TDMPP activation of estrogen receptor 2a regulates smc2 and p53 signaling to interfere with liver development in zebrafish (Danio rerio).

Tris (2,6-dimethylphenyl) phosphate (TDMPP), a novel organic phosphorus flame retardant (OPFR), has been found to have estrogenic activity. Estrogens are critical in regulating various biological responses during liver development. However, the effects of TDMPP on zebrafish liver development remain largely unexplored. Here, we utilized a chemical genetic screening approach to assess the estrogenic effects of TDMPP on liver development and to elucidate the underlying molecular mechanism. Our findings revealed that zebrafish larvae exposed to environmentally relevant concentrations of TDMPP (0.05 and 0.5 µM) exhibited concentration-dependent liver impairments, including reduced liver size, histopathological changes, and hepatocyte apoptosis. In addition, E2 caused similar adverse effects to TDMPP, but the pharmacological blockade of estrogen synthesis alleviated the effects on liver development. Chemical inhibitors and morpholino knockdown assays indicated that the reduction of esr2a blocked TDMPP-induced liver impairments, which was further confirmed in the esr2a-/- mutant line. Subsequently, transcriptomic analysis showed that the estrogen receptor activated by TDMPP inhibited the expression of smc2, which was linked to the suppression of liver development through p53 activation. Consistently, overexpression of smc2 and inhibition of p53 evidently rescued hepatic damages induced by TDMPP. Taken together, the above findings identified esr2a, downstream smc2, and p53 as important regulators for the estrogenic effects of TDMPP on liver development. Our work fills crucial gaps in the current knowledge of TDMPP's hepatotoxicity, providing new insights into the adverse effects of TDMPP and the molecular mechanisms of action. These findings underscore the need for further ecological risk assessment and regulatory considerations.

Gene expression profiles to clarify the effect of low-dose benzo(a)pyrene on crystalline silica induced acute lung injury in mice.

Published evidences have suggested that air pollutant benzo(a)pyrene (BaP) may modify the toxicity and adverse effects produced by other toxicants. However, the precise role of short-term exposure to low-dose BaP on acute lung injury (ALI) induced by crystalline silica (CS) and the underlying mechanisms remain to be clarified. To investigate this issue, a mouse co-exposure model was established by intratracheal instillation of 2.5 mg CS and BaP alone or in combination. Our data found that CS exposure resulted in ALI as evidenced by lung histological changes, elevated lactate dehydrogenase activity, increased level of pro-inflammatory markers and enhanced oxidative damage. Although exposure to BaP alone had little effect on the pathological changes of mice lung tissues except for occasionally mild inflammation, it could aggravate the CS-induced ALI in a dose-dependent manner. Bioinformatic analysis of transcriptome sequencing suggested that the expression changes of significantly differentially expressed genes were closely related to the severity of ALI. The joined analysis of STC and WGCNA found that "NOD-like receptor signaling pathway", "toll-like receptor signaling pathway", "TNF signaling pathway", and "NF-kappa B signaling pathway" associated with immune and inflammatory response were the most prominent significant pathways. TLR2/9 and Nod2 might be the key inflammation-related genes that were differentially expressed in the combined lung toxicity induced by CS and BaP exposure. All these findings suggest that co-exposure of CS and low-dose BaP can cause more severe lung inflammation and oxidative damage in mice than exposure alone, which may be useful in the management and prevention of silicosis. The roles of TLR2/9 and Nod2 as candidate targets in the combined toxicity need further exploration.

Genomic analysis of foodborne Staphylococcus aureus obtained from unannounced food inspections between 2012 and 2021 in East China.

Staphylococcus aureus is a significant cause of foodborne illness in China. Our investigation concentrated on the genetic characterization of foodborne S. aureus identified during unannounced inspections conducted in Suzhou from 2012 to 2021. Dominant clones included CC1, CC398, CC188, and CC7, with CC398 notably increasing in 2020-2021. The isolates commonly contained 1-3 plasmids, with rep5a (48.55%) and rep16 (44.51%) predominating. A concerning 24.3% showed multi-drug resistance, particularly to penam (blaZ, mecA) and fosfomycin (fosB), with resistance rates rising from 32.7% to 53.3%, potentially linked to the increase in CC types like CC5, CC20, and CC25. Most isolates carried genes for virulence factors such as aureolysin, hemolysin, staphylokinase, and staphylococcal complement inhibitor. A significant increase in virulence genes, especially the enterotoxin gene sea, was observed, possibly associated with shifts in CC1 and CC7 prevalence. This underscores the necessity for ongoing surveillance to understand genomic traits of S. aureus in ensuring food safety.

