Echocardiographic findings and pregnancy outcomes for fetuses with complete closure of the ductus arteriosus.

OBJECTIVE: We aimed to analyze the echocardiographic characteristics and pregnancy outcomes for fetuses with premature complete closure of the fetal ductus arteriosus. METHODS: A retrospective analysis was performed for eight cases of premature ductus arteriosus closure diagnosed by prenatal ultrasonography in the Hunan Maternal and Child Health Hospital from July 2019 to August 2022, and the characteristics of fetal echocardiography and pregnancy outcomes of the eight cases were analyzed and summarized. RESULTS: In all cases, the intima of the ductus arteriosus was thickened and occluded, the ductus arteriosus could be seen with slightly hyperechogenic, and no blood flow signal was found in the ductus arteriosus by Doppler ultrasonography. The right heart was enlarged in seven cases, and the whole heart was enlarged in one case. Tricuspid valve regurgitation was observed to different degrees, of which seven cases were severe and one case was moderate. The pulmonary arteries of eight patients had varying degrees of widening. All eight cases were delivered by cesarean section, and one newborn died after follow-up. The prognosis of the other newborns was good. CONCLUSION: The parameters of prenatal echocardiography are helpful for the prognosis of fetuses with premature closure of the ductus arteriosus. Early prenatal detection, close observation, and clinical guidance can be used to select the right time of delivery.

Automatic measurement of fetal anterior neck lower jaw angle in nuchal translucency scans.

This study aims at suggesting an end-to-end algorithm based on a U-net-optimized generative adversarial network to predict anterior neck lower jaw angles (ANLJA), which are employed to define fetal head posture (FHP) during nuchal translucency (NT) measurement. We prospectively collected 720 FHP images (half hyperextension and half normal posture) and regarded manual measurement as the gold standard. Seventy percent of the FHP images (half hyperextension and half normal posture) were used to fit models, and the rest to evaluate them in the hyperextension group, normal posture group (NPG), and total group. The root mean square error, explained variation, and mean absolute percentage error (MAPE) were utilized for the validity assessment; the two-sample t test, Mann-Whitney U test, Wilcoxon signed-rank test, Bland-Altman plot, and intraclass correlation coefficient (ICC) for the reliability evaluation. Our suggested algorithm outperformed all the competitors in all groups and indices regarding validity, except for the MAPE, where the Inception-v3 surpassed ours in the NPG. The two-sample t test and Mann-Whitney U test indicated no significant difference between the suggested method and the gold standard in group-level comparison. The Wilcoxon signed-rank test revealed significant differences between our new approach and the gold standard in personal-level comparison. All points in Bland-Altman plots fell between the upper and lower limits of agreement. The inter-ICCs of ultrasonographers, our proposed algorithm, and its opponents were graded good reliability, good or moderate reliability, and moderate or poor reliability, respectively. Our proposed approach surpasses the competition and is as reliable as manual measurement.

Determination of the oil absorption value of inorganic powder by tracer-assisted headspace gas chromatography.

This paper reports a method for determining the oil absorption value of inorganic powder based on tracer-assisted headspace gas chromatographic (HS-GC) technique. The method was carried out by adding 25 µL droplet of toluene-Dioctyl Phthalate solution onto the surface of 1.0 g inorganic powder, then sealing the headspace vial and shaking it to make the powder spherical. The amount of toluene that not been adsorbed by inorganic powder was quantified using HS-GC with the optimal equilibrium temperature and time conditions of 100 °C and 7 min, respectively. A new mathematical model shows that the oil absorption value can be determined from the signal of toluene. The results show that the employed method has good precision (the relative standard deviation < 3.6 %) and accuracy (R2 = 0.993). This method is simple and accurate, and can be an reliable tool for testing the oil absorption value of inorganic powder sample.

Validity evidence for simulator-based obstetric ultrasound competency assessment tool: a multi-center study.

