Early evolution of the ecdysozoan body plan.

Extant ecdysozoans (moulting animals) are represented by a great variety of soft-bodied or articulated organisms that may or may not have appendages. However, controversies remain about the vermiform nature (i.e. elongated and tubular) of their ancestral body plan. We describe here Beretella spinosa gen. et sp. nov. a tiny (maximal length 3 mm) ecdysozoan from the lowermost Cambrian, Yanjiahe Formation, South China, characterized by an unusual sack-like appearance, single opening, and spiny ornament. Beretella spinosa gen. et sp. nov has no equivalent among animals, except Saccorhytus coronarius, also from the basal Cambrian. Phylogenetic analyses resolve both fossil species as a sister group (Saccorhytida) to all known Ecdysozoa, thus suggesting that ancestral ecdysozoans may have been non-vermiform animals. Saccorhytids are likely to represent an early off-shot along the stem-line Ecdysozoa. Although it became extinct during the Cambrian, this animal lineage provides precious insight into the early evolution of Ecdysozoa and the nature of the earliest representatives of the group.

Enhanced expression of miR-20a driven by nanog exacerbated the degradation of extracellular matrix in thoracic aortic dissection.

Thoracic aortic dissection (TAD) is a life-threatening vascular disease manifested as intramural bleeding in the medial layers of the thoracic aorta. The key histopathologic feature of TAD is medial degeneration, characterized by depletion of vascular smooth muscle cells (VSMCs) and degradation of extracellular matrix (ECM). MicroRNA, as essential epigenetic regulators, can inhibit the protein expression of target genes without modifying the sequences. This study aimed to elucidate the role and underlying mechanism of miR-20a, a member of the miR-17-92 cluster, in regulating ECM degradation during the pathogenesis of TAD. The expression of the miR-17-92 cluster was significantly increased in synthetic VSMCs derived from TAD lesions compared to contractile VSMCs isolated from normal thoracic aortas. Notably, the expression of miR-20a was increased in VSMCs in response to serum exposure and various stimuli. In TAD lesions, the expression of miR-20a was significantly negatively correlated with that of elastin. Elevated expression of miR-20a was also observed in thoracic aortas of TAD mice induced by ß-aminopropionitrile fumarate and angiotensin II. Overexpression of miR-20a via mimic transfection enhanced the growth and invasive capabilities of VSMCs, with no significant impact on their migratory activity or the expression of phenotypic markers (α-SMA, SM22, and OPN). Silencing of miR-20a with inhibitor transfection mitigated the hyperactivation of MMP2 in VSMCs stimulated by PDGF-bb, as evidenced by reduced levels of active-MMP2 and increased levels of pro-MMP2. Subsequently, TIMP2 was identified as a novel target gene of miR-20a. The role of miR-20a in promoting the activation of MMP2 was mediated by the suppression of TIMP2 expression in VSMCs. In addition, the elevated expression of miR-20a was found to be directly driven by Nanog in VSMCs. Collectively, these findings indicate that miR-20a plays a crucial role in maintaining the homeostasis of the thoracic aortic wall during TAD pathogenesis and may represent a potential therapeutic target for TAD.

Development of a multiple convolutional neural network-facilitated diagnostic screening program for immunofluorescence images of IgA nephropathy and idiopathic membranous nephropathy.

Background: Immunoglobulin A nephropathy (IgAN) and idiopathic membranous nephropathy (IMN) are the most common glomerular diseases. Immunofluorescence (IF) tests of renal tissues are crucial for the diagnosis. We developed a multiple convolutional neural network (CNN)-facilitated diagnostic program to assist the IF diagnosis of IgAN and IMN. Methods: The diagnostic program consisted of four parts: a CNN trained as a glomeruli detection module, an IF intensity comparator, dual-CNN (D-CNN) trained as a deposition appearance and location classifier and a post-processing module. A total of 1573 glomerular IF images from 1009 patients with glomerular diseases were used for the training and validation of the diagnostic program. A total of 1610 images of 426 patients from different hospitals were used as test datasets. The performance of the diagnostic program was compared with nephropathologists. Results: In >90% of the tested images, the glomerulus location module achieved an intersection over union >0.8. The accuracy of the D-CNN in recognizing irregular granular mesangial deposition and fine granular deposition along the glomerular basement membrane was 96.1% and 93.3%, respectively. As for the diagnostic program, the accuracy, sensitivity and specificity of diagnosing suspected IgAN were 97.6%, 94.4% and 96.0%, respectively. The accuracy, sensitivity and specificity of diagnosing suspected IMN were 91.7%, 88.9% and 95.8%, respectively. The corresponding areas under the curve (AUCs) were 0.983 and 0.935. When tested with images from the outside hospital, the diagnostic program showed stable performance. The AUCs for diagnosing suspected IgAN and IMN were 0.972 and 0.948, respectively. Compared with inexperienced nephropathologists, the program showed better performance. Conclusion: The proposed diagnostic program could assist the IF diagnosis of IgAN and IMN.