Neuronal and Molecular Mechanisms Underlying Chronic Pain and Depression Comorbidity in the Paraventricular Thalamus.

Patients with chronic pain often develop comorbid depressive symptoms, which makes the pain symptoms more complicated and refractory. However, the underlying mechanisms are poorly known. Here, in a repeated complete Freund's adjuvant (CFA) male mouse model, we reported a specific regulatory role of the paraventricular thalamic nucleus (PVT) glutamatergic neurons, particularly the anterior PVT (PVA) neurons, in mediating chronic pain and depression comorbidity (CDC). Our c-Fos protein staining observed increased PVA neuronal activity in CFA-CDC mice. In wild-type mice, chemogenetic activation of PVA glutamatergic neurons was sufficient to decrease the 50% paw withdrawal thresholds (50% PWTs), while depressive-like behaviors evaluated with immobile time in tail suspension test (TST) and forced swim test (FST) could only be achieved by repeated chemogenetic activation. Chemogenetic inhibition of PVA glutamatergic neurons reversed the decreased 50% PWTs in CFA mice without depressive-like symptoms and the increased TST and FST immobility in CFA-CDC mice. Surprisingly, in CFA-CDC mice, chemogenetically inhibiting PVA glutamatergic neurons failed to reverse the decrease of 50% PWTs, which could be restored by rapid-onset antidepressant S-ketamine. Further behavioral tests in chronic restraint stress mice and CFA pain mice indicated that PVA glutamatergic neuron inhibition and S-ketamine independently alleviate sensory and affective pain. Molecular profiling and pharmacological studies revealed the 5-hydroxytryptamine receptor 1D (Htr1d) in CFA pain-related PVT engram neurons as a potential target for treating CDC. These findings identified novel CDC neuronal and molecular mechanisms in the PVT and provided insight into the complicated pain neuropathology under a comorbid state with depression and related drug development.

Evaluation of a biomarker (NO) dynamics in inflammatory zebrafish and periodontitis saliva samples via a fast-response and sensitive fluorescent probe.

Many pathological processes include nitric oxide (NO), a signaling transduction molecule. Tumors, cardiovascular, cerebrovascular, neurodegenerative, and other illnesses are linked to abnormal NO levels. Thus, evaluating NO levels in vitro and in vivo is crucial for studying chemical biology process of associated disorders. This work devised and manufactured a coumarin-based fluorescent probe ZPS-NO to detect nitric oxide (NO). The reaction between ZPS-NO and NO produced a highly selective and sensitive optical response that caused a powerful fluorescence "turn-on" effect with a ultra-low NO detection limit of 14.5 nM. Furthermore, the probe was applied to sense and image NO in living cells and inflammatory model of zebrafish, as well as to detect NO in periodontitis patients' saliva samples. We anticipate that probe ZPS-NO will serve as a practical and effective tool for assessing the interactions and evaluation of periodontitis development.

Advances in Roles of Salicylic Acid in Plant Tolerance Responses to Biotic and Abiotic Stresses.

A multitude of biotic and abiotic stress factors do harm to plants by bringing about diseases and inhibiting normal growth and development. As a pivotal signaling molecule, salicylic acid (SA) plays crucial roles in plant tolerance responses to both biotic and abiotic stresses, thereby maintaining plant normal growth and improving yields under stress. In view of this, this paper mainly discusses the role of SA in both biotic and abiotic stresses of plants. SA regulates the expression of genes involved in defense signaling pathways, thus enhancing plant immunity. In addition, SA mitigates the negative effects of abiotic stresses, and acts as a signaling molecule to induce the expression of stress-responsive genes and the synthesis of stress-related proteins. In addition, SA also improves certain yield-related photosynthetic indexes, thereby enhancing crop yield under stress. On the other hand, SA acts with other signaling molecules, such as jasmonic acid (JA), auxin, ethylene (ETH), and so on, in regulating plant growth and improving tolerance under stress. This paper reviews recent advances in SA's roles in plant stress tolerance, so as to provide theoretical references for further studies concerning the decryption of molecular mechanisms for SA's roles and the improvement of crop management under stress.

