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Sertoli cells (SCs) maintain testicular homeostasis and promote spermatogenesis by forming the blood-testis barrier (BTB) and secreting growth factors. The pro-proliferative and anti-apoptotic effects of nerve growth factor (NGF) on SCs have been proved previously. It is still unclear whether the damage effect of arsenic on testis is related to the inhibition of NGF expression, and whether NGF can mitigate arsenic-induced testicular damage by decreasing the damage of SCs induced by arsenic. Here, the lower expression of NGF in testes of arsenic exposed mice (freely drinking water containing 15 mg/l of NaAsO 2) was observed through detection of Western blot and Real-time PCR. Subsequently, hematoxylin and eosin (HE) staining, Evans blue staining and transmission electron microscopy were used to evaluate the pathology, BTB permeability and tight junction integrity in testes of control mice, arsenic exposed mice (freely drinking water containing 15 mg/l of NaAsO 2) and arsenic + NGF treated mice (freely drinking water containing 15 mg/l of NaAsO 2 + intraperitoneal injection with 30 μg/kg of NGF), respectively. Evidently, spermatogenic tubule epithelial cells in testis of arsenic exposed mice were disordered and the number of cell layers was reduced, accompanied by increased permeability and damaged integrity of the tight junction in BTB, but these changes were less obvious in testes of mice treated with arsenic + NGF. In addition, the sperm count, motility and malformation rate of mice treated with arsenic + NGF were also improved. On the basis of the above experiments, the viability and apoptosis of primary cultured SCs treated with arsenic (10 μM NaAsO 2) or arsenic + NGF (10 μM NaAsO 2 + 100 ng/mL NGF) were detected by Cell counting kit-8 (CCK8) and transferase-mediated DUTP-biotin nick end labeling (TUNEL) staining, respectively. It is found that NGF ameliorated the decline of growth activity and the increase of apoptosis in arsenic-induced SCs. This remarkable biological effect that NGF inhibited the increase of Bax expression and the decrease of Bcl-2 expression in arsenic-induced SCs was also determined by western blot and Real-time PCR. Moreover, the decrease in transmembrane resistance (TEER) and the expression of tight junction proteins ZO-1 and occludin was mitigated in SCs induced by arsenic due to NGF treatment. In conclusion, the above results confirmed that NGF could ameliorate the injury effects of arsenic on testis, which might be related to the function of NGF to inhibit arsenic-induced SCs injury. [Display omitted] • NGF mitigated tight junction breakdown of BTB in arsenic exposed mice. • NGF improved the decreased sperm count/motility in arsenic-exposed mice. • NGF inhibited sperm malformation in arsenic exposed mice. • NGF mitigated the apoptosis of SCs induced by arsenic. • NGF enhanced the expression of tight junction protein in arsenic-induced SCs. [ABSTRACT FROM AUTHOR]

• Tracking model properties with time-invariant models on adaptive segment lengths. • Optimal partitioning of data by Bayesian model class selection. • Optimal partitioning determined efficiently by dynamic programming. • Application to tracking modal properties in OMA. Structural health monitoring (SHM) quite often involves continually tracking the temporal variation of some properties of interest, where statistical information about variations under normal situation can be obtained and potential anomalies may be detected for further attention. Structural-related properties such as natural frequency and stiffness often need to be identified with a physics-based model that relates them to measured data. Conventional approaches empirically divide data into non-overlapping segments with equal lengths and identify the model parameters within each segment based on a time-invariant model. Potentially time-varying model properties are then investigated based on the variation of identified results from one data segment to another. Challenges do exist, e.g., how to choose segment length to balance modeling error and identification accuracy, how to set criterion for anomaly detection, etc., which should be addressed with proper extraction of probabilistic information from data. In this work, the SHM problem is formulated as a Bayesian model selection problem, where the data can be 'partitioned' in an arbitrary manner, whose optimal choice, and hence points of significant change, are determined together with the model inference process by maximizing the probabilistic evidence supported by data. An efficient algorithm based on dynamic programming is proposed to determine the optimal partitioning and associated piecewise-constant properties, which is otherwise computationally prohibitive. The methodology is applied to tracking modal properties, e.g., natural frequency and damping ratio, of structures using output-only ambient vibration data. It is investigated with synthetic data and then applied to field data of a tall building during a typhoon event. [ABSTRACT FROM AUTHOR]

