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Increased temperature and acidification are two important environmental factors affecting algal growth in marine ecosystems with the increase of atmospheric CO2. The dinoflagellate Amphidinium carterae and the diatom Phaeodactylum tricornutum were chosen to study the effect of warming and acidification on their sulfate assimilation and reduction processes by continuous incubation at different temperatures (15, 20 and 25 °C) and pHNBS values (8.10, 7.80 and 7.60). Variations in associated sulfur compounds, namely sulfate, dimethylsulfoniopropionate (DMSP), dimethylsulfide (DMS) and acrylic acid (AA) were observed. The largest sulfate uptake was at 25 °C for A. carterae and at 20 °C for P. tricornutum, however, the optimal growth temperature for both microalgae was 20 °C. The release of DMSP and DMS decreased in A. carterae while they increased in P. tricornutum under the condition of increased temperature. Seawater acidification increased the uptake of sulfate and promoted the growth of the microalgae. Acidification also reduced the release of DMSP, dissolved DMSP (DMSPd), DMS and AA from A. carterae with mean values of 55%, 22%, 9% and 40%, respectively. However, acidification increased the release of DMSP and DMSPd by P. tricornutum with mean values of 44% and 186%, the release of DMS was inhibited (25%) and with no significant difference in the release of AA (2%). Amino acids were found to inhibit the uptake of sulfate by the two microalgae, and the inhibitory effect of cysteine was found to be stronger than that of methionine. The inhibitory effect of amino acids was temperature sensitive and relatively weak at 20 °C. Besides, acidification could enhance the inhibitory effect and was evident in A. carterae. The sulfur metabolism intermediates (cysteine and methionine) have a feedback regulation effect on the sulfate absorption process of algae. [ABSTRACT FROM AUTHOR]

Dimethyl sulfide (DMS) is an important and dominant trace gas that is transferred from the ocean to the atmosphere; however, the production of DMS from marine algae is still rudimentary, with the enzymatic cleavage of dimethylsulfoniopropionate (DMSP) to DMS and acrylic acid (AA), one of the main considered pathways. Dissolved DMSP (DMSPd) was supplied to batch cultures of Prorocentrum minimum at different algal growth stages and the kinetics of overall DMSPd consumption and DMS (AA) production were investigated. The kinetics of overall DMSPd consumption and DMS (AA) production from DMSPd were different during the growth cycle. The cultures displayed Michaelis–Menten-type kinetics for DMS production during the entire growth period, which yielded an apparent half-saturation constant (Km(app)) value of 37.8 ± 12.8 μM and a maximum rate (Vmax) value of 75.6 ± 12.2 nmol min−1 (1010 cells)−1. The production rates of AA had a nearly linear fit over the concentration range of the added DMSPd except during mid-exponential growth phase. A Km(app) value of 1.73 ± 0.75 μM and a Vmax value of 2.36 ± 0.12 μmol min−1 (1010 cells)−1 were observed. The ratio of DMS/AA increased with the concentration of the added DMSPd, which was less than 12% during the entire growth period. The low ratios of DMS/(DMSP + AA), which ranged from 0.01 to 1.83%, demonstrate that degradation of DMSP tends to take a non-DMS-production pathway. The ratios of AA/(DMSP + AA) varied from 9 to 95% during the stationary phase and from 6 to 69% during the senescent phase and declined with substrate concentration when different concentrations of DMSPd were added. The degradation ratios of DMSPd were related to the initial concentrations of DMSPd. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO) is a non-traditional regulator of the growth of plants and phytoplankton. Here, the growth of five marine phytoplankton species, Platymonas helgolandica var. tsingtaoensis, Platymonas subcordiformis, Skeletonema costatum, Gymnodinium sp., and Prorocentrum donghaiense, was monitored, and carbonate system parameters in the culture media were determined after adding different concentrations of NO and sodium nitroprusside (SNP, NO donor) solutions. The two dietary algae (P. helgolandica var. tsingtaoensis and P. subcordiformis) and three red tide algae (S. costatum, Gymnodinium sp., and P. donghaiense) showed different responses to the same NO concentration. The red tide algae were more sensitive to exogenous NO than the dietary algae. NO with a concentration of 1.4 × 10−6 mol L−1 had the optimal stimulatory effect on the growth of the microalgae and increased the cell density by 9.8–38.3%. SNP solution with a concentration of 100 μmol L−1 inhibited the growth of the two dietary algae, and the cell density decreased by 38.8–84.3%. The addition of 10 μmol L−1 SNP solution to the three red tide algae decreased the cell density by 95.3–99.9%. Low concentrations of SNP (0.1 μmol L−1 for the two dietary algae and 0.01 μmol L−1 for the red tide algae) slightly promoted the growth of microalgae. High concentrations of NO (100 μmol L−1 SNP) inhibited CO2 assimilation, whereas low concentrations of NO (0.01–1.0 μmol L−1 SNP) promoted CO2 assimilation, indicating that NO participates in the regulation of photosynthesis. [ABSTRACT FROM AUTHOR]

Ocean acidification and global warming might affect the production of dimethylsulfoniopropionate (DMSP), dimethylsulfide (DMS), and dissolved acrylic acid (AAd) by marine phytoplankton. Monoculture incubation experiments were conducted with the dinoflagellate Amphidinium carterae to investigate the effects of elevated CO2 concentration and temperature on growth and productions of DMSP, DMS, and AAd. Two pCO2 levels were set as 400 and 1000 μatm, and two temperatures were set as 20 and 23 °C. The growth of A. carterae remained unaffected by an increase of CO2 to 1000 μatm and a rise of temperature of 3 °C. Moreover, the elevated CO2 concentration and temperature had no significant effects on the concentrations and cell-normalized concentrations of DMSP, DMS, and AAd. No additive or synergistic effects of elevated CO2 concentration and temperature on A. carterae were observed, indicating that A. carterae was insensitive to elevated CO2 and temperature in short time incubation. [ABSTRACT FROM AUTHOR]