Identifying Suitable Targets for Alzheimer's Disease and Other Eight Common Neurological Disorders Using the Human Plasma Proteome: A Mendelian Randomization Study.

Background: Neurological disorders, such as Alzheimer's disease (AD), comprise a major cause of health-related disabilities in human. However, biomarkers towards pathogenesis or novel targets are still limited. Objective: To identify the causality between plasma proteins and the risk of AD and other eight common neurological diseases using a Mendelian randomization (MR) study. Methods: Exposure data were obtained from a genome-wide association study (GWAS) of 2,994 plasma proteins in 3,301 healthy adults, and outcome datasets included GWAS summary statistics of nine neurological disorders. Inverse variance-weighted MR method as the primary analysis was used to estimate causal effects. Results: Higher genetically proxied plasma myeloid cell surface antigen CD33 level was found to be associated with increased risk of AD (odds ratio [OR] 1.079, 95% confidence interval [CI] 1.047-1.112, p = 8.39×10-7). We also discovered the causality between genetically proxied elevated prolactin and higher risk of epilepsy (OR = 1.068, 95% CI = 1.034-1.102; p = 5.46×10-5). Negative associations were identified between cyclin-dependent kinase 8 and ischemic stroke (OR = 0.927, 95% CI = 0.896-0.959, p = 9.32×10-6), between neuralized E3 ubiquitin-protein ligase 1 and migraine (OR = 0.914, 95% CI = 0.878-0.952, p = 1.48×10-5), and between Fc receptor-like protein 4 and multiple sclerosis (MS) (OR = 0.929, 95% CI = 0.897-0.963, p = 4.27×10-5). Conclusion: The findings identified MR-level protein-disease associations for AD, epilepsy, ischemic stroke, migraine, and MS.

Adulthood bisphenol A exposure induces anxiety in male mice via downregulation of alpha-1D adrenergic receptor in paraventricular thalamus.

Bisphenol A (BPA), a ubiquitous endocrine disrupting chemical, is widely used in household plastic products. Large amounts of evidence indicate prenatal and postnatal BPA exposure causes neurodevelopmental disorders such as anxiety and autism. However, the neuronal mechanisms underlying the neurotoxic effects of adulthood BPA exposure remain poorly understood. Here, we provided evidences that adult mice treated with BPA (0.45 mg/kg/day) during 3 weeks exhibited sex-specific anxiety like behaviors. We demonstrated that the BPA-induced anxiety in male mice, but not in female mice, was closely associated with hyperactivity of glutamatergic neurons in the paraventricular thalamus (PVT). Acute chemogenetic activation of PVT glutamatergic neurons caused similar effects on anxiety as observed in male mice exposed to BPA. In contrast, acute chemogenetic inhibition of PVT glutamatergic neurons reduced BPA-induced anxiety in male mice. Concomitantly, the BPA-induced anxiety was related with a down-regulation of alpha-1D adrenergic receptor in the PVT. Taken together, the present study indicated a previously unknown target region in the brain for neurotoxic effects of BPA on anxiety and implicated a possible molecular mechanism of action.

Causal effects of COVID-19 on structural changes in specific brain regions: a Mendelian randomization study.

