LncRNA DCRT Protects Against Dilated Cardiomyopathy by Preventing NDUFS2 Alternative Splicing by Binding to PTBP1.

BACKGROUND: Dilated cardiomyopathy is characterized by left ventricular dilation and continuous systolic dysfunction. Mitochondrial impairment is critical in dilated cardiomyopathy; however, the underlying mechanisms remain unclear. Here, we explored the cardioprotective role of a heart-enriched long noncoding RNA, the dilated cardiomyopathy repressive transcript (DCRT), in maintaining mitochondrial function. METHODS: The DCRT knockout (DCRT-/-) mice and DCRT knockout cells were developed using CRISPR-Cas9 technology. Cardiac-specific DCRT transgenic mice were generated using α-myosin heavy chain promoter. Chromatin coimmunoprecipitation, RNA immunoprecipitation, Western blot, and isoform sequencing were performed to investigate the underlying mechanisms. RESULTS: We found that the long noncoding RNA DCRT was highly enriched in the normal heart tissues and that its expression was significantly downregulated in the myocardium of patients with dilated cardiomyopathy. DCRT-/- mice spontaneously developed cardiac dysfunction and enlargement with mitochondrial impairment. DCRT transgene or overexpression with the recombinant adeno-associated virus system in mice attenuated cardiac dysfunction induced by transverse aortic constriction treatment. Mechanistically, DCRT inhibited the third exon skipping of NDUFS2 (NADH dehydrogenase ubiquinone iron-sulfur protein 2) by directly binding to PTBP1 (polypyrimidine tract binding protein 1) in the nucleus of cardiomyocytes. Skipping of the third exon of NDUFS2 induced mitochondrial dysfunction by competitively inhibiting mitochondrial complex I activity and binding to PRDX5 (peroxiredoxin 5) and suppressing its antioxidant activity. Furthermore, coenzyme Q10 partially alleviated mitochondrial dysfunction in cardiomyocytes caused by DCRT reduction. CONCLUSIONS: Our study revealed that the loss of DCRT contributed to PTBP1-mediated exon skipping of NDUFS2, thereby inducing cardiac mitochondrial dysfunction during dilated cardiomyopathy development, which could be partially treated with coenzyme Q10 supplementation.

LncRNA ZNF593-AS Alleviates Contractile Dysfunction in Dilated Cardiomyopathy.

[Figure: see text].

New high-density fermentation method for producing high molecular weight polysialic acid based on the combination fermentation strategy.

Polysialic acid (PSA) is a long-chain linear amino polysaccharide with broad application prospects; however, its relatively low molecular weight limits its application range. This study aims to explore a new fermentation method of combining the three-phase pH control strategy, three-phase mixing speed control strategy, and exogenous substance to produce high molecular weight PSA. In brief, Escherichia coli K235 6E61 (CCTCC M208088) was used as a fermentation strain. 3 g·L-1 Na5P3O10 was added to the initial medium. At 0-12 h, the mixing speed was controlled to 250 r·min-1, and the pH was maintained at 7.2. At 12-20 h, the mixing speed was increased to 400 r·min-1, the pH was changed to 6.8, and 0.75% n-hexadecane was added at hour 16. After 20 h, the mixing speed was adjusted to 250 r·min-1; the pH was restored to 7.2. Air flow was regulated to 1.2 vvm throughout the experiment. The combination fermentation strategy greatly improved the molecular weight of PSA up to 498 kDa at 32 h, which is currently the maximum molecular weight of PSA produced through microbial fermentation. The yield of PSA reached 6.27 g·L-1 at the end of fermentation (36 h), which is also currently the highest yield of PSA produced by natural bacteria. Therefore, the proposed strategy could simultaneously increase the molecular weight and yield of PSA and is of great importance to the industrial production of high molecular weight PSA. Key points • A new fermentation process was explored to produce high molecular weight PSA. • The yield and molecular weight were improved by the combination fermentation strategy. • The maximum molecular weight and highest yield of PSA were obtained.

Nuclear miR-320 Mediates Diabetes-Induced Cardiac Dysfunction by Activating Transcription of Fatty Acid Metabolic Genes to Cause Lipotoxicity in the Heart.