Cardiomyocyte proliferation and regeneration are key to the functional recovery of myocardial tissue from injury. In the recent years, studies on cardiomyocyte proliferation overturned the traditional belief that adult cardiomyocytes permanently withdraw from the cell cycle activity. Hence, targeting cardiomyocyte proliferation is one of the potential therapeutic strategies for myocardial regeneration and repair. To achieve this, a deep understanding of the fundamental mechanisms involved in cardiomyocyte cell cycle as well as differences between neonatal and adult cardiomyocytes' cell cycle activity is required. This review focuses on the recent progress in understanding of cardiomyocyte cell cycle activity at different life stages viz., gestation, birth, and adulthood. The temporal expression/activities of major cell cycle activators (cyclins and CDKs), inhibitors (p21, p27, p57, p16, and p18), and cell-cycle-associated proteins (Rb, p107, and p130) in cardiomyocytes during gestation and postnatal life are described in this review. The influence of different transcription factors and microRNAs on the expression of cell cycle proteins is demonstrated. This review also deals major pathways (PI3K/AKT, Wnt/β-catenin, and Hippo-YAP) associated with cardiomyocyte cell cycle progression. Furthermore, the postnatal alterations in structure and cellular events responsible for the loss of cell cycle activity are also illustrated. [ABSTRACT FROM AUTHOR]

Production of dimethylsulfoniopropionate (DMSP), dimethylsulfide (DMS), and acrylic acid (AA) from 22 marine microalgae representing six phyla were examined at different growth stages. The concentrations of DMSP, DMS, and AA per cell in the media showed significant changes during the whole growth period, and the highest concentrations were found at the stationary growth phase or the senescent phase. Different species had different concentration levels of DMSP, DMS, and AA, among which Pyrrhophyta, Bacillariophyte, and Chrysophyta had relatively large release. The highest concentrations of DMSP, DMS, and AA were 56.70, 0.86, and 44.60 fmol cell−1 in Scrippsiella trochoidea , Prymnesiacee , and Karenia mikimotoi , respectively. The ratios of DMS/DMSP and AA/(DMSP+AA) in the 22 marine microalgae differed dramatically over the growth cycle. The DMS/DMSP ratios were <25%, indicating that only a small fraction of DMSP was converted to DMS by enzymatic cleavage. Moreover, there was a higher ratio of enzymatic degradation of DMSP in the senescent growth stage. The AA/(DMSP+AA) ratio, representing the degradation ratio of DMSP, increased significantly at the beginning of growth period and then decreased. Hence, the changes in these ratios could approximately illustrate the degradation mechanism of DMSP among diverse species at different growth phases. • High DMSP, DMS and AA concentrations were detected in Pyrrophyta and Bacillariophyta. • The maximum concentrations of DMSP and DMS appeared in the stationary growth stage. • The highest release of AA was observed in the early exponential growth period. • The maximum value of DMSP enzymatic degradation appeared in late growth phase. [ABSTRACT FROM AUTHOR]

Sialic acid (SA), as the ultimate epitope of polysaccharides, can act as a cap at the end of polysaccharide chains to prevent their overextension. Sialylation is the enzymatic process of transferring SA residues onto polysaccharides and is catalyzed by a group of enzymes known as sialyltransferases (SiaTs). It is noteworthy that the sialylation level of glycoproteins is significantly altered when digestive cancer occurs. And this alteration exhibits a close correlation with the progression of these cancers. In this review, from the perspective of altered SiaTs expression levels and changed glycoprotein sialylation patterns, we summarize the pathogenesis of gastric cancer (GC), colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC), and hepatocellular carcinoma (HCC). Furthermore, we propose potential early diagnostic biomarkers and prognostic indicators for different digestive cancers. Finally, we summarize the therapeutic value of sialylation in digestive system cancers. [Display omitted] • Sialylation level significantly altered during the oncogenesis of digestive cancers. • Structures of sialylated glycoproteins and interactions between SiaTs are complex. • Altered sialylation levels can be detected in sera, paving the way for diagnosis. • Reducing the burden of SAs weakens the function of sialylation in tumor cells. • The diagnostic and therapeutic value of sialylation need clinical trials to verify. [ABSTRACT FROM AUTHOR]

To examine the sulfate assimilation and reduction process and the regulation of illumination, diatom Phaeodactylum tricornutum and dinoflagellate Amphidinium carterae were selected for continuous simulation incubation under different photon flux densities (PFDs) (54, 108 and 162 μmol photons m−2 s−1), and concentration variations of related sulfur compounds sulfate, dimethylsulfoniopropionate (DMSP), dimethylsulfide (DMS) and acrylic acid (AA) in the culture system were observed. The optimal PFD for the growth of two microalgae was 108 μmol photons m−2 s−1. However, the maximum sulfate absorption occurred at 162 μmol photons m−2 s−1 for P. tricornutum and at 54 μmol photons m−2 s−1 for A. carterae. With the increase of PFD, the release of DMSP by P. tricornutum decreased while A. carterae increased. The largest release amount of DMS was 0.59 ± 0.05 fmol cells−1 for P. tricornutum and 2.61 ± 0.89 fmol cells−1 for A. carterae under their optimum growth light condition. The sulfate uptake of P. tricornutum was inhibited by the addition of amino acids, cysteine had a greater inhibitory effect than methionine, and the absorption process was controlled by light. The intermediate products of sulfur metabolism had an up–control effect on the sulfate uptake process of P. tricornutum. However, the addition of amino acids had no obvious effect on the sulfate absorption of A. carterae. • Illumination regulated sulfate assimilation of P. tricornutum and A. carterae. • 108 μmol photons m−2 s−1 was the optimum light condition for the algal growth. • Related sulfur compounds concentrations varied under different illumination. • Sulfur metabolic intermediates inhibited the sulfate uptake of P. tricornutum. • Sulfur metabolic intermediates had no obvious regulative law on A. carterae. [ABSTRACT FROM AUTHOR]