PURPOSE: To collect validity evidence for a simulator-based obstetric ultrasound competency assessment tool (OUCAT). METHODS: 89 sonographers from three centers (XY, MC, DT), including novices (n=21), experienced trainees (n=44), and experts (n=24), participated in the competency assessment. Validity evidence of OUCAT was collected according to Standards for Educational and Psychological Testing. Content validity was ensured by reviewing guidelines and reaching expert consensus. The response process was ensured via training raters. Internal structure was explored through internal consistency, inter-rater reliability, and test-retest reliability. Relations to other variables were explored by comparing OUCAT scores of sonographers with different experience. Evidence for consequences was collected by determining the pass/fail level. RESULTS: OUCAT included 123 items, of which 117 items could effectively distinguish novices from experts (P<0.05). The internal consistency was represented by the Cronbach's α coefficient (0.978). The inter-rater reliability was high, with XY being 0.868, MC being 0.877, and DT being 0.937 (P<0.001). Test-retest reliability was 0.732 (P=0.001). The performance of experts was significantly better than experienced trainees, and the performance of experienced trainees was significantly better than novices (70.3±10.7 vs. 39.8±15.0 vs. 20.5±10.6, P<0.001). The pass/fail level determined by contrast group method was 45 points. The passing rate of novices, experienced trainees and experts was 0% (0/21), 31.8% (14/44), and 100% (24/24), respectively. CONCLUSION: Simulator-based OUCAT exhibits good reliability and validity in assessing obstetric ultrasound skills.

Evaluation of the changes in cardiac morphology of fetuses with congenital heart disease using fetalHQ.

Objective: To evaluate the changes in cardiac morphology of fetuses with congenital heart disease (CHD) using the fetal heart quantitative technique (fetalHQ).Methods: A total of 20 normal pregnant women (control group) and 20 pregnant women suspected of fetal CHD (case group) were included in this study. The dynamic images of the four-chamber view of the fetal heart were recorded and analyzed using fetalHQ. The global sphericity index (GSI) and 24-segment SI of the two groups were compared. The differences in the left and right ventricular 24-segment SI for each group were investigated.Results: There was no statistically significant difference in the GSI between the two groups (p > 0.05). The difference in the SI values of left ventricular segments 1-2 between the case group and control group was statistically significant (all p < 0.05), while the intergroup difference in SI of left ventricular segments 3-24 was not significant (all p > 0.05). The SI of the 24 segments of the right ventricle showed no significant intergroup difference (all p > 0.05). The difference in the left and right ventricular 24-segment SI in the case group did not reach statistical significance (all p > 0.05). In the control group, the SI values between the left and right ventricles were significantly different in segments 18-24 (all p < 0.05), and no significant difference was found in segments 1-17 (all p > 0.05). There was a statistically significant intergroup difference in the percentage of unusual left ventricular SI, determined based on Z-score (p < 0.05), and the percentage of outliers for the right ventricle between the two groups showed no significant difference (p > 0.05).Conclusion: The fetalHQ is regarded as a straightforward and reliable approach for assessing the cardiac GSI and 24-segment SI of left and right ventricles in fetuses diagnosed with CHD. While CHD may not significantly impact the overall shape of the fetal heart or the geometric shape of the right ventricle, in this study, a notable increase in SI values for the left ventricular 1-2 segments was observed, indicating a more flattened ventricular chamber. Additionally, the morphological distinctions between the left and right ventricles in fetuses with CHD are no longer discernible.

Intrauterine transmission of SARS-CoV-2 to and prenatal ultrasound abnormal findings in the fetus of a pregnant woman with mild COVID-19.