Peptide derived from SLAMF1 prevents TLR4-mediated inflammation in vitro and in vivo.

Inflammation plays a crucial role in the development and progression of many diseases, and is often caused by dysregulation of signalling from pattern recognition receptors, such as TLRs. Inhibition of key protein-protein interactions is an attractive target for treating inflammation. Recently, we demonstrated that the signalling lymphocyte activation molecule family 1 (SLAMF1) positively regulates signalling downstream of TLR4 and identified the interaction interface between SLAMF1 and the TLR4 adaptor protein TRIF-related adapter molecule (TRAM). Based on these findings, we developed a SLAMF1-derived peptide, P7, which is linked to a cell-penetrating peptide for intracellular delivery. We found that P7 peptide inhibits the expression and secretion of IFNß and pro-inflammatory cytokines (TNF, IL-1ß, IL-6) induced by TLR4, and prevents death in mice subjected to LPS shock. The mechanism of action of P7 peptide is based on interference with several intracellular protein-protein interactions, including TRAM-SLAMF1, TRAM-Rab11FIP2, and TIRAP-MyD88 interactions. Overall, P7 peptide has a unique mode of action and demonstrates high efficacy in inhibiting TLR4-mediated signalling in vitro and in vivo.

Decreased expression of RPL15 and RPL18 exacerbated the calcification of valve interstitial cells during aortic valve calcification.

Calcific aortic valve disease (CAVD) is the most common valvular heart disease, with an increasing prevalence due to an aging population. The pathobiology of CAVD is a multifaceted and actively regulated process, but the detailed mechanisms have not been elucidated. The present study aims to identify the differentially expressed genes (DEGs) in calcified aortic valve tissues, and to analyze the correlation between DEGs and clinical features in CAVD patients. The DEGs were screened by microarray in normal and CAVD groups (n = 2 for each group), and confirmed by quantitative real-time polymerase chain reaction in normal (n = 12) and calcified aortic valve tissues (n = 34). A total of 1048 DEGs were identified in calcified aortic valve tissues, including 227 upregulated mRNAs and 821 downregulated mRNAs. Based on multiple bioinformatic analyses, three 60S ribosomal subunit components (RPL15, RPL18, and RPL18A), and two 40S ribosomal subunit components (RPS15 and RPS21) were identified as the top 5 hub genes in the protein-protein interaction network of DEGs. The expression of RPL15 and RPL18 was also found significantly decreased in calcified aortic valve tissues (both p < .01), and negatively correlated with the osteogenic differentiation marker OPN in CAVD patients (both p < .01). Moreover, inhibition of RPL15 or RPL18 exacerbated the calcification of valve interstitial cells under osteogenic induction conditions. The present study proved that decreased expression of RPL15 and RPL18 was closely associated with aortic valve calcification, which provided valuable clues to find therapeutic targets for CAVD.

[Vertical Differences in Grassland Bacterial Community Structure During Non- Growing Season in Eastern Ulansuhai Basin].