Telomerase is a promising diagnostic and prognostic biomarker for cancers. Sensitive, simple, and reliable telomerase activity detection is vital for cancer diagnosis. Herein, we developed an ultrasensitive visualized assay for telomerase activity that combined the exponential amplification reaction (EXPAR) and lateral flow assay for easy and quick signal readout, which we termed as a lateral flow readout-EXPAR (LFR-EXPAR) assay. In the LFR-EXPAR assay, telomerase elongation products initiate the exponential amplification reaction, the generated trigger hybridizes with the reporter to form the recognition site of the nicking enzyme, and the nicking enzyme cuts the reporter strand. The degradation of the reporter can be detected with a universal lateral flow dipstick and read out with the naked eye. After conducting a series of proof-of-concept investigations, the LFR-EXPAR assay was found to achieve a sensitivity comparable to that of a TRAP (telomere repeat amplification protocol) assay. The LFR-EXPAR assay can be used to realize ultrasensitive and point-of-care detection of telomerase without requiring specialized instruments, holding great promise for early cancer diagnosis. [ABSTRACT FROM AUTHOR]

Acrylic acid (AA), a short-chain fatty acid found in the ocean, is derived from the microbial cleavage of dimethylsulfoniopropionate in addition to terrestrial input. The aqueous photochemical transformation of AA in natural seawater, artificial seawater, and Milli-Q water was studied under artificial light (using a photochemical reactor) and natural light (by exposure to sunlight). A degradation study on field seawater was conducted inside and outside Jiaozhou Bay, which is located in the north of China. Kinetic studies showed that the degradation and reaction rate of AA in natural seawater were obviously higher than those in the other aqueous media under artificial and natural light, with the degradation characteristics in artificial seawater and Milli-Q water being similar. The degradation and reaction rate of AA in natural seawater significantly increased with decreased concentration. AA in different media exhibited relatively lower reaction rates under natural light than those under artificial light. However, AA at different concentrations had similar degradation and reaction rates under these two irradiation types. Visible light seemed more efficient for the degradation reaction than ultraviolet A and ultraviolet B rays. The concentrations and degradation of AA inside and outside the Jiaozhou Bay showed significantly seasonal variations, and the photochemical and microbial degradation both showed the maximum rates in autumn. The photochemical reaction rates were found to be lower than the microbial degradation rates in four seasons. The photochemical degradation inside the bay was always lower than that outside. The photochemical transformation of AA depended on seawater composition and field conditions. [ABSTRACT FROM AUTHOR]

By analyzing the sequencing results, we found that PKM2 was significantly enriched in the KEGG pathway associated with muscle development and was screened as a hub gene in the fast-growing group; hence, we speculate that PKM2 may be associated with the growth and development of Bian chickens. Keywords: miRNA-seq; skeletal muscle; Bian chicken; growth and development EN miRNA-seq skeletal muscle Bian chicken growth and development N.PAG N.PAG 15 04/26/22 20220415 NES 220415 1. Apart from research on genes related to Bian chicken growth, there are few studies on miRNA functions in Bian chicken growth. miRNA is a noncoding sequence with a length of approximately 22 nt, which inhibits the expression of target genes by binding to the 3'UTR region of mRNA [[5]]. In order to further explore the key DEMs and predicted target genes, we performed an interaction network analysis of genes enriched in KEGG pathways associated with muscle growth and development. [Extracted from the article]

Early diagnosis is important for improving the outcomes of keratoconus (KC). Stable expression and a closed-loop structure of circular RNAs (circRNAs) make them ideal for the diagnosis and treatment of diseases. However, the expression pattern and potential function of circRNAs in KC is not studied yet. Hence, this study explored the circRNA expression profile of KC corneas through transcriptome sequencing and circRNA expression profile analysis. The diagnostic potential of blood circRNAs for KC was explored by analysing the circRNAs' expression levels of fifty paired blood samples from patients with KC and normal controls. The results showed that 107 significantly upregulated and 145 significantly downregulated circRNAs (|fold change| ≥ 2.0, p -value <0.05) were identified in KC tissues. Eight top differently expressed circRNAs were further validated in more cornea samples. Among them, five circRNAs expressed in peripheral blood, and four circRNAs (circ_0006156, circ_0006117, circ_0000284 and circ_0001801) showed significant downregulation in KC patients' peripheral blood too. The blood circ_0000284 expression levels of early, moderate, and advanced KC patients both were significantly lower than the controls. The blood circ_0006117 expression levels present a positive correlation with corrected distance visual acuity values, and a negative correlation with back elevation values of KC eyes. Notably, the expression levels of these circRNAs distinguished KC patients from their healthy counterparts, with the area under the curve (AUC) of circ_0000284, circ_0001801, and circ_0006117 being 0.7306, 0.6871 and 0.6701, respectively. Further, the AUC value for five circRNAs under the logistic regression model was 0.8203, indicating that they can function as effective biomarkers for the KC diagnostics. In conclusion, the expression of circRNAs showed a relationship with KC, with four significantly differentially expressed circRNAs demonstrating potential as biomarkers for the disease. • The expression profile of circRNAs in the corneas was analysed by RNA-Seq. • A group of significantly regulated circRNAs in keratoconus tissues were identified. • Four significantly differentially expressed circRNAs in blood were identified. • Four circRNAs demonstrating potential as circulating biomarkers for the keratoconus. • Hsa_circ_0000284 has the best diagnostic performance in the diagnosis of keratoconus. [ABSTRACT FROM AUTHOR]

