological changes. In addition to alleviating the key features of asthma in obese mice, we confirmed that AUDA reduced the expression of pro-inflammatory factor, such as interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumornecrosisfactor-α (TNF-α) in adipose tissue and serum. Moreover, AUDA could remarkedly reduce Lipopolysaccharide (LPS)-elevated IL-1ß, IL-6 and TNF-α in RAW264.7 macrophage cells. Mechanistically, AUDA effectively reduced inflammation in adipose tissue, resulting in reduced systemic inflammation, by inhibiting M1-type macrophage polarization and promoting M2-type macrophage polarization. These processes were found to act through ERK1/2 signaling pathway. Herein, we proved that inhibition of sEH expression helped to mitigate multiple parameters of obese asthma by regulating the balance of M1/M2 macrophage polarization in adipose tissue.

Morphine compromises androgen biosynthesis by immature Leydig cells from pubertal rat testes in vitro.

Morphine is an analgesic in the opiate family, isolated from many plants. It can inhibit androgen biosynthesis by Leydig cells. Whether morphine directly inhibits androgen biosynthesis and underlying mechanism remains unclear. To investigate the influence of morphine on androgen secretion by rat immature Leydig cells (ILCs) and possible mechanism. Rat ILCs were treated with 0.5-50 µM morphine for 3 h in vitro. Morphine at ≥0.5 µM significantly reduced total androgen secretion. Morphine at 50 µM also compromised luteinizing hormone (LH, 10 mg/kg), 8Br-cAMP (1 mM), and 22R-hydroxycholesterol (20 µM) stimulated total androgen, androstanediol, and testosterone secretion, without affecting pregnenolone, progesterone, androstenedione mediated androgen secretion and testosterone and dihydrotestosterone mediated androstanediol secretion. Further analysis revealed that morphine at ≥0.5 µM downregulated Star expression and at ≥5 µM downregulated Cyp11a1 expression. Morphine also significantly reduced STAR (≥0.5 µM) and reduced CYP11A1 (≥5 µM) levels. 0.5 µM naloxone significantly antagonized morphine-mediated action. In conclusion, morphine might cause side effects by suppressing androgen biosynthesis via u opioid receptor.

Differential metabolic networks in three energy substances of flaxseed (Linum usitatissimum L.) during germination.

Germinated flaxseed (Linum usitatissimum L.) is an essential potential food ingredient, but the major energy substances (proteins, lipids, and carbohydrates) metabolites and metabolic pathways are unknown. Comprehensive metabolomic analyses were performed using Fourier transform infrared spectroscopy and high-performance liquid chromatography mass spectrometry on flaxseed from 0 to 7 d. Additionally, the critical metabolites pathways networks of three energy substances metabolites during flaxseed germination were exhibited. The results showed that arginine was the most active metabolite during germination, strongly associated with the arginine biosynthesis and arginine and proline metabolism pathways. Carbohydrates predominantly comprised sucrose on 0-3 d, which participated in galactose metabolism and starch and sucrose metabolism. The main flaxseed phospholipid molecules were phosphatidic acid, phosphatidylethanolamine, lysophosphatidic acid, and lysophosphatidylcholine during germination. This study underscores the paramount metabolic pathways in proteins, lipids and carbohydrates were arginine and proline metabolism, linoleic acid metabolism, arachidonic acid metabolism, and ascorbate and aldarate metabolism during germination.

Strong and Durable Wood Designed by Cell Wall Bulking Combined with Cell Lumen Filling.

Traditional wood-polymer composite (WPC) based on the in situ polymerization of ethylene unsaturated monomers in the cellular cavity of wood is significant for the high-value-added utilization of low-quality wood. However, this type of WPC has the problems of volatile monomers, low conversion rates, odor residue, and poor compatibility between the polymer and wood interface, which hinder its promotion and application. In this study, a two-step process of cell wall bulking in combination with cell lumen filling was prepared to modify wood using Maleic anhydride (MAN) as the bulking agent and GMA-EGDMA (molar ratio 2:1) as the active monomer system. The results indicate that the modulus of rupture (MOR) (125.19 ± 8.41 MPa), compressive strength (116.38 ± 7.69 MPa), impact toughness (55.4 ± 2.95 KJ m-2), and hardness (6187 ± 273 N) of the bulking-filling wood composite materials were improved by 54%, 56%, 36%, and 66%, respectively, compared with those of poplar wood. These properties were superior to those of the traditional styrene (PSt)-WPC and even exceeded the performance of Xylosma congesta (Lour.) Merr, a high-quality wood from northeast China. Meanwhile, the mass loss of wood composite materials with bulking-filling treatment was only 2.35 ± 0.05%, and the internal structure remained intact, presenting excellent decay resistance. Additionally, the treatment also significantly improved the thermal and dimensional stability of the wood composites. This study provides a theoretical basis and guidance for realizing the high-value-added application of low-quality wood and the preparation of highly durable wood-based composites.

