Identification and coregulation pattern analysis of long noncoding RNAs in the mouse brain after Angiostrongylus cantonensis infection.

BACKGROUND: Angiostrongyliasis is a highly dangerous infectious disease. Angiostrongylus cantonensis larvae migrate to the mouse brain and cause symptoms, such as brain swelling and bleeding. Noncoding RNAs (ncRNAs) are novel targets for the control of parasitic infections. However, the role of these molecules in A. cantonensis infection has not been fully clarified. METHODS: In total, 32 BALB/c mice were randomly divided into four groups, and the infection groups were inoculated with 40 A. cantonensis larvae by gavage. Hematoxylin and eosin (H&E) staining and RNA library construction were performed on brain tissues from infected mice. Differential expression of long noncoding RNAs (lncRNAs) and mRNAs in brain tissues was identified by high-throughput sequencing. The pathways and functions of the differentially expressed lncRNAs were determined by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses. The functions of the differentially expressed lncRNAs were further characterized by lncRNA‒microRNA (miRNA) target interactions. The potential host lncRNAs involved in larval infection of the brain were validated by quantitative real-time polymerase chain reaction (qRT‒PCR). RESULTS: The pathological results showed that the degree of brain tissue damage increased with the duration of infection. The transcriptome results showed that 859 lncRNAs and 1895 mRNAs were differentially expressed compared with those in the control group, and several lncRNAs were highly expressed in the middle-late stages of mouse infection. GO and KEGG pathway analyses revealed that the differentially expressed target genes were enriched mainly in immune system processes and inflammatory response, among others, and several potential regulatory networks were constructed. CONCLUSIONS: This study revealed the expression profiles of lncRNAs in the brains of mice after infection with A. cantonensis. The lncRNAs H19, F630028O10Rik, Lockd, AI662270, AU020206, and Mexis were shown to play important roles in the infection of mice with A. cantonensis infection.

Identification of hub genes in calcific aortic valve disease.

Calcific aortic valve disease (CAVD) is a heart valve disorder characterized primarily by calcification of the aortic valve, resulting in stiffness and dysfunction of the valve. CAVD is prevalent among aging populations and is linked to factors such as hypertension, dyslipidemia, tobacco use, and genetic predisposition, and can result in becoming a growing economic and health burden. Once aortic valve calcification occurs, it will inevitably progress to aortic stenosis. At present, there are no medications available that have demonstrated effectiveness in managing or delaying the progression of the disease. In this study, we mined four publicly available microarray datasets (GSE12644 GSE51472, GSE77287, GSE233819) associated with CAVD from the GEO database with the aim of identifying hub genes associated with the occurrence of CAVD and searching for possible biological targets for the early prevention and diagnosis of CAVD. This study provides preliminary evidence for therapeutic and preventive targets for CAVD and may provide a solid foundation for subsequent biological studies.

Interactive Prognosis Framework Between Deep Learning and a Stochastic Process Model for Remaining Useful Life Prediction.

Uncertainty quantification of the remaining useful life (RUL) for degraded systems under the big data era has been a hot topic in recent years. A general idea is to execute two separate steps: deep-learning-based health indicator (HI) construction and stochastic process-based degradation modeling. However, there exists a critical matching defect between the constructed HI and a degradation model, which seriously affects the RUL prediction accuracy. Toward this end, this article proposes an interactive prognosis framework between deep learning and a stochastic process model for the RUL prediction. First, we resort to stacked contractive autoencoders to fuse multiple sensor information of historical systems for constructing the HI in a typical unsupervised manner. Then, considering the nonlinear characteristic of the constructed HI, an exponential-like degradation model is introduced to construct its degradation evolving model, and theoretical expressions of the prediction results are derived under the concept of the first hitting time. Furthermore, we design an optimization objective function by integrating the HI construction and degradation modeling for the RUL prediction. To minimize the designed objective function of the proposed interactive prognosis framework, a gradient descent algorithm is employed to update the model parameters. Based on the well-trained interactive prognosis model, we can obtain the HI of a field system from stacked contractive autoencoders with sensor data and the probability density function (pdf) of the predicted RUL on the basis of the estimated parameters. Finally, the effectiveness and superiority of the proposed interactive prognosis method are verified by two case studies associated with turbofan engines.

Exploration of animal models to study the life cycle of Fasciola hepatica.

