Dysregulated autophagy is associated with many pathological disorders such as cardiovascular diseases. Emerging evidence has suggested that circular RNAs (circRNAs) have important roles in some ...biological processes. However, it remains unclear whether circRNAs participate in the regulation of autophagy. Here we report that a circRNA, termed autophagy-related circular RNA (ACR), represses autophagy and myocardial infarction by targeting Pink1-mediated phosphorylation of FAM65B. ACR attenuates autophagy and cell death in cardiomyocytes. Moreover, ACR protects the heart from ischemia/reperfusion (I/R) injury and reduces myocardial infarct sizes. We identify Pink1 as an ACR target to mediate the function of ACR in cardiomyocyte autophagy. ACR activates Pink1 expression through directly binding to Dnmt3B and blocking Dnmt3B-mediated DNA methylation of Pink1 promoter. Pink1 suppresses autophagy and Pink1 transgenic mice show reduced myocardial infarction sizes. Further, we find that FAM65B is a downstream target of Pink1 and Pink1 phosphorylates FAM65B at serine 46. Phosphorylated FAM65B inhibits autophagy and cell death in the heart. Our findings reveal a novel role for the circRNA in regulating autophagy and ACR-Pink1-FAM65B axis as a regulator of autophagy in the heart will be potential therapeutic targets in treatment of cardiovascular diseases.
•Summarized the over-growth risks of non-pathogenic CRB.•Presented the genus, sources and chlorine resistance of all the isolated CRB strains.•Demonstrated the lack of widely-accepted method to ...evaluate chlorine resistance.•Proposed a recommended evaluating method for chlorine resistance.•Proposed a quantitative definition of chlorine-resistant bacteria.
Chlorine-resistant bacteria (CRB) are commonly defined as bacteria with high resistance to chlorine disinfection or bacteria which can survive or even regrow in the residual chlorine. Chlorine disinfection cannot completely control the risks of CRB, such as risks of pathogenicity, antibiotic resistance and microbial growth. Currently, researchers pay more attention to CRB with pathogenicity or antibiotic resistance. The microbial growth risks of non-pathogenic CRB in water treatment and reclamation systems have been neglected to some extent. In this review, these three kinds of risks are all analyzed, and the last one is also highlighted. In order to study CRB, various methods are used to evaluate chlorine resistance. This review summarizes the evaluating methods for chlorine resistance reported in the literatures, and collects the important information about the typical isolated CRB strains including their genera, sources and levels of chlorine resistance. To our knowledge, few review papers have provided such systematic information about CRB. Among 44 typical CRB strains from 17 genera isolated by researchers, Mycobacterium, Bacillus, Legionella, Pseudomonas and Sphingomonas were the five genera with the highest frequency of occurrence in literatures. They are all pathogenic or opportunistic pathogenic bacteria. In addition, although there are many studies on CRB, information about chlorine resistance level is still limited to specie level or strain level. The difference in chlorine resistance level among different bacterial genera is less well understood. An inconvenient truth is that there is still no widely-accepted method to evaluate chlorine resistance and to identify CRB. Due to the lack of a unified method, it is difficult to compare the results about chlorine resistance level of bacterial strains in different literatures. A recommended evaluating method using logarithmic removal rate as an index and E. coli as a reference strain is proposed in this review based on the summary of the current evaluating methods. This method can provide common range of chlorine resistance of each genus and it is conducive to analyzing the distribution and abundance of CRB in the environment.
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An ideal bone repair scaffold is expected to possess superior architectural characteristics to facilitate the adhesion, proliferation, and migration of bone‐repair‐related cells, while excluding ...nonosteogenic cells and fibrous tissues from interfering with normal bone regeneration. Unfortunately, such scaffold material has rarely been reported. Herein, nanocomposite scaffolds with a radially ordered porous structure are presented, manufactured using a modified directional freeze‐casting method, and are promising bone defect repair materials to satisfy this requirement. The prepared nanocomposite scaffolds consist of a natural bio‐macromolecule, chitosan, and bioactive hydroxyapatite nanoparticles derived from porcine cortical bone, demonstrating favorable biocompatibility and biological functions. Both in vitro cell studies and in vivo animal studies reveal the great superiority of the radially oriented porous structure of the scaffolds in guiding bone regeneration, while simultaneously preventing the invasion of surrounding nonosteogenic cells and fibrous tissue, compared to the axially oriented porous structure. This work indicates the distinctive potential of radially oriented porous scaffolds for repairing tabular and lacunar bone defects.
