A deep learning model for DNA enhancer prediction based on nucleotide position aware feature encoding.

Enhancers, genomic DNA elements, regulate neighboring gene expression crucial for biological processes like cell differentiation and stress response. However, current machine learning methods for predicting DNA enhancers often underutilize hidden features in gene sequences, limiting model accuracy. Hence, this article proposes the PDCNN model, a deep learning-based enhancer prediction method. PDCNN extracts statistical nucleotide representations from gene sequences, discerning positional distribution information of nucleotides in modifier-like DNA sequences. With a convolutional neural network structure, PDCNN employs dual convolutional and fully connected layers. The cross-entropy loss function iteratively updates using a gradient descent algorithm, enhancing prediction accuracy. Model parameters are fine-tuned to select optimal combinations for training, achieving over 95% accuracy. Comparative analysis with traditional methods and existing models demonstrates PDCNN's robust feature extraction capability. It outperforms advanced machine learning methods in identifying DNA enhancers, presenting an effective method with broad implications for genomics, biology, and medical research.

Gestodene causes masculinization of the western mosquitofish (Gambusia affinis): Insights from ovary metabolomics.

Gestodene (GES) is a common synthetic progesterone frequently detected in aquatic environments. Chronic exposure to GES can cause masculinization of a variety of fish; however, whether metabolism is closely related to the masculinization has yet to be explored. Hence, the ovary metabolome of adult female western mosquitofish (Gambusia affinis) after exposing to GES (0.0, 5.0, 50.0, and 500.0 ng/L) for 40 days was analyzed by using high-performance liquid chromatography ionization with quadrupole time-of-flight tandem mass spectrometry (HPLC-QTOF-MS). The results showed that GES increased the levels of cysteine, taurine, ophthalmic acid and cAMP while decreased methionine, these metabolites changes may owing to the oxidative stress of the ovaries; while taurcholic acid and uric acid were decreased along with induced oocyte apopotosis. Steroids hormone metabolism was also significantly affected, with progesterone and cortisol being the most affected. Enzyme-linked immunoassay results showed that estradiol levels were decreased while testosterone levels were increased with GES exposure. In addition, correlation analysis showed that the differential metabolites of some amino acids (e.g. leucine) were strongly correlated with the levels of steroids hormones secreted by the pituitary gland. The results of this study suggest that GES affects ovarian metabolism via the hypothalamus-pituitary-gonad and hypothalamic-pituitary-adrenal axes, impair antioxidant capacity, induce apoptosis in the ovary of G. affinis, and finally caused masculinization.

Metabolic changes and potential biomarkers in "Candidatus Liberibacter solanacearum"-infected potato psyllids: implications for psyllid-pathogen interactions.

Psyllid yellows, vein-greening (VG), and zebra chip (ZC) diseases, which are primarily transmitted by potato psyllid (PoP) carrying Candidatus Liberibacter solanacearum (CLso), have caused significant losses in solanaceous crop production worldwide. Pathogens interact with their vectors at the organic and cellular levels, while the potential changes that may occur at the biochemical level are less well reported. In this study, the impact of CLso on the metabolism of PoP and the identification of biomarkers from infected psyllids were examined. Using ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) analysis, metabolomic changes in CLso-infected psyllids were compared to uninfected ones. A total of 34 metabolites were identified as potential biomarkers of CLso infection, which were primarily related to amino acid, carbohydrate, and lipid metabolism. The significant increase in glycerophospholipids is thought to be associated with CLso evading the insect vector's immune defense. Matrix-assisted Laser Desorption Ionization Mass Spectrometry Imaging (MALDI-MSI) was used to map the spatial distribution of these biomarkers, revealing that 15-keto-Prostaglandin E2 and alpha-D-Glucose were highly expressed in the abdomen of uninfected psyllids but down-regulated in infected psyllids. It is speculated that this down-regulation may be due to CLso evading surveillance by immune suppression in the PoP midgut. Overall, valuable biochemical information was provided, a theoretical basis for a better understanding of psyllid-pathogen interactions was offered, and the findings may aid in breaking the transmission cycle of these diseases.

The Effectiveness of Cochlear Implantation for Children of Hereditary Deafness: A Multicenter Retrospective Study.

