Serum circRNA (Circ)_0051386 assists in the diagnosis of acute ST-segment elevation myocardial infarction and prediction of the occurrence of major adverse cardiovascular events after percutaneous coronary intervention.

BACKGROUND: This study aimed to uncover the diagnostic value of circRNA (Circ)_0051386 in acute ST-segment elevation myocardial infarction (STEMI) and its predictive value for the occurrence of adverse major adverse cardiovascular events (MACEs). METHODS: This study included 166 patients with STEMI and 83 health donors. The expression levels of serum Circ_0051386 in these participants were quantified using real-time quantitative polymerase chain reaction (RT-qPCR). Additionally, the incidence of MACEs during a 6-month follow-up period after percutaneous coronary intervention (PCI) was collected in the STEMI patient cohort. RESULTS: Before and after propensity score matching (PSM), Circ_0051386 all had higher expression levels in the patients with STEMI than the normal subjects (all p < .001)and robust diagnosis values for the STEMI (AUC = 0.766, 0.779). Kaplan-Meier curves showed the high expression Circ_0051386 group had a higher occurrence rate of MACEs during a 6-month follow-up after PCI in patients with STEMI and this phenomenon was confirmed by internal validation (all p < .05). In addition, the multivariate COX regression showed gensini score (HR = 1.020, 95% CI = 1.002 - 1.038, p = .028) and Circ_0051386 (HR = 2.468, 95% CI =1.548-3.935, p < .001)were independent risk factors of the occurrence of MACEs in patients with STEMI after PCI. Pearson analysis presented that Circ_0051386 was positively correlated with gensini scores (r = 0.33), IL-1ß (r = 0.55)and TNF-α(r = 0.41). CONCLUSION: Our study indicated that Circ_0051386 is a biomarker of the diagnostic for STEMI and the predictor of the MACEs in STEMI patients after PCI. Its potential role in STEMI may be the regulation of inflammation in the vascular endothelial.

Comparative analysis of the synergetic effects of Diwuyanggan prescription on high fat diet-induced non-alcoholic fatty liver disease using untargeted metabolomics.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver disorders worldwide and had no approved pharmacological treatments. Diwuyanggan prescription (DWYG) is a traditional Chinese medicine preparation composed of 5 kinds of herbs, which has been used for treating chronic liver diseases in clinic. Whereas, the synergistic mechanism of this prescription for anti-NAFLD remains unclear. In this study, we aimed to demonstrate the synergetic effect of DWYG by using the disassembled prescriptions and untargeted metabolomics research strategies. The therapeutic effects of the whole prescription of DWYG and the individual herb were divided into six groups according to the strategy of disassembled prescriptions, including DWYG, Artemisia capillaris Thunb. (AC), Curcuma longa L. (CL), Schisandra chinensis Baill. (SC), Rehmannia glutinosa Libosch. (RG) and Glycyrrhiza uralensis Fisch. (GU) groups. The high fat diets-induced NAFLD mice model was constructed to evaluate the efficacy effects of DWYG. An untargeted metabolomics based on the UPLC-QTOF-MS/MS approach was carried out to make clear the synergetic effect on the regulation of metabolites dissecting the united mechanisms. Experimental results on animals revealed that the anti-NAFLD effect of DWYG prescription was better than the individual herb group in reducing liver lipid deposition and restoring the abnormality of lipidemia. In addition, further metabolomics analysis indicated that 23 differential metabolites associated with the progression of NAFLD were identified and 19 of them could be improved by DWYG. Compared with five single herbs, DWYG showed the most extensive regulatory effects on metabolites and their related pathways, which were related to lipid and amino acid metabolisms. Besides, each individual herb in DWYG was found to show different degrees of regulatory effects on NAFLD and metabolic pathways. SC and CL possessed the highest relationship in the regulation of NAFLD. Altogether, these results provided an insight into the synergetic mechanisms of DWYG from the metabolic perspective, and also supported a scientific basis for the rationality of clinical use of this prescription.