A nanocomposite scaffold with a radially oriented porous structure is engineered via a modified freeze‐casting method. The unique structural feature renders the nanocomposite scaffold with great superiority in guiding the infiltration and migration of bone‐repair‐related cells into the scaffold, while preventing the invasion of surrounding nonosteogenic cells and fibrous tissues from interfering with the normal bone regeneration process.
A new three‐dimensional (3D) framework, Ni(btzip)(H2btzip)⋅2 DMF⋅2 H2O (1) (H2btzip=4,6‐bis(triazol‐1‐yl)isophthalic acid) as an acidic heterogeneous catalyst was constructed by the reaction of ...nickel wire and a triazolyl‐carboxyl linker. Framework 1 possesses intersected 2D channels decorated by free COOH groups and uncoordinated triazolyl N atoms, leading to not only high CO2 and C2H6 adsorption capacity but also significant selective capture for CO2 and C2H6 over CH4 and CO in 273–333 K. Moreover, 1 reveals chemical stability toward water. Grand Canonical Monte Carlo simulations confirmed the multiple CO2‐ and C2H6‐philic sites. As a result of the presence of accessible Brønsted acidic COOH groups in the channels, the activated framework demonstrates highly efficient catalytic activity in the cycloaddition reaction of CO2 with propylene oxide/4‐chloromethyl‐1,3‐dioxolan‐2‐one/3‐butoxy‐1,2‐epoxypropane into cyclic carbonates.
Through employing a triazolyl‐carboxyl linker, a stable porous Ni metal–organic framework (MOF) was constructed, which contains free carboxyl groups in channels and reveals not only high CO2 and C2H6 loadings but also significant selective capture for CO2 and C2H6 over CH4 and CO, as well as highly efficient catalytic activity in the cycloaddition reaction of CO2 with epoxides. The multi‐point framework–CO2/C2H6 interactions were confirmed by Grand Canonical Monte Carlo simulations (see scheme).
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•A novel compound containing active amine groups of polyphosphazene (PBFA) were successfully synthesized.•PBFA showed excellent properties in decreasing the PHRR, THR and TSP.•The ...mechanical performances were not worsened with a high loading of PBFA.
A novel compound containing active amine groups of polyphosphazene (PBFA) was successfully synthesized and applied as a reactive flame-retardant additive in epoxy (EP) resin. It was synthesized from N-aminoethylpiperazine and hexachlorocyclotriphosphazene using a simple method, and its structure was well-characterized. The results indicated that introducing PBFA into EP composites significantly improves the resistance to fire and suppresses smoke generation. An EP composite with 9.0 wt% PBFA can pass the vertical burning tests V-0 rating, the peak heat release rate and total heat release of the sample decreased by 46.7% and 29.3%, respectively. Moreover, it decreased the total smoke release by 48.0%. Thermogravimetric analysis showed that the presence of PBFA can accelerate EP decomposition at comparatively low temperatures and lead to the formation of a stable char layer, which protects the matrix from fire, therefore improving the amount of char residue at 800 °C. The degree of small molecule degradation characterized by gas chromatograph/mass spectrometer, which was lower than that of pure EP, demonstrating that PBFA reduces the risk of fire. The glass transition temperature of EP composites increased with the amount of PBFA increasing owing to the presence of active amine groups. Notably, its mechanical properties were not degraded.