The complete mitochondrial genome of Anthrenus museorum (Coleoptera: Bostrichiformia: Dermestidae) from China.

Dermestid beetles (Coleoptera: Bostrichiformia: Dermestidae) are important pests of various storage products and pose a potential threat to international trade. In this study, the whole mitogenome of Anthrenus museorum was first sequenced and annotated and was found to have the same gene order observed in known dermestid beetles. It comprised 13 protein-coding genes (PCGs), 22 transfer RNAs, 2 ribosomal RNAs and a control region. The typical ATN start codon was observed in all PCGs, except for ND3 (TTG), and all 13 PCGs showed three types of stop codons (TAA, TAG, and T-). Phylogenetic analysis based on the PCGs indicated that the relationships within Bostrichiformia were reconstructed, with the exception of one early emerging species of Bostrichidae that actually makes the group polyphyletic, as (Dermestidae + (Bostrichidae + Anobiidae)). Moreover, it revealed a close relationship between A. museorum and A. verbasci using maximum likelihood and Bayesian inference analysis.

Multi-domain-fusion deep learning for automatic modulation recognition in spatial cognitive radio.

Automatic modulation recognition (AMR) is a critical technology in spatial cognitive radio (SCR), and building high-performance AMR model can achieve high classification accuracy of signals. AMR is a classification problem essentially, and deep learning has achieved excellent performance in various classification tasks. In recent years, joint recognition of multiple networks has become increasingly popular. In complex wireless environments, there are multiple signal types and diversity of characteristics between different signals. Also, the existence of multiple interference in wireless environment makes the signal characteristics more complex. It is difficult for a single network to accurately extract the unique features of all signals and achieve accurate classification. So, this article proposes a time-frequency domain joint recognition model that combines two deep learning networks (DLNs), to achieve higher accuracy AMR. A DLN named MCLDNN (multi-channel convolutional long short-term deep neural network) is trained on samples composed of in-phase and quadrature component (IQ) signals, to distinguish modulation modes that are relatively easy to identify. This paper proposes a BiGRU3 (three-layer bidirectional gated recurrent unit) network based on FFT as the second DLN. For signals with significant similarity in the time domain and significant differences in the frequency domain that are difficult to distinguish by the former DLN, such as AM-DSB and WBFM, FFT (Fast Fourier Transform) is used to obtain frequency domain amplitude and phase (FDAP) information. Experiments have shown that the BiGUR3 network has superior extraction performance for amplitude spectrum and phase spectrum features. Experiments are conducted on two publicly available datasets, the RML2016.10a and RML2016.10b, and the results show that the overall recognition accuracy of the proposed joint model reaches 94.94% and 96.69%, respectively. Compared to a single network, the recognition accuracy is significantly improved. At the same time, the recognition accuracy of AM-DSB and WBFM signals has been improved by 17% and 18.2%, respectively.

Dynamics of composition, structure, and metabolism of three energy substances in flaxseed (Linum usitatissimum L.) during germination.

The composition and structure changes of three energy substances (protein, lipid, and sugar) and minerals during flaxseed germination were investigated. Na, Ca, Fe, and total free amino acids fluctuating increased and peaked at 7 d. Oil and ɑ-linolenic acid contents increased initially and reached the maximal increment by 14.8 % and 1.4 % (p < 0.05) at 2 d, after which it declined. Soluble sugar mainly consisted of sucrose (50.47 %-72.77 %), glucose, and fructose during germination. Semi-cylindrical depression was enhanced on flaxseed granule surface, and oil bodies distribution from relatively uniform toward cell wall during 0-2 d. Protein order and stability were varied firstly, then grew steadily at 4-7 d and peaked at 7 d. Metabolic sequence (sugar, protein, and lipid) and related tricarboxylic acid pathway were proposed. Conclusively, germinated flaxseed at 2 and 4 d had higher physicochemical and structural properties, which could serve as high-quality resources for lipid and protein processing respectively.