BACKGROUND: Previous studies have found a correlation between coronavirus disease 2019 (COVID-19) and changes in brain structure and cognitive function, but it remains unclear whether COVID-19 causes brain structural changes and which specific brain regions are affected. Herein, we conducted a Mendelian randomization (MR) study to investigate this causal relationship and to identify specific brain regions vulnerable to COVID-19. METHODS: Genome-wide association study (GWAS) data for COVID-19 phenotypes (28,900 COVID-19 cases and 3,251,161 controls) were selected as exposures, and GWAS data for brain structural traits (cortical thickness and surface area from 51,665 participants and volume of subcortical structures from 30,717 participants) were selected as outcomes. Inverse-variance weighted method was used as the main estimate method. The weighted median, MR-Egger, MR-PRESSO global test, and Cochran's Q statistic were used to detect heterogeneity and pleiotropy. RESULTS: The genetically predicted COVID-19 infection phenotype was nominally associated with reduced cortical thickness in the caudal middle frontal gyrus (ß = - 0.0044, p = 0.0412). The hospitalized COVID-19 phenotype was nominally associated with reduced cortical thickness in the lateral orbitofrontal gyrus (ß = - 0.0049, p = 0.0328) and rostral middle frontal gyrus (ß = - 0.0022, p = 0.0032) as well as with reduced cortical surface area of the middle temporal gyrus (ß = - 10.8855, p = 0.0266). These causal relationships were also identified in the severe COVID-19 phenotype. Additionally, the severe COVID-19 phenotype was nominally associated with reduced cortical thickness in the cuneus (ß = - 0.0024, p = 0.0168); reduced cortical surface area of the pericalcarine (ß = - 2.6628, p = 0.0492), superior parietal gyrus (ß = - 5.6310, p = 0.0408), and parahippocampal gyrus (ß = - 0.1473, p = 0.0297); and reduced volume in the hippocampus (ß = - 15.9130, p = 0.0024). CONCLUSIONS: Our study indicates a suggestively significant association between genetic predisposition to COVID-19 and atrophy in specific functional regions of the human brain. Patients with COVID-19 and cognitive impairment should be actively managed to alleviate neurocognitive symptoms and minimize long-term effects.

Causal relationship between gastroesophageal reflux disease, Barrett's esophagus, and epilepsy: A bidirectional Mendelian randomization study.

BACKGROUND: The incidence of gastroesophageal reflux disease (GERD) has been shown to be elevated in individuals with epilepsy. Traditional observational studies have led to a limited understanding of the effects of GERD and BE on epilepsy due to the interference of reverse causation and potential confounders. METHODS: We conducted a bidirectional two-sample Mendelian randomization (MR) analysis to determine whether GERD and BE can increase the risk of epilepsy. Genome-wide association study data on epilepsy and its subgroups were obtained from the International League Against Epilepsy consortium for primary analysis using three MR approaches and the FinnGen consortium for replication and meta-analysis. We calculated causal estimates between the two esophageal diseases and epilepsy using the inverse-variance weighted method. Sensitivity analysis was conducted to detect heterogeneity and pleiotropy. RESULTS: We found a potential effect of genetically predicted GERD on the risk of epilepsy (odds ratio [OR] = 1.078; 95% confidence interval [CI], 1.014-1.146, p = .016). Specifically, GERD showed an effect on the risk of generalized epilepsy (OR = 1.163; 95% CI, 1.048-1.290, p = .004) but not focal epilepsy (OR = 1.059, 95% CI, 0.992-1.131, p = .084). Notably, BE did not show a significant causal relationship with the risks of generalized and focal epilepsy. CONCLUSIONS: Under MR assumptions, our findings suggest a potential risk-increasing effect of GERD on epilepsy, especially generalized epilepsy. Considering the exploratory nature of our study, the association between GERD and epilepsy needs to be confirmed by future prospective studies.

Exposure to tris(2,6-dimethylphenyl) phosphate interferes with sexual differentiation via estrogen receptors 2a and 2b in zebrafish.

Tris(2,6-dimethylphenyl) phosphate (TDMPP), an emerging organophosphate flame retardant, is frequently detected in multiple environmental media. Although TDMPP has been proven as a compound with estrogenic activity, its feminizing effects on reproductive system remain unclear. This study investigated the adverse effects of TDMPP on gonadal development by exposing zebrafish for 105 days from 15 days post-fertilization. Exposure to TDMPP (0.5 and 5 µM, corresponding to about 200 and 2000 µg/L) induced ovarian formation in aromatase mutant (cyp19a1a-/-) line which normally presents all-male phenotype for deficiency of endogenous estrogen (E2), suggesting its feminizing effect on sexual differentiation. In addition, TDMPP also interfered with other aspects of reproduction by delaying puberty onset, retarding sexual maturation, impairing gametogenesis and subfertility. Molecular docking and reporter gene assay indicated that all three nuclear estrogen receptors (nERs) can be binded to and activated by TDMPP. Using a series of nERs mutant lines, we confirmed the indispensable role of esr2a and esr2b in mediating the feminizing effects of TDMPP. Further analysis revealed that the prominent effects of TDMPP on sexual differentiation correlated to upregulation of female-promoting genes and downregulation of male-promoting genes. Taken together, the present study provided unequivocal genetic evidence for estrogenic effects of TDMPP on reproductive system and its molecular mechanisms of action.

