miR-212 Promotes Cardiomyocyte Hypertrophy through Regulating Transcription Factor 7 Like 2.

To explore the role and possible mechanism of miRNA-212 in heart failure (HF). The rat model of abdominal aortic constriction was constructed, the changes of myocardial morphology were observed by hematoxylin-eosin (HE) staining, and the hypertrophy-related marker molecules were detected by quantitative real-time polymerase chain reaction (qRT-PCR). At the cellular level, phenylephrine and angiotensin II were added to induce cardiomyocyte hypertrophy. The overexpression of miR-212 adenovirus was constructed, and the expression of miR-212 was overexpressed, and its effect on cardiac hypertrophy (CH) was detected by immunofluorescence and qRT-PCR. Then, the mechanism of miR-212 regulating CH was verified by website prediction, luciferase reporter gene assay, qRT-PCR, and western blotting assay. In the successfully constructed rat model of abdominal aortic constriction and cardiomyocyte hypertrophy, ANP and myh7 were dramatically increased, myh6 expression was decreased, and miRNA-212 expression was increased. Overexpression of miRNA-212 in cardiomyocytes can promote cardiomyocyte hypertrophy, while knocking down miR-212 in cardiomyocytes can partially reverse cell hypertrophy. In addition, miR-212 targets TCF7L2 and inhibits the expression of this gene. miRNA-212 targets TCF7L2 and inhibits the expression of this gene, possibly through this pathway to promote cardiomyocyte hypertrophy.

Analysis on the polymorphisms of site RS4977574, and RS1333045 in region 9p21 and the susceptibility of coronary heart disease in Chinese population.

BACKGROUND: Rs4977574 (A > G) and Rs1333045 (C > T) are both single nucleotide polymorphisms (SNPs) related with coronary artery disease, locating on chromosome 9p21.3. The study aimed to identify the correlation between rs4977574 and rs1333045 polymorphism genotypes and coronary heart disease (CHD) in a Chinese population. METHODS: Blood samples were collected from 855 subjects. A case-control study was used in this experiment, and 598 cases in the CHD group and 257 subjects in the control group were enrolled. Genotyping was identified by the Agena MassARRAY system. Statistical analysis was conducted by SPSS (Ver 16.0) and plink (Ver. 1.07, Shaun Purcell). Haplotype analysis was performed using Haploview software. RESULTS: Association analysis by plink indicated a significant difference in the allele distribution for single nucleotide polymorphisms between cases and controls (rs4977574 P = 0.003, rs1333045 P = 0.035). Fisher's exact test by plink proved that allele G may be associated with a higher risk of CHD (P = 0.003, odds ratio (OR) = 1.371) and the T allele was likely to reduce the risk of coronary events (P = 0.035, OR = 0.798). The serum levels of apolipoprotein A (ApoA) were higher in subjects with the AG + AA genotype of rs4977574 compared to those with the GG genotype (P = 0.028). In the dominant model of rs1333045, the levels of ApoA were higher and LDL levels were lower in the TC + TT genotype than in the CC genotype. CONCLUSIONS: The present study examined the association between the 9p21 chromosome rs4977574 and rs1333045 polymorphism genotypes and CHD in a population of Chinese patients. The G allele of rs4977574 and the C allele of rs1333045 are the susceptibility sites of CHD.

The effectiveness of quarantine of Wuhan city against the Corona Virus Disease 2019 (COVID-19): A well-mixed SEIR model analysis.

A novel coronavirus pneumonia, first identified in Wuhan City and referred to as COVID-19 by the World Health Organization, has been quickly spreading to other cities and countries. To control the epidemic, the Chinese government mandated a quarantine of the Wuhan city on January 23, 2020. To explore the effectiveness of the quarantine of the Wuhan city against this epidemic, transmission dynamics of COVID-19 have been estimated. A well-mixed "susceptible exposed infectious recovered" (SEIR) compartmental model was employed to describe the dynamics of the COVID-19 epidemic based on epidemiological characteristics of individuals, clinical progression of COVID-19, and quarantine intervention measures of the authority. Considering infected individuals as contagious during the latency period, the well-mixed SEIR model fitting results based on the assumed contact rate of latent individuals are within 6-18, which represented the possible impact of quarantine and isolation interventions on disease infections, whereas other parameter were suppose as unchanged under the current intervention. The present study shows that, by reducing the contact rate of latent individuals, interventions such as quarantine and isolation can effectively reduce the potential peak number of COVID-19 infections and delay the time of peak infection.