Diet Restriction Impact on High-Fat-Diet-Induced Obesity by Regulating Mitochondrial Cardiolipin Biosynthesis and Remodeling.

Diet restriction (DR) ameliorates obesity by regulating mitochondrial function. Cardiolipin (CL), a mitochondrial phospholipid, is closely associated with mitochondrial function. This study aimed to evaluate the anti-obesity effects of graded levels of DR based on mitochondrial CL levels in the liver. Obese mice were treated with 0%, 20%, 40%, and 60% reductions in the normal diet compared to normal animals (0 DR, 20 DR, 40 DR, and 60 DR groups, respectively). Biochemical and histopathological analyses were performed to evaluate the ameliorative effects of DR on obese mice. The altered profile of mitochondrial CL in the liver was explored using a targeted metabolomics strategy by ultra-high-pressure liquid chromatography MS/MS coupled with quadrupole time-of-flight mass spectrometry. Finally, gene expression associated with CL biosynthesis and remodeling was quantified. Tissue histopathology and biochemical index evaluations revealed significant improvements in the liver after DR, except for the 60 DR group. The variation in mitochondrial CL distribution and DR levels showed an inverted U-shape, and the CL content in the 40 DR group was the most upregulated. This result is consistent with the results of the target metabolomic analysis, which showed that 40 DR presented more variation. Furthermore, DR led to increased gene expression associated with CL biosynthesis and remodeling. This study provides new insights into the mitochondrial mechanisms underlying DR intervention in obesity.

Highly stable and low-temperature-tolerant zinc ion storage enabled by carbitol electrolyte additive engineering.

Aqueous zinc (Zn)-ion energy storage system is widely regarded as a promising candidate for future electrochemical energy storage applications but suffers insufficient lifespan and limited operating temperature. To address these issues, we introduce a carbitol additive for a novel hybrid electrolyte to enhance cycling stability and temperature adaptability by optimizing the coordination structure of Zn ion. The modified electrolyte not only restrains the hydrogen evolution, but also promotes a high-orientation Zn deposition and significantly limits the Zn dendrite growth. Taking advantage of improved electrolyte properties, the Zn symmetric cells with 10 % carbitol-modified electrolyte exhibit long-term cycle stability for 5000 h at 25 °C, and 400 h at -10 °C. More notably, the carbitol-modified electrolyte endows a stable reversible capacitance for Zn ion hybrid supercapacitors to be operated at different temperatures. Our work affords a reasonable electrolyte engineering strategy to fabricate a highly stable and low-temperature-tolerant Zn ion storage system.

Exploration of the hypoglycemic mechanism of Fuzhuan brick tea based on integrating global metabolomics and network pharmacology analysis.

Introduction: Fuzhuan brick tea (FBT) is a worldwide popular beverage which has the appreciable potential in regulating glycometabolism. However, the reports on the hypoglycemic mechanism of FBT remain limited. Methods: In this study, the hypoglycemic effect of FBT was evaluated in a pharmacological experiment based on Kunming mice. Global metabolomics and network pharmacology were combined to discover the potential target metabolites and genes. In addition, the real-time quantitative polymerase chain reaction (RT-qPCR) analysis was performed for verification. Results: Seven potential target metabolites and six potential target genes were screened using the integrated approach. After RT-qPCR analysis, it was found that the mRNA expression of VEGFA, KDR, MAPK14, and PPARA showed significant differences between normal and diabetes mellitus mice, with a retracement after FBT treatment. Conclusion: These results indicated that the hypoglycemic effect of FBT was associated with its anti-inflammatory activities and regulation of lipid metabolism disorders. The exploration of the hypoglycemic mechanism of FBT would be meaningful for its further application and development.

Improvement of RTT Fairness Problem in BBR Congestion Control Algorithm by Gamma Correction.