In reverse osmosis (RO) system for wastewater reclamation, biofouling is an inevitable issue. Chlorine disinfection is commonly used in pretreatment to control biofouling. Some chlorine-resistant ...bacteria could survive after chlorine disinfection and the microbial community structure in feed water changes significantly, thus leading to the change of biofouling potential. In this study, the effect of chlorine disinfection on the biofouling of RO membrane was investigated using a laboratory cross-flow RO system. Chlorine disinfection inactivated most bacteria in feed water. However, during the operation of RO system, with the increase of chlorine dosage the flux decline became more severe after a period of operation. The final normalized flux after 21 days was 0.27, 0.26, 0.20, and 0.21 with 0, 1, 5, and 15 mg-Cl2/L chlorine as pretreatment, respectively. After the operation, the numbers of active bacteria in the foulants on the fouled membrane were on the same level regardless of the chlorine dosage, whereas the thickness of the foulants increased with the chlorine dosage significantly. Additionally, the higher total organic carbon concentration indicated more extracellular polymeric substances (EPS) in foulants. Microbial community structure analysis showed that the abundance and the species number of chlorine-resistant bacteria increased significantly with the chlorine dosage. Typical chlorine-resistant bacteria, including Methylobacterium, Pseudomonas, Sphingomonas, and Acinetobacter, were identified as significantly distinctive genera in the foulants after the pretreatment by 15 mg-Cl2/L chlorine. Compared with the bacteria without chlorine disinfection, these remaining bacteria produced more EPS with higher molecular weight, which could be the major contribution to more severe RO membrane fouling after chlorine disinfection.
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•Studied effect of chlorine disinfection on biofouling of reverse osmosis (RO) system.•Applied lab RO systems, multiple microscopy, gene sequencing and organic analysis.•Chlorine disinfection changed the microbial community structure in foulants.•Four dominant chlorine-resistant strains were found in foulants with 15 mg-Cl2/L.•Extracellular polymeric substance produced by these strains caused severe biofouling.
Hemophagocytic lymphohistiocytosis (HLH) is an immune-regulatory disorder characterized by excessive production of inflammatory cytokines. The treatment recommendations of the HLH-1994 and HLH-2004 ...protocols have long been used in HLH therapy, but some patients still do not respond well to or have unacceptable side effects from conventional therapies. It is believed that cytokine-targeted strategies that directly target disease-driving pathways will be promising options for HLH. This prospective study aimed to investigate the efficacy and safety of ruxolitinib, a Janus kinase (JAK) 1/2 inhibitor, as a front-line therapy in children with secondary HLH. Twelve newly diagnosed patients without previous treatment were enrolled in this study with a median follow-up of 8.2 (7.1-12.0) months, including 8 cases of Epstein-Barr virus associated HLH (EBV-HLH), 2 cases of autoinflammatory disorder (AID)- associated HLH, and 2 cases of unknown etiology. Patients received oral ruxolitinib dosed on 2.5 mg, 5 mg or 10 mg twice daily depending on the body weight for 28 consecutive days. The overall response rate at the end of treatment (day 28) was 83.3% (10/12), with 66.7% (8/12) in complete response (CR), 8.3% (1/12) in partial response (PR), and 8.3% (1/12) in HLH improvement. Among the patients achieving CR, 87.5% (7/8) maintained CR condition for>6 months, and one patient with EBV-HLH relapsed following CR. For the EBV-HLH subgroup, all 8 patients responded to ruxolitinib, with a CR rate of 75% and a PR rate of 25%. Two patients with AID-associated HLH had quite different responses, with one showing reversal of the HLH abnormalities soon and the other showing no improvement, as did the two cases of unknown etiology. Patients who had no response or discontinued ruxolitinib all responded well to the subsequent HLH-1994 regimen. The expected 6-month event-free survival (EFS) rate was 58.3%±10.2%. No serious adverse effects were reported. Our study provides further support for the possibility of ruxolitinib targeted therapy for secondary HLH in children. This study was registered in the Chinese Clinical Trials Registry Platform (http://www.chictr.org.cn/) as ChiCTR2000029977.
•Pretreatment by high dosage of UV aggravated RO membrane fouling.•The organic matter amount in the foulants increased after UV disinfection.•The content of proteins and polysaccharides in foulants ...increased with high UV dosage.•Typical UV-resistant bacteria were selected in the foulants with high UV dosage.•Residual bacteria after UV disinfection secreted more amounts of EPS.