Quantitative proteomics reveals the regulatory networks of circular RNA BTBD7_hsa_circ_0000563 in human coronary artery.

BACKGROUND: BTBD7_hsa_circ_0000563, which is located on chromosome 14, contains conserved binding sites with miR-155/130a and RNA-binding proteins according to bioinformatic prediction. We investigated the association of BTBD7_hsa_circ_0000563 expression in coronary artery segments with atherosclerotic stenosis and identified the proteome-wide BTBD7_hsa_circ_0000563-regulated proteins in human coronary artery. METHODS: The atherosclerotic grade and extent in coronary artery segments were determined by hematoxylin and eosin staining. BTBD7_hsa_circ_0000563 expression in eight coronary artery segments from one patient was quantified by RT-qPCR assay. A proteomic approach was adopted to reveal significant differences in protein expression between among four groups differing in their BTBD7_hsa_circ_0000563 expression levels. RESULTS: The RT-qPCR assay revealed that coronary artery segments with severe atherosclerotic stenosis had significantly low BTBD7_hsa_circ_0000563 levels. The proteomic analysis identified 49 differentially expressed proteins among the segment groups with different BTBD7_hsa_circ_0000563 expression levels, of which 10 were downregulated and 39 were upregulated with increases in the BTBD7_hsa_circ_0000563 level. The 10 downregulated proteins were P61626 (LYSC_HUMAN), P02760 (AMBP_HUMAN), Q02985 (FHR3_HUMAN), P01701 (LV151_HUMAN), P06312(KV401_HUMAN), P01624 (KV315_HUMAN), P13671 (CO6_HUMAN), P01700(LV147_HUMAN), Q9Y287(ITM2B_HUMAN), and A0A075B6I0 (LV861_HUMAN). The top 10 upregulated proteins were Q92552 (RT27_HUMAN), Q9UJY1(HSPB8_HUMAN), Q9Y235(ABEC2_HUMAN), P19022 (CADH2_HUMAN), O43837(IDH3B_HUMAN), Q9H479(FN3K_HUMAN), Q9UM22(EPDR1_HUMAN), P48681(NEST_HUMAN), Q9NRP0(OSTC_HUMAN), and Q15628(TRADD_HUMAN). CONCLUSION: BTBD7_hsa_circ_0000563 is involved in the atherosclerotic changes in human coronary artery segments. Verification, mechanistic, and function studies are needed to confirm whether patients with coronary artery disease would benefit from such personalized medicine in the future.

Mir-21 Promotes Cardiac Fibrosis After Myocardial Infarction Via Targeting Smad7.

BACKGROUND/AIMS: Cardiac fibrosis after myocardial infarction (MI) has been identified as an important factor in the deterioration of heart function. Previous studies have demonstrated that miR-21 plays an important role in various pathophysiological processes in the heart. However, the role of miR-21 in fibrosis regulation after MI remains unclear. METHODS: To induce cardiac infarction, the left anterior descending coronary artery was permanently ligated of mice. First, we explored the expression of miR-21 in the infarcted zone in mice model of MI via RT-qPCR. Next, we examined the effects of TGF-ß1 on miR-21 expression in cardiac fibroblasts (CFs). Then, CFs were infected with miR-21 mimics or miR-21 inhibitors to investigate the effects of miR-21 on the process of CFs activation in vitro. Further, bioinformatics analysis and luciferase reporter assay were performed to identify and validate the target gene of miR-21. At last, in-vivo study was done to confirm MiR-21 regulated myocardial fibrosis after MI in mice. RESULTS: MiR-21 was up-regulated in the infarcted zone after MI in vivo. TGF-ß1 treatment increased miR-21 expression in CFs. Overexpression of miR-21 promoted the effects of TGF-ß1-induced activation of CFs, evidenced by increased expression of Col-1, α-SMA and F-actin, whereas inhibition of miR-21 attenuated the process of fibrosis. Bioinformatics, Western blot analysis and luciferase reporter assay demonstrated that Smad7 is a direct target of miR-21. In addition, in-vivo study revealed that MiR-21 regulated myocardial fibrosis after MI in mice. CONCLUSION: These findings suggested that miR-21 has a critical role in CF activation and cardiac fibrosis after MI through via TGF-ß/Smad7 signaling pathway. Thus, miR-21 promises to be a potential therapy in treatment of cardiac fibrosis after MI.