Hypoxia inducible factor-1α (HIF-1α) up-regulates the expression of programmed death ligand-1 (PD-L1) in some extracranial malignancies. However, whether it could increase PD-L1 expression in intracranial tumor is still unknown. Here, we explored the relationship between HIF-1α and PD-L1 expression in glioma, and investigated their clinical significance. In glioma patients, HIF-1α and PD-L1 were overexpressed in high grade glioma tissues and were significantly associated with poor survival. In glioma cells, PD-L1 expression was induced under hypoxia condition, and the enhanced PD-L1 expression was abrogated by either HIF-1α knock-down or HIF-1α inhibitor treatment. Furthermore, ChIP-qPCR analysis showed the direct binding of HIF-1α to PD-L1 proximal promoter region, providing evidence that HIF-1α up-regulates PD-L1 in glioma. In glioma murine model, the combination treatment with HIF-1α inhibitor and anti-PD-L1 antibody caused a more pronounced suppressive effect on tumor growth compared to either monotherapy. Immunologically, the combination treatment improved both dendritic cell (DC) and CD8+ T cell activation. Overall, our results demonstrated that positive correlation between PD-L1 and HIF-1α in glioma, and provide an alternative strategy, inhibiting HIF-1α, as combination therapies with immunotherapies to advance glioma treatment. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the effects of in vitro‐induced drug resistance on the virulence of Streptococcus. Micro‐dilution method was used to determine the minimal inhibitory concentration (MIC). In vitro‐induced drug resistance was conducted for S. agalactiae (CVCC1886) and S. dysgalactiae (CVCC3701) by gradually increasing the antimicrobial concentration (strains were from IVDC, China). PCR was used to detect the resistance and virulence genes of the strains before and after resistance induction. Colony morphology was observed to compare the physiological and biochemical properties of the strains. A total of 88 clean‐grade Kunming mice (obtained from Inner Mongolia University, Hohhot, China) were used in half of the lethal dose (LD50) test for detecting the changes in virulence of strains. The results showed that S. agalactiae (CVCC1886) and S. dysgalactiae (CVCC3701) developed resistance against seven kinds of antibiotics, respectively. Resistance and virulence genes of CVCC3701 were changed when treated by the Penicillin‐inducing. The growth of the CVCC3701‐PEN was decreased compared to the CVCC3701. Virulence test in mice indicated that the LD50 of CVCC3701 before induction and CVCC3701‐PEN after induction were 5.45 × 106 and 5.82 × 108 CFU/ml, respectively. Compared with the untreated bacteria, the bacterial virulence was reduced 1.1 × 102 times after resistance induction. In conclusion, S. dysgalactiae (CVCC3701) is a susceptible strain of drug resistance to antibiotics, in vitro‐induced drug resistance reduced the virulence of CVCC3701, but the virulence is still existing and also could result in the death of mice. For public health safety, it must be alert to the emergence of drug resistance of Streptococcus in animal production. [ABSTRACT FROM AUTHOR]

• NOx in wetlands was mainly generated from vegetation-covered sediments. • Denitrifiers dominated NO production, showing sensitivity to environmental gradients. • NO emissions would be underestimated without considering tidal pulses. Intertidal wetland sediments are an important source of atmospheric nitrogen oxides (NO x), but their contribution to the global NO x budget remains unclear. In this work, we conducted year-round and diurnal observations in the intertidal wetland of Jiaozhou Bay to explore their regional source-sink patterns and influence factors on NO x emissions (initially in the form of nitric oxide) and used a dynamic soil reactor to further extend the mechanisms underlying the tidal pulse of nitric oxide (NO) observed in our investigations. The annual fluxes of NO x in the vegetated wetland were significantly higher than those in the wetland without vegetation. Their annual variations could be attributed to changes in temperature and the amount of organic carbon in the sediment, which was derived from vegetated plants and promoted the carbon-nitrogen cycle. Anaerobic denitrifiers had advantages in the intertidal wetland sediment and accounted for the major NO production (63.8 %) but were still limited by nitrite and nitrate concentrations in the sediment. Moreover, the tidal pulse was likely a primary driver of NO x emissions from intertidal wetlands over short periods, which was not considered in previous investigations. The annual NO exchange flux considering the tide pulse contribution (8.93 ± 1.72 × 10–2 kg N ha–1 yr–1) was significantly higher than that of the non-pulse period (4.14 ± 1.13 × 10–2 kg N ha–1 yr–1) in our modeling result for the fluxes over the last decade. Therefore, the current measurement of NO x fluxes underestimated the actual gas emission without considering the tidal pulse. [Display omitted] [ABSTRACT FROM AUTHOR]

Brain-derived neurotrophic factor (BDNF) is one of the most abundantneurotrophins in the central nervous system. Numerous studies suggestthat BDNF has extensive roles by binding to its specific receptor, tropomyosin-related kinase receptor B (TrkB), and thereby triggering downstream signaling pathways. Recently, growing evidence highlightsthat the BDNF/TrkB pathway is expressed in the cardiovascular system andclosely associated with the development and outcome of cardiovascular diseases (CVD), including coronary artery disease, heart failure, cardiomyopathy, hypertension, and metabolic diseases. Furthermore, circulating BDNF has also been revealed as a new potential biomarker for both diagnosis and prognosis of CVD. In this review, we discuss the current evidence of the emerging role of BDNF/TrkBsignalingand address the challenges that remain in translating these discoveries to novel therapeutic strategies for CVD. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO) has been identified as a key physiological modulator and signaling molecule in animals and plants. However, due to its high reactivity, our knowledge of its production and consumption pathways in the ocean remain limited. Laboratory experiments showed that Ulva prolifera can produce NO, producing as much as 0.44 ± 0.04 nmol h−1 g−1. During the growth period, U. prolifera released NO, but during the decay period NO was absorbed by U. prolifera and bacteria. Furthermore, field investigations examined NO concentrations in the coastal waters of the Yellow Sea off Qingdao, where the U. prolifera green tide occurred in summer 2018. The average concentrations of NO in the surface seawater were 70.2 ± 38.2 pmol L−1 and 18.9 ± 10.3 pmol L−1 in the late- and after-bloom periods, respectively. NO release by U. prolifera was the primary contributor to the high NO concentrations during the late-bloom period. The study area was a net source of NO to the atmosphere during the study period, with average NO sea-air fluxes from the Qingdao coastal waters being 1.5 × 10−12 mol m−2 s−1 and 0.4 × 10−12 mol m−2 s−1 in the late- and after-bloom periods, respectively. This study concluded that the coastal waters of the Yellow Sea off Qingdao contributed more NO to the atmosphere during the bloom of U. prolifera than afterward. Image 1 • The growing U. prolifera could produce NO with the maximum rate of 0.44 nmol h−1 g−1. • The rate of NO release by U. prolifera was lower than the photoproduction rate. • NO concentration during the late-bloom was 2.7 times higher than after the bloom. • The study area acted as a source of NO to the air with a higher flux during a bloom. [ABSTRACT FROM AUTHOR]