BACKGROUND: Whether intrauterine transmission of COVID-19 occurs remains uncertain, and it remains unclear whether the disease affects fetuses. We present a case of intrauterine transmission of SARS-CoV-2 infection and the prenatal ultrasonographic findings of the fetus in a pregnant woman with mild COVID-19. CASE PRESENTATION: A 30-year-old woman was admitted to our hospital for ultrasound examination in January 2023 at 26+ 3 weeks' gestation. Twenty-one days prior, her COVID-19 nucleic acid test was positive, and she had mild symptoms, including fever (38.3 °C), headache, chills, ankle pain and cough. After receiving symptomatic treatment, she fully recovered. Prenatal ultrasound revealed that the placenta was diffusely distributed with punctate echogenic foci, hepatomegaly, and the volume of bilateral lungs decreased significantly, with enhanced echo. In addition, we found that the surface of the fetal brain demonstrated widened gyri with a flattened surface. The prenatal MRI confirmed these fetal abnormalities. Amniotic fluid was tested for SARS-CoV-2, and the sample tested was positive for the virus. After careful consideration, the pregnant woman decided to terminate the pregnancy. CONCLUSION: The intrauterine transmission of COVID-19 is certain. Moreover, the intrauterine transmission of COVID-19 may cause abnormalities in various organs of the fetus.

Evolocumab prevents atrial fibrillation in rheumatoid arthritis rats through restraint of PCSK9 induced atrial remodeling.

INTRODUCTION: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is implicated in the pathogenesis and progression of autoimmune disease. Patients with rheumatoid arthritis (RA) are at high risk of developing atrial fibrillation (AF), while whether PCSK9 is involved in the onset of AF among RA patients remains unclear. OBJECTIVES: To explore the role of PCSK9 in the occurrence of AF in RA patients and decipher the underlying mechanism. METHODS: We established a rat model of collagen-induced arthritis (CIA) by immunization with type II collagen in Freund's incomplete adjuvant. Atrial electrophysiological test was used to evaluate AF susceptibility. We performed a clinical study to examine the correlation between PCSK9 level and AF, which recruited healthy control, RA patients and RA patients complicated with AF. Evolocumab (a monoclonal antibody of PCSK9) is administered via intraperitoneal injection in CIA rats to assess the role of PCSK9 in RA-related AF. LPS-RS (LPS inhibitor), clodronate liposomes (depletion of macrophages), and cell co-culture model were used to dissect the mechanism underlying PCSK9 promotes AF. RESULTS: AF inducibility and duration were higher in CIA rats, accompanied by elevated plasma and atrial PCSK9. Interestingly, compared with healthy control subjects, patients with RA showed an increase in PCSK9, and the PCSK9 is much higher in RA patients complicated with AF. The level of PCSK9 was independently associated with AF risk in RA patients. In the in vivo experiment, evolocumab reduced AF susceptibility, and ameliorated atrial structural remodeling of CIA rats. Mechanistically, augmented LPS in CIA rats led to an increase in PCSK9, which exacerbated fibrosis of cardiac fibroblasts and apoptosis of cardiac myocytes by enhancement of M1 macrophages polarization and inflammation, thereby contributing to AF. CONCLUSION: This study suggests that elevated PCSK9 causes atrial structural remodeling by enhancement of M1 macrophages polarization in atria, and evolocumab can effectively protects CIA rats from AF.

Determination of the water vapor transmission rate of cellulose-based papers by multiple headspace extraction analysis.

This paper presents a multiple headspace extraction (MHE) analysis technique to determine the water vapor transmission rate of cellulose-based papers. The water vapor passing through the sample in a closed headspace vial is determined by MHE-gas chromatography. The results show that the employed method offers good precision (the relative standard deviation < 3.49 %) and good accuracy. The method is rapid and accurate, and is promising for the determination of the water vapor transmission rate of cellulose-based papers in future studies.

Polyethylene Glycol Functionalized Silicon Nanowire Field-Effect Transistor Biosensor for Glucose Detection.

Accurate monitoring of blood glucose levels is crucial for the diagnosis of diabetes patients. In this paper, we proposed a simple "mixed-catalyzer layer" modified silicon nanowire field-effect transistor biosensor that enabled direct detection of glucose with low-charge in high ionic strength solutions. A stable screening system was established to overcome Debye screening effect by forming a porous biopolymer layer with polyethylene glycol (PEG) modified on the surface of SiNW. The experimental results show that when the optimal ratio (APTMS:silane-PEG = 2:1) modified the surface of silicon nanowires, glucose oxidase can detect glucose in the concentration range of 10 nM to 10 mM. The sensitivity of the biosensor is calculated to be 0.47 µAcm-2mM-1, its fast response time not exceeding 8 s, and the detection limit is up to 10 nM. This glucose sensor has the advantages of high sensitivity, strong specificity and fast real-time response. Therefore, it has a potential clinical application prospect in disease diagnosis.