Schwann Cells Transplantation Improves Locomotor Recovery in Rat Models with Spinal Cord Injury: a Systematic Review and Meta-Analysis.

BACKGROUND/AIMS: Schwann cells (SCs) which were demonstrated to be responsible for axonal myelination and ensheathing are widely studied and commonly used for cell transplantation to treat spinal cord injury (SCI). We performed this meta-analysis to summarize the effects of SCs versus controls for locomotor recovery in rat models of traumatic SCI. METHODS: Studies of the BBB scores after transplantation of SCs were searched out from Pubmed, Cochrane Library Medline databases and analyzed by Review Manager 5.2.5. RESULTS: Thirteen randomized controlled animal trials were selected with 283 rats enrolled. The studies were divided to different subgroups by different models of SCI, different cell doses for transplantation, different sources of SCs and different transplantation ways. The pooled results of this meta-analysis suggested that SCs transplantation cannot significantly improve the locomotor recovery at a short time after intervention (1 week after transplantation) in both impacted and hemi-sected SCI models. However, at a longer time after intervention (3, 5-7 and over 8 weeks after transplantation), significant improvement of BBB score emerged in SCs groups compared with control groups. Subgroup analyses revealed that SCs transplantation can significantly promote locomotor recovery regardless of in high or low doses of cells, from different sources (isolated from sciatic nerves or differentiated from bone marrow stromal cells(BMSCs)) and with or without scaffolding. CONCLUSION: SCs seem to demonstrate substantial beneficial effects on locomotor recovery in a widely-used animal models of SCI.

Wearable Triboelectric Visual Sensors for Tactile Perception.

Tactile sensors with visible light feedback functions, such as wearable displays and electronic skin and biomedical devices, are becoming increasingly important in various fields. However, existing methods cannot meet the application requirements for the tactile perception of intensity feedback and extended intersection due to their limited light-mapping performance and insufficient portability. Herein, a freely constructible self-powered visual tactile sensor is proposed, which consists of a high-output triboelectric nanogenerator (TENG) and a visual light source. The transferred charge of the TENG is enhanced to 746 nC by the structural design of the triboelectric material and device, which can easily drive the light source to generate a light signal with a brightness of 9.8 cd m-2 . Notably, the application of the TENG enables to realization visual sensing of the palm-grasp state and strength feedback without an external power supply. This visual feedback and power-free tactile sensors are expected to have potential application in the field of artificial intelligence as a new interactive medium for smart protective clothing and robotics.

Fabrication of Advanced Cellulosic Triboelectric Materials via Dielectric Modulation.

The rapid rise of triboelectric nanogenerators (TENGs), which are emerging energy conversion devices in advanced electronics and wearable sensing systems, has elevated the interest in high-performance and multifunctional triboelectric materials. Among them, cellulosic materials, affording high efficiency, biodegradability, and customizability, are becoming a new front-runner. The inherently low dielectric constant limits the increase in the surface charge density. However, owing to its unique structure and excellent processability, cellulose shows great potential for dielectric modulation, providing a strong impetus for its advanced applications in the era of Internet of Things and artificial intelligence. This review aims to provide comprehensive insights into the fabrication of dielectric-enhanced cellulosic triboelectric materials via dielectric modulation. The exceptional advantages and research progress in cellulosic materials are highlighted. The effects of the dielectric constant, polarization, and percolation threshold on the charge density are systematically investigated, providing a theoretical basis for cellulose dielectric modulation. Typical dielectric characterization methods are introduced, and their technical characteristics are analyzed. Furthermore, the performance enhancements of cellulosic triboelectric materials endowed by dielectric modulation, including more efficient energy harvesting, high-performance wearable electronics, and impedance matching via material strategies, are introduced. Finally, the challenges and future opportunities for cellulose dielectric modulation are summarized.