Genetic analysis of activin/inhibin ß subunits in zebrafish development and reproduction.

Activin and inhibin are both dimeric proteins sharing the same ß subunits that belong to the TGF-ß superfamily. They are well known for stimulating and inhibiting pituitary FSH secretion, respectively, in mammals. In addition, activin also acts as a mesoderm-inducing factor in frogs. However, their functions in development and reproduction of other species are poorly defined. In this study, we disrupted all three activin/inhibin ß subunits (ßAa, inhbaa; ßAb, inhbab; and ßB, inhbb) in zebrafish using CRISPR/Cas9. The loss of ßAa/b but not ßB led to a high mortality rate in the post-hatching stage. Surprisingly, the expression of fshb but not lhb in the pituitary increased in the female ßA mutant together with aromatase (cyp19a1a) in the ovary. The single mutant of ßAa/b showed normal folliculogenesis in young females; however, their double mutant (inhbaa-/-;inhbab-/-) showed delayed follicle activation, granulosa cell hypertrophy, stromal cell accumulation and tissue fibrosis. The ovary of inhbaa-/- deteriorated progressively after 180 dpf with reduced fecundity and the folliculogenesis ceased completely around 540 dpf. In addition, tumor- or cyst-like tissues started to appear in the inhbaa-/- ovary after about one year. In contrast to females, activin ßAa/b mutant males showed normal spermatogenesis and fertility. As for activin ßB subunit, the inhbb-/- mutant exhibited normal folliculogenesis, spermatogenesis and fertility in both sexes; however, the fecundity of mutant females decreased dramatically at 270 dpf with accumulation of early follicles. In summary, the activin-inhibin system plays an indispensable role in fish reproduction, in particular folliculogenesis and ovarian homeostasis.

Metabolic Competency of Larval Zebrafish in Drug-Induced Liver Injury: A Case Study of Acetaminophen Poisoning.

Larval zebrafish is emerging as a new model organism for studying drug-induced liver injury (DILI) with superiorities in visual assessment, genetic engineering as well as high throughput. Metabolic bioactivation to form reactive intermediates is a common event that triggers DILI. This study first addressed the correlation between acetaminophen metabolism and hepatotoxicity in zebrafish larvae (3-day postfertilization) and demonstrated the occurrence of cytochrome P450 enzymes-mediated acetaminophen (APAP) bioactivation at early developmental stage through characterizing the dose-effect (0-1.6 mg/ml) and the time course (0-72 h) of liver injury and metabolism in the AB strain and LiPan transgenic line Tg(lfabp10a: DsRed; elaA:egfp) expressing the liver-specific fluorescent protein. APAP caused multiorgan developmental retardation and elicited dose- and time-dependent hepatotoxicity. Liver imaging revealed significant changes earlier than histological and biochemical measurements. APAP bioactivation in larval zebrafish was first confirmed by the detection of the glutathione conjugate of the reactive intermediate NAPQI (NAPQI-GSH) and subsequent mercapturate derivatives NAPQI-cysteine and NAPQI-N-acetylcysteine after even short (0.5-h postexposure) or low (0.2 mg/ml) APAP exposure. APAP overdose impaired metabolic function, in particular sulfation, whereas facilitated GSH depletion and APAP sulfate excretion. Meanwhile, APAP displayed triphasic accumulation in the larvae, agreeing with fluctuating metabolic capabilities with sulfation dominating the early larval developmental stage. Most importantly, the dose-response effects and time course of APAP accumulation and metabolism agree well with those of the liver injury development. Overall, larval zebrafish has developed mammalian-like metabolic function, enabling it an ideal model organism for high-throughput screening hepatotoxicity and mechanistic study of bioactivation-based DILI.

The antiestrogen-like activity and reproductive toxicity of 2,6-DCBQ on female zebrafish upon sub-chronic exposure.

