Transcriptome analysis highlights the influence of temperature on hydrolase and traps in nematode-trapping fungi.

Pine wilt disease caused by Bursaphelenchus xylophilus poses a serious threat to the economic and ecological value of forestry. Nematode trapping fungi trap and kill nematodes using specialized trapping devices, which are highly efficient and non-toxic to the environment, and are very promising for use as biological control agents. In this study, we isolated several nematode-trapping fungi from various regions and screened three for their high nematocidal efficiency. However, the effectiveness of these fungi as nematicides is notably influenced by temperature and exhibits different morphologies in response to temperature fluctuations, which are categorized as "NA," "thin," "dense," and "sparse." The trend of trap formation with temperature was consistent with the trend of nematocidal efficiency with temperature. Both of which initially increased and then decreased with increasing temperature. Among them, Arthrobotrys cladodes exhibited the highest level of nematocidal activity and trap formation among the tested species. Transcriptome data were collected from A. cladodes with various trap morphologies. Hydrolase activity was significantly enriched according to GO and KEGG enrichment analyses. Eight genes related to hydrolases were found to be consistent with the trend of trap morphology with temperature. Weighted gene co-expression analysis and the Cytoscape network revealed that these 8 genes are associated with either mitosis or autophagy. This suggests that they contribute to the formation of "dense" structures in nematode-trapping fungi. One of these genes is the serine protein hydrolase gene involved in autophagy. This study reveals a potentially critical role for hydrolases in trap formation and nematocidal efficiency. And presents a model where temperature affects trap formation and nematocidal efficiency by influencing the serine protease prb1 involved in the autophagy process.

Ultrabright Fluorescent Nanorod-Based Immunochromatographic with Low Background for Advancing Detection Performance.

Nanomaterials-based immunochromatographic assays (ICAs) are of great significance in point-of-care testing (POCT), yet it remains challenging to explore low background platforms and high chromogenic intensity probes to improve detection performance. Herein, we reported a low interference and high signal-to-noise ratio fluorescent ICA platform based on ultrabright persistent luminescent nanoparticles (PLNPs) Zn2GeO4: Mn, which could produce intense photoluminescence at 254 nm excitation to reduce background interference from ICA substrates and samples. The prepared immunosensor was successfully applied in T-2 toxin detection with a remarkable limit of detection of 0.025 ng/mL, which was 22-fold more sensitive compared with that of traditional gold nanoparticles. Ultimately, a portable 3D-printed detection device equipped with a smartphone analyzing application was fabricated for quantitative readout in POCT, achieving favorable recoveries in practical sample detection. This work provides a creative attempt for ultrabright PLNP-based low background ICA, and it also guarantees its feasibility in practical POCT.

Substrate-dependent interaction of SPOP and RACK1 aggravates cardiac fibrosis following myocardial infarction.

Speckle-type pox virus and zinc finger (POZ) protein (SPOP), a substrate recognition adaptor of cullin-3 (CUL3)/RING-type E3 ligase complex, is investigated for its role in cardiac fibrosis in our study. Cardiac fibroblasts (CFs) activation was achieved with TGF-ß1 (20 ng/mL) and MI mouse model was established by ligation of the left anterior descending coronary, and lentivirus was employed to mediate interference of SPOP expression. SPOP was increased both in fibrotic post-MI mouse hearts and TGF-ß1-treated CFs. The gain-of-function of SPOP promoted myofibroblast transformation in CFs, and exacerbated cardiac fibrosis and cardiac dysfunction in MI mice, while the loss-of-function of SPOP exhibited the opposite effects. Mechanistically, SPOP bound to the receptor of activated protein C kinase 1 (RACK1) and induced its ubiquitination and degradation by recognizing Ser/Thr-rich motifs on RACK1, leading to Smad3-mediated activation of CFs. Forced RACK1 expression canceled the effects of SPOP on cardiac fibrosis. The study reveals therapeutic targets for fibrosis-related cardiac diseases.

MetBil as a novel molecular regulator in ischemia-induced cardiac fibrosis via METTL3-mediated m6A modification.