Effect of germination pretreatment on the physicochemical properties and lipid concomitants of flaxseed oil.

This study investigated the effects of germination pretreatment on the physicochemical properties, lipid concomitants, and antioxidant activity of flaxseed oil in three varieties. The results indicated that the oil content of flaxseed decreased by 2.29-7.40% during the 5 days germination period. Germinated flaxseed oil showed a significantly higher acid value and lower peroxide value. The unsaturated fatty acid content was slightly increased by germination. Germination pretreatment resulted in significant increases in the α-tocopherol, stigmasterol, pigments, total phenols, and antioxidant activity. As germination time progressed to 5 days, α-tocopherol which was traditionally recognized as having the highest antioxidant activity form of vitamin E in humans increased from 3.07-6.82 mg kg-1 to 258.11-389.78 mg kg-1. Germinated oil had 1.63 to 2.05 times higher stigmasterol content than non-germinated oil. The chlorophyll and carotenoid also increased exponentially. The total phenol content of flaxseed oil increased from 64.29-75.85 mg kg-1 to 236.30-297.78 mg kg-1. Germinated flaxseed oil showed important antioxidant activity. Compared with other varieties during germination, the oil from Gansu showed a higher level of α-linolenic acid, tocopherols, and carotenoid, and a maximum increase level of tocopherols and phytosterols. The comprehensive evaluation of germination time by correlation and principal component analysis showed that when germination time exceeded 2 days, the lipid concomitants and antioxidant capacity of flaxseed oil were significantly improved.

Indication of the color change on the oxidation properties of fragrant rapeseed oil during shelf storage.

The cause and trend of color change and their links to oxidative properties were investigated by simulating shelf storage conditions for fragrant rapeseed oils (FROs). Under illumination, the L* value gradually increased with the storage time. The a* and b* values showed different trends depending on brands. The photodegradation rates of chlorophylls were 8.6 âˆ¼ 15 times higher than those of carotenoids. The change in color of FROs was mainly caused by the light-induced photodegradation of chlorophyll. Compared with the hydroperoxides, the contents of some secondary oxidation products [i.e., 2-butenal, octane, (Z)-2-octene, 2,4-octadiene, (Z)-2-heptenal, (E, E)-2,4-heptadienal, and (E)-2-decenal] were more closely associated with the color variation with correlation coefficients of 0.6 âˆ¼ 0.94. Significant negative correlation was found between α-tocopherol content and oil color difference. Therefore, illumination was the main reason for the color degradation of the FROs. The varying degree of color difference was strongly linked to the quality deterioration caused by oxidation.

Trichlorfon blocks androgen synthesis and metabolism in rat immature Leydig cells.

Trichlorfon is a widely used organophosphorus insecticide. It has been reported that it has reproductive toxicity to animal models. However, whether trichlorfon affects testosterone biosynthesis and metabolism remains unclear. In this study, we explored the effects of trichlorfon on the steroidogenesis and the expression of genes in androgen biosynthetic and metabolic cascades in immature Leydig cells isolated from pubertal male rats. Immature Leydig cells were treated with trichlorfon (0.5-50 µM) for 3 h. Trichlorfon significantly inhibited total androgen output under basal condition at 5 and 50 µM, and under LH- and cAMP-stimulated conditions at 50 µM. Trichlorfon also downregulated the expression of Star, Sod2, and Gpx1 and their proteins at 5 and 50 µM and the expression of Cyp11a1, Hsd3b1, Cyp17a1, and Srd5a1 at 50 µM. Trichlorfon significantly inhibited total androgen output at 50 µM, which was partially reversed by 400 µg/ml vitamin E, which alone had no effects on androgen output. In conclusion, trichlorfon downregulates the expression of steroidogenesis-related genes and antioxidants, which leads to a decrease in androgen production in rat immature Leydig cells.

Chemicals of environmental concern as inhibitors of human placental 3ß-hydroxysteroid dehydrogenase 1 and aromatase: Screening and docking analysis.