RATIONALE: Diabetes mellitus is often associated with cardiovascular complications, which is the leading cause of morbidity and mortality among patients with diabetes mellitus, but little is known about the mechanism that connects diabetes mellitus to the development of cardiovascular dysfunction. OBJECTIVE: We aim to elucidate the mechanism underlying hyperglycemia-induced cardiac dysfunction on a well-established db/db mouse model for diabetes mellitus and diabetic complications that lead to heart failure. METHODS AND RESULTS: We first profiled the expression of microRNAs (miRNAs) by microarray and quantitative reverse transcription polymerase chain reaction on db/db mice and identified miR-320 as a key miRNA associated with the disease phenotype. We next established the clinical relevance of this finding by showing the upregulation of the same miRNA in the failing heart of patients with diabetes mellitus. We demonstrated the causal role of miR-320 in inducing diabetic cardiomyopathy, showing that miR-320 overexpression exacerbated while its inhibition improved the cardiac phenotype in db/db mice. Unexpectedly, we found that miR-320 acts as a small activating RNA in the nucleus at the level of transcription. By chromatin immunoprecipitation sequencing and chromatin immunoprecipitation quantitive polymerase chain reaction analysis of Ago2 (argonaute RISC catalytic component 2) and RNA polymerase II in response to miR-320 induction, we identified CD36 (fatty acid translocase) as a key target gene for this miRNA and showed that the induced expression of CD36 is responsible for increased fatty acid uptake, thereby causing lipotoxicity in the heart. CONCLUSIONS: These findings uncover a novel mechanism for diabetes mellitus-triggered cardiac dysfunction, provide an endogenous case for small activating RNA that has been demonstrated to date only with synthetic RNAs in transfected cells, and suggest a potential strategy to develop a miRNA-based therapy to treat diabetes mellitus-associated cardiovascular complications.

MiR-30c/PGC-1ß protects against diabetic cardiomyopathy via PPARα.

BACKGROUND: Metabolic abnormalities have been implicated as a causal event in diabetic cardiomyopathy (DCM). However, the mechanisms underlying cardiac metabolic disorder in DCM were not fully understood. RESULTS: Db/db mice, palmitate treated H9c2 cells and primary neonatal rat cardiomyocytes were employed in the current study. Microarray data analysis revealed that PGC-1ß may play an important role in DCM. Downregulation of PGC-1ß relieved palmitate induced cardiac metabolism shift to fatty acids use and relevant lipotoxicity in vitro. Bioinformatics coupled with biochemical validation was used to confirm that PGC-1ß was one of the direct targets of miR-30c. Remarkably, overexpression of miR-30c by rAAV system improved glucose utilization, reduced excessive reactive oxygen species production and myocardial lipid accumulation, and subsequently attenuated cardiomyocyte apoptosis and cardiac dysfunction in db/db mice. Similar effects were also observed in cultured cells. More importantly, miR-30c overexpression as well as PGC-1ß knockdown reduced the transcriptional activity of PPARα, and the effects of miR-30c on PPARα was almost abated by PGC-1ß knockdown. CONCLUSIONS: Our data demonstrated a protective role of miR-30c in cardiac metabolism in diabetes via targeting PGC-1ß, and suggested that modulation of PGC-1ß by miR-30c may provide a therapeutic approach for DCM.

MiR-21 protected against diabetic cardiomyopathy induced diastolic dysfunction by targeting gelsolin.