Cardiac fibrosis is a common pathological manifestation in multiple cardiovascular diseases and often results in myocardial stiffness and cardiac dysfunctions. LncRNA (long noncoding RNA) participates in a number of pathophysiological processes. However, its role in cardiac fibrosis remains unclear. The purpose of this study was to investigate the role and molecular mechanism of MetBil in regulating cardiac fibrosis. Our data showed that METTL3 binding lncRNA (MetBil) was significantly increased both in fibrotic tissue following myocardial infarction (MI) in mice and in cardiac fibroblasts (CFs) exposed to TGF-ß1 (20 ng/mL) or 20% FBS. Overexpression of MetBil augmented collagen deposition, CF proliferation and activation while silencing MetBil exhibited the opposite effects. Importantly, heterozygous knockout of MetBil alleviated cardiac fibrosis and improved cardiac function after MI. RNA pull-down and RNA-binding protein immunoprecipitation assay showed that METTL3 is a direct downstream target of MetBil; consistently, MetBil and METTL3 were co-localized in both the nucleus and cytoplasm of CFs. Interestingly, MetBil regulated METTL3 expression at protein level, but not mRNA level, in ubiquitin-proteasome pathway. Enforced expression of METTL3 canceled the antifibrotic effects of silencing MetBil reflected by increased collagen production, CF proliferation and activation. Most notably, the m6A-modified fibrosis-regulated genes mediated by METTL3 are profoundly involved in the regulation of MetBil in the cardiac fibrosis following MI. Our study reveals that MetBil as a novel regulator of fibrosis promotes cardiac fibrosis via interacting with METTL3 and regulating the expression of the methylated fibrosis-associated genes, providing a new intervening target for fibrosis-associated cardiac diseases.

A portable kit based on thiol-ene Michael addition for acrylamide detection in thermally processed foods.

Accurate, sensitive, and selective analysis of acrylamide generated in thermally processed foods is of great significance for food safety. Herein, a novel acrylamide sensing platform is designed for both sensitive on-site colorimetric analysis and accurate UV-vis spectroscopy quantification, by integrating thiol-ene Michael addition with gold nanoparticles-mediated catalytical oxidation. The Michael addition reaction between acrylamide and glutathione efficiently alleviates glutathione-induced catalytic activity inhibition of gold nanoparticles, evoking the chromogenic reaction of H2O2-mediated 3,3',5,5'-tetramethylbenzidine. With increasing the concentration of acrylamide, the oxidation of 3,3',5,5'-tetramethylbenzidine is accelerated, presenting a series of shades from colorless to blue. The sensing platform exhibits excellent detection performance of acrylamide in the range of 0.5-175 µM with a detection limit of 0.16 µM, and is successfully employed in food samples. Especially, a portable assay kit based on the proposed platform is developed for visual determination of acrylamide, opening an avenue for smart sensors of food safety hazards.

A colorimetric and fluorescent dual-readout probe based on red emission carbon dots for nitrite detection in meat products.

Nitrite (NO2-) is widely present in the human environment and accurate, sensitive and selective detecting of nitrite is of vital significance for food safety and water quality. Herein, a novel red emission carbon dots (r-CDs) fluorescent probe was fabricated for dual-mode detection of nitrite, which was capable of both convenient colorimetric analysis and accurate fluorometric detection. When NO2- is added to the rose-red r-CDs solution, NO2- interacts with the amino groups which on the surface of r-CDs to form diazotized substance, resulting in that the colorimetric color of r-CDs solution realizes the transition from rose red to light purple, and the red fluorescence is gradually quenched. The detection limits of colorimetric and fluorescence for NO2- were 0.193 µM and 0.149 µM, respectively. Furthermore, the dual-readout probe revealed satisfactory recovery and reliability when analyzing the concentration of NO2- in ham and bacon samples..

LncRNA-H19 Drives Cardiomyocyte Senescence by Targeting miR-19a/socs1/p53 Axis.