The endothelium is crucially involved in the pathogenesis of atherosclerosis according to accumulating evidence. Moreover, recent studies have showed that lncRNAs could serve as biomarkers of cardiovascular diseases, in particular atherosclerosis. However, the underlying mechanism of endothelial dysfunction involving lncRNAs in atherosclerosis remains unknown. This study investigated the mechanism of lncRNA XXYLT1-AS2 in endothelial dysfunction in atherosclerosis. The levels of lncRNA XXYLT1-AS2 , FUS, VCAM-1, MCP-1, p-AKT, and p-P65 were measured in arteries and HUVEC cell lines via quantitative real-time PCR or Western blot. FISH assay demonstrated that XXYLT1-AS2 and FUS are localized in the nucleus. HUVECs were transfected with si- XXYLT1-AS2 or XXYLT1-AS2 to further assess cell proliferation, migration, and adhesion. Furthermore, bioinformatics analysis, RNA immunoprecipitation and immunofluorescence were performed to investigate the target genes of XXYLT1-AS2 and possible signal pathways. Overexpression of XXYLT1-AS2 inhibited cell proliferation and migration, reduced the expression of adhesion molecules (VCAM-1) and chemoattractant proteins (MCP-1), and restrained monocyte adhesion to endothelial cells. Mechanistic investigations indicated that XXYLT1-AS2 directly interacts with the target gene FUS/cyclin D1 and modulates the proliferation and migration of endothelial cells (ECs). Moreover, XXYLT1-AS2 exerts a protective role against the inflammatory response in atherosclerosis by blocking NF-κB activity. Clinically, the involvement of XXYLT1-AS2 /FUS was also observed in human arteries and the results were consistent with the in vitro analysis. Our study identified a novel long non-coding RNA (XXYLT1-AS2) and suggests that it might act as an underlying therapeutic target in atherosclerosis-related diseases by regulating ECs functions. Image 1 • LncRNA XXYLT1-AS2 modulates endothelial dysfunction to serve as a critical repressor of atherosclerosis. • LncRNA XXYLT1-AS2 upregulated FUS expression, thereby inhibiting HUVEC proliferation and migration via repressing cyclin D1. • LncRNA XXYLT1-AS2 negatively regulated monocyte adhesion and the level of VCAM-1 and MCP-1 by targeting NF-κB pathway. [ABSTRACT FROM AUTHOR]

Angiogenesis is the physiological process of new blood vessel formation from existing capillary vessels or posterior capillary veins. Its dysfunction could result in a number of diseases, such as cardiovascular diseases and cancer, contributing to death and disability worldwide. Circular RNAs (circRNAs) are a class of novel identified RNA molecules with a special covalent loop structure without a 5′ cap and 3' tail, which can lead to novel back-splicing or skipping events from precursor mRNAs. Accumulating evidence suggests that circRNA play critical roles in diseases; in particular, they are abundantly and abnormally expressed in angiogenesis-related diseases. In this review, we describe the role of circRNA under pathological conditions, discuss the association between circRNA and angiogenesis, classify the regulatory mechanisms and suggest that circRNA can be used as potential therapeutic targets for angiogenesis-related diseases under clinical evaluation. Image 1 • circRNAs are critically involved in angiogenesis, angiocardiopathy and cancer. • circRNAs are stable and abundantly distributed indicating a potential role in diseases. • circRNA might target miRNA as a sponge and are an emerging therapeutic target for angiogenesis-related diseases. • The research of coding potential of circRNA suggests the possible effective treatment of related diseases in the future. [ABSTRACT FROM AUTHOR]

Brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) pathway is associated with ischemic heart diseases (IHD). 7,8-dihydroxyflavone (7,8-DHF), BDNF mimetic, is a potent agonist of TrkB. We aimed to investigate the effects and the underlying mechanisms of 7,8-DHF on cardiac ischemia. Myocardial ischemic mouse model was induced by ligation of left anterior descending coronary artery. 7,8-DHF (5 mg/kg) was administered intraperitoneally two days after ischemia for four weeks. Echocardiography, HE staining and transmission electron microscope were used to examine the function, histology and ultrastructure of the heart. H9c2 cells were treated with hydrogen peroxide (H 2 O 2), 7,8-DHF or TrkB inhibitor ANA-12. The effects of 7,8-DHF on cell viability, mitochondrial membrane potential (MMP) and mitochondrial superoxide generation were examined. Furthermore, mitochondrial fission and protein expression of mitochondrial dynamics (Mfn2 [mitofusin 2], OPA1 [optic atrophy 1], Drp1 [dynamin-related protein 1] and Fis-1 [fission 1]) was detected by mitotracker green staining and western blot, respectively. 7,8-DHF attenuated cardiac dysfunction and cardiomyocyte abnormality of myocardial ischemic mice. Moreover, 7,8-DHF increased cell viability and reduced cell death accompanied by improving MMP, inhibiting mitochondrial superoxide and preventing excessive mitochondrial fission of H 2 O 2 -treated H9c2 cells. The cytoprotective effects of 7,8-DHF were antagonized by ANA-12. Mechanistically, 7,8-DHF repressed OMA1-dependent conversion of L-OPA1 into S-OPA1, which was abolished by Akt inhibitor. In conclusion, 7,8-DHF protects against cardiac ischemic injury by inhibiting the proteolytic cleavage of OPA1. These findings provide a novel pharmacological effect of 7,8-DHF on mitochondrial dynamics and a new potential target for IHD. Image 1 • 7,8-DHF attenuates ischemia/H 2 O 2 -induced cardiomyocyte injury. • 7,8-DHF inhibits excessive mitochondrial fission in ischemic heart. • 7,8-DHF inhibits OMA1-dependent conversion of L-OPA1 into S-OPA1. • Akt inhibitor abolished the effects of 7,8-DHF on mitochondrial dynamics. [ABSTRACT FROM AUTHOR]