BACKGROUND: Diabetes is a leading cause of mortality and morbidity across the world. Over 50% of deaths among diabetic patients are caused by cardiovascular diseases. Cardiac diastolic dysfunction is one of the key early signs of diabetic cardiomyopathy, which often occurs before systolic dysfunction. However, no drug is currently licensed for its treatment. METHODS: Type 9 adeno-associated virus combined with cardiac Troponin T promoter were employed to manipulate miR-21 expression in the leptin receptor-deficient (db/db) mice. Cardiac structure and functions were measured by echocardiography and hemodynamic examinations. Primary cardiomyocytes and cardiomyocyte cell lines were used to perform gain/loss-of-function assays in vitro. RESULTS: We observed a significant reduction of miR-21 in the diastolic dysfunctional heart of db/db mice. Remarkably, delivery of miR-21 efficiently protected against the early impairment in cardiac diastolic dysfunction, represented by decreased ROS production, increased bioavailable NO and relieved diabetes-induced cardiomyocyte hypertrophy in db/db mice. Through bioinformatic analysis and Ago2 co-immunoprecipitation, we identified that miR-21 directly targeted gelsolin, a member of the actin-binding proteins, which acted as a transcriptional cofactor in signal transduction. Moreover, down-regulation of gelsolin by siRNA also attenuated the early phase of diabetic cardiomyopathy. CONCLUSION: Our findings reveal a new role of miR-21 in attenuating diabetic cardiomyopathy by targeting gelsolin, and provide a molecular basis for developing a miRNA-based therapy against diabetic cardiomyopathy.

MicroRNA-21 Lowers Blood Pressure in Spontaneous Hypertensive Rats by Upregulating Mitochondrial Translation.

BACKGROUND: Excessive reactive oxygen species generated in mitochondria has been implicated as a causal event in hypertensive cardiomyopathy. Multiple recent studies suggest that microRNAs (miRNAs) are able to translocate to mitochondria to modulate mitochondrial activities, but the medical significance of such a new miRNA function has remained unclear. Here, we characterized spontaneous hypertensive rats (SHRs) in comparison with Wistar rats, finding that micro RNA-21 (miR-21) was dramatically induced in SHRs relative to Wistar rats. We designed a series of experiments to determine whether miR-21 is involved in regulating reactive oxygen species generation in mitochondria, and if so, how induced miR-21 may either contribute to hypertensive cardiomyopathy or represent a compensatory response. METHODS: Western blotting was used to compare the expression of key nuclear genome (nDNA)-encoded and mitochondrial genome (mtDNA)-encoded genes involved in reactive oxygen species production in SHRs and Wistar rats. Bioinformatics was used to predict miRNA targets followed by biochemical validation using quantitative real-time polymerase chain reaction and Ago2 immunoprecipitation. The direct role of miRNA in mitochondria was determined by GW182 dependence, which is required for miRNA to function in the cytoplasm, but not in mitochondria. Recombinant adeno-associated virus (type 9) was used to deliver miRNA mimic to rats via tail vein, and blood pressure was monitored with a photoelectric tail-cuff system. Cardiac structure and functions were assessed by echocardiography and catheter manometer system. RESULTS: We observed a marked reduction of mtDNA-encoded cytochrome b (mt-Cytb) in the heart of SHRs. Downregulation of mt-Cytb by small interfering RNA in mitochondria recapitulates some key disease features, including elevated reactive oxygen species production. Computational prediction coupled with biochemical analysis revealed that miR-21 directly targeted mt-Cytb to positively modulate mt-Cytb translation in mitochondria. Circulating miR-21 levels in hypertensive patients were significantly higher than those in controls, showing a positive correlation between miR-21 expression and blood pressure. Remarkably, recombinant adeno-associated virus-mediated delivery of miR-21 was sufficient to reduce blood pressure and attenuate cardiac hypertrophy in SHRs. CONCLUSIONS: Our findings reveal a positive function of miR-21 in mitochondrial translation, which is sufficient to reduce blood pressure and alleviate cardiac hypertrophy in SHRs. This observation indicates that induced miR-21 is part of the compensatory program and suggests a novel theoretical ground for developing miRNA-based therapeutics against hypertension.

Phosphate solubilization and promotion of maize growth by Penicillium oxalicum P4 and Aspergillus niger P85 in a calcareous soil.