Carbene-Catalyzed Activation of 2-Aminobenzaldehyde for Access to Chiral Fluorescent Quinazolinone.

A carbene-catalyzed reaction to synthesize a chiral quinazolinone with a new activation mode of an "aniline-like" N-H moiety is disclosed. Addition of the nitrogen atom of diphenyl o-aminobenzaldehydes via NHC activation to imines leads to chiral quinazolinones with high yields and optical purities. The acidity of the N-H moiety was extremely increased through the formation of an acyl azolium intermediate, which was investigated by DFT calculations. Moreover, the chiral quinazolinones were found to have high fluorescence quantum efficiency.

Determination of carbonate content in barite ore by headspace gas chromatography.

This paper reports a method for determining the carbonate content in barite ore using headspace gas chromatography. Based on the acidification reaction, the carbonate in the barite ore was converted to CO2 in a closed headspace vial. When the carbonate content was significant, the pressure caused changes in the CO2 and O2 signals and affected the measurement accuracy. It was found that carbonate content is proportional to the intensity ratio of the CO2 to O2 signals. Thus, the carbonate content in barite ore can be measured indirectly using a theoretical model. The results showed that the carbonate in 3 g of barite ore sample with a particle size of 74 µm could react completely with a hydrochloric acid solution (2 mol/L) at 65°C for 5 min. The method described herein had good precision (relative standard deviation < 4.14%) and accuracy (relative differences < 6.12%). Further, the limit of quantification was 0.07 mol/L. Owing to its simplicity and speed, this method can be used for the batch determination of carbonate content in barite ore.

Protein function annotation based on heterogeneous biological networks.

BACKGROUND: Accurate annotation of protein function is the key to understanding life at the molecular level and has great implications for biomedicine and pharmaceuticals. The rapid developments of high-throughput technologies have generated huge amounts of protein-protein interaction (PPI) data, which prompts the emergence of computational methods to determine protein function. Plagued by errors and noises hidden in PPI data, these computational methods have undertaken to focus on the prediction of functions by integrating the topology of protein interaction networks and multi-source biological data. Despite effective improvement of these computational methods, it is still challenging to build a suitable network model for integrating multiplex biological data. RESULTS: In this paper, we constructed a heterogeneous biological network by initially integrating original protein interaction networks, protein-domain association data and protein complexes. To prove the effectiveness of the heterogeneous biological network, we applied the propagation algorithm on this network, and proposed a novel iterative model, named Propagate on Heterogeneous Biological Networks (PHN) to score and rank functions in descending order from all functional partners, Finally, we picked out top L of these predicted functions as candidates to annotate the target protein. Our comprehensive experimental results demonstrated that PHN outperformed seven other competing approaches using cross-validation. Experimental results indicated that PHN performs significantly better than competing methods and improves the Area Under the Receiver-Operating Curve (AUROC) in Biological Process (BP), Molecular Function (MF) and Cellular Components (CC) by no less than 33%, 15% and 28%, respectively. CONCLUSIONS: We demonstrated that integrating multi-source data into a heterogeneous biological network can preserve the complex relationship among multiplex biological data and improve the prediction accuracy of protein function by getting rid of the constraints of errors in PPI networks effectively. PHN, our proposed method, is effective for protein function prediction.

Small ubiquitin-related modifier (SUMO)ylation of SIRT1 mediates (-)-epicatechin inhibited- differentiation of cardiac fibroblasts into myofibroblasts.