Grassland is an important part of the regional ecosystem, and its micro ecological structures play key roles in the process of element migration and the evolution of ecological diversity systems. To discover the spatial difference of the grassland soil bacterial community, we collected five total soil samples at 30 cm depth and 60 cm depth in Eastern Ulansuhai Basin in early May (before the beginning of the new growing season, with a minimum influence of human activities and other factors). Based on 16S rRNA gene-based high-throughput sequencing technology, the vertical characteristic of the bacterial community was analyzed in detail. First, Actinobacteriota, Proteobacteria, Chloroflexi, Acidobacteriota, Gemmatimonadota, Planctomycetota, Methylomirabilota, and Crenarchacota all appeared in the 30 cm and 60 cm samples, with the relative contents all being higher than 1%. In addition, there were a total of six phyla, five genera, and eight OTUs in the 60 cm sample with relative contents higher than those in the 30 cm sample. As a result, the relative abundance changes in dominant bacterial phyla, genera, and even OTUs at different sample depths did not correspond to their contribution to the bacterial community structure. Second, because of the unique contribution to the bacterial community structure in 30 cm and 60 cm samples, the norank_f__norank_o__norank_c__norank_p__Armatimonadota and Candidatus_Xiphinematobacter could be utilized as key bacterial genera during ecological system analysis, belonging to the Armatimonadota and Verrucomicrobiota, respectively. Finally, the relative abundances of ko00190, ko00910, and ko01200 were all higher in 60 cm samples than those in 30 cm samples, which showed that through the increase in metabolic function abundance, the relative contents of C, N, and P elements in grassland soil had been reduced with the increase in depth. These results will provide references for further study on the spatial change of bacterial communities in typical grassland.

Long-term outcomes after aortic valve surgery in patients with aortic regurgitation with preserved ejection fraction and left ventricular dilation.

OBJECTIVES: This study aims to assess the long-term outcomes and prognostic predictors of asymptomatic patients with severe aortic regurgitation (AR) accompanied by left ventricular ejection fraction (LVEF) ≥ 55% and left ventricular end-diastolic diameter (LVEDD) > 65 mm undergoing aortic valve replacement (AVR). METHODS: We retrospectively studied 291 consecutive asymptomatic patients with severe AR accompanied by LVEF ≥ 55% and LVEDD > 65 mm undergoing AVR from January 2000 to December 2013. The long-term outcomes and prognostic predictors were evaluated. RESULTS: There were 2 (0.7%) in-hospital deaths caused by multiple organ failure. The overall survival rate was 95.2% at 5 years, 89.9% at 10 years, 85.9% at 15 years, and 85.9% at 20 years. The left ventricular end-systolic volume index (LVESVi) was an independent predictor of overall mortality, with 59 ml/m2 being the best cut-off value. The left ventricular (LV) dimension decreased within 1 year after surgery and sustained thereafter. There were 15.5% of patients had incomplete LV reverse remodeling. LVESVi was an independent predictor of incomplete LV reverse remodeling, with 56 ml/m2 being the best cut-off value. CONCLUSIONS: AVR can be performed with an acceptable outcome in patients with severe AR accompanied by LVEF ≥ 55% and LVEDD > 65 mm. The LVESVi has the best predictive value for prognosis and the cut-off value is 59 ml/m2, and has the best predictive value for incomplete LV reverse remodeling and the cut-off value is 56 ml/m2.

Bayesian learners in gradient boosting for linear mixed models.

Selection of relevant fixed and random effects without prior choices made from possibly insufficient theory is important in mixed models. Inference with current boosting techniques suffers from biased estimates of random effects and the inflexibility of random effects selection. This paper proposes a new inference method "BayesBoost" that integrates a Bayesian learner into gradient boosting with simultaneous estimation and selection of fixed and random effects in linear mixed models. The method introduces a novel selection strategy for random effects, which allows for computationally fast selection of random slopes even in high-dimensional data structures. Additionally, the new method not only overcomes the shortcomings of Bayesian inference in giving precise and unambiguous guidelines for the selection of covariates by benefiting from boosting techniques, but also provides Bayesian ways to construct estimators for the precision of parameters such as variance components or credible intervals, which are not available in conventional boosting frameworks. The effectiveness of the new approach can be observed via simulation and in a real-world application.

Mitral valve repair and concomitant maze procedure versus catheter ablation in the treatment of atrial functional mitral regurgitation.