Alternative tactics for improving phosphorus nutrition in crop production are needed in China and elsewhere, as the overapplication of phosphatic fertilizers can adversely impact agricultural sustainability. Penicillium oxalicum P4 and Aspergillus niger P85 were isolated from a calcareous soil in China that had been exposed to excessive application of phosphatic fertilizer for decades. Each isolate excreted a number of organic acids into, acidified, and solubilized phosphorus in a synthetic broth containing insoluble tricalcium phosphate or rock phosphate. Isolate P4, applied as a seed treatment, increased maize fresh mass per plant when rock phosphate was added to the calcareous soil in greenhouse pot studies. Isolate P85 did not increase maize fresh mass per plant but did significantly increase total phosphorus per plant when rock phosphate was added. Significant increases in 7 and 4 organic acids were detected in soil in association with isolates P4 and P85, respectively, relative to the soil-only control. The quantity and (or) number of organic acids produced by these isolates increased when rock phosphate was added to the soil. Both isolates also significantly increased available phosphorus in soil in the presence of added rock phosphate and effectively colonized the maize rhizosphere. Studies reported here indicate that isolate P4 is adapted to and capable of promoting maize growth in a calcareous soil. Plant-growth promotion by this isolate is likely due, at least in part, to increased phosphorus availability resulting from the excretion of organic acids into, and the resulting acidification of, this soil.

A novel mutation in the CD40 ligand gene in a Chinese boy with X-linked hyper-IgM syndrome.

X-linked hyper-IgM Syndrome (XHIGM) is caused by a mutation of CD40 ligand (CD40L), which is normally expressed on activated CD4+ T cells and is responsible for immunoglobulin class switching. A 7-year-old boy with recurrent sino-pulmonary infections since the age of 3 months had normal CD3+, CD4+, CD8+T lymphocytes, and CD19+B lymphocytes and NK cells, but significantly elevated IgM and extremely decreased IgG and IgA. Sequencing of genomic DNA revealed that the patient had a 34 base deletion in intron 3 and exon 4 of CD40L(g.8172_8205del34bp), which lead to the entire deletion of exon 4 in cDNA (c.347_409del63bp, i.e.,exon 4 skipping) and an in-frame deletion of 21 amino acids in CD40L protein. Moreover, the patient had negligible CD40L expression on activated CD3+CD8-T lymphocytes. His mother and sister were carriers of the CD40L mutation. Our studies demonstrated a novel mutation in CD40L, which, to our knowledge, has not been reported previously.

[Screening, identification of P-dissolving fungus P83 strain and its effects on phosphate solubilization and plant growth promotion].

OBJECTIVE: To isolate phosphate-solubilizing microorganisms from farmland, and to provide P-solubilizing microbial resource for bio-fertilizer production. METHODS: Phosphate-solubilizing fungus was identified using morphological and cultural characteristics and ITS rDNA sequence analysis. The phosphate-solubilizing capacity of strain P83 was measured by Petri dishes, broth medium and soil pot experiment. The effect of strain P83 on plant growth was studied in field trials. RESULTS: Strain P83 was identified as Penicillium decumbens with a strong ability to dissolve insoluble phosphates. P83 dissolved 42.68% Ca3 (PO4) 2 (5 g/L) and the concentration of available phosphorus was 956 mg/L during a 10-d shaking incubation. The concentration of available phosphorus dissolved from Yonghe rock phosphate by P83 was 152.8 mg/L after 10d shaking incubation at 28 degrees C and a speed of 180r/min. P. decumbens P83 had a significant growth promotion effect on corn in Chao soil under three phosphates such as Ca3 (PO4) 2, Zn3 (PO4) 2 and rock phosphate. Compared with the control, inoculation with P83 increased the fresh weight of corn biomass by 9.5% - 89.2% and dry weight of corn biomass by 35% - 231%, and soil available phosphorus content increased 2.1 mg/kg -40.5 mg/ kg. Field trials show that P. decumbens P83 had a greater effect on enhancement of corn grain yield, the yield was average 9.2t/hm2 and 35.3% higher than the control. CONCLUSION: One new phosphate- solubilizing strain P83 was obtained and identified as P. decumbens. It solubilized insoluble phosphates in petri dishes, broth medium and pot experiments. P. decumbens P83 could increase corn yield significantly in field trials. P. decumbens P83 strain has the potential for biofertilizer production in the future.

Effects of In Vitro Fermentation of Polysialic Acid and Sialic Acid on Gut Microbial Community Composition and Metabolites in Healthy Humans.