Many environmental pollutants act as endocrine-disrupting compounds by inhibiting human placental 3ß-hydroxysteroid dehydrogenase/Δ5-4 isomerase type 1 (HSD3B1) and aromatase (CYP19A1) activities. In this study, we screened 13 chemicals of environmental concern for their ability to inhibit human HSD3B1 and CYP19A1 by measuring the conversion of pregnenolone to progesterone for HSD3B1 activity and the conversion of testosterone to 17ß-estradiol for CYP19A1 activity in human JEG-3 choriocarcinoma cell microsomes. HSD3B1 had an apparent Km of 0.323 µM and an apparent Vmax of 0.111 nmol/mg/min and CYP19A1 had an apparent Km of 56 nM and an apparent Vmax of 0.177 nmol/mg protein/min. 17ß-Estradiol, bisphenol A, and bisphenol AF competitively inhibited HSD3B1 with Ki values of 0.8, 284.1, and 141.2 µM, respectively, while diethylstilbestrol had a mixed inhibition on human HSD3B1 with the Ki of 8.0 µM. Ketoconazole, bisphenol A, and bisphenol AF noncompetitively inhibited CYP19A1 with Ki values of 10.3, 54.4, and 45.7 µM, respectively, while diethylstilbestrol and zearalenone competitively suppressed CYP19A1 with Ki values of 63.0 and 16.6 µM, respectively. Docking analysis showed that 17ß-estradiol, diethylstilbestrol, bisphenol A, and bisphenol AF bound the steroid binding pocket facing the catalytic residues Y155 and K159 of HSD3B1, and that ketoconazole, bisphenol A, and bisphenol AF bound heme binding pocket while diethylstilbestrol and zearalenone bound the steroid binding site of CYP19A1. In conclusion, 17ß-estradiol, diethylstilbestrol, bisphenol A, and bisphenol AF are human HSD3B1 inhibitors, and ketoconazole, zearalenone, diethylstilbestrol, bisphenol A, and bisphenol AF are human CYP19A1 inhibitors.

Functional Properties and Structural Characteristics of Starch-Fatty Acid Complexes Prepared at High Temperature.

The effects of fatty acid type (myristic, palmitic, stearic, oleic, linoleic, and linolenic acid) on the characteristics of starch-lipid complexes under high temperature were investigated. Fatty acids with a shorter carbon chain or a greater number of double bonds contributed to the formation of V-type starch-lipid complexes. The thermostability of starch-unsaturated fatty acid (UFA) complexes prepared at high temperature was increased compared with those obtained at lower temperature. Resistant starch (RS) contents and melting temperatures had a strong significant positive correlation. Complexes with better thermostability were more resistant to enzymatic hydrolysis. Among them, the starch-stearic acid complexes possessed the highest RS content. The paste of starch-linolenic acid complexes had the lowest internal friction and the strongest thixotropy. The broken of double bonds in UFAs probably accounted for the increased starch-lipid complexes. The crystalline, thermal, rheological, and digestion properties of samples treated at high temperature were significantly affected.

Shp2 regulates PM2.5-induced airway epithelial barrier dysfunction by modulating ERK1/2 signaling pathway.

The impact of fine particulate matter (PM2.5) on public health has received increasing attention. Through various biochemical mechanisms, PM2.5 alters the normal structure and function of the airway epithelium, causing epithelial barrier dysfunction. Src homology domain 2-containing protein tyrosine phosphatase 2 (Shp2) has been implicated in various respiratory diseases; however, its role in PM2.5-induced epithelial barrier dysfunction remains unclear. Herein, we assessed the regulatory effects of Shp2 on PM2.5-mediated epithelial barrier function and tight junction (TJ) protein expression in both mice and human pulmonary epithelial (16HBE) cells. We observed that Shp2 levels were upregulated and claudin-4 levels were downregulated after PM2.5 stimulation in vivo and in vitro. Mice were exposed to PM2.5 to induce acute lung injury, and disrupted epithelial barrier function, with decreased transepithelial electrical resistance (TER) and increased paracellular flux that was observed in 16HBE cells. In contrast, the selective inhibition or knockdown of Shp2 retained airway epithelial barrier function and reversed claudin-4 downregulation that triggered by PM2.5, and these effects may occur through the ERK1/2 MAPK signaling pathway. These data highlight an important role of Shp2 in PM2.5-induced airway epithelial barrier dysfunction and suggest a possible new course of therapy for PM2.5-induced respiratory diseases.