BACKGROUND: To compare mitral valve (MV) repair and concomitant maze procedure with catheter ablation in treating patients with atrial functional mitral regurgitation (AFMR). METHODS: We retrospectively identified 126 patients with AFMR from January 2012 to December 2015. Of these patients, 60 patients underwent MV repair and concomitant maze procedure, and 66 patients received catheter ablation. Patients were followed up for 7.98 ± 2.01 years. The survival, readmission of heart failure (HF), persistent atrial fibrillation (AF), persistent moderate-severe mitral regurgitation (MR) and tricuspid Regurgitation (TR), and echocardiographic data were analyzed in the follow-up. Predictors of readmission of HF were analyzed. RESULTS: There was no significant difference in baseline and echocardiographic characteristics, in-hospital mortality, and other adverse events postoperatively between two groups. The surgical group was associated with lower rates of MR > 2 + grade either at discharge (P = 0.0023) or in the follow-up (P = 0.0001). There was no significant difference in the incidence of overall survival between the two groups. The surgical group was associated with a lower rate of readmission of HF and AF in the follow-up. Univariable and multivariable analysis confirmed AF at discharge, moderate-severe MR at discharge, no MV surgery, moderate-severe TR at discharge, and LA volume as predictors of readmission of HF. Both groups experienced significant reverse cardiac remodeling. CONCLUSIONS: Our results suggest that for the treatment of AFMR with persistent or long-standing persistent AF and moderate-severe MR, MV repair and concomitant maze procedure may achieve a better outcome than catheter ablation procedure.

Low-Temperature Solution-Processed Cu2AgBiI6 Films for High Performance Photovoltaics and Photodetectors.

Recently, Cu2AgBiI6 semiconductor has been investigated due to the high absorption coefficient, direct bandgap, and low exciton binding energy, which are promising for eco-friendly photoelectric devices. Herein, pyridine is introduced as solvent additive to completely dissolve the solutes and form clear Cu2AgBiI6 precursor solution, which results in high-quality films and may provide a general approach for high-quality film growth of other bismuth-based metal halide semiconductors. In addition, the electronic structure of Cu2AgBiI6 has been demonstrated for the first time and shows an intrinsically weak n-type semiconductor. Furthermore, phenethylammonium iodide for surface passivation significantly improves the film quality, slightly n-dopes the material, and shifts up the band level. Finally, the photovoltaics and photodetector performance for n-i-p planar heterojunction devices have been investigated. The efficiency is up to 1%, highest for Cu2AgBiI6 solar cells and comparable with other lead-free bismuth based metal halide solar cells. Moreover, photodetectors with fast speed of rising and decaying time, especially the excellent specific photodetectivity of ∼1012 Jones within the wavelength of ∼350-600 nm, are achieved, which paves an alternative and promising strategy for the design of future commercial photodetectors that are self-powered, stable, nontoxic, etc.

[Characteristics of Bacterial Community Structure in Wuliangsu Lake During an Irrigation Interval in Hetao Plain].

In order to study the bacterial community composition and corresponding function in Wuliangsu Lake at the end of the Hetao Plain during the irrigation gap period, lake samples were collected in September 2020, and the pH, TN, TP, DIP, DTP, NH4+-N, Chla, EC, SAL, and other indicators were analyzed. The 16S rRNA high-throughput sequencing method was used to explore the attached bacteria and bacterioplankton in 15 samples of the surface water in Wuliangsu Lake. The experimental results showed that:① the alpha diversity Chao and Shannon indices of attached bacteria were greater than that of bacterioplankton, but the median of Shannoneven index was the same. ② In each sampling point, the bacterioplankton of Proteobacteria and Actinobacteria in the top five dominant bacteria phyla were higher than that of attached bacteria, and the abundance of attached bacteria and bacterioplankton of Bacteroidota were staggered. On the contrary, the contents of attached bacteria of Verrucomicrobiota and Cyanobacteria were all higher than that of bacterioplankton. ③ Redundant analysis showed that pH had the most significant effect on dominant attached bacteria, and the effect of conductivity and salinity in dominant bacterioplankton was the most significant. ④ PICRUSt2 function prediction analysis showed that attached bacteria and planktonic bacteria had the strongest metabolic functions, showing abundant metabolic functions. There were 29 nitrogen-related effective KOs and 88 phosphorus-related effective KOs, with the greatest nitrogen-fixing function and strong inorganic phosphorus-dissolving function, and bacterioplankton played a greater role in the two functions.

Weighted envelope spectrum based on the spectral coherence for bearing diagnosis.