Aim: To study the effectiveness of cochlear implantation in deaf children with gene mutation. Method: 420 children from three medical centers with cochlear implants were selected. Before wearing the cochlear implant and 6 months after wearing the cochlear implant, the children's rehabilitation efficacy was evaluated through categories of auditory performance (CAP) and speech intelligibility rating (SIR). The SSF-MCDI and MUSS before and after the treatment were also compared. Results: The CAP and SIR scores of the children after the intervention were higher than those before the intervention (P < 0.05). Univariate analysis found that the age of cochlear implantation, parents' education level, and monthly family income were all influencing factors of the CAP score of children with prelingual cochlear implantation (P < 0.05). Multivariate logistic regression analysis shows that the age of cochlear implantation <5 years, parents' education level, and monthly household income are all independent risks of CAP scores in children with prelingual deaf cochlear implantation. Univariate analysis found that the age of cochlear implantation, parents' education level, and monthly household income are all based on the SIR scores of children with prelingual cochlear implantation. Multivariate logistic regression analysis can be obtained: the age of cochlear implantation less than 5 years, the education level of parents, and the monthly family income are independent risk factors for SIR scores in children with prelingual deaf cochlear implantation (P < 0.05). Conclusion: The rehabilitation effect of cochlear implants is significant, and the age of cochlear implantation, parents' education level, and monthly family income are all related factors that affect the rehabilitation effect.

The synthesis of strigolactone is affected by endogenous ascorbic acid in transgenic rice for l-galactono-1, 4-lactone dehydrogenase suppressed or overexpressing.

Rice tillering, which determines the panicle number per plant, is an important agronomic trait for grain production. In higher plants, ascorbic acid (Asc) plays a major role in ROS-scavenging activity. l-Galactono-1, 4-lactone dehydrogenase (GalLDH, EC1.3.2.3) is an enzyme that catalyzes the last step of Asc biosynthesis in plants. Previously, we have reported that homozygous L-GalLDH-suppressed transgenic rice plants (GI) display a reduced tiller number and a lower level of foliar carotenoids (Car) compared with wild type. Strigolactones (SL), which play an important role in the suppression of shoot branching, are synthesized in the roots of rice plant using Car as substrates. In this paper, the relationship between Asc, SL, the accumulation of H2O2, changes in antioxidant capacity, enzyme activities, and gene transcriptions related to the synthesis of SL were analyzed in transgenic rice plants for L-GalLDH suppressed (GI-1 and GI-2) and overexpressing (GO-2). The results showed that the altered level of Asc in the L-GalLDH transgenic rice plants leads to a change in redox homeostasis, resulting in a marked accumulation of H2O2 and decreased antioxidant capacity in GI-1 and GI-2, but lower H2O2 content and increased antioxidant capacity in GO-2. Meanwhile, the altered level of Asc also leads to altered enzyme activities and gene transcript abundances related to SL synthesis in L-GalLDH transgenics. These observations support the conclusion that Asc influences tiller number in the L-GalLDH transgenics by affecting H2O2 accumulation and antioxidant capacity, and altering those enzyme activities and gene transcript abundances related to SL synthesis.

NLRP3 Inflammasome and Its Critical Role in Gynecological Disorders and Obstetrical Complications.

Inflammasomes, intracellular, multimeric protein complexes, are assembled when damage signals stimulate nucleotide-binding oligomerization domain receptors (NLRs). Several inflammasomes have been reported, including the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3), NLRP1, NLRP7, ice protease-activating factor (IPAF), absent in melanoma 2 (AIM2) and NLR family CARD domain-containing protein 4 (NLRC4). Among these inflammasomes, the NLRP3 inflammasome is the most well-studied in terms of structure and function. Unlike other inflammasomes that can only be activated by a finite number of pathogenic microorganisms, the NLRP3 inflammasome can be activated by the imbalance of the internal environment and a large number of metabolites. The biochemical function of NLRP3 inflammasome is to activate cysteine-requiring aspartate proteinase-1 (caspase-1), which converts pro-IL-1ß and pro-IL-18 into their active forms, namely, IL-1ß and IL-18, which are then released into the extracellular space. The well-established, classic role of NLRP3 inflammasome has been implicated in many disorders. In this review, we discuss the current understanding of NLRP3 inflammasome and its critical role in gynecological disorders and obstetrical complications.