Membrane fouling is a prominent problem that hinders the stable and efficient operation of the reverse osmosis (RO) system for wastewater reclamation. Previous studies showed that chlorine disinfection, which was commonly used in industrial RO systems as pretreatment, could lead to significant change in microbial community structure and resulted in serious biofouling. In order to prevent biofouling during wastewater reclamation, the effect of ultraviolet (UV) disinfection on RO membrane fouling was investigated and the mechanism was also revealed in this study. With the disinfection pretreatment by UV of 20, 40 and 80 mJ/cm2, the bacteria in the feed water were inactivated significantly with a log reduction of 1.11, 2.55 and 3.61-log, respectively. However, RO membrane fouling aggravated with higher UV dosage. Especially, in the group with the UV dosage of 80 mJ/cm2, the normalized RO membrane flux decreased by 15% compared with the control group after 19-day operation. The morphology of the fouled RO membranes indicated serious biofouling in all groups. The analysis on the microbial amount of the foulants showed that the heterotrophic plate counts (HPC) and ATP content on the fouled RO membranes with and without UV disinfection were at the same level. However, the total organic carbon content of the foulants with the UV dosage of 40 and 80 mJ/cm2 was significantly higher than the control group, with higher content of proteins and polysaccharides as indicated by EEM and FTIR spectrum. Microbial community structure analysis showed that some typical UV-resistant bacteria were selected and remained on the RO membrane after disinfection with high UV dosage, including. These residual bacteria after disinfection with high UV dosage showed higher extracellular polymeric substances (EPS) secretion compared with those without UV disinfection, and thus aggravated RO membrane fouling. Thicker EPS could decrease the transmission of UV rays, and thus bacteria with higher EPS secretion might be selected after UV disinfection.
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Long-distance entanglement distribution is essential for both foundational tests of quantum physics and scalable quantum networks. Owing to channel loss, however, the previously achieved distance was ...limited to ~100 kilometers. Here we demonstrate satellite-based distribution of entangled photon pairs to two locations separated by 1203 kilometers on Earth, through two satellite-to-ground downlinks with a summed length varying from 1600 to 2400 kilometers. We observed a survival of two-photon entanglement and a violation of Bell inequality by 2.37 ± 0.09 under strict Einstein locality conditions. The obtained effective link efficiency is orders of magnitude higher than that of the direct bidirectional transmission of the two photons through telecommunication fibers.
Intramuscular fat (IMF) is known to enhance beef palatability and can be markedly increased by castration. However, there is little understanding of the molecular mechanism underlying the IMF ...deposition after castration of beef cattle. We hypothesize that genetic regulators function differently in IMF from bulls and steers. Therefore, after detecting serum testosterone and lipid parameter, as well as the contents of IMF at 6, 12, 18 and 24 months, we have investigated differentially expressed (DE) microRNAs (miRNAs) and mRNAs in IMF of bulls and steers at 24 months of age in Qinchuan cattle using next-generation sequencing, and then explored the possible biopathways regulating IMF deposition. Serum testosterone levels were significantly decreased in steers, whereas IMF content, serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TGs) were markedly increased in steers. Comparing the results of steers and bulls, 580 upregulated genes and 1,120 downregulated genes in IMF tissues were identified as DE genes correlated with IMF deposition. The upregulated genes were mainly associated with lipid metabolism, lipogenesis and fatty acid transportation signalling pathways, and the downregulated genes were correlated with immune response and intracellular signal transduction. Concurrently, the DE miRNAs-important players in adipose tissue accumulation induced by castration-were also examined in IMF tissues; 52 DE miRNAs were identified. The expression profiles of selected genes and miRNAs were also confirmed by quantitative real-time PCR (qRT-PCR) assays. Using integrated analysis, we constructed the microRNA-target regulatory network which was supported by target validation using the dual luciferase reporter system. Moreover, Ingenuity Pathway Analysis (IPA) software was used to construct a molecular interaction network that could be involved in regulating IMF after castration. The detected molecular network is closely associated with lipid metabolism and adipocyte differentiation, which is supported by functional identification results of bta-let-7i on bovine preadipocytes. These results provided valuable insights into the molecular mechanisms of the IMF phenotype differences between steers and bulls.
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