Network pharmacological analysis of Xuefu Zhuyu decoction in the treatment of atherosclerosis.

Objective: Using a network pharmacological approach, this study will evaluate the effect of Xuefu Zhuyu Decoction in the treatment of atherosclerosis. Methods: The data were imported into the STRING database to construct a protein-protein interaction network, and the network topology was analysed with the Bisogenet plug-in by Cytoscape 3.7.2. Using the R language Bioconductor platform, Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis for potential targets of Xuefu Zhuyu Decoction in the treatment of atherosclerosis were performed, and import the results were imported into Cytoscape 3.7.2. To map the results and create a KEGG network diagram, we used Cytoscape 3.7.2 for analysis. Results: A total of 91 chemical components and 1320 disease targets were obtained, including 138 cross-targets. TNF, AKT1 and ALB were identified as important targets, and Gene Ontology functional analysis indicated that biological process was the primary cause of oxidative stress. The primary action of molecular function is binding. KEGG has explored and enriched 149 signalling pathways, including the AGE-RAGE signalling system and the TNF signalling network. According to a study involving molecular docking, quercetin and ß-carotene have a strong binding affinity for AKT1 and ALB. Conclusion: The potential of Xuefu Zhuyu Decoction to treat atherosclerosis through multiple components and targets provides a way to further study its mechanism.

Carbon Black/Multi-Walled Carbon Nanotube-Based, Highly Sensitive, Flexible Pressure Sensor.

Flexible piezoresistive pressure sensors have promising applications in wearable devices, artificial intelligence, and other fields. However, developing low-cost and high-performance pressure sensors still poses a great challenge. Herein, we utilize low-cost carbon black (CB) and multi-walled carbon nanotubes (MWCNTs) mixed in porous polydimethylsiloxane to assemble a flexible piezoresistive pressure sensor combined with interdigitated electrodes. Simultaneously, the COMSOL Multiphysics simulation analysis was performed to predict the sensing behavior of the pressure sensor, which was verified by experiments; the preparation of the pressure sensor was guided according to the prediction. Additionally, we studied the effects of the mixed conductive filler's weight ratio, the shape of the interdigital electrode, and the line width and spacing of the interdigital electrode on the performance of the sensor. Based on the interaction of the 3D porous structure and the synergistic conductive network of CB/MWCNTs, the prepared pressure sensor exhibits a high sensitivity of 3.57 kPa-1 (∼21 kPa), a wide detection range of 0-275 kPa, fast response time (96 ms), fast recovery time (198 ms), good durability (about 3000 cycles), and good flexibility. Moreover, the fabricated sensor can monitor and recognize human activities (such as finger bending and mouse clicking), indicating that it has great potential in flexible wearable devices and other fields. It is worth noting that the preparation process of the entire pressure sensor was simple, low cost, and environmentally friendly, which provides a certain basis for industrial and commercial applications.

Sludge Derived Carbon Modified Anode in Microbial Fuel Cell for Performance Improvement and Microbial Community Dynamics.

The conversion of activated sludge into high value-added materials, such as sludge carbon (SC), has attracted increasing attention because of its potential for various applications. In this study, the effect of SC carbonized at temperatures of 600, 800, 1000, and 1200 °C on the anode performance of microbial fuel cells and its mechanism are discussed. A pyrolysis temperature of 1000 °C for the loaded electrode (SC1000/CC) generated a maximum areal power density of 2.165 ± 0.021 W·m-2 and a current density of 5.985 ± 0.015 A·m-2, which is 3.017- and 2.992-fold that of the CC anode. The addition of SC improves microbial activity, optimizes microbial community structure, promotes the expression of c-type cytochromes, and is conducive to the formation of electroactive biofilms. This study not only describes a technique for the preparation of high-performance and low-cost anodes, but also sheds some light on the rational utilization of waste resources such as aerobic activated sludge.

Effects of different N-acyl-serine lactone signaling molecules on the performance of anaerobic granular sludge.