2,6-Dichloro-1,4-benzoquinone (2,6-DCBQ), an emerging water disinfection by-product, is widely detected in water resources. However, its potential effects on the reproductive system are largely unknown. Here, we investigated the long-term effects of 2,6-DCBQ on gonadal development by exposing zebrafish from 15 to 180 days postfertilization (dpf). Following exposure to 2,6-DCBQ (20 and 100 µg/L), female-specific effects including delayed puberty onset, retarded ovarian growth and breakdown of the zona radiata were observed, resulting in subfertility in adult females. Adverse effects in folliculogenesis disappeared two months after cessation of 2,6-DCBQ administration. In contrast, no adverse impacts were noted in male testes. The effects on females were associated with significant reduction in 17ß-estradiol (E2) level, suggesting a role for 2,6-DCBQ in anti-estrogenic activity. E2 level change in blood was further supported by dysregulated expression of genes (cyp19a1a, fshb, kiss3, esr2b, vtg1, and vtg3) related to the hypothalamic-pituitary-gonad-liver (HPGL) axis. The present study demonstrates for the first time that 2,6-DCBQ induces reproductive impairments in female zebrafish through disrupting 17ß-estradiol level.

Understanding the roles of copper dopant and oxygen vacancy in promoting nitrogen oxides removal over iron-based catalyst surface: A collaborative experimental and first-principles study.

In this work, we proposed a novel strategy of copper (Cu) doping to enhance the nitrogen oxides (NOx) removal efficiency of iron (Fe)-based catalysts at low temperature through a simple citric acid mixing method, which is critical for its practical application. The doping of Cu significantly improves the deNOx performance of Fe-based catalysts below 200 °C, and the optimal catalyst is (Cu0.22Fe1.78)1-δO3, which deNOx efficiency can reach 100% at 160-240 °C. From the macro aspects, the main reasons for the excellent catalytic activity of the (Cu0.22Fe1.78)1-δO3 catalyst are the large number of oxygen vacancies (Ovac), appropriate Fe3+ and Cu2+ contents, stronger surface acidity and redox ability. From the micro aspects, the Ovac plays a key role in enhancing molecular adsorption, oxidation, and the deNOx reaction over the Fe-based catalyst surface, which promoting order is CuOvac > Ovac > Cu. This work provides a new insight for the mechanism study of oxygen vacancy engineering and also accelerates the development of CuFe bimetal composite catalysts at low temperature.

LncRNA MEG3 alleviates PFOS induced placental cell growth inhibition through its derived miR-770 targeting PTX3.

Perfluorooctane sulfonic acid (PFOS) is a persistent environmental pollutant. Exposure to PFOS has been associated with abnormal fetal development. The long non-coding RNA (lncRNA) has been showed to play a role in fetal growth restriction (FGR), preeclampsia (PE) and other pregnancy complications. Whether the lncRNA contributes to PFOS-induced toxicity in the placenta remains unknown. In this study, we investigated the function of lncRNA MEG3 and its derived miR-770 in PFOS-induced placental toxicity. Pregnant mice received gavage administration of different concentrations of PFOS (0.5, 2.5, and 12.5 mg/kg/day) from GD0 to GD17, and HTR-8/SVneo cells were treated with PFOS in the concentrations of 0, 10-1, 1, 10 µM. We found that expression levels of miR-770 and its host gene MEG3 were reduced in mice placentas and HTR-8/SVneo cells with exposure of PFOS. A significant hypermethylation was observed at MEG3 promoter in placentas of mice gestational-treated with PFOS. We also confirmed that MEG3 and miR-770 overexpression alleviated the cell growth inhibition induced by PFOS. Furthermore, PTX3 (Pentraxin 3) was identified as the direct target of miR-770 and it was enhanced after PFOS exposure. In summary, our results suggested that MEG3 alleviate PFOS-induced placental cell inhibition through MEG3/miR-770/PTX3 axis.

Rapid Detection of Cysticercus cellulosae by an Up-Converting Phosphor Technology-Based Lateral-Flow Assay.

Cysticercosis is a neglected tropical disease caused by the larvae of Taenia solium in pigs and humans. The current diagnosis of porcine cysticercosis is difficult, and traditional pathological tests cannot meet the needs of detection. This study established a UPT-LF assay for the detection of Cysticercus cellulosae. UCP particles were bound to two antigens, TSOL18 and GP50; samples were captured, and the signal from the UCP particles was converted into a detectable signal for analysis using a biosensor. Compared to ELISA, UPT-LF has higher sensitivity and specificity, with a sensitivity of 93.59% and 97.44%, respectively, in the case of TSOL18 and GP50 antigens and a specificity of 100% for both. Given its rapidness, small volume, high sensitivity and specificity, and good stability and reproducibility, this method could be used in the diagnosis of cysticercosis.