The amphibian metamorphosis assay (AMA) was proposed by the Organization for Economic Cooperation and Development (OECD) to screen thyroid disruptors of vertebrate species. The general experimental design of the AMA exposes Nieuwkoop and Faber (NF) stage 51 Xenopus laevis tadpoles to test chemical concentrations for 21 d. However, recent studies demonstrated that thyroid gland began to function after NF stage 45 in X. laevis. Thus, in this study, we initiated exposure with NF stage 48 tadpoles when the thyroid gland is still in a preliminary development period, to compare the sensitivity of the AMA with NF 48 stage and NF 51 stage tadpoles. Further, the application and sensitivity of the optimized AMA were evaluated and validated by two known thyroid toxicants methimazole (MMI) and sodium perchlorate (SP). The observational endpoints are developmental stage, hind limb length (HLL), snout–vent length (SVL), wet weight, and daily observations of mortality. The results were as follows. Although the sensitivity to endpoint of growth, such as wet weight and SVL was similar between the two assays, our optimized AMA detected delaying effects of 1 mg/L MMI and 32 μg/L SP on metamorphosis development both on day 7 and at test termination, which were lower than those in AMA. Additionally, it is easier to get a large number of animals at NF stage 48 than NF stage 51 in a short time. Thus, it is suggested that the NF stage 48 tadpoles might be applied to the AMA for efficiently screening the thyroid-active substances. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text. Background: The adult mammalian cardiomyocytes lose their proliferative capacity, which is responsible for cardiac dysfunction and heart failure following injury. The molecular mechanisms underlying the attenuation of adult cardiomyocyte proliferation remain largely unknown. Because long noncoding RNAs (lncRNAs) have a critical role in the development of cardiovascular problems, we investigated whether lncRNAs have any role in the regulation of cardiomyocyte proliferation and cardiac repair. Methods: Using bioinformatics and initial analysis, we identified an lncRNA, named CPR (cardiomyocyte proliferation regulator), that has a potential regulatory role in cardiomyocyte proliferation. For in vivo experiments, we generated CPR knockout and cardiac-specific CPR-overexpressing mice. In isolated cardiomyocytes, we used adenovirus for silencing (CPR–small interfering RNA) or overexpressing CPR. To investigate the mechanisms of CPR function in cardiomyocyte proliferation, we performed various analyses including quantitative reverse transcription–polymerase chain reaction, Western blot, histology, cardiac function (by echocardiography), transcriptome analyses (microarray assay), RNA pull-down assay, and chromatin immunoprecipitation assay. Results: CPR level is comparatively higher in the adult heart than in the fetal stage. The silencing of CPR significantly increased cardiomyocyte proliferation in postnatal and adult hearts. Moreover, CPR deletion restored the heart function after myocardial injury, which was evident from increased cardiomyocyte proliferation, improvement of myocardial function, and reduced scar formation. In contrast, the neonatal cardiomyocyte proliferation and cardiac regeneration were remarkably suppressed in CPR-overexpressing mice or adeno-associated virus serotype 9–CPR—overexpressing heart. These results indicate that CPR acts as a negative regulator of cardiomyocyte proliferation and regeneration. Next, we found that CPR targets minichromosome maintenance 3, an initiator of DNA replication and cell cycle progression, to suppress cardiomyocyte proliferation. CPR silenced minichromosome maintenance 3 expression through directly interacting and recruiting DNMT3A to its promoter cysteine-phosphate-guanine sites, as evident from decreased minichromosome maintenance 3 promoter methylation and increased minichromosome maintenance 3 expression in CPR knocked-down cardiomyocytes and CPR knockout mouse heart. These results were confirmed in CPR-overexpressing cardiomyocytes and CPR-overexpressing mouse heart. Conclusions: Together, our findings identified that CPR is a suppressor of cardiomyocyte proliferation and indicated that lncRNAs take part in the regulation of cardiomyocyte proliferation and cardiac repair. Our study provides an lncRNA-based therapeutic strategy for effective cardiac repair and regeneration. [ABSTRACT FROM AUTHOR]

Peroxisome proliferator-activated receptors (PPARs) play vital roles in cardiovascular pathophysiology, such as energy balance, cell proliferation/apoptosis, inflammatory response, and adipocyte differentiation. These vital roles make PPARs potential targets for therapeutic prevention of cardiovascular diseases (CVDs). Emerging evidence indicates that the crosstalk of microRNAs (miRNAs) and PPARs contributes greatly to CVD pathogenesis. PPARs are inhibited by miRNAs at posttranscriptional mechanisms in the progress of pulmonary hypertension and vascular dysfunction involving cell proliferation/apoptosis, communication, and normal function of endothelial cells and vascular smooth muscle cells. In the development of atherosclerosis and stroke, the activation of PPARs could change the transcripts of target miRNA through miRNA signalling. Furthermore, the mutual regulation of PPARs and miRNAs involves cell proliferation/apoptosis, cardiac remodeling, and dysfunction in heart diseases. In addition, obesity, an important cardiovascular risk, is modulated by the regulatory axis of PPARs/miRNAs, including adipogenesis, adipocyte dysfunction, insulin resistance, and macrophage polarization in adipose tissue. In this review, the crosstalk of PPARs and miRNAs and their emerging regulatory roles are summarized in the context of CVDs and risks. This provides an understanding of the underlying mechanism of the biological process related to CVD pathophysiology involving the interaction of PPARs and miRNAs and will lead to the development of PPARs/miRNAs as effective anti-CVD medications. [ABSTRACT FROM AUTHOR]

Autophagy, which is an evolutionarily conserved process according to the lysosomal degradation of cellular components, plays a critical role in maintaining cell homeostasis. Autophagy and mitochondria autophagy (mitophagy) contribute to the preservation of cardiac homeostasis in physiological settings. However, impaired or excessive autophagy is related to a variety of diseases. Recently, a close link between autophagy and cardiac disorders, including myocardial infarction, cardiac hypertrophy, cardiomyopathy, cardiac fibrosis, and heart failure, has been demonstrated. MicroRNAs (miRNAs) are a class of small non-coding RNAs with a length of approximately 21–22 nucleotides (nt), which are distributed widely in viruses, plants, protists, and animals. They function in mediating the post-transcriptional gene silencing. A growing number of studies have demonstrated that miRNAs regulate cardiac autophagy by suppressing the expression of autophagy-related genes in a targeted manner, which are involved in the pathogenesis of heart diseases. This review summarizes the role of microRNAs in cardiac autophagy and related cardiac disorders. Furthermore, we mainly focused on the autophagy regulation pathways, which consisted of miRNAs and their targeted genes. [ABSTRACT FROM AUTHOR]