Purpose: Cardiomyocyte senescence is associated with a progressive decline in cardiac physiological function and the risk of cardiovascular events. lncRNA H19 (H19), a well-known long noncoding RNA (lncRNA), is involved in the pathophysiological process of multiple cardiovascular disease such as heart failure, cardiac ischemia and fibrosis. However, the role of H19 in cardiomyocyte senescence remains to be further explored. Methods: Senescence-associated ß-galactosidases (SA-ß-gal) staining was used to detect cardiomyocyte senescence. Western blot, qRT-PCR and luciferase reporter assay were employed to evaluate the role of H19 in cardiomyocyte senescence and its underling molecular mechanism. Results: H19 level was significantly increased in high glucose-induced senescence cardiomyocytes and aged mouse hearts. Overexpression of H19 enhanced the number of SA-ß-gal-positive cells, and the expression of senescence-related proteins p53 and p21, whereas H19 knockdown exerted the opposite effects. Mechanistically, H19 was demonstrated as a competing endogenous RNA (ceRNA) for microRNA-19a (miR-19a): H19 overexpression downregulated miR-19a level, while H19 knockdown upregulated miR-19a. The expression of SOSC1 was dramatically increased in senescence cardiomyocytes and aged mouse hearts. Further experiments identified SOCS1 as a downstream target of miR-19a. H19 upregulated SOCS1 expression and activated the p53/p21 pathway by targeting miR-19a, thus promoting the cardiomyocytes senescence. Conclusion: Our results show that H19 is a pro-senescence lncRNA in cardiomyocytes acting as a ceRNA to target the miR-19a/SOCS1/p53/p21 pathway. Our research reveals a molecular mechanism of cardiomyocyte senescence regulation and provides a novel target of the therapy for senescence-associated cardiac diseases.

Macro-meso-microporous carbon composite derived from hydrophilic metal-organic framework as high-performance electrochemical sensor for neonicotinoid determination.

Electrochemical analysis enables pesticides monitoring become rapid and efficient. Herein, novel three dimensional nitrogen-doped macro-meso-microporous carbon composites (N/Cu-HPC) derived from polyvinylpyrrolidone (PVP) doped Cu-metal organic framework were successfully formed via one-pot solvothermal method followed by pyrolysis, which were further applied in high-performance electrochemical determination of neonicotinoid. The introduction of PVP endows the N/Cu-HPC good hydrophilicity preventing aggregation as well as more highly electronegative nitrogen species boosting electro-catalytic property dramatically. Interestingly, the macro-meso-microporous architecture improves mass and charge transports between neonicotinoid molecules and active sites such as Cu nanoparticles and carbon atoms possessing Lewis basicity next to pyridinic-N. Based on the N/Cu-HPC, imidacloprid (IDP), thiamethoxam (THA) and dinotefuran (DNF) were detected with wide linear detection ranges (0.5-60 µM for both IDP and DNF, 1-60 µM for THA) and low detection limits (0.026 µM for IDP, 0.062 µM for THA and 0.01 µM for DNF). Meanwhile, this sensor can be successfully used for determination of IDP, THA and DNF in oat, corn and rice with good recoveries (92.0-100.9%, RSD ≤ 4.8%), demonstrating that the N/Cu-HPC possesses a high potential to be an advanced sensing device for monitoring neonicotinoid in agricultural products.

Silencing of METTL3 attenuates cardiac fibrosis induced by myocardial infarction via inhibiting the activation of cardiac fibroblasts.

Cardiac fibrosis is characterized by the activation of cardiac fibroblasts and accumulation of extracellular matrix. METTL3, a component of methyltransferase complex, participates in multiple biological processes associated with mammalian development and disease progression. However, the role of METTL3 in cardiac fibrosis is still unknown. We performed fibroblasts activation with TGF-ß1 (20 ng/mL) in vitro and established in vivo mouse models with lentivirus to assess the effects of METTL3 on cardiac fibroblasts proliferation and collagen formation. Methylated RNA immunoprecipitation (MeRIP) was used to define the potential fibrosis-regulated gene. The expression level of METTL3 was increased in cardiac fibrotic tissue of mice with chronic myocardial infarction and cultured cardiac fibroblats (CFs) treated with TGF-ß1. Enforced expression of METTL3 promoted proliferation and fibroblast-to-myofibroblast transition and collagens accumulation, while silence of METTL3 did the opposite. Silence of METTL3 by lentivirus carrying METTL3 siRNA markedly alleviated cardiac fibrosis in MI mice. Transcriptome and N6-methyladenosine (m6 A) profiling analyses revealed that the expression and m6 A level of collagen-related genes were altered after silence of METTL3. METTL3-mediated m6 A modification is critical for the development of cardiac fibrosis, providing a molecular target for manipulating fibrosis and the associated cardiac diseases.

Aggregation behavior of aqu/nC60 produced via extended mixing: Influence of sunlight and agitation intensity.