CONTEXT: (-)-Epicatechin (EPI) is a crucial substance involved in the protective effects of flavanol-rich foods. Previous studies have indicated EPI has a cardioprotective effect, but the molecular mechanisms in inhibition of cardiac fibrosis are unclear. OBJECTIVE: We evaluated the effect of EPI in preventing cardiac fibrosis and the underlying molecular mechanism related to the SIRT1-SUMO1/AKT/GSK3ß pathway. MATERIALS AND METHODS: Cardiac fibrosis mice model was established with transaortic constriction (TAC). Male C57BL/6 mice were randomly separated into 4 groups. Mice received 1 mg/kg/day of EPI or vehicle orally for 4 weeks. The acutely isolated cardiac fibroblasts were induced to myofibroblasts with 1 µM angiotensin II (Ang II). The cardiac function was measured with the ultrasonic instrument. Histological analysis of mice's hearts was determined with H&E or Masson method. The protein level of fibrosis markers, SUMOylation of SIRT1, and AKT/GSK3ß pathway were quantified by immunofluorescence and western blot. RESULTS: EPI treatment (1 mg/kg/day) could reverse the TAC-induced decline in LVEF (TAC, 61.28% ± 1.33% vs. TAC + EPI, 74.00% ± 1.64%), LVFS (TAC, 28.16% ± 0.89% vs. TAC + EPI, 37.18% ± 1.29%). Meantime, we found that 10 µM EPI blocks Ang II-induced transformation of cardiac fibroblasts into myofibroblasts. The underlying mechanism of EPI-inhibited myofibroblasts transformation involves activation of SUMOylation of SIRT1 through SP1. Furthermore, SUMOylation of SIRT1 inhibited Ang II-induced fibrogenic effect via the AKT/GSK3ß pathway. CONCLUSION: EPI plays a protective effect on cardiac fibrosis by regulating the SUMO1-dependent modulation of SIRT1, which provides a theoretical basis for use in clinical therapies.

Cross-sectional reference values of cerebral ventricle for Chinese neonates born at 25-41 weeks of gestation.

To establish the cross-sectional reference values of cerebral ventricular size for the Chinese newborns by the most correlated explanatory variables. The anterior horn width (AHW), thalamo-occipital distance (TOD), and ventricular index (VI) were collected prospectively from 1- to 7-day neonates without potential neurological problems. All neonates were delivered or treated at the Hunan Provincial Maternal and Child Health Care Hospital or Second Xiangya Hospital of Central South University between February and August 2021. The most correlated explanatory variables were identified with the max-min normalization and multiple regression. The reference values were then established based on the above variables. Additionally, intraclass correlation coefficients (ICC) were applied to evaluate the reliability of the overall data collection process. This prospective study consisted of 1848 neonates. The AHW was most highly correlated with GA; the TOD and VI were most strongly correlated with birth weight. All the foregoing correlations were positive ones. Heteroscedasticity and influential points existed in both TOD and VI. The ICCAHW was the largest to a specific rater or between raters, the ICCTOD the second largest, and the ICCVI the smallest. CONCLUSIONS: We recommend using the GA-based AHW reference values and birth weight-based TOD and VI ones. We also present a comparison of GA-based upper limits from all available reference intervals. Moreover, we determine that measurement errors are the primary cause of influential points and heteroscedasticity in TOD and VI studies and infer that the studies of TOD and VI are vulnerable to them. WHAT IS KNOWN: • Reference values of infantile cerebral ventricles are vital in diagnosing and treating cerebral ventricular dilatation. • Precursors established gestational age-based reference values subjectively. WHAT IS NEW: • We set cross-sectional reference values based on the most correlated variables for Chinese neonates and compared all available gestational age-based upper limits. • Influential points and heteroscedasticity mainly caused by measurement errors are common in TOD and VI studies.

Accurate Determination of Moisture Content in Flavor Microcapsules Using Headspace Gas Chromatography.

This study demonstrates an accurate method for determining the moisture content in flavor microcapsules using headspace gas chromatography. The method involves measuring the gas chromatography signals of water from vapor in a headspace vial containing flavor microcapsules at a temperature of 125 °C. The measurements were recorded over four headspace extractions, from which the moisture content in the microcapsule samples was extrapolated via simple vapor-phase calibration. The results revealed that the proposed method demonstrated good precision (a relative standard deviation of <3.11%) and accuracy. The proposed method is accurate, highly sensitive, automated, and suitable for testing the moisture content of flavor microcapsules and related products.