17α-ethynylestradiol (EE2), a synthetic estrogen commonly used in the oral contraceptive pills, disrupts the sexual differentiation, gonadal development and reproduction in aquatic species. Nowadays aquatic species and even humans still have the potential risks of exposure to EE2. However, the mechanism of EE2 endocrine disruption is still unclear. Aiming to elucidate molecular mechanisms, we analyzed transcriptome profiling of gonads, gonadal histology and the sex steroid hormones in response to EE2 in G. rarus . Through this study, we obtained eight RNA-Seq libraries upon EE2 exposure, and found some key genes and pathways in correlation with the disruption effects of EE2. We found EE2 could disrupt oocyte development and spermatogenesis in adult G. rarus , and EE2 has more obvious disruption effects on male G. rarus than females. Interestingly, EE2 was indicated to be an exogenous DPC-inducing agent and ppp2r3b was suggested to be a spermatogenesis candidate gene in rare minnow. The differential gene expressions of rps30 , samp9 , ppp2r3b and spartan upon EE2 exposure suggest EE2's disruption effects on gonads could attribute to altered pathways of translation, ribosome biogenesis and cell division. [ABSTRACT FROM AUTHOR]

The effects of synthetic androgen 17α-methyltestosterone (MT) on endocrine impairment were examined in crucian carp. Immature 7-month old mono-female Pengze crucian carp (Pcc) F2 offspring were exposed to 50 and 100 μg/L of MT (week 2, 4, and 8). Gonadosomatic index, hepatosomatic index and intestine weight altered considerably and oocyte development was repressed. In the treatment groups, ovarian 11-ketotestosterone decreased, whereas 17β-estradiol and testosterone increased, and ovarian aromatase activities increased at week 4. However, in the brain tissue, those values significantly decreased. Quantitative RT-PCR analysis demonstrated changes in steroid receptor genes and upregulation of steroidogenic genes (Pcc- 3bhsd , Pcc- 11bhsd2 Pcc- cyp11a1 ), while the other three steroidogenic genes (Pcc- cyp17a1 , Pcc- cyp19a1a and Pcc- star ) decreased from week 4 to week 8. Ovarian, hepatic Pcc- vtg B and vitellogenin concentration increased in both 50 and 100 μg/L of MT exposure groups. This study adds further information regarding the effects of androgens on the development of previtellogenic oocytes, which suggests that MT could directly target estrogen signaling pathway, or indirectly affect steroidogenesis and vitellogenesis. [ABSTRACT FROM AUTHOR]

Abstract: Signal transducers and activators of transcription (STAT) family proteins transduce pivotal biological effects of various cytokines and hormones. STAT3 proteins are known to play a central role in the regulation of growth, differentiation, and survival of many types of cells. However, the function of STAT3 in myogenesis still remains largely unknown. We now provided direct evidence that STAT3 could induce myogenic differentiation and this effect might be mediated by interaction with MyoD—the essential transcription factor during myogenic differentiation. Furthermore, leukemia inhibitory factor (LIF) might be the upstream factor which activated JAK2/STAT3 pathway to stimulate muscle cell differentiation. Taken together, these results provide a molecular basis for further understanding of the muscle regeneration mechanism. [Copyright &y& Elsevier]

Abstract: Tuberculosis (TB) remains to be a global health problem. New drugs are badly needed to drastically reduce treatment time and overcome some of the challenges with tuberculosis treatment, such as multi-drug resistant (MDR) strain infected patients or tuberculosis/HIV co-infected patients. The essentiality of mycobacterial aromatic amino acid biosynthesis pathways and their absence from human host indicate that the member enzymes of these pathways promising drug targets for therapeutic agents against pathogen mycobacteria. Prephenate dehydrogenase (PDH) is a key regulatory enzyme in tyrosine biosynthesis, catalyzing the NAD+-dependent conversion of prephenate to p-hydroxyphenylpyruvate, making it a potential drug target for antibiotics discovery. The recombinant PDH with an N-terminal His-tag (His-rMtPDH) was first purified in Escherichia coli, and using enterokinase rMtPDH was obtained by cleaving the N-terminal fusion partner. The effect of pH, temperature and the cation-Na+ on purified enzyme activity was characterized. The N-terminal fusion partner was found to have little effect on the biochemical properties of PDH. We also provide in vitro evidence that Mycobacterium tuberculosis PDH does not possess any chorismate mutase (CM) activity, which suggests that, unlike many other enteric bacteria (where PDH exists as a fusion protein with CM), M. tuberculosis PDH is a monofunctional protein. [Copyright &y& Elsevier]