Aggregation of C60, as an important process governing its mobility and toxicity, has been quantitatively investigated. However, effects of sunlight and agitation intensity on the aggregation behavior of aqu/nC60 produced via extended mixing, have not been clarified. Therefore, in the present study, the aggregation behavior of aqu/nC60 produced at 500 and 800 rpm in the absence and presence of sunlight was investigated. Aggregation with increasing concentrations could be accelerated, while changes of Zave and zeta potential were not obvious. Critical coagulation concentrations (CCCs) of aqu/nC60 obtained at 800 rpm in the absence/presence of sunlight and that at 500 rpm under sunlight were 330, 205 and 170 mM NaCl, and 10.0, 2.6 and 3.1 mM CaCl2, respectively. These CCCs indicated that the aqu/nC60 prepared by the extended mixing were more stable than those produced by other methods. Salt-induced aggregation occurred more easily for aqu/nC60 formed under sunlight than that formed in the dark. Extra surface oxidation induced by high agitation intensity remarkably increased the stability of aqu/nC60 in NaCl solutions. In contrast, in CaCl2 solutions, aqu/nC60 formed at high agitation intensity had similar stability or even inadequate stability to that obtained at low agitation intensity due to the charge neutralization and cross-link bridging.

LncRNA ACART protects cardiomyocytes from apoptosis by activating PPAR-γ/Bcl-2 pathway.

Cardiomyocyte apoptosis is an important process occurred during cardiac ischaemia-reperfusion injury. Long non-coding RNAs (lncRNA) participate in the regulation of various cardiac diseases including ischaemic reperfusion (I/R) injury. In this study, we explored the potential role of lncRNA ACART (anti-cardiomyocyte apoptosis-related transcript) in cardiomyocyte injury and the underlying mechanism for the first time. We found that ACART was significantly down-regulated in cardiac tissue of mice subjected to I/R injury or cultured cardiomyocytes treated with hydrogen peroxide (H2 O2 ). Knockdown of ACART led to significant cardiomyocyte injury as indicated by reduced cell viability and increased apoptosis. In contrast, overexpression of ACART enhanced cell viability and reduced apoptosis of cardiomyocytes treated with H2 O2 . Meanwhile, ACART increased the expression of the B cell lymphoma 2 (Bcl-2) and suppressed the expression of Bcl-2-associated X (Bax) and cytochrome-C (Cyt-C). In addition, PPAR-γ was up-regulated by ACART and inhibition of PPAR-γ abolished the regulatory effects of ACART on cell apoptosis and the expression of Bcl-2, Bax and Cyt-C under H2 O2 treatment. However, the activation of PPAR-γ reversed the effects of ACART inhibition. The results demonstrate that ACART protects cardiomyocyte injury through modulating the expression of Bcl-2, Bax and Cyt-C, which is mediated by PPAR-γ activation. These findings provide a new understanding of the role of lncRNA ACART in regulation of cardiac I/R injury.

Prediction of octanol-air partition coefficients for PCBs at different ambient temperatures based on the solvation free energy and the dimer ratio.

Temperature-dependent octanol-air partition coefficients (KOA) are of great importance in assessing the environmental behavior and fate of persistent organic pollutants including polychlorinated biphenyls (PCBs). Due to the tremendous amounts of time, effort and cost needed for the experimental determination of KOA, it is desirable to develop a rapid and precise predictive method to estimate KOA just based on molecular structure. In the present study, a predictive model for log KOA of PCBs at ambient temperatures was developed based on the thermodynamic relationship between KOA and the solvation free energy from air to octanol (ΔGOA). For the calculation of ΔGOA of PCBs, the optimal combination of theoretical method and basis-set was identified to be HF/MIDI!6D for both geometry optimization and energy calculation. Dimer formation could affect the partition behavior and promote the apparent KOA values of PCBs. After taking the effect of dimer formation into account, the goodness-of-fit, predictive ability, and robustness of the predictive model were significantly improved. Apparent log KOA values of PCBs at different ambient temperatures ranging from 283.15 to 303.15 K were predicted. Compared with other reported models, the model developed in the present study had not only comparable goodness-of-fit and predictive ability, but also a universal application domain and the relative independency of experimental data. Therefore, the solvation free energy method could be a promising method for the prediction of KOA.

LncRNA PCFL promotes cardiac fibrosis via miR-378/GRB2 pathway following myocardial infarction.