The key idea behind demodulation analysis for bearing diagnosis is to determine the fault-induced frequency band and directly detect the potential bearing fault characteristic frequency (FCF) in the demodulated spectrum. Till now, most demodulation methods are based on the optimal selection of only one informative frequency band. However, the unwanted in-band noise will be retained or some fault information may be ignored in the case of the discrete resonant frequency band or multiple informative frequency bands. To address the issue, a FCF-oriented criterion is proposed to determine all the informative frequency bands rather than only one specified frequency band. A new weighting vector is obtained to control the contribution of each spectral frequency in the demodulated spectrum. Subsequently, a weighted envelope spectrum (WES) is introduced by integrating the spectral correlation over the full spectral frequency band and assigning the new weighting vector on each spectral frequency. In this way, all frequency components with fault information are enhanced while other components are inhibited. Furthermore, expanded to the diagnosis of compound-fault, the FCF-oriented criterion can provide the different weighting vectors relevant to the different potential faults, and the separated fault features can be identified directly in the generated WESs. Finally, the advantages of WES over the traditional methods are testified by the simulated signal and experimental data.

Noninvasive preoperative differential diagnosis of gallbladder carcinoma and xanthogranulomatous cholecystitis: A retrospective cohort study of 240 patients.

BACKGROUND: Xanthogranulomatous cholecystitis (XGC) is an extremely rare entity. Due to XGC's clinical and radiological resemblance to gallbladder carcinoma (GBC), intraoperative frozen section during cholecystectomy is often performed to exclude the diagnosis of GBC. Our study is aiming to find a noninvasive indicator of XGC. To our knowledge, this is the largest XGC cohort ever studied. METHODS: This study retrospectively collected clinical characteristics, serological tests, and imaging features of 150 GBC patients and 90 XGC patients. The diagnosis of these 150 GBC patients and 90 XGC patients was based on intraoperative frozen section histopathology. T-test was utilized to compare differences between XGC and GBC. Receiver operating characteristic (ROC) curve was conducted and the area under the curve (AUC) was managed to evaluate the validity. RESULTS: The carcinoembryonic antigen (CEA) level in blood tests was significantly elevated in GBC patients than in XGC patients (p = 0.007). The presence of submucosal hypo-attenuated nodules (80% in XGC, 16% in GBC, p < 0.001), low density border (60% in XGC, 21% in GBC, p = 0.001), and nodular thickening in the bottom of the gallbladder with calcification (70% in XGC, 37% in GBC, p = 0.004) is significantly associated with XGC patients, whereas massive hilar infiltration (0% in XGC, 21% in GBC, p < 0.001), multiple lymph nodes in the hilar area (10% in XGC, 72% in GBC, p = 0.001), and gallbladder mucosal line continuity (50% in XGC, 95% in GBC, p = 0.002) are highly associated with GBC patients. The ROC curve was performed and the gallbladder mucosal line continuity (AUC = 0.708) and the AUC of low density border around the occupation (AUC = 0.654) showed a good prediction of XGC. CONCLUSIONS: Gallbladder mucosal line continuity and low density border around the occupation presented good indication value for the diagnosis of XGC. Our study proposed a noninvasive differential diagnosis method for XGC and GBC.

Unravelling the collateral damage of antibiotics on gut bacteria.

Antibiotics are used to fight pathogens but also target commensal bacteria, disturbing the composition of gut microbiota and causing dysbiosis and disease1. Despite this well-known collateral damage, the activity spectrum of different antibiotic classes on gut bacteria remains poorly characterized. Here we characterize further 144 antibiotics from a previous screen of more than 1,000 drugs on 38 representative human gut microbiome species2. Antibiotic classes exhibited distinct inhibition spectra, including generation dependence for quinolones and phylogeny independence for ß-lactams. Macrolides and tetracyclines, both prototypic bacteriostatic protein synthesis inhibitors, inhibited nearly all commensals tested but also killed several species. Killed bacteria were more readily eliminated from in vitro communities than those inhibited. This species-specific killing activity challenges the long-standing distinction between bactericidal and bacteriostatic antibiotic classes and provides a possible explanation for the strong effect of macrolides on animal3-5 and human6,7 gut microbiomes. To mitigate this collateral damage of macrolides and tetracyclines, we screened for drugs that specifically antagonized the antibiotic activity against abundant Bacteroides species but not against relevant pathogens. Such antidotes selectively protected Bacteroides species from erythromycin treatment in human-stool-derived communities and gnotobiotic mice. These findings illluminate the activity spectra of antibiotics in commensal bacteria and suggest strategies to circumvent their adverse effects on the gut microbiota.

RIPK1 activation mediates neuroinflammation and disease progression in multiple sclerosis.