Abstract: Pyrroline-5-carboxylate reductase (P5CR) plays an important role in the survival of Mycobacterium tuberculosis and is related to virulence of this pathogen. RT-PCR analysis indicated that proC, encoding P5CR, was expressed at the transcriptional level cultured in vitro. The His-rMtP5CR with an N-terminal His-tag (His-rMtP5CR) was firstly purified in Escherichia coli and rMtP5CR was obtained by removal of the N-terminal fusion partner using enterokinase. His-rMtP5CR had considerable β-pleated sheet analyzed by circular dichroism spectroscopy. The effect of pH, temperature, cations, denaturants, and detergents on the purified enzyme activity and stability was characterized. The N-terminal fusion partner was found to have very little effect on the biochemical properties of P5CR. [Copyright &y& Elsevier]

Metals in acid mine drainages (AMD) have posed a great threat to environment, and in situ economic environment-friendly remediation technologies need to be developed. Moreover, the effects of acidophiles on biosorption and migrating behaviors of metals in AMD have not been previously reported. In this study, the extremely thermoacidophilic Archaea , Acidianus manzaensis YN25 (A. manzaensis YN25) was used as a bio-adsorbent to adsorb metals (Cu2+, Ni2+, Cd2+ and Zn2+) from acidic solutions which were taken to imitate AMD. The values of their maximum biosorption capacities at both high (1 mM) and low (0.1 mM) metal concentrations followed the order: Cu2+ > Ni2+ > Cd2+ > Zn2+. With the elevations of temperature and pH value, the adsorption amounts of metals increased. The results also indicated that A. manzaensis YN25 had the highest adsorption affinity to Cu2+ in coexisting system of quaternary metals. Acid-base titration data revealed that carboxyl and phosphoryl groups provided adsorption sites for metals via deprotonation. Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) further corroborated that amino played an important role in the biosorption process. The fitted Langmuir model illustrated monolayer adsorption occurring on cell surface. The possible adsorption mechanism of A. manzaensis YN25 mainly involved in electrostatic attraction and complexes formation. This study gives a profound insight into the biosorption behavior of heavy metals in acidic solution by thermoacidophilic Archaea and provides a probable novel strategy for in situ remediation of heavy metals pollution in AMD. • Protonation/deprotonation contributed to heavy metal ions adsorption. • The archaea had the best affinity for Cu2+ compared to Ni2+, Cd2+ and Zn2+. • A positive correlation between pH value and adsorption capacity. • Monolayer adsorption occurred on the cell surface of A. manzaensis YN25. • The biosorption mechanism refer to electrostatic attraction and complexation. [ABSTRACT FROM AUTHOR]

Abstract: The emergence of multi-drug resistant (MDR) strains of Mycobacterium tuberculosis is the main reason why tuberculosis (TB) continues to be a major health problem worldwide. It is urgent to discover novel anti-mycobacterial agents based on new drug targets for the treatment of TB, especially MDR-TB. Tryptophan biosynthetic pathway, which is essential for the survival of M. tuberculosis and meanwhile absent in mammals, provides potential anti-TB drug targets. One of the promising drug targets in this pathway is anthranilate synthase component I (TrpE), whose role is to catalyze the conversion of chorismate to anthranilate using ammonia as amino source. In order to get a deep understanding of TrpE, a study on purification and characteristic identification of TrpE is required. In this work, the putative trpE gene of M. tuberculosis H37Rv was expressed as a fusion protein with a 6× His-tag on the N-terminal (His-TrpE) in Escherichia coli. The recombinant TrpE protein was successfully purified and then its enzymatic characteristics were analyzed. The native TrpE without His-tag was obtained by removal of the N-terminal fusion partner of His-TrpE using enterokinase. It was found that N-terminal fusion partner had little influence on TrpE catalytic activity. In addition, the key residues related to enzyme catalytic activity and that involved in l-tryptophan inhibition were predicted in the structure of M. tuberculosis H37Rv TrpE. These results would be beneficial to the designing of novel anti-TB drugs with high potency and selectivity. [Copyright &y& Elsevier]