The parasite Fasciola hepatica is an important zoonotic parasite. The development of an animal model of F. hepatica's life cycle is critical for studying the biological characteristics of the parasite in snails and mammals. Eggs of F. hepatica of bovine origin were cultured, and metacercariae were obtained after infection of Galba pervia snails. The life cycle system of F. hepatica was initiated in 2 different animals by orally infecting rabbits, SD rats and Kunming mice with the metacercariae. The animals' survival after infection, parasite migration in the animals and pathological damage to the liver were observed. We discovered that rabbits died due to acute suppurative hepatitis 60­69 days after infection, and eggs were found in the feces on day 63 of infection. The liver of SD rats showed punctate lesions on day 3 of infection, and further changes occurred as the infection progressed. However, liver repair was observed at week 9. SD rats survived for more than a year after infection and continued the F. hepatica life cycle. The liver lesions in Kunming mice after infection were similar but more severe than those in SD rats. Death was observed on the 31st post-infection day. We discovered that while rabbits, SD rats and Kunming mice can all be used as animal models of F. hepatica, SD rats are more suitable experimental animals in terms of tolerance and pathological response.

Tracing Clostridium perfringens strains from beef processing of slaughter house by pulsed-field gel electrophoresis, and the distribution and toxinotype of isolates in Shaanxi province, China.

The purpose of this study was to investigate the distribution and specify the transmission and cross-contamination of Clostridium perfringens (C. perfringens) in the beef slaughtering and butchering process. The prevalence of 21.2% (150/708) yielded 208 isolates of C. perfringens, including 80.8% type A and 19.2% type D, 0.4% (3/708) samples carried both type A and D strains, and 72.5% type D isolates carried both cpe and atyp.cpb2 genes. C. perfringens were identified through the whole slaughtering process but no type F (cpe and cpa isolates) was found. 69 isolates were further analyzed and classified into 28 PFGE genotypes and clade I contained 94.2% isolates and 24 PFGE genotypes, which showed the genetic diversity and epidemic correlation. Our study traced C. perfringens contamination along the handling processes and showed a gradually ascending contamination rate during the whole process, revealing widespread cross-contamination from the feces and hides of slaughtered cattle to the carcass in the slaughtering workshop, so as from tools and personnel to meat of the cutting workshops. Strains from different slaughterhouses (regions) have high homology, and type A is the predominant toxinotype. It is necessary to monitor and control several key points of cross-contamination during slaughtering process to reduce a risk of C. perfringens infection.

Neurotoxicity and Underlying Mechanisms of Endogenous Neurotoxins.

Endogenous and exogenous neurotoxins are important factors leading to neurodegenerative diseases. In the 1980s, the discovery that 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) contributes to Parkinson's disease (PD) symptoms led to new research investigations on neurotoxins. An abnormal metabolism of endogenous substances, such as condensation of bioamines with endogenous aldehydes, dopamine (DA) oxidation, and kynurenine pathway, can produce endogenous neurotoxins. Neurotoxins may damage the nervous system by inhibiting mitochondrial activity, increasing oxidative stress, increasing neuroinflammation, and up-regulating proteins related to cell death. This paper reviews the biological synthesis of various known endogenous neurotoxins and their toxic mechanisms.

PINK1/Parkin-mediated mitophagy in mechanical ventilation-induced diaphragmatic dysfunction.

BACKGROUND: Mechanical ventilation (MV) often leads to ventilation-induced diaphragm dysfunction (VIDD). Although the development of this disorder had been linked to oxidative stress, mitochondrial energy deficiency, autophagy activation, and apoptosis in the diaphragm, it remains unclear whether the activation of mitophagy can induce VIDD. With our research, our endeavor is to uncover whether PTEN-induced putative kinase 1 (PINK1)/Parkin-mediated mitophagy affects the MV-caused diaphragmatic dysfunction. METHODS: Sprague-Dawley rats were subjected to MV treatment for 6 h (MV-6h), 12 h (MV-12h), or 24 h (MV-24h). Post MV, the diaphragm muscle compound action potential (CMAP) and cross-sectional areas (CSAs) of the diaphragm of these rats were measured. The levels of proteins of interest were examined to assess muscle health, mitochondrial dynamics, and mitophagy in the diaphragm. The co-localization of PINK1 with the mitochondrial protein marker tom20 was examined, as well as transmission electron microscopy analysis to detect changes in diaphragm mitochondrial ultrastructure. RESULTS: MV-12h and MV-24h treatments resulted in a decrease in CSA of diaphragm and CMAP amplitude. In addition, the expressions of F-box (MFAbx), muscle-specific ring finger 1 (MURF1), PINK1, and p62 were elevated in rats treated with MV for 12 h and 24 h, while mfn2 expression was reduced. Rats following MV-24h treatment displayed an increase in mitochondrial dynamic protein (Drp1) and Parkin expression and microtubule-associated protein 1 light chain 3/1 (LC3II/I) ratio. Moreover, decreased SOD and GSH activity and membrane potential were observed after MV-12h and MV-24h treatment, while H2O2 activity increased after MV-24h treatment. In addition, a strong co-localization between PINK1 and tom20 was identified. CONCLUSION: These results reveal that MV leads to various changes in mitochondrial dynamics and significantly increases the mitophagy levels, which subsequently cause the variation in diaphragmatic function and muscle atrophy, indicating that mitophagy could be one of the possible mechanisms by which MV induces diaphragmatic dysfunction.The reviews of this paper are available via the supplemental material section.