The influence of polysialic acid (PSA) and sialic acid (SA) on the gut microbial community composition and metabolites in healthy humans was investigated using a bionic gastrointestinal reactor. The results indicated that PSA and SA significantly changed the gut microbiota and metabolites to different degrees. PSA can increase the relative abundances of Faecalibacterium and Allisonella, whereas SA can increase those of Bifidobacterium and Megamonas. Both can significantly increase the content of short-chain fatty acids. The results of metabolome analysis showed that PSA can upregulate ergosterol peroxide and gallic acid and downregulate the harmful metabolite N-acetylputrescine. SA can upregulate 4-pyridoxic acid and lipoic acid. PSA and SA affect gut microbiota and metabolites in different ways and have positive effects on human health. These results will provide a reference for the further development of PSA- and SA-related functional foods and health products.

Fibroblast-localized lncRNA CFIRL promotes cardiac fibrosis and dysfunction in dilated cardiomyopathy.

CFIRL is a long noncoding RNA (lncRNA), we previously identified as the most significantly upregulated lncRNA in the failing hearts of patients with dilated cardiomyopathy (DCM). In this study, we determined the function of CFIRL and its role in DCM. Real-time polymerase chain reaction and in situ hybridization assays revealed that CFIRL was primarily localized in the nucleus of cardiac fibroblasts and robustly increased in failing hearts. Global knockdown or fibroblast-specific knockout of CFIRL attenuated transverse aortic constriction (TAC)-induced cardiac dysfunction and fibrosis in vivo. Overexpression of CFIRL in vitro promoted fibroblast proliferation and aggravated angiotensin II-induced differentiation to myofibroblasts. CFIRL knockdown attenuated these effects. Mechanistically, RNA pull-down assay and gene expression profiling revealed that CFIRL recruited ENO1, a newly identified noncanonical transcriptional factor, to activate IL-6 transcription. IL-6 exerted a paracrine effect on cardiomyocytes to promote cardiac hypertrophy, which can be prevented by CFIRL knockdown. These findings uncover the critical role of CFIRL, a fibroblast-associated lncRNA, in heart failure by facilitating crosstalk between fibroblasts and cardiomyocytes. CFIRL knockdown might be a potent strategy to prevent cardiac remodeling in heart failure, particularly in DCM.

Lymphocyte and neutrophil count combined with intestinal bacteria abundance predict the severity of COVID-19.

IMPORTANCE: The 2019 coronavirus disease (COVID-19) patients had a unique profile of gut bacteria. In this study, we characterized the intestinal bacteria in our COVID-19 cohorts and found that there was an increased incidence of severe cases in COVID-19 patients with decreased lymphocytes and increased neutrophils. Levels of lymphocytes and neutrophils and abundances of intestinal bacteria correlated with the severity of COVID-19.

Circulating miR-30a, miR-126 and let-7b as biomarker for ischemic stroke in humans.

BACKGROUND: Recently, plasma miRNAs have been reported as biomarkers for various diseases. However, the knowledge on the association of plasma miRNAs with ischemic stroke is still lacking. In this study, we investigated whether plasma concentrations of miR-30a, miR-126 and let-7b may be biomarkers for ischemic stroke in humans. METHODS: One hundred ninety seven patients with ischemic stroke were recruited and their blood samples were collected at 24 h, 1 week, 4 weeks, 24 weeks and 48 weeks after symptoms onset, and fifty healthy volunteers were selected as control. Levels of miRNA were quantified by quantitative real-time PCR. Relative expression level of miRNA was calculated using 2(-ΔΔct) method. The ability to distinguish the ischemic stroke group from control group was characterized by receiver operating characteristic (ROC) curve, and the area under ROC curve (AUC) was calculated. RESULTS: Circulating miR-30a and miR-126 levels were markedly down-regulated in all patients with ischemic stroke until 24 weeks. However, circulating let-7b was lower in patients with large-vessel atherosclerosis than healthy volunteers, whereas circulating let-7b had higher level in patients with other kinds of ischemic stroke until 24 weeks. Among all patients, circulating miRNAs levels returned to normal 48 weeks after symptom onset. Receiver operating characteristic (ROC) curve analysis showed that the areas under the curve (AUC) of plasma miR-30a were 0.91, 0.91, 0.92 and 0.93, the miR-126 were 0.92, 0.94, 0.93 and 0.92, and let-7b were 0.93, 0.92, 0.92 and 0.91 at 24 h, 1 w, 4 w and 24 w, respectively. CONCLUSIONS: These data suggest that miR-30a, miR-126 and let-7b might be useful biomarkers for ischemic stroke in humans.