Exogenous addition of acyl-homoserine lactone (AHL) signaling molecules can improve or inhibit the methane production performance of anaerobic granular sludge (AnGS) by quorum sensing (QS). To explore the specific effect of AHLs on AnGS, 2 µM of signal molecules were added to the reactor and we analyzed their effects on AnGS biodiversity, extracellular polymeric substance (EPS), specific methanogenic activity (SMA) and chemical oxygen demand (COD) removal rate of AnGS. The results indicated that the four types of AHLs improve the COD removal rate, SMA and organic composition of AnGS. The addition of N-(ß-ketocaproyl)-dl-homoserine lactone (3O-C6-HSL) yielded the greatest increase in methanogenic activity, reaching a maximum of 30.83%. The four types of AHLs stimulate the secretion of EPS in AnGS by group sensing regulation. The addition of N-hexanoyl-l-homoserine lactone (C6-HSL), N-octanoyl-dl-lactone (C8-HSL) and 3O-C6-HSL induced the enrichment of Actinobacteria. Thus, the process of hydrolysis and acidification of AnGS is accelerated. The addition of N-butyryl-dl-homoserine lactone (C4-HSL), C6-HSL and 3O-C6-HSL promote the potential methanogenic metabolic pathway of AnGS. The addition of all AHLs directly or indirectly enhanced the methane metabolism pathway of sludge and improved the specific methane generation activity of AnGS. These results are expected to provide preliminary research data for enhancing the methane production efficiency of reactors and enriching the biological activity of AnGS.

Proteomic landscape of human coronary artery atherosclerosis.

In order to investigate novel biomarkers for the detection of coronary artery disease for effective therapeutic targets, a comprehensive understanding of the protein networks and protein expression abundance in coronary artery samples is required. This was established by means of liquid chromatography (LC)­mass spectrometry (MS)/MS analysis in the present study. A total of 20 human coronary artery specimens from 2 autopsied adults were employed in the present study. The natural history and histological classification of the atherosclerotic lesions of the coronary artery samples were analyzed by hematoxylin and eosin (H&E) staining, and the human coronary arterial proteome and proteomics features were characterized by MS analysis. The present study identified 2,135 proteins in the 20 coronary artery segments samples from the 2 cases. Combined with the results of H&E staining of the coronary artery samples, a total of 174 proteins, including 4 upregulated proteins and 164 downregulated proteins (excluding 6 proteins with inconsistent expression tendencies), were shown to be associated with coronary artery disease. In addition, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment of the differentially expressed proteins revealed that the mitochondrial energy metabolism may be responsible for the occurrence and development of coronary artery atherosclerosis. The human coronary arterial proteome can be considered as a complex network whose architectural characteristics vary considerably as a function of the presence or absence, and histological classification of coronary artery atherosclerosis. These data thus suggest that the prevention of mitochondrial dysfunction via the retrieval of the mitochondrial associated proteins expression may be a promising target in coronary artery disease.

The epidemiological characteristics of cluster transmission of coronavirus disease 2019 (COVID-19): a multi-center study in Jiangsu Province.

Coronavirus Disease 2019 (COVID-19) pandemic has rapidly spread across the globe while little multi-center research about the epidemiological characteristics of cluster transmission is conducted. To provide a more comprehensive description of the epidemiological characteristics of cluster transmission and the virulence of SARS-CoV-2 carried by asymptomatic carriers, we studied the epidemiological characteristics of 70 clusters. 70 clusters including 311 consecutive subjects from January 20, 2020, to March 10, 2020, were enrolled. Of 70 clusters, 5 were infected by asymptomatic or presymptomatic carriers. We gathered and analyzed information about their demographic, epidemiological, clinical, diagnostic classification, and cluster characteristics. Among the 66 asymptomatic carriers in Jiangsu Province, 49 asymptomatic were observed in 311 subjects distributed in 70 clusters. We demonstrated that there is a significance between the severity of cases infected by asymptomatic carriers and cases infected by symptomatic patients (P=0.033) and the former usually presented with milder symptoms. A significant difference was shown regarding the level distribution of age (P=0.006) and the frequency distribution of gender (P=0.014) and disease severity of COVID-19 (P=0.008) among the seven groups classified by the relationship with the index cases. The average age of infected medical staff was the youngest and the majority of infected medical are females while the infected patients were generally oldest and usually accompanied by severest symptoms. We concluded that asymptomatic carriers are mainly screened out of clusters and the patients infected by asymptomatic carriers present with milder symptoms than those infected by symptomatic patients, which indicated that the SARS-CoV-2 shares decreased virulence among asymptomatic carriers. Effective measures should be taken to prevent transmission in hospitals to protect doctors, nurses, and patients.