Akkermansia muciniphila prevents cold-related atrial fibrillation in rats by modulation of TMAO induced cardiac pyroptosis.

BACKGROUND: Cold exposure is one of the most important risk factors for atrial fibrillation (AF), and closely related to the poor prognosis of AF patients. However, the mechanisms underlying cold-related AF are poorly understood. METHODS: Various techniques including 16S rRNA gene sequencing, fecal microbiota transplantation, and electrophysiological examination were used to determine whether gut microbiota dysbiosis promotes cold-related AF. Metabonomics were performed to investigate changes in fecal trimethylamine (TMA) and plasma trimethylamine N-oxide (TMAO) during cold exposure. The detailed mechanism underlying cold-related AF were examined in vitro. Transgenic mice were constructed to explore the role of pyroptosis in cold-related AF. The human cohort was used to evaluate the correlation between A. muciniphila and cold-related AF. FINDINGS: We found that cold exposure caused elevated susceptibility to AF and reduced abundance of Akkermansia muciniphila (A. muciniphila) in rats. Intriguingly, oral supplementation of A. muciniphila ameliorated the pro-AF property induced by cold exposure. Mechanistically, cold exposure disrupted the A. muciniphila, by which elevated the level of trimethylamine N-oxide (TMAO) through modulation of the microbial enzymes involved in trimethylamine (TMA) synthesis. Correspondingly, progressively increased plasma TMAO levels were validated in human subjects during cold weather. Raised TMAO enhanced the infiltration of M1 macrophages in atria and increased the expression of Casp1-p20 and cleaved-GSDMD, ultimately causing atrial structural remodeling. Furthermore, the mice with conditional deletion of caspase1 exhibited resistance to cold-related AF. More importantly, a cross-sectional clinical study revealed that the reduction of A. muciniphila abundance was an independent risk factor for cold-related AF in human subjects. INTERPRETATION: Our findings revealed a novel causal role of aberrant gut microbiota and metabolites in pathogenesis of cold-related AF, which raises the possibility of selectively targeting microbiota and microbial metabolites as a potential therapeutic strategy for cold-related AF. FUNDING: This work was supported by grants from the State Key Program of National Natural Science Foundation of China (No.81830012), and National Natural Science Foundation of China (No.82070336, No.81974024), Youth Program of the National Natural Science Foundation of China (No.81900374, No.81900302), and Excellent Young Medical Talents supporting project in the First Affiliated Hospital of Harbin Medical University (No. HYD2020YQ0001).

SUMOylation of SIRT1 activating PGC-1α/PPARα pathway mediates the protective effect of LncRNA-MHRT in cardiac hypertrophy.

Long noncoding RNA-Myosin heavy chain associated RNA transcript (LncRNA-MHRT) has been reported to prevent pathological cardiac hypertrophy. However, the underlying inhibition mechanism has not been fully elucidated. Further, whether MHRT inhibits hypertrophy by regulating post-translational modification of certain proteins remains unclear. Therefore, this study aims to find potential role of MHRT in inhibiting cardiac hypertrophy via regulating modification of certain proteins. Here, Angiotensin II (Ang II) -treated neonatal rat cardiomyocytes and transverse aortic constriction (TAC) mice were used to investigate the effect and mechanism of MHRT in cardiac hypertrophy in vitro and in vivo. Moreover, the regulatory effects of MHRT on SUMOylation of NAD-dependent protein deacetylase sirtuin-1 (SIRT1), peroxisome proliferator-activated receptor γ coactivator-1 α (PGC-1α)/peroxisome proliferator-activated receptor-α (PPARα), specificity protein 1 (SP1)/histone deacetylase 4 (HDAC4) pathway were investigated. Here, we found that MHRT improved heart function by attenuating pathological cardiac hypertrophy in vivo and in vitro. MHRT also promoted the SUMOylation of SIRT1 protein that activated PGC1-α/PPAR-α pathway. Furthermore, MHRT enhanced SUMOylation of SIRT1 by upregulating SP1/HDAC4. Our findings suggested that SUMOylation of SIRT1 could mediate the protective effect of MHRT in cardiac hypertrophy. The new regulatory pathway provides a potential new therapeutic target for pathological cardiac hypertrophy.