PROTEOMIC ANALYSIS OF TAENIA SOLIUM CYST FLUID BY SHOTGUN LC-MS/MS.

Taenia solium cysts were collected from pig skeletal muscle and analyzed via a shotgun proteomic approach to identify known proteins in the cyst fluid and to explore host-parasite interactions. Cyst fluid was aseptically collected and analyzed with shotgun liquid chromatography-tandem mass spectrometry (LC-MS/MS). Gene alignment and annotation were performed using Blast2GO software followed by gene ontology analysis of the annotated proteins. The pathways were further analyzed with the Kyoto Encyclopedia of Genes and Genomes (KEGG), and a protein-protein interaction (PPI) network map was generated using STRING software. A total of 158 known proteins were identified, most of which were low-molecular-mass proteins. These proteins were mainly involved in cellular and metabolic processes, and their molecular functions were predominantly related to catalytic activity and binding functions. The pathway enrichment analysis revealed that the known proteins were mainly enriched in the PI3K-Akt and glycolysis/gluconeogenesis signaling pathways. The nodes in the PPI network mainly consisted of enzymes involved in sugar metabolism. The cyst fluid proteins screened in this study may play important roles in the interaction between the cysticerci and the host. The shotgun LC-MS/MS, gene ontology, KEGG, and PPI network map data will be used to identify and analyze the cyst fluid proteome of cysticerci, which will provide a basis for further exploration of the invasion and activities of T. solium.

Regulation of DNA methylation on key parasitism genes of Cysticercus cellulosae revealed by integrative epigenomic-transcriptomic analyses.

BACKGROUND: The life cycle of Taenia solium is characterized by different stages of development, requiring various kinds of hosts that can appropriately harbor the eggs (proglottids), the oncospheres, the larvae and the adults. Similar to other metazoan pathogens, T. solium undergoes transcriptional and developmental regulation via epigenetics during its complex lifecycle and host interactions. RESULT: In the present study, we integrated whole-genome bisulfite sequencing and RNA-seq technologies to characterize the genome-wide DNA methylation and its effect on transcription of Cysticercus cellulosae of T. solium. We confirm that the T. solium genome in the cysticercus stage is epigenetically modified by DNA methylation in a pattern similar to that of other invertebrate genomes, i.e., sparsely or moderately methylated. We also observed an enrichment of non-CpG methylation in defined genetic elements of the T. solium genome. Furthermore, an integrative analysis of both the transcriptome and the DNA methylome indicated a strong correlation between these two datasets, suggesting that gene expression might be tightly regulated by DNA methylation. Importantly, our data suggested that DNA methylation might play an important role in repressing key parasitism-related genes, including genes encoding excretion-secretion proteins, thereby raising the possibility of targeting DNA methylation processes as a useful strategy in therapeutics of cysticercosis.

Effect of doping Cr on NH3 adsorption and NO oxidation over the FexOy/AC surface: A DFT-D study.

Activated carbon supported iron-based catalysts (FexOy/AC) show good deNOx efficiency at low temperature. The doping of chromium (Cr) greatly improves the catalyst activity. However, the detailed effect of doping Cr over FexOy/AC surface at molecular level is still a grey area. In this study, the roles of Cr dopant on gas adsorption and NO oxidation were deeply investigated by a DFT-D3 method. Results show that the synergy of Cr-Fe bimetal improves the binding capacity of Fe2O3/AC and Fe3O4/AC surfaces after doping Cr. NH3 can be adsorbed on Cr and Fe sites to form coordinated NH3. Doping Cr greatly improves the NH3 adsorption property on the Fe3O4/AC surface. NO molecule can combine with Cr, Fe, and O sites to form nitrosyl and nitrite. The doping of Cr increases the adsorption performance of NO on the Fe2O3/AC and Fe3O4/AC surfaces, especially for Fe3O4/AC surface. Furthermore, NO can be oxidized to NO2 by adsorption oxygen or active O sites of FexOy clusters. The doping of Cr restrains the formation of insoluble chelating bidentate nitrates and greatly reduces the reaction energy barrier of NO oxidation on the FexOy/AC surface, which can promote the deNOx reaction.