Receptor interacting protein kinase 1 (RIPK1) mediates cell death and inflammatory signaling and is increased in multiple sclerosis (MS) brain samples. Here, we investigate the role of glial RIPK1 kinase activity in mediating MS pathogenesis. We demonstrate RIPK1 levels correlate with MS disease progression. We find microglia are susceptible to RIPK1-mediated cell death and identify an inflammatory gene signature that may contribute to the neuroinflammatory milieu in MS patients. We uncover a distinct role for RIPK1 in astrocytes in regulating inflammatory signaling in the absence of cell death and confirm RIPK1-kinase-dependent regulation in human glia. Using a murine MS model, we show RIPK1 inhibition attenuates disease progression and suppresses deleterious signaling in astrocytes and microglia. Our results suggest RIPK1 kinase activation in microglia and astrocytes induces a detrimental neuroinflammatory program that contributes to the neurodegenerative environment in progressive MS.

Aspirin plus ticagrelor or clopidogrel on graft patency one year after coronary bypass grafting: a single-center, randomized, controlled trial.

BACKGROUND: Dual antiplatelet therapy (DAPT) improves early post-operative graft patency, but the optimal DAPT strategy for the patients after coronary artery bypass grafting (CABG) has not been confirmed. We sought to evaluate the effect of aspirin plus ticagrelor versus aspirin plus clopidogrel on saphenous vein graft (SVG) patency within 1 year after CABG. METHODS: Between October 2017 and December 2018, 147 consecutive patients undergoing elective CABG at Changhai Hospital were randomized into two groups: group AT, receiving aspirin 100 mg/d plus ticagrelor 2×90 mg/d; group AC, receiving aspirin 100 mg/d plus clopidogrel 75 mg/d. Both DAPTs should be administered within 24 h when clinical stability was ensured. 64-multislice computed tomography angiography (MSCTA) was used to assess the graft patency at 12 months after CABG.CYP2C19 gene variants were measured to assess the clopidogrel efficacy on graft patency. RESULTS: Among the 147 participants who completed the study, one (0.7%) patient from the AC group died at 5 weeks after surgery due to severe infection. All other patients were treated with DAPT for 12 months and underwent 64-MSCTA according to schedule. There were no significant differences in pre-operative characteristics and intraoperative transit-time flow measurement findings between the two groups. Besides, no significant differences in the incidence of major adverse cardiac events (MACEs) and major bleeding were observed. A 64-MSCTA showed that SVG patency was 91.0% (141 of 155) in the AT group and 89.9% (161 of 179) in the AC group (P=0.751). No significant associations were found between different CYP2C19 genotypes and SVG patency (P>0.05). CONCLUSIONS: Either aspirin plus ticagrelor or aspirin plus clopidogrel can maintain a fairly high graft patency rate in the early phase after CABG, regardless of CYP2C19 genotypes.

Prostaglandin E2 stimulates cAMP signaling and resensitizes human leukemia cells to glucocorticoid-induced cell death.

Glucocorticoid (GC) resistance remains a clinical challenge in pediatric acute lymphoblastic leukemia where response to GC is a reliable prognostic indicator. To identify GC resistance pathways, we conducted a genome-wide, survival-based, short hairpin RNA screen in murine T-cell acute lymphoblastic leukemia (T-ALL) cells. Genes identified in the screen interfere with cyclic adenosine monophosphate (cAMP) signaling and are underexpressed in GC-resistant or relapsed ALL patients. Silencing of the cAMP-activating Gnas gene interfered with GC-induced gene expression, resulting in dexamethasone resistance in vitro and in vivo. We demonstrate that cAMP signaling synergizes with dexamethasone to enhance cell death in GC-resistant human T-ALL cells. We find the E prostanoid receptor 4 expressed in T-ALL samples and demonstrate that prostaglandin E2 (PGE2) increases intracellular cAMP, potentiates GC-induced gene expression, and sensitizes human T-ALL samples to dexamethasone in vitro and in vivo. These findings identify PGE2 as a target for GC resensitization in relapsed pediatric T-ALL.

Period-oriented multi-hierarchy deconvolution and its application for bearing fault diagnosis.