The biological effects of radiation-induced liver damage and its natural protective medicine.

The biological damage caused by the environmental factors such as radiation and its control methods are one of the frontiers of life science research that has received widespread attention. Ionizing radiation can directly interact with target molecules (such as DNA, proteins and lipids) or decomposed by radiation from water, leading to changes in oxidative events and biological activities in cells. Liver is a radiation-sensitive organ, and its radiosensitivity is second only to bone marrow, lymph, gastrointestinal tissue, gonads, embryos and kidneys. In addition, as a key organ of mammals, liver performs a series of functions, including the production of bile, the metabolism of nutrients, the elimination of waste, the storage of glycogen, and the synthesis of proteins. Therefore, liver is prone to various pathophysiological changes. In this review, the effects of radiation on liver injury, its pathogenesis, bystander effect and the natural traditional Chinese medicine to protect the radiation induced liver damage are discussed.

Abnormal expression of rno_circRNA_014900 and rno_circRNA_005442 induced by ketamine in the rat hippocampus.

BACKGROUND: Recent studies have shown that circular RNA (circRNA) is rich in microRNA (miRNA) binding sites. We have previously demonstrated that the antidepressant effect of ketamine is related to the abnormal expression of various miRNAs in the brain. This study determined the expression profile of circRNAs in the hippocampus of rats treated with ketamine. METHODS: The aberrantly expressed circRNAs in rat hippocampus after ketamine injection were analyzed by microarray chip, and we further validated these circRNAs by quantitative reverse-transcription PCR (qRT-PCR). The target genes of the different circRNAs were predicted using bioinformatic analyses, and the functions and signal pathways of these target genes were investigated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. RESULTS: Microarray analysis showed that five circRNAs were aberrantly expressed in rat hippocampus after ketamine injection (fold change > 2.0, p < 0.05). The results from the qRT-PCR showed that one of the circRNAs was significantly increased (rno_circRNA_014900; fold change = 2.37; p = 0.03), while one was significantly reduced (rno_circRNA_005442; fold change = 0.37; p = 0.01). We discovered a significant enrichment in several GO terms and pathways associated with depression. CONCLUSION: Our findings showed the abnormal expression of ketamine-induced hippocampal circRNAs in rats.

[Sepsis impairs aggregation of nicotinic acetylcholine receptors on murine skeletal muscle cell membranes by inhibiting AKT/GSK3ß phosphorylation].

OBJECTIVE: To investigate the role of the protein-serine-threonine kinase (AKT)/glycogen synthase kinase 3ß (GSK3ß) signaling pathway in nicotinic acetylcholine receptors (nAChRs) aggregation disorder on skeletal muscle cell membranes induced by sepsis. METHODS: Mouse C2C12 myoblasts were differentiated into myotubes by horse serum, and then C2C12 myotubes were randomly divided into four groups: the Sham group treated with serum from sham-operated mice, the Sepsis group treated with serum from septic mice, the Sepsis+D group treated with serum from septic mice and dimethyl sulfoxide (DMSO), the Sepsis+SB group treated with serum from septic mice and GSK3ß inhibitor SB216763. Agrin was added into the cell culture to induce nAChRs aggregation before the treatment. After serum treatment for 5.5 h, the myotubes were examined for nAChRs clusters using Alexa Fluor 594-conjugated α-bungarotoxin (α- BTX). The expression levels of AKT, GSK3ß and CLIP- associated protein 2 (CLASP2) and the phosphorylation of AKT, GSK3ß were examined with Western blotting. The phosphorylation of CLASP2 and the interaction between CLASP2 and α-tubulin were detected with co-immunoprecipitation (Co-IP) assay. RESULTS: Compared with the serum from sham-operated mice, the serum from septic mice caused significant reduction in the area and density of nAChRs clusters on C2C12 myotubes, lowered the levels of phosphorylated AKT (p-AKT) and phosphorylated GSK3ß (p-GSK3ß), increased the expression of phosphorylated CLASP2 (p-CLASP2), and obviously reduced the binding between CLASP2 and α-tubulin. Compared with DMSO, SB216763 significantly increased the area and density of nAChRs clusters on C2C12 myotubes treated with serum from septic mice, decreased the expression of p-CLASP2, and enhanced the interaction between CLASP2 and α-tubulin. CONCLUSIONS: Septic mouse serum impairs nAChRs aggregation on C2C12 myotubes possibly by suppressing AKT/GSK3ß phosphorylation to cause reduced interaction between CLASP2 and α-tubulin.