[Variance analysis on polysaccharide,total flavonoids and total phenols of Lycium barbarum leaves from different production areas].

To compare the polysaccharides( LBLP),total flavonoids( LBLTF) and total phenols( LBLTP) of Lycium barbarum leaves from 14 production areas from Ningxia,Qinghai and Gansu at different harvesting time. Our results showed that there were significant difference of LBLP,LBLTF and LBLTP among different production areas. The LBLP collected from Xiangride township production area,Dulan,Qinghai was as high as 15. 02%. The LBLTF collected from Dagele township production area,Geermu,Qinghai was as high as28. 63%. The LBLTP collected from Keluke township production area,Delingha,Qinghai was as high as 16. 7%. There were also significant difference of these 3 components between different harvest periods. The average LBLP in May( 10. 20%) was significantly higher than that in June( 8. 49%). However,the average LBLTF( 17. 71%) and LBLTP( 12. 77%) in June was significantly higher than that in May( 14. 15%,11. 19%). The LBLTF and LBLTP have a positive correlation with the altitude of production areas,but there was no significant association between LBLP and altitude. The LBLP,LBLTF and LBLTP in different production areas and harvesting time was significant difference,the results provide some references for furthermore development and utilization of L. barbarum leaves.

The SIRT2 inhibitor AK-7 decreases cochlear cell apoptosis and attenuates noise-induced hearing loss.

Oxidative damage plays a critical role in cochlear cell apoptosis, which is central to the physiopathology of noise-induced hearing loss (NIHL). Sirtuin 2 (SIRT2) is an NAD-dependent deacetylase that regulates cellular response to oxidative stress, however, its role in NIHL remains poorly understood. Here, we report that SIRT2 is upregulated in the cochlea after noise exposure. Functionally, the treatment of AK-7, one specific SIRT2 inhibitor, attenuates the progression of NIHL. In addition, AK-7 treatment reduces oxidative nuclear DNA damage and apoptosis in the cochlea after noise exposure. Moreover, AK-7 treatment reduces apoptosis of mouse inner ear HEI-OC1 cells exposed to oxidative stress in vitro. Taken together, these results suggest that SIRT2 inhibition with AK-7 reduces cochlear cell apoptosis through attenuating oxidative stress-induced damage, which may underlie its protective role against NIHL. This study also implies that AK-7 may have potential therapeutic significance in the intervention of NIHL.

A mechanistic study of Toxoplasma gondii ROP18 inhibiting differentiation of C17.2 neural stem cells.

BACKGROUND: Congenital infection of Toxoplasma gondii is an important factor causing birth defects. The neural stem cells (NSCs) are found to be one of the target cells for the parasite during development of the brain. As a key virulence factor of the parasite that hijacks host cellular functions, ROP18 has been demonstrated to mediate the inhibition of host innate and adaptive immune responses through specific binding different host immunity related molecules. However, its pathogenic actions in NSCs remain elusive. RESULTS: In the present study, ROP18 recombinant adenovirus (Ad-ROP18) was constructed and used to infect C17.2 NSCs. After 3d- or 5d-culture in differentiation medium, the differentiation of C17.2 NSCs and the activity of the Wnt/ß-catenin signaling pathway were detected. The results showed that the protein level of ßIII-tubulin, a marker of neurons, in the Ad-ROP18-transfected C17.2 NSCs was significantly decreased, indicating that the differentiation of C17.2 NSCs was inhibited by the ROP18. The ß-catenin level in the Ad-ROP18-transfected C17.2 NSCs was found to be lower than that in the Ad group. Also, neurogenin1 (Ngn1) and neurogenin2 (Ngn2) were downregulated significantly (P < 0.05) in the Ad-ROP18-transfected C17.2 NSCs compared to the Ad group. Accordingly, the TOP flash/FOP flash dual-luciferase report system showed that the transfection of Ad-ROP18 decreased the Wnt/ß-catenin pathway activity in the C17.2 NSCs. CONCLUSIONS: The inhibition effect of the ROP18 from T. gondii (TgROP18) on the neuronal differentiation of C17.2 NSCs was at least partly mediated through inhibiting the activity of the Wnt/ß-catenin signaling pathway, eventually resulting in the downregulation of Ngn1 and Ngn2. The findings help to better understand potential mechanisms of brain pathology induced by TgROP18.