Long noncoding RNAs (lncRNAs) are a class of novel molecular regulators in cardiac development and diseases. However, the role of specific lncRNAs in cardiac fibrosis remains to be fully explored. The aim of the present study was to investigate the effects and underlying mechanisms of lncRNA PCFL (pro-cardiac fibrotic lncRNA) on cardiac fibrosis after myocardial infarction (MI). Cardiac fibroblasts (CFs) with gain and loss of function of PCFL and mice with global knockout or overexpression of PCFL were used to explore the effects of PCFL on cardiac fibrosis. The data showed that PCFL was significantly increased in hearts of mice subjected to MI and CFs treated with transforming growth factor-ß1 (TGF-ß1). Overexpression of PCFL promoted collagen production and CF proliferation, while silencing PCFL exhibited the opposite effects. Compared with wild type MI mice, heterozygous knockout of PCFL (PCFL+/-) in mice significantly improved heart function and reduced cardiac fibrosis after MI. While overexpression of PCFL impaired cardiac function and aggravated MI-induced cardiac fibrosis. The mechanistic data demonstrated that PCFL functioned as a sponge of miR-378. Luciferase reporter assay confirmed the interaction of PCFL with miR-378. MiR-378 inhibited collagen production by suppressing its target gene, GRB2 (growth factor receptor bound protein 2). Knockdown of PCFL led to an increase of miR-378. Silencing of miR-378 reserved the inhibitory effects of PCFL knockdown on collagen production, cell proliferation and GRB2 expression. In conclusion, the study identifies a novel pro-fibrotic lncRNA, PCFL, and the mechanism involves the direct interaction of PCFL with miR-378, which in turn relieves the inhibition effect of miR-378 on GRB2 and promotes cardiac fibrosis.

Increase of late sodium current contributes to enhanced susceptibility to atrial fibrillation in diabetic mice.

Studies demonstrated that the incidence of atrial fibrillation is significantly increased in patients with diabetes mellitus. Increase of late sodium current (INaL) has been associated with atrial arrhythmias. However, the role of INaL in the setting of atrial fibrillation in diabetes mellitus remained unknown. In this study, we investigated the alteration of INaL in the atria of diabetic mice and the therapeutic effect of its inhibitor (GS967) on the susceptibility of atrial fibrillation. The whole-cell patch-clamp technique was used to detect single cell electrical activities. The results showed that the density of INaL in diabetic cardiomyocytes was larger than that of the control cells at the holding potential of -100 mV. The action potential duration at both 50% and 90% repolarization, APD50 and APD90, respectively, was markedly increased in diabetic mice than in controls. GS967 application inhibited INaL and shortened APD of diabetic mice. High-frequency electrical stimuli were used to induce atrial arrhythmias. We found that the occurrence rate of atrial fibrillation was significantly increased in diabetic mice, which was alleviated by the administration of GS967. In GS967-treated diabetic mice, the INaL current density was reduced and APD was shortened. In conclusion, the susceptibility to atrial fibrillation was increased in diabetic mice, which is associated with the increased late sodium current and the consequent prolongation of action potential. Inhibition of INaL by GS967 is beneficial against the occurrence of atrial fibrillation in diabetic mice.

Involvement of lncR-30245 in Myocardial Infarction-Induced Cardiac Fibrosis Through Peroxisome Proliferator-Activated Receptor-γ-Mediated Connective Tissue Growth Factor Signalling Pathway.

BACKGROUND: Long noncoding RNAs (lncRNAs) are emerging as important mediators of cardiac pathophysiology. The aim of the present study is to investigate the effects of lncR-30245, an lncRNA, on cardiac fibrogenesis and the underlying mechanism. METHODS: Myocardial infarction (MI) and transforming growth factor (TGF)-ß1 were used to induce fibrotic phenotypes. Cardiac fibrosis was detected by Masson's trichrome staining. Cardiac function was evaluated by echocardiography. Western blot, quantitative reverse transcription-polymerase chain reaction, and pharmacological approaches were used to investigate the role of lncR-30245 in cardiac fibrogenesis. RESULTS: Expression of lncR-30245 was significantly increased in MI hearts and TGF-ß1-treated cardiac fibroblasts (CFs). LncR-30245 was mainly located in the cytoplasm. Overexpression of lncR-30245 promoted collagen production and CF proliferation. Knockdown of lncR-30245 significantly inhibited TGF-ß1-induced collagen production and CF proliferation. LncR-30245 overexpression inhibited the antifibrotic role of peroxisome proliferator-activated receptor (PPAR)-γ and increased connective tissue growth factor (CTGF) expression, whereas lncR-30245 knockdown exerted the opposite effects. Rosiglitazone, a PPAR-γ agonist, significantly inhibited lncR-30245-induced CTGF upregulation and collagen production in CFs. In contrast, T0070907, a PPAR-γ antagonist, attenuated the inhibitory effects of lncR-30245 small interfering RNA (siRNA) on TGF-ß1-induced CTGF expression and collagen production. LncR-30245 knockdown significantly enhanced ejection fraction and fractional shortening and attenuated cardiac fibrosis in MI mice. CONCLUSION: Our study indicates that the lncR-30245/PPAR-γ/CTGF pathway mediates MI-induced cardiac fibrosis and might be a therapeutic target for various cardiac diseases associated with fibrosis.