MicroRNA-140 inhibits skeletal muscle glycolysis and atrophy in endotoxin-induced sepsis in mice via the WNT signaling pathway.

Sepsis is a systemic inflammatory response syndrome resulting from infection. This study aimed at exploring the role of microRNA-140 (miR-140) in septic mice. Wnt family member 11 (WNT11) was verified to be a target gene of miR-140 after bioinformatic prediction and dual luciferase reporter gene assay. Importantly, miR-140 negatively regulated WNT11. We initially induced the model of sepsis by endotoxin, and then ectopic expression and knockdown experiments were performed to explore the functional role of miR-140 in sepsis. Additionally, cross-sectional areas of muscle fiber, lactic acid production, 3-methylhistidine (3-MH) and tyrosine (Tyr) production in extensor digitorium longus (EDL) muscles, and serum levels of inflammatory factors were examined. The effect of miR-140 on the expression of WNT signaling pathway-related and apoptosis-related factors in skeletal muscle tissue was determined. The experimental results indicated that upregulated miR-140 or silenced WNT11 increased cross-sectional areas of muscle fiber while decreasing lactic acid production, skeletal muscle cell apoptosis [corresponding to downregulated B cell lymphoma 2 (Bcl-2)-associated X protein (Bax) and caspase-3 and upregulated Bcl-2], and the proteolytic rate of Tyr and 3-MH. Also, overexpressed miR-140 or silenced WNT11 reduced inflammation as reflected by decreased serum levels of IL-6, IL-10, and TNF-α. Furthermore, overexpression of miR-140 was shown to suppress the activation of the WNT signaling pathway, accompanied by decreased expression of WNT11, ß-catenin, and GSK-3ß. Taken together, upregulation of miR-140 could potentially inhibit skeletal muscle lactate release, an indirect measure of glycolysis, and atrophy in septic mice through suppressing the WNT signaling pathway via inhibiting WNT11 expression.

An Integrated Reliability Estimation Approach With Stochastic Filtering and Degradation Modeling for Phased-Mission Systems.

Reliability estimation is central to enhance safety, availability, and effectiveness of phased-mission systems (PMSs). With the development of information and sensing technologies, condition monitoring (CM) data are now available in many real-world PMSs, and then a more interesting question: how can we dynamically estimate the reliability of PMSs using the in-situ CM data, is of considerable significance to industrial practitioners. In this paper, using the CM data and degradation data of PMS, we present a novel condition-based approach to resolve this question under dynamic operating scenarios. This paper differs from most existing methods which only consider the static scenario without using real-time information, and estimate the reliability only for a population of PMSs but not for an individual PMS in service. To establish a linkage between the historical data and real-time data of the individual PMS, a stochastic filtering model is first utilized to model the phase duration. As such, the updated estimation of the mission time can be obtained by Bayesian law at each phase. To account for the dependency of the degradation progression of PMS on the mission process, the degradation process of PMS is modeled by a Brownian motion with a mission phase-dependent drift coefficient. The corresponding lifetime is derived and the lifetime distribution of PMS can be updated under Bayesian framework once new information is available. Unique to this paper is the union of the CM data and degradation data of PMS to real-time estimate the mission reliability through the estimated distribution of the mission time in conjunction with the estimated lifetime distribution, in which the estimated lifetime considers the dependency of the degradation rate of PMS on mission phase. The effectiveness of the proposed approach is verified by a numerical simulation and a case study.

[Formation and Characteristics of Fasciola hepatica Metacercariae].

The Fasciola hepatica miracidia were used to infect 10 Galba pervia in a random manner. Beginning from day 44 after infection on which 10 metacercariae were found and a total of 495 metacercariae found in 24 days. No signs of cercaria escape or metacercaria formation in the early morning observed during 8 : 00-24 : 00, regardless of the environmental change. Metacercaria formation occurred mainly in the early morning. The metacercariae could attach to any object in water, but were easy to detach themselves. The findings suggest that F. hepatica cercaria escape and metacercaria formation mainly occur in the early morning in Dali.