Google proposed the bottleneck bandwidth and round-trip propagation time (BBR), which is a new congestion control algorithm. BBR creates a network path model by measuring the available bottleneck bandwidth and the minimum round-trip time (RTT) to maximize delivery rate and minimize latency. However, some studies have shown that there are serious RTT fairness problems in the BBR algorithm. The flow with longer RTT will consume more bandwidth and the flows with shorter RTT will be severely squeezed or even starved to death. Moreover, these studies pointed out that even small RTT differences will lead to the throughput of BBR flows being unfair. In order to solve the problem of RTT fairness, an improved algorithm BBR-gamma correction (BBR-GC) is proposed. BBR-GC algorithm takes RTT as feedback information, and then uses the gamma correction function to fit the adaptive pacing gain. This approach can make different RTT flows compete for bandwidth more fairly, thus alleviating the RTT fairness issue. The simulation results of Network Simulator 3 (NS3) show that that BBR-GC algorithm cannot only ensure the channel utilization, but also alleviate the RTT fairness problem of BBR flow in different periods. Through the BBR-GC algorithm, RTT fairness is improved by 50% and the retransmission rate is reduced by more than 26%, compared with that of the original BBR in different buffer sizes.

Cervical Intervertebral Disc Degeneration Contributes to Dizziness: A Clinical and Immunohistochemical Study.

OBJECTIVES: Dizziness often happens in patients with chronic neck pain with only cervical disc degeneration but without cervical radiculopathy or myelopathy. We prospectively selected a series of patients who showed cervical disc degeneration with concomitant chronic neck pain and intractable dizziness who did not respond to conservative treatment to test a new diagnostic method for this dizziness, to analyze the results of anterior cervical discectomy and fusion (ACDF) surgery based on the test, and to explore its pathogenesis. METHODS: Seventy-seven patients who had a transient neck pain and dizziness relief after injection of bupivacaine into a suspected disc were included in the study. In total, 52 underwent ACDF as surgery group, and 25 refused surgery and accepted conservative treatments as conservative group from June, 2015 to October, 2016 with subsequent follow-up to 1 year. The outcomes were visual analogue scale for neck pain, Neck Disability Index, and intensity and frequency of dizziness. During ACDF, the 72 specimens of degenerative cervical discs were collected to determine the innervation in degenerative cervical discs immunohistochemically. RESULTS: After surgery, the patients experienced a significant reduction in neck pain and dizziness. Symptomatic relief in surgery group was obviously better than conservative group at each time point of follow-up (P = 0.001). Ruffini corpuscles and substance P-positive free nerve fibers were obviously increased in the number and deeply ingrown into the inner degenerative cervical discs. CONCLUSIONS: Current clinical and immunohistochemical studies strongly suggest that chronic neck pain and intractable dizziness in this series of patients stem from the degenerative cervical discs.

Recapitulating X-Linked Juvenile Retinoschisis in Mouse Model by Knock-In Patient-Specific Novel Mutation.

X-linked juvenile retinoschisis (XLRS) is a retinal disease caused by mutations in the gene encoding retinoschisin (RS1), which leads to a significant proportion of visual impairment and blindness. To develop personalized genome editing based gene therapy, knock-in animal disease models that have the exact mutation identified in the patients is extremely crucial, and that the way which genome editing in knock-in animals could be easily transferred to the patients. Here we recruited a family diagnosed with XLRS and identified the causative mutation (RS1, p.Y65X), then a knock-in mouse model harboring this disease-causative mutation was generated via TALEN (transcription activator-like effector nucleases). We found that the b-wave amplitude of the ERG of the RS1-KI mice was significantly decreased. Moreover, we observed that the structure of retina in RS1-KI mice has become disordered, including the disarray of inner nuclear layer and outer nuclear layer, chaos of outer plexiform layer, decreased inner segments of photoreceptor and the loss of outer segments. The novel knock-in mice (RS1-KI) harboring patient-specific mutation will be valuable for development of treatment via genome editing mediated gene correction.

Relationships among stop codon usage bias, its context, isochores, and gene expression level in various eukaryotes.