Clinical and Autoimmune Characteristics of Severe and Critical Cases of COVID-19.

In this study we report on the clinical and autoimmune characteristics of severe and critical novel coronavirus pneumonia caused by severe acute respiratory syndrome-associated coronavirus 2 (SARS-CoV-2). The clinical, autoimmune, and laboratory characteristics of 21 patients who had laboratory-confirmed severe and critical cases of coronavirus disease 2019 (COVID-19) from the intensive care unit of the Huangshi Central Hospital, Hubei Province, China, were investigated. A total of 21 patients (13 men and 8 women), including 8 (38.1%) severe cases and 13 (61.9%) critical cases, were enrolled. Cough (90.5%) and fever (81.0%) were the dominant symptoms, and most patients (76.2%) had at least one coexisting disorder on admission. The most common characteristics on chest computed tomography were ground-glass opacity (100%) and bilateral patchy shadowing (76.2%). The most common findings on laboratory measurement were lymphocytopenia (85.7%) and elevated levels of C-reactive protein (94.7%) and interleukin-6 (89.5%). The prevalence of anti-52 kDa SSA/Ro antibody, anti-60 kDa SSA/Ro antibody, and antinuclear antibody was 20%, 25%, and 50%, respectively. We also retrospectively analyzed the clinical and laboratory data from 21 severe and critical cases of COVID-19. Autoimmune phenomena exist in COVID-19 subjects, and the present results provide the rationale for a strategy of preventing immune dysfunction and optimal immunosuppressive therapy.

Circular RNA profile in coronary artery disease.

Circular RNAs (circRNAs) are potential biomarkers and therapeutic targets of coronary artery disease due to their high stability, covalently closed structure. And implied roles in gene regulation. The aim of this study was to identify and characterize circRNAs from human coronary arteries. Epicardial coronary arteries were removed during the autopsy of an 81-year-old man who died from heart attack. The natural history and histological classification of atherosclerotic lesions in coronary artery segments were analyzed by hematoxylin and eosin staining, and their circRNA expression profiles were characterized by RNA sequencing. RNA sequencing identified 1259 annotated and 381 novel circRNAs. Combined with the results of histologic examination, intersection analysis identified 54 upregulated and 12 downregulated circRNAs, representing 4.0% of the total number. Coronary artery segments with or without severe atherosclerosis showed distinctly different circRNA profiles on the basis of hierarchical clustering. Our results suggest that these 66 circRNAs contribute to the pathology underlying coronary artery atherosclerosis and may serve as diagnostic or therapeutic targets in coronary artery disease.

Curcumin exerts its tumor suppressive function via inhibition of NEDD4 oncoprotein in glioma cancer cells.

Glioblastoma is the most common brain cancer in adults. It represents one of the top ten malignant tumors with an average survival time of nine months despite treatments with surgery, radiotherapy and chemotherapy. Curcumin is a phytochemical turmeric isolated from root of the Curcuma longa plant. Accumulating evidence have proved that curcumin targets numerous cancer signaling pathways. The E3 ubiquitin ligase NEDD4, neural precursor cell expressed developmentally downregulated protein 4, is frequently overexpressed in various cancers. However, whether curcumin regulates NEDD4 expression has not been described in human cancers. Therefore, in this study, we explored the roles of NEDD4 in glioma cell proliferation, apoptosis and mobility. We further investigated whether curcumin exerts its antitumor activities via suppressing NEDD4 expression. We found that curcumin reduced the expression of NEDD4 and Notch1 and pAKT, leading to glioma cell growth inhibition, apoptosis, and suppression of migration and invasion. Moreover, deletion of NEDD4 expression enhanced the sensitivity of glioma cells to curcumin treatment. Thus, inactivation of NEDD4 by curcumin could be a promising approach for therapeutic intervention.