[Experimental infection of Galba pervia, Radix swinhoei and Physa acuta with Fasciola hepatica in Dali, Yunnan].

OBJECTIVE: To determine the intermediate host of Fasciola hepatica in Dali of Yunnan Province, and investigate its development and characteristics. METHODS: F. hepatica eggs from cattle were collected from July 2012 to July 2013, and placed in 28 degrees C water bath for incubation. Galba pervia, Radix swinhoei, and Physa acuta were collected from Dali, and used to be infected with F. hepatica in the laboratory. Trematode infections were excluded from the snails before experiment. All the snails were infected with F. hepatica miracidia, reared in mud pots. Dead snails were dissected for observing the development of F. hepatica. The metacercariae were collected and identified by PCR amplification of partial sequence of mitochondrial cytochrome oxidase subunit I (COX1) gene. RESULTS: A total of 1 146 R. swinhoei, 996 P. acuta, and 3 307 G. pervia snails were infected with F. hepatica, respectively. Mother rediae were found in two R. swinhoei snails, but no child rediae were observed in the snails. No larval forms were found in P. acuta. G. pervia was infected by F. hepatica with an infection rate of 27.2% (900/3307). The miracidium escaped from the egg and penetrated into G. pervia at temperature 22 degrees C, developed into a sporocyst after 7-15 days, which transformed into mother redia at the 11 st-20th day post-infection. The mother redia developed into daughter redia at the 30th-37th day, and produced cercaria with longtail, and became metacercaria at the 42nd-55th day. PCR confirmed that the metacercariae were that of F. hepatica, with an obvious band (approximately 500 bp). CONCLUSION: Among the three potential intermediate hosts in Dali, G. pervia is experimentally infected with F. hepatica.

[Molluscicidal effect of WPN and MNSC on Lymnaea].

OBJECTIVE: To evaluate the molluscicidal effect of wettable powder of 50% niclosamide ethanolamide salt (WPN) and suspension concentrate of 26% metaldehyde and niclosamide (MNSC) on Lymnaea. METHODS: WPN and MNSC were prepared as a series of solutions containing the active ingredient concentrations of 0.06, 0.13, 0.25, 0.50, 1.00, 2.00 mg/L and 4.00 mg/L, and the adult Lymnaea snails were soaked in the above mentioned series of solutions in the laboratory, and the LC50 values were calculated. The doses of active ingredient concentrations of 0.03, 0.06, 0.13, 0.25, 0.50, 1.00 g/m2 and 2.00 g/m2 of WPN and MNSC were adopted to spray on Lymnaea snails in the laboratory, and the LC50 values were calculated. A series of solutions containing the active ingredient concentrations of 1.00 mg/L, 0.50 mg/L, 0.25 mg/L, and 0.13 mg/L of WPN and MNSC were prepared, and the adult Lymnaea snails were put into the bowls with each concentration solution above mentioned and the climbing situation of the snails was observed at different time. RESULTS: By the immersion method, LC50 values of WPN at 48 h and 72 h were 0.93 mg/L and 0.64 mg/L respectively; LC50 values of MNSC at 48 h and 72 h were 0.74 mg/L and 0.51 mg/L respectively; by the spray method, when active ingredient concentrations of WPN and MNSC were 1.00 g/m2 or more, the death rates were both 100% after 3 days. In the climbing test, the Lymnaea snails did not climb in the solutions containing the active ingredient concentration of 1.00 mg/L of WPN and MNSC, however, a few snails climbed in the low concentrations. CONCLUSIONS: WPN and MNSC both have the effect of killing Lymnaea snails and inhibiting their climbing. By using the immersion method in the field, the active ingredient concentration of 2.00 mg/L of WPN and MNSC for 48 h is appropriate; by using the spray method, the active ingredient content of 1.00 g/m2 of WPN and MNSC for 3 days is appropriate.

[Survey of the number of eggs in Taenia asiatica gravid proglottids in Dali Prefecture of Yunnan Province].

OBJECTIVE: To observe the number of eggs in the gravid proglottids of Taenia asiatica. METHODS: Twenty gravid proglottids at each end of two adults of T. asiatica were digested by 1% pepsin. Then, the collected eggs were observed and counted by a microscope. RESULTS: The number of eggs in each gravid proglottid were not the same, with the maximum of 132 500, minimum of 44 180, and the average number of 90 051, and there was a significant difference among the different gravid proglottids (t = -3.487, P = 0.003). CONCLUSION: The number of eggs in different gravid proglottids of T. asiatica is evidently different.