As a prominent member of freshwater and coastal fish faunas, Coilia nasus migrates annually from the sea up the Yangtze River in China to spawn. It is traditionally believed that C. nasus generally do not feed during their spawning migration. However, we recently documented the occurrence of food intake phenomenon in C. nasus following voluntary fasting. The purpose of the current study is to explore the metabolic mechanisms on C. nasus in response to food intake during migration. A total of 23,159 differentially expressed mRNA molecules and 204 metabolites were identified in transcriptome and metabolome analyses. Our results provide insights into the activation of energy consumption and reinforcement of energy storage during migration, and also identify key genes involved in food intake regulation. Our findings will be useful for future research on population recruitment and energy utilization in wild C. nasus. • Metabolic changes in feeding C. nasus were quantified for the first time. • Energy consumption was activated by feeding. • Energy storage was reinforced by feeding. • Metabolic mechanisms lay a foundation for the study of migratory ecology in C. nasus. [ABSTRACT FROM AUTHOR]

Abstract Parasites from the family Anisakidae are capable of infecting a range of marine fish species worldwide. Coilia nasu s, which usually feeds and overwinters in coastal waters and spawns in freshwater, is highly susceptible to infection by Anisakidae. In this study, we used scanning electron microscopes to show that C. nasu s infected by Anisakidae exhibited damage and fibrosis of the liver tissue. To better understand host immune reaction and metabolic changes to Anisakidae infection, we used a combination of transcriptomic and metabolomic method to characterize the key genes and metabolites, and the signaling pathway regulation of C. nasus infected by Anisakidae. We generated 62,604 unigenes from liver tissue and identified 391 compounds from serum. Of these, Anisakidae infection resulted in significant up-regulation of 545 genes and 28 metabolites, and significant down-regulation of 416 genes and 37 metabolites. Seventy-four of the 961 differentially expressed genes were linked to immune response, and 1, 2-Diacylglycerol, an important immune-related metabolite, was significantly up-regulated after infection. Our results show activation of antigen processing and presentation, initiation of the T cell receptor signaling pathway, disruption of the TCA cycle, and changes to the amino acid and Glycerolipid metabolisms, which indicate perturbations to the host immune system and metabolism following infection. This is the first study describing the immune responses and metabolic changes in C. nasus to Anisakidae infection, and thus improves our understanding of the interaction mechanisms between C. nasus and Anisakidae. Our findings will be useful for future research on the population ecology of C. nasus. Highlights • Microscopic observation showed that C. nasu s infected by Anisakidae exhibited damage and fibrosis of the liver tissue. • We profiled the differences in gene and metabolite expression between control and Anisakidae-infected C. nasu s. • We generated 62,604 unigenes from liver tissue and identified 391 compounds from serum. • Anisakidae infection resulted in several major perturbations to the host immune responses and to metabolic changes. • These data will be useful for future research on population ecology of C. nasus. [ABSTRACT FROM AUTHOR]

Abstract The expression of Notch1 plays an important role in the occurrence and development of various tumors. Previous studies have shown that Notch1 plays a negative regulatory role in response to radiation-induced DNA damage responses. It also has been reported that Notch1 was highly expressed in cervical cancer. It is well known that the first-line chemotherapy drug for treating cervical cancer, cisplatin, targets double-stranded DNA and induces apoptosis in the cells. However, the tolerability of cisplatin is an issue to overcome in the treatment of cervical cancer. Cisplatin has been reported to induce the up-regulation of Notch1 intracellular domain (NICD) through the γ-proteolytic enzyme complex, a complex that mediates Notch1 activation. Therefore, whether Notch1 is highly expressed in the cells or cisplatin induced high expression of NICD in cervical cancer has not been specifically discussed in these studies. More importantly, whether the inhibition of Notch1 activation would enhance DNA damage induced by cisplatin and/or cellular apoptosis mediated via ATM/CHK2/P53 pathway has not been reported in cervical cancer. In this study, we observed an enhanced DNA damage and cellular apoptosis via the ATM/CHK2/P53 pathway(s) in HeLa and SiHa cells treated with cisplatin combined with DAPT of Notch1 inhibitor. Our findings provide an alternative therapeutic strategy for the treatment of cervical cancer in the clinic. Highlights • Cisplatin induced DNA damage and apoptosis through ATM-CHK2 -P53 pathway in cervical cancer cells. • Notch1 is involved in DNA damage induced by cisplatin in cervical cancer cells. • Notch1 inhibition enhances cisplatin-induced DNA damage and apoptosis in cervical cancer cells via the ATM-CHK2-P53 pathway. [ABSTRACT FROM AUTHOR]