Epididymal white adipose tissue promotes angiotensin II-induced cardiac fibrosis in an exosome-dependent manner.

Cardiac fibrosis is a process characterized by extracellular matrix accumulation leading to myocardial dysfunction. Angiotensin II (Ang II) has been shown to play an important role in the pathogenesis of cardiac fibrosis. However, the underlying mechanisms are not well established. Dysfunction of adipose tissue has been shown to promote remote organ injury, but its role in Ang II-induced cardiac remodeling is still unclear. In this study, we demonstrated that epididymal white adipose tissue (eWAT) promoted Ang II-induced cardiac fibrosis and subsequent cardiac dysfunction in an exosome-dependent manner. Both eWAT removal and administration of an inhibitor of exosome biogenesis strongly attenuated Ang II-induced abnormalities. Moreover, exosomes isolated from Ang II-stimulated adipocytes promoted cardiac fibroblasts (CFs) activity. A mechanistic study identified that the miR-23a-3p level was significantly increased in exosomes derived from Ang II-challenged adipocytes and serum exosomes from Ang II-infused mice. Importantly, tail vein injection of ago-miR-23a-3p caused cardiac fibrosis and dysfunction, while antago-miR-23a-3p inhibited Ang II-induced cardiac fibrosis. Bioinformatics analysis and further validation experiments revealed that RAP1 is a direct downstream target of miR-23a-3p, and overexpression of RAP1 reversed the profibrotic effect of miR-23a-3p. Taken together, these findings elucidated the role of eWAT in Ang II-induced myocardial fibrosis and indicated that adipocyte-derived exosomes mediate pathologic communication between dysfunctional adipose tissue and the heart by transporting miR-23a-3p into CFs, transforming fibroblasts into myofibroblasts and promoting excessive collagen deposition by targeting RAP1. Prevention of abnormal adipocyte exosome production, inhibition of miR-23a-3p biogenesis, and treatment with a miR-23a-3p antagonist are novel strategies for treating cardiac fibrosis.

A tensor-based bi-random walks model for protein function prediction.

BACKGROUND: The accurate characterization of protein functions is critical to understanding life at the molecular level and has a huge impact on biomedicine and pharmaceuticals. Computationally predicting protein function has been studied in the past decades. Plagued by noise and errors in protein-protein interaction (PPI) networks, researchers have undertaken to focus on the fusion of multi-omics data in recent years. A data model that appropriately integrates network topologies with biological data and preserves their intrinsic characteristics is still a bottleneck and an aspirational goal for protein function prediction. RESULTS: In this paper, we propose the RWRT (Random Walks with Restart on Tensor) method to accomplish protein function prediction by applying bi-random walks on the tensor. RWRT firstly constructs a functional similarity tensor by combining protein interaction networks with multi-omics data derived from domain annotation and protein complex information. After this, RWRT extends the bi-random walks algorithm from a two-dimensional matrix to the tensor for scoring functional similarity between proteins. Finally, RWRT filters out possible pretenders based on the concept of cohesiveness coefficient and annotates target proteins with functions of the remaining functional partners. Experimental results indicate that RWRT performs significantly better than the state-of-the-art methods and improves the area under the receiver-operating curve (AUROC) by no less than 18%. CONCLUSIONS: The functional similarity tensor offers us an alternative, in that it is a collection of networks sharing the same nodes; however, the edges belong to different categories or represent interactions of different nature. We demonstrate that the tensor-based random walk model can not only discover more partners with similar functions but also free from the constraints of errors in protein interaction networks effectively. We believe that the performance of function prediction depends greatly on whether we can extract and exploit proper functional similarity information on protein correlations.