Ultrasensitive Colorimetric Chromium Chemosensor Based on Dye Color Switching under the Cr(VI)-Stimulated Au NPs Catalytic Activity.

In view of the high toxicity of Cr(VI), simple and rapid on-site analytical approaches are in high demand for environment monitoring. Herein, an innovative chemosensor is developed for on-site sensitive detection of Cr(VI) in minutes by the naked eye. The chemosensor consists of gallic acid-capped gold nanoparticles (GA-Au NPs), methylene blue (MB), and NaBH4. In the presence of Cr(VI) ions, the reduction of MB by NaBH4 is able to greatly accelerate due to the Cr(VI)-stimulated catalytic activity of GA-Au NPs, resulting in a color switching of MB from blue to colorless for the quantitative detection of Cr(VI). The chemosensor in solution exhibits excellent selectivity and ultrahigh sensitivity to Cr(VI), with the detection limits of 0.05 nM by UV-vis spectroscopy and 0.1 nM by the naked eye. Similarly, a paper-based chemosensor is obtained by immobilization of GA-Au NPs and MB onto a piece of filter paper, offering a more convenient approach for rapid on-site detection of Cr(VI). In addition, H2O2 as an oxidizing agent is employed to convert Cr(III) into Cr(VI), thus achieving speciation analysis of Cr. The applicability of a chemosensor is also validated by the detection of Cr speciation in water samples with satisfactory recoveries.

Selenocarrageenan-inspired hybrid graphene hydrogel as recyclable adsorbent for efficient scavenging of dyes and Hg2+ in water environment.

It remains a real challenge to treat the industrial wastewater containing hardly-decomposed dyes and heavy metal ions. Herein, an environment-friendly hybrid hydrogel is prepared by a simple mixing of selenocarrageenan (SeCA) and graphene oxide (GO) under heating and stirring for 5 min without any other reagent. Such a selenocarrageenan hybrid graphene hydrogel (SeCA-GH) without volume shrinkage exhibits excellent adsorption capacity and selective binding to dyes and Hg2+. The maximum adsorption capacity of methylene blue and Hg2+ on SeCA-GH is 168 mg g-1 and 331 mg·g-1 at 25 °C, respectively. Furthermore, the adsorption characteristics of SeCA-GH are investigated in detail, including saturated adsorption capacity, adsorption isotherm, and kinetic adsorption process. Notably, SeCA-GH can be easily regenerated and reused for multiple cycles without release of SeCA and GO. SeCA-GH as recyclable adsorbent offers a promising candidate for sustainable, affordable, and efficient removal of dyes and Hg2+ in water environment.

LncRNA ZFAS1 as a SERCA2a Inhibitor to Cause Intracellular Ca2+ Overload and Contractile Dysfunction in a Mouse Model of Myocardial Infarction.