PIWI proteins and piRNAs primarily functions as a safeguard of germline cells by activating epigenetic regulations, silencing transposons and maintaining chromatin structure. Increasing evidences reveal that PIWI proteins and piRNAs have broader functions in many vital biological processes including cell proliferation, differentiation and survival. They have been recognized as a crucial factor in the cellular events due their role in controlling mRNA expression, turnover and translation. PIWIs, with or without its partner non-coding RNA (piRNA), govern the expression and activity of many transcription factors and signaling molecules by mastering their expression and/or post-translational modifications by directly interacting with them. In this review, we focus on the functional role of PIWI family of proteins and piRNA in physiological and pathological conditions. We compile the current knowledge about the impact of alterations of PIWI and/or piRNA on expression and activities of signaling mediators and transcriptional networks associated with cell differentiation, proliferation and survival. [ABSTRACT FROM AUTHOR]

Brain-derived neurotrophic factor (BDNF)/tyrosine kinase receptor B (TrkB) pathway is a therapeutic target in cardiac diseases. A BDNF mimetic, 7,8-dihydroxyflavone (7,8-DHF), is emerging as a protective agent in cardiomyocytes; however, its potential role in cardiac fibroblasts (CFs) and fibrosis remains unknown. Thus, we aimed to explore the effects of 7,8-DHF on cardiac fibrosis and the possible mechanisms. Myocardial ischemia (MI) and transforming growth factor-β1 (TGF-β1) were used to establish models of cardiac fibrosis. Hematoxylin & eosin and Masson's trichrome stains were used for histological analysis and determination of collagen content in mouse myocardium. Cell viability kit, EdU (5-ethynyl-2′-deoxyuridine) assay and immunofluorescent stain were employed to examine the effects of 7,8-DHF on the proliferation and collagen production of CFs. The levels of collagen I, α-smooth muscle actin (α-SMA), TGF-β1, Smad2/3, and Akt as well as circadian rhythm-related signals including brain and muscle Arnt-like protein 1 (Bmal1), period 2 (Per2), and cryptochrome 2 (Cry2) were analyzed. Treatment with 7,8-DHF markedly alleviated cardiac fibrosis in MI mice. It inhibited the activity of CFs accompanied by decreasing number of EdU-positive cells and downregulation of collagen I, α-SMA, TGF-β1, and phosphorylation of Smad2/3. 7,8-DHF significantly restored the dysregulation of Bmal1, Per2, and Cry2, but inhibited the overactive Akt. Further, inhibition of Bmal1 by SR9009 effectively attenuated CFs proliferation and collagen production of CFs. In summary, these findings indicate that 7,8-DHF attenuates cardiac fibrosis and regulates circadian rhythmic signals, at least partly, by inhibiting Bmal1/Akt pathway, which may provide new insights into therapeutic cardiac remodeling. [Display omitted] • 7,8-DHF alleviates ischemia-induced cardiac fibrosis. • 7,8-DHF inhibits the proliferation and differentiation of cardiac fibroblasts. • 7,8-DHF restores circadian rhythm and Akt signals in cardiac fibrosis. • Inhibition of Bmal1 by SR9009 inhibits the activity of cardiac fibroblasts. [ABSTRACT FROM AUTHOR]

As the degradation products of dimethylsulfoniopropionate (DMSP), dimethylsulfide (DMS) and acrylic acid (AA) are crucial to the sulfur cycle in the ocean. However, the biogeochemical processes of DMSP, DMS, and AA remain unclear. A monthly investigation was conducted to determine the DMSP, DMS, and AA concentrations and related parameters in the surface water of Jiaozhou Bay, a semi-enclosed bay in the western Yellow Sea, from December 2010 to November 2011. The monthly mean concentrations of DMSP, DMS, and AA were in the ranges of 5.02–27.25 nmol L−1, 0.41–3.14 nmol L−1, and below the detection limit–301.75 nmol L−1, respectively, showing significant seasonal variations with higher concentrations in summer than in autumn. The results were attributed to a combination of biogenic factors, including phytoplankton, zooplankton, and bacteria, as well as environmental factors, such as temperature and nutrients. The DMSP, DMS, and AA concentrations were not significantly correlated with chlorophyll a and bacterial abundance because of the influence of the community structure and anthropogenic activities. DMS was mainly produced by the enzymatic cleavage of DMSP, whereas AA was affected primarily by terrigenous input. The monthly mean sea-to-air fluxes of DMS ranged from 0.74 (in Apr) to 6.55 (in Jan) μmol m−2 d−1 with an average of 2.80 μmol m−2 d−1. • DMSP, DMS, and AA showed significant seasonal variations. • Biogenic sulfur variation was a combination of biogenic and environmental factors. • The monthly mean sea-to-air fluxes of DMS was estimated. [ABSTRACT FROM AUTHOR]

Necrosis is programmed and is one of the main forms of cell death in the pathological process in cardiac diseases. MicroRNAs (miRNAs) have emerged as key gene regulators in many diseases. However, how miRNAs contribute to programmed necrosis is poorly defined. Here we report that miR-2861 and adenine nucleotide translocase 1 (ANT1) constitute an axis that regulates necrotic cell death in the heart. Our results show that ANT1 inhibits H 2 O 2 -induced cardiomyocytes necrosis. ANT1 also antagonizes myocardial necrosis in a mouse ischemia/reperfusion (I/R) model. We further demonstrate that miR-2861 directly binds to the coding sequence of ANT1 and suppresses the expression of ANT1 mRNA and protein. MiR-2861 induces necrotic cell death. In contrast, knockdown of miR-2861 attenuates H 2 O 2 -induced necrosis in cardiomyocytes. Also, miR-2861 knockdown protects heart from I/R injury and necrotic cell death in vivo. MiR-2861 regulates necrosis and myocardial infarction through targeting ANT1. Collectively, these data identify miR-2861 and ANT1 as two novel regulators of cardiomyocyte necrosis and myocardial infarction, and suggest potential therapeutic targets in treatment of cardiac diseases. [ABSTRACT FROM AUTHOR]