Deconvolution methods have been proven to be effective tools to extract excitation sources from the noisy measured signal. However, its application is confined by the extraction of incomplete information. To tackle this problem, a new deconvolution method, named period-oriented multi-hierarchy deconvolution (POMHD) is proposed in this paper. Various filters are designed adaptively by the iterative algorithm to update the filter coefficient using the harmonic-to-noise ratio as the deconvolution orientation. Additionally, a novel index, called normalized proportion of harmonics, is proposed as the evaluation criteria for the fault feature. Based on upon, a harmonics proportion diagram is constructed for the diagnostic decisions. The new deconvolution method overcomes the disadvantages of the traditional methods. More importantly, without an accurate fault period as the prior knowledge, the proposed POMHD can simultaneously extract multiple latent fault components by using the adaptive filter and intuitively present different fault information in one diagram. Finally, the simulated and experimental data which includes the signals collected from bearings with both single faults and compound faults is used to evaluate the new method. The results validate the feasibility and robustness of the proposed POMHD.

Dysregulated long non-coding RNAs involved in regulation of matrix degradation during type-B aortic dissection pathogenesis.

Thoracic aortic dissection (TAD) is a catastrophic disease with the rupture of aortic media resulted mainly from the degradation of extracellular matrix. With the deep study of long non-coding RNAs (lncRNAs) in cardiovascular diseases, the correlation between lncRNAs and the TAD pathogenesis is under revealed. In this study, we aimed to screen the differentially expressed lncRNAs involved in the regulation of matrix degradation during type-B aortic dissection (TBAD), whose pathogenesis is more similar to atherosclerosis. A total of 393 aberrantly expressed lncRNAs and 432 aberrantly expressed mRNAs were identified in the descending aortic samples from TBAD patients. Then, co-expression analysis was applied to analyze the correlation between the top five differentially expressed lncRNAs and aberrantly expressed mRNAs, so as to screen the lncRNAs involved in the regulation of matrix degradation. The results showed that two transcripts from lnc-TNFSF14 (lnc-TNFSF14-2, and lnc-TNFSF14-3) were negatively interacted with MMP14 and MMP19. Subsequently, quantitative real-time PCR assay confirmed that lnc-TNFSF14-2 were negatively correlated with MMP14 (rs = - 0.8180) and MMP19 (rs = - 0.8449), and lnc-TNFSF14-3 was also negatively correlated with MMP14 (rs = - 0.7098) and MMP19 (rs = - 0.7728) in descending aorta from TBAD patients (n = 20). Overall, our study found the aberrant lncRNAs expression profiles in TBAD, and identified lnc-TNFSF14 as a potential target regulating matrix degradation. The results also provided crucial clues for lncRNAs function research on TBAD development.

Transcribed ultraconserved region uc.242 is a novel regulator of cardiomyocyte hypertrophy induced by angiotensin II.

Cardiomyocyte hypertrophy is a response to stress or hormone stimulation and is characterized by an increase of cardiomyocyte size. Abnormal long non-coding RNA (lncRNA) expression profile has been identified in various cardiovascular diseases. Though some lncRNAs had been reported to participate in regulation of cardiac hypertrophy, the universal lncRNA profile of cardiomyocyte hypertrophy had not been established. In the present study, we aimed to identify the differentially expressed lncRNA-mRNA network in angiotensin II-stimulated cardiomyocytes, and screen the potential lncRNAs involved in regulation of cardiomyocyte hypertrophy. The hypertrophic cardiomyocytes were induced by angiotensin II (0.1 µmol/L) for 48 hours. High-throughput microarray analysis combined with quantitative real-time PCR assay were then performed to screen the differentially expressed lncRNAs and mRNAs. A total of 1577 lncRNAs and 496 mRNAs transcripts were identified differentially expressed in hypertrophic cardiomyocytes. Among them, 59 transcribed ultraconserved non-coding RNAs (T-UCRs) were found by evolutionary conservation analysis. Subsequently, the lncRNA-mRNA coexpression network was constructed based on Pearson's correlation analysis results, including 4 T-UCRs and 215 mRNAs. The results revealed that uc.242 was positively interacted with prohypertrophic genes (Hgf and Tnc). Functional study showed that inhibition of uc.242 dramatically decreased hypertrophic marker expression levels and cardiomyocyte surface area under the condition of angiotensin II stimulation. The expression of Hgf and Tnc was also decreased in cardiomyocytes after silencing of uc.242. Summarily, the present study provided crucial clues to explore therapeutic targets for pathological cardiac hypertrophy.