RATIONALE: Ca2+ homeostasis-a critical determinant of cardiac contractile function-is critically regulated by SERCA2a (sarcoplasmic reticulum Ca2+-ATPase 2a). Our previous study has identified ZFAS1 as a new lncRNA biomarker of acute myocardial infarction (MI). OBJECTIVE: To evaluate the effects of ZFAS1 on SERCA2a and the associated Ca2+ homeostasis and cardiac contractile function in the setting of MI. METHODS AND RESULTS: ZFAS1 expression was robustly increased in cytoplasm and sarcoplasmic reticulum in a mouse model of MI and a cellular model of hypoxia. Knockdown of endogenous ZFAS1 by virus-mediated silencing shRNA partially abrogated the ischemia-induced contractile dysfunction. Overexpression of ZFAS1 in otherwise normal mice created similar impairment of cardiac function as that observed in MI mice. Moreover, at the cellular level, ZFAS1 overexpression weakened the contractility of cardiac muscles. At the subcellular level, ZFAS1 deleteriously altered the Ca2+ transient leading to intracellular Ca2+ overload in cardiomyocytes. At the molecular level, ZFAS1 was found to directly bind SERCA2a protein and to limit its activity, as well as to repress its expression. The effects of ZFAS1 were readily reversible on knockdown of this lncRNA. Notably, a sequence domain of ZFAS1 gene that is conserved across species mimicked the effects of the full-length ZFAS1. Mutation of this domain or application of an antisense fragment to this conserved region efficiently canceled out the deleterious actions of ZFAS1. ZFAS1 had no significant effects on other Ca2+-handling regulatory proteins. CONCLUSIONS: ZFAS1 is an endogenous SERCA2a inhibitor, acting by binding to SERCA2a protein to limit its intracellular level and inhibit its activity, and a contributor to the impairment of cardiac contractile function in MI. Therefore, anti-ZFAS1 might be considered as a new therapeutic strategy for preserving SERCA2a activity and cardiac function under pathological conditions of the heart.

Three-dimensional molybdenum disulfide/graphene hydrogel with tunable heterointerfaces for high selective Hg(II) scavenging.

A hierarchical and hybridized hydrogel with rational structure and composition as adsorbent possesses a series of distinct advantages, e.g., fast ion diffusion, high selectivity and good stability. Herein, a novel three-dimensional (3D) molybdenum disulfide (MoS2)-reduced graphene oxide (rGO) hydrogel with two-dimensional heterointerfaces is fabricated by an eco-friendly one-pot hydrothermal method. The heterointerfacial area could be readily tuned by the regulation of MoS2/rGO ratio, in order to improve the adsorption capacity and selectivity. The 3D MoS2-rGO hydrogel with 70 wt% MoS2 shows high selectivity for Hg(II) ions, with a distribution coefficient value (Kd) of 7.49 × 106 mL g-1 even in the presence of other coexisting ions. More attractively, the free-standing and flexible 3D MoS2-rGO hydrogel can be used as a column-packed device, providing an efficient pathway for the fast removal of 80 mg L-1 Hg(II) within 7 min to achieve a tolerable concentration of < 2 µg L-1 in 30 mL water with 5 mg of 3D MoS2-rGO hydrogel. Considering that the direct-contact adsorption is more efficient than oscillating adsorption, the 3D MoS2-rGO hydrogel as nanobuilding block shows a promising potential for cleaning the point-of-use water.

Suppression of microRNA-16 protects against acute myocardial infarction by reversing beta2-adrenergic receptor down-regulation in rats.

microRNA-16 (miR-16) has been shown to be up-regulated in ischemic heart. Beta2-adrenoreceptor (ß2-AR) exerts cardioprotective property in ischemic injury. This study aims to determine the effect of miR-16 in cardiac injury in rats and the possible involvement of ß2-AR in this process. Acute myocardial infarction (AMI) model in rats was induced by ligation of left coronary artery. Neonatal rat ventricular cells (NRVCs) were cultured in vitro tests. The cardiomyocyte model of oxidative injury was mimicked by hydrogen peroxide. The expression of miR-16 was obviously up-regulated and ß2-AR was remarkably down-regulated in both AMI rats and NRVCs under oxidative stress. miR-16 over-expression in NRVCs reduced cell viability and increased apoptosis. Conversely, inhibition of endogenous miR-16 with its specific inhibitor reversed these changes. Over-expression of miR-16 using an miR-16 lentivirus in AMI rats markedly increased cardiac infarct area, lactate dehydrogenase and creatine kinase activity, and exacerbated cardiac dysfunction. Lentivirus-mediated knockdown of miR-16 alleviated acute cardiac injury. Moreover, miR-16 over-expression significantly suppressed ß2-AR protein expression in both cultured NRVCs and AMI rats, while inhibition of miR-16 displayed opposite effect on ß2-AR protein expression. Luciferase assay confirmed that miR-16 could directly target the 3'untranslated region of ß2-AR mRNA. miR-16 is detrimental to the infarct heart and suppression of miR-16 protects rat hearts from ischemic injury via up-regulating of ß2-AR by binding to the 3'untranslated region of ß2-AR gene. This study indicates that targeting miR-16/ß2-AR axis may be a promising strategy for ischemic heart disease.