The reduction of insulin secretion due to pancreatic β cell injury caused by autoimmune reaction is the pathological basis of Type 1 diabetes mellitus (T1DM). Therefore, seeking new molecular targets for alleviating pancreatic β cell injury will provide experimental basis for the prevention and treatment of T1DM. SRY-box 9 (Sox9) is not only an important molecule regulating the development of various organs, but also its high expression can aggravate the pathological process of various diseases. In addition, Sox9+ cells are also pancreatic progenitor cells, participating in pancreatic repair reaction induced by injury. In our study, elevated blood glucose and lack of pancreatic β cells almost returned to normal over time after streptozotocin (STZ)-induced pancreatic β cell damage, implying that pancreatic β cells were regenerated after STZ-induced injury. In particular, the expression of Sox9 was significantly elevated during pancreatic β cell regeneration. On this basis, we conducted in vitro experiments to verify whether overexpression of Sox9 could inhibit the damage of pancreatic β cells by inflammatory factors. Our results showed that overexpression of Sox9 alleviated the damage of pancreatic β cells by inflammatory factors and improved the inhibitory effect of inflammatory factors on insulin secretion of pancreatic β cells. Unsurprising, blood glucose levels, insulin content and pancreatic β cell number failed to return to near-normal levels timely after pancreatic β cells specific knockout Sox9 mice were treated with STZ, further confirming the importance of Sox9 in facilitating pancreatic β cell repair or regeneration. Our study indicate that enhanced Sox9 activity might protect pancreatic β cells from autoimmune induced damage and thus improve the pathological process of T1DM. [ABSTRACT FROM AUTHOR]

Highlights: [•] Full-length cDNAs of figla, scp3 and sox9a of Gobiocypris rarus were obtained. [•] The effective EE2 dosage for feminization in male G. rarus might be at least 25ng/L. [•] Spermatogenesis of adult male G. rarus could be severely disturbed by EE2. [•] Figla, foxl2 and scp3 can be used as sensitive molecular biomarkers. [Copyright &y& Elsevier]

Highlights: [•] The full-length cDNA of four nr5as were isolated and characterized from G. rarus. [•] 17 Steroidogenesis-related genes expression was studied after BPA exposure. [•] Gene expression was dependent on BPA concentration and exposure duration. [•] BPA actions might involve Esr/Fshr pathway and transcription factors. [ABSTRACT FROM AUTHOR]

Fermentation is considered as one of the most useful biological modification techniques to increase the bioactivity of polysaccharides. In this study, Saccharomyces cerevisiae and Bacillus subtilis were used to ferment wheat bran, and the effects of the fermentation on the structural characteristics and antioxidant activity of wheat bran polysaccharides were investigated. Two polysaccharides were isolated from unfermented and fermented wheat bran and labelled as wheat bran polysaccharides-1 (WBP-1) and fermented wheat bran polysaccharides-1 (FWBP-1), respectively. The results showed fermentation increased the content of total polysaccharides, enhanced the proportions of rhamnose, xylose and arabinose and improved the proportion of fucose to a detectable level. After fermentation, the molecular weight of FWBP-1 (21.19 kDa) was lower than that of WBP-1 (52.02 kDa). In vitro , FWBP-1 exhibited higher reducing power and stronger 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and hydroxyl radical scavenging activities. In zebrafish model, FWBP-1 also displayed superior protective effects against 2,2′-azobis(2-methylpropionamidine) dihydrochloride (AAPH)-induced reactive oxygen species (ROS) production, lipid peroxidation, and cell death. Taken together, S. cerevisiae and B. subtilis fermentation could change the structural characteristics and enhance the antioxidant activity of polysaccharides from wheat bran. Image 1 • Saccharomyces cerevisiae and Bacillus subtilis were used to ferment wheat bran (WB). • Fermentation altered the structural characteristics of WB polysaccharides. • In vitro , fermented-polysaccharides displayed higher reducing power and free radical scavenging activities. • In zebrafish model, fermented-polysaccharides exhibited superior protective effects against AAPH-induced oxidative stress. [ABSTRACT FROM AUTHOR]