Targeting non-coding RNAs in sEVs: The biological functions and potential therapeutic strategy of diabetic cardiomyopathy.

Diabetic cardiomyopathy (DCM) is defined as abnormalities in myocardial structure and function in the setting of diabetes and in the absence of cardiovascular diseases, such as coronary artery disease, hypertension, and valvular heart disease. DCM is one of the leading causes of mortality in patients with diabetes. However, the underlying pathogenesis of DCM has not been fully elucidated. Recent studies have revealed that non-coding RNAs (ncRNAs) in small extracellular vesicles (sEVs) are closely associated with DCM and may act as potential diagnostic and therapeutic targets. Here, we introduced the role of sEV-ncRNAs in DCM, summarized the current therapeutic advancements and limitations of sEV-related ncRNAs against DCM, and discussed their potential improvement.

A Comparative Study of the Effects of Whole Cereals and Refined Cereals on Intestinal Microbiota.

Cereals are one of the most important foods on which human beings rely to sustain basic life activities and are closely related to human health. This study investigated the effects of different steamed buns on intestinal microbiota. Three steamed buns were prepared using refined flour (RF), 1:1 mixed flour (MF), and whole wheat flour (WF). In vitro digestion simulations were conducted using a bionic gastrointestinal reactor (BGR) to examine their influence on intestinal microbiota. The results showed that at 0.5% addition, butyric acid and short-chain fatty acids in WF were significantly different from those in RF and MF (p < 0.05). WF also promoted the proliferation of beneficial microbiota, such as Megamonas and Subdoligranulum. At 0.5%, 1.0%, and 1.5% additions of WF, acetic acid and short-chain fatty acids at 1.5% WF increased by 1167.5% and 11.4% from 0.5% WF, respectively, and by 20.2% and 7.6% from 1.0% WF, respectively. WF also promoted the proliferation of Bifidobacterium, Lactobacillus, and Bacteroides and inhibited the growth of pathogenic microbiota, such as Streptococcus, Enterococcus, and Klebsiella. These findings support the consumption of whole cereals and offer insights into the development of new functional foods derived from wheat.

A Kaposi's sarcoma-associated herpes virus-encoded microRNA contributes to dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) is the leading cause of heart transplantation. By microRNA (miRNA) array, a Kaposi's sarcoma-associated herpes virus (KSHV)-encoded miRNA, kshv-miR-K12-1-5p, was detected in patients with DCM. The KSHV DNA load and kshv-miR-K12-1-5p level in plasma from 696 patients with DCM were measured and these patients were followed-up. Increased KSHV seropositivity and quantitative titers were found in the patients with DCM compared with the non-DCM group (22.0% versus 9.1%, p < 0.05; 168 versus 14 copies/mL plasma, p < 0.05). The risk of the individual end point of death from cardiovascular causes or heart transplantation was increased among DCM patients with the KSHV DNA seropositivity during follow-up (adjusted hazard ratio 1.38, 95% confidence interval 1.01-1.90; p < 0.05). In heart tissues, the KSHV DNA load was also increased in the heart from patients with DCM in comparison with healthy donors (1016 versus 29 copies/105 cells, p < 0.05). The KSHV and kshv-miR-K12-1-5p in DCM hearts were detected using immunofluorescence and fluorescence staining in situ hybridization. KSHV itself was exclusively detectable in CD31-positive endothelium, while kshv-miR-K12-1-5p could be detected in both endothelium and cardiomyocytes. Moreover, kshv-miR-K12-1-5p released by KSHV-infected cardiac endothelium could disrupt the type I interferon signaling pathway in cardiomyocytes. Two models of kshv-miR-K12-1-5p overexpression (agomiR and recombinant adeno-associated virus) were used to explore the roles of KSHV-encoded miRNA in vivo. The kshv-miR-K12-1-5p aggravated known cardiotropic viruses-induced cardiac dysfunction and inflammatory infiltration. In conclusion, KSHV infection was a risk factor for DCM, providing developmental insights of DCM involving virus and its miRNA ( https://clinicaltrials.gov . Unique identifier: NCT03461107).