It is well known that stop codons play a critical role in the process of protein synthesis. However, little effort has been made to investigate whether stop codon usage exhibits biases, such as widely seen for synonymous codon usage. Here we systematically investigate stop codon usage bias in various eukaryotes as well as its relationships with its context, GC3 content, gene expression level, and secondary structure. The results show that there is a strong bias for stop codon usage in different eukaryotes, i.e., UAA is overrepresented in the lower eukaryotes, UGA is overrepresented in the higher eukaryotes, and UAG is least used in all eukaryotes. Different conserved patterns for each stop codon in different eukaryotic classes are found based on information content and logo analysis. GC3 contents increase with increasing complexity of organisms. Secondary structure prediction revealed that UAA is generally associated with loop structures, whereas UGA is more uniformly present in loop and stem structures, i.e., UGA is less biased toward having a particular structure. The stop codon usage bias, however, shows no significant relationship with GC3 content and gene expression level in individual eukaryotes. The results indicate that genomic complexity and GC3 content might contribute to stop codon usage bias in different eukaryotes. Our results indicate that stop codons, like synonymous codons, exhibit biases in usage. Additional work will be needed to understand the causes of these biases and their relationship to the mechanism of protein termination.

Refined phylogenetic profiles method for predicting protein-protein interactions.

MOTIVATION: The increasing availability of complete genome sequences provides excellent opportunity for the further development of tools for functional studies in proteomics. Several experimental approaches and in silico algorithms have been developed to cluster proteins into networks of biological significance that may provide new biological insights, especially into understanding the functions of many uncharacterized proteins. Among these methods, the phylogenetic profiles method has been widely used to predict protein-protein interactions. It involves the selection of reference organisms and identification of homologous proteins. Up to now, no published report has systematically studied the effects of the reference genome selection and the identification of homologous proteins upon the accuracy of this method. RESULTS: In this study, we optimized the phylogenetic profiles method by integrating phylogenetic relationships among reference organisms and sequence homology information to improve prediction accuracy. Our results revealed that the selection of the reference organisms set and the criteria for homology identification significantly are two critical factors for the prediction accuracy of this method. Our refined phylogenetic profiles method shows greater performance and potentially provides more reliable functional linkages compared with previous methods.

[Experimental study on prevention and treatment of osteoporosis by phytoestrogen].

OBJECTIVE: To observe the effect of phytoestrogen (PE) in preventing and treating osteoporosis in ovariectomized rats. METHODS: Forty-five Wistar female rats, 3 months old, were randomly divided into the sham-operated group, the model group, low dose and high dose PE groups, and the positive control group, 9 in each group. All rats, except that those in the sham operated group were simutaneously operated, were ovariectomized. The medication started from the 31st days after operation by daily given saline per os to the sham-operated group and the model group, PE per os to the PE groups, and estradiol by intramuscular injection to the positive control group. The animals were sacrificed 90 days later, their sera were collected for determination of biochemical parameters, their right femoral bone was taken to detect the bone mineral density (BMD), left femoral bone to examine pathology of bone trabecula, and whole uterus was weighed to calculate the uterine index. RESULTS: PE could increase the BMD level, serum estradiol and inorganic phosphorus content, and uterine index, lower serum BGP, tartrate-resistant acid phosphatase (TRAP), alkaline phosphatuse (AKP) and interleukin-6 levels. Pathological examination showed that in the model group, the cortex of bone thinned, bone trabecula thinned also, with poor integrity, distorted, broken and decreased in size, while in the PE groups, the above-mentioned changes were significantly alleviated. CONCLUSION: PE is effective in preventing and treating osteoporosis in ovariectomized rats.

Prediction of prokaryotic promoters based on prediction of transcriptional units.

Identification of promoters is very important in understanding gene regulating relationships in an organism, and computational identification of promoters has been a long standing problem in computational biology. A new method was presented to predict promoter regions in prokaryotic organism. The method predicted transcription unit (TU) first and the TU was divided into singlet that contains only one single gene in a TU, and operon that contains more than one gene. Based on these predicted TUs, promoter was predicted for each TU using hidden Markov model including explicit state duration density. Both predicted TUs and promoters were satisfying.