Summary MicroRNAs (miRNAs) are small non-coding RNAs, and they bind to complementary sequences in the three prime untranslated regions (3′ UTRs) of target mRNA transcripts, thereby inhibiting mRNA translation or promoting mRNA degradation. Excessive reactive oxygen species (ROS) can cause cell-damaging effects through oxidative modification of macromolecules leading to their inappropriate functions. Such oxidative modification is related to cancers, aging, and neurodegenerative and cardiovascular diseases. Here we report that miRNAs can be oxidatively modified by ROS. We identified that miR-184 upon oxidative modification associates with the 3′ UTRs of Bcl-xL and Bcl-w that are not its native targets. The mismatch of oxidized miR-184 with Bcl-xL and Bcl-w is involved in the initiation of apoptosis in the study with rat heart cell line H9c2 and mouse models. Our results reveal a model of ROS in regulating cellular events by oxidatively modifying miRNA. [ABSTRACT FROM AUTHOR]

Long noncoding RNAs (lncRNAs) are emerging as new players in gene regulation, but whether lncRNAs operate in the processing of miRNA primary transcript is unclear. Also, whether lncRNAs are involved in the regulation of the mitochondrial network remains to be elucidated. Here, we report that a long noncoding RNA, named mitochondrial dynamic related lncRNA (MDRL), affects the processing of miR-484 primary transcript in nucleus and regulates the mitochondrial network by targeting miR-361 and miR-484. The results showed that miR-361 that predominantly located in nucleus can directly bind to primary transcript of miR-484 (pri-miR-484) and prevent its processing by Drosha into pre-miR-484. miR-361 is able to regulate mitochondrial fission and apoptosis by regulating miR-484 levels. In exploring the underlying molecular mechanism by which miR-361 is regulated, we identified MDRL and demonstrated that it could directly bind to miR-361 and downregulate its expression levels, which promotes the processing of pri-miR-484. MDRL inhibits mitochondrial fission and apoptosis by downregulating miR-361, which in turn relieves inhibition of miR-484 processing by miR-361. Our present study reveals a novel regulating model of mitochondrial fission program which is composed of MDRL, miR-361 and miR-484. Our work not only expands the function of the lncRNA pathway in gene regulation but also establishes a new mechanism for controlling miRNA expression. [ABSTRACT FROM AUTHOR]

The rhythmic contraction of cardiomyocytes consumes a lot of energy. 90% of ATP in cardiomyocytes is produced by mitochondria. Maintenance of a healthy population of mitochondria by mitophagy is critical for cardiomyocyte survival and normal function. Mitophagy refers to selective removal of damaged mitochondria by autophagy mechanism. The process of mitophagy must be restricted to dysfunctional mitochondria and maintained at a balanced level. Disruption in the balance inevitably leads to cardiomyocyte injury and dysfunction. Accumulating evidence suggests that mitophagy plays a pivotal role in ischaemia/reperfusion‐induced cardiomyocyte injury. In this review, we focus on the current understanding of mitophgy in cardiomyocyte function, the implications for cardiomyocyte injury in response to ischaemia/reperfusion as well as their underlying potential mechanisms. [ABSTRACT FROM AUTHOR]

Background: The adult mammalian cardiomyocytes lose their proliferative capacity, which is responsible for cardiac dysfunction and heart failure following injury. The molecular mechanisms underlying the attenuation of adult cardiomyocyte proliferation remain largely unknown. Because long noncoding RNAs (lncRNAs) have a critical role in the development of cardiovascular problems, we investigated whether lncRNAs have any role in the regulation of cardiomyocyte proliferation and cardiac repair.Methods: Using bioinformatics and initial analysis, we identified an lncRNA, named CPR (cardiomyocyte proliferation regulator), that has a potential regulatory role in cardiomyocyte proliferation. For in vivo experiments, we generated CPR knockout and cardiac-specific CPR-overexpressing mice. In isolated cardiomyocytes, we used adenovirus for silencing (CPR-small interfering RNA) or overexpressing CPR. To investigate the mechanisms of CPR function in cardiomyocyte proliferation, we performed various analyses including quantitative reverse transcription-polymerase chain reaction, Western blot, histology, cardiac function (by echocardiography), transcriptome analyses (microarray assay), RNA pull-down assay, and chromatin immunoprecipitation assay.Results: CPR level is comparatively higher in the adult heart than in the fetal stage. The silencing of CPR significantly increased cardiomyocyte proliferation in postnatal and adult hearts. Moreover, CPR deletion restored the heart function after myocardial injury, which was evident from increased cardiomyocyte proliferation, improvement of myocardial function, and reduced scar formation. In contrast, the neonatal cardiomyocyte proliferation and cardiac regeneration were remarkably suppressed in CPR-overexpressing mice or adeno-associated virus serotype 9-CPR-overexpressing heart. These results indicate that CPR acts as a negative regulator of cardiomyocyte proliferation and regeneration. Next, we found that CPR targets minichromosome maintenance 3, an initiator of DNA replication and cell cycle progression, to suppress cardiomyocyte proliferation. CPR silenced minichromosome maintenance 3 expression through directly interacting and recruiting DNMT3A to its promoter cysteine-phosphate-guanine sites, as evident from decreased minichromosome maintenance 3 promoter methylation and increased minichromosome maintenance 3 expression in CPR knocked-down cardiomyocytes and CPR knockout mouse heart. These results were confirmed in CPR-overexpressing cardiomyocytes and CPR-overexpressing mouse heart.Conclusions: Together, our findings identified that CPR is a suppressor of cardiomyocyte proliferation and indicated that lncRNAs take part in the regulation of cardiomyocyte proliferation and cardiac repair. Our study provides an lncRNA-based therapeutic strategy for effective cardiac repair and regeneration. [ABSTRACT FROM AUTHOR]

Recently, high-entropy alloy thin films (HEATFs) with nanocrystalline structures and high hardness were developed by magnetron sputtering technique and have exciting potential to make small structure devices and precision instruments with sizes ranging from nanometers to micrometers. However, the strength and deformation mechanisms are still unclear. In this work, nanocrystalline Al0.3CoCrFeNi HEATFs with a thickness of ~4 μm were prepared. The microstructures of the thin films were comprehensively characterized, and the mechanical properties were systematically studied. It was found that the thin film was smooth, with a roughness of less than 5 nm. The chemical composition of the high entropy alloy