Biological Functions and Clinical Prospects of Extracellular Non-Coding RNAs in Diabetic Cardiomyopathy: an Updated Review.

Diabetic cardiomyopathy (DCM) is one of the major causes of heart failure in diabetic patients. However, the pathogenesis of diabetic cardiomyopathy has not been fully elucidated. Diagnosis and therapeutic strategy of DCM is still challenging. Various non-coding RNAs (ncRNA) are implicated in the onset and progression of DCM. Interestingly, ncRNAs not only are regulators intracellularly, but also can exist and function in extracellular space. Recent evidences have demonstrated that extracellular ncRNAs play emerging roles in both intracardiac and inter-organ communication during the pathogenesis of DCM; thus, extracellular ncRNAs are attractive diagnostic biomarkers and potential therapeutic targets for DCM. This article will review the current knowledge of the roles of extracellular ncRNAs in DCM, especially focusing on their physio-pathological properties and perspectives of potential clinical translation for biomarkers and therapies. Recent evidences have demonstrated that extracellular ncRNA play emerging roles in both intracardiac and inter-organ communication involved in the pathogenesis of diabetic cardiomyopathy (DCM), thus shown as attractive diagnostic biomarkers and potential therapeutics for DCM. In the current review, we first summarize the progress regarding the paracrine role of extracellular ncRNA in DCM. miRNAs and circRNAs have been shown to mediate the communication among cardiomyocytes, endothelial cells, and vascular smooth muscle cells in the diabetic heart. Subsequently, we systematically describe that extracellular ncRNAs contribute to the crosstalk between the heart and other organs in the context of diabetes. Researches have indicated that miRNAs acted as hepatokines and adipokines to mediates the injure effect of distal organs on hearts. As for clinical application, extracellular ncRNAs are promising biomarker and have therapeutic potential. (Created with BioRender.com).

Enhancement of Underwater Tribological Properties of Hybrid PTFE/Nomex Fabric Laminate Composites by Epoxy Resins.

Hybrid poly(tetrafluoroethylene) (PTFE)/Nomex fabric laminate composites were prepared with phenolic and epoxy resins. A pin-on-disc tribometer was used to perform tribological tests with different applied loads and rotational speeds. The wear surface, transfer film, and cross section were analyzed by scanning electron microscopy (SEM) and optical microscopy. The results showed that the epoxy resin with high strength and good binding properties can enhance underwater tribological and mechanical properties. The underwater surface hardness was also improved by the epoxy resin. The underwater strength and adhesiveness of the phenolic resin reduced and the underwater surface hardness also decreased, causing a decrease in underwater tribological and mechanical properties of the phenolic resin.

Enhancement of Underwater Tribological Properties of Hybrid PTFE/Nomex Fabric/Epoxy Resin Multilayer Composites by Mixed Graphite and MoS2 Fillers.

This work studied the effect of mixed graphite and MoS2 fillers on tribological properties of hybrid polytetrafluoroethylene (PTFE)/Nomex fabric/epoxy multilayer composites under water lubrication. A ring-on-block tribometer was used to perform the tribological test under dry sliding and water lubrication conditions. The worn surface was analyzed by scanning electron microscopy and optical microscopy. The results showed mixed fillers with 2.5 wt % graphite and 5 wt % MoS2 had the best underwater tribological properties with the lowest friction coefficient (COF) of 0.067 and the lowest wear amount of 1.7 mg. Mixed fillers optimize epoxy resin properties, thereby increasing shore hardness, reducing water absorption, and improving wear resistance. This study also explained the reasons of the wear amount was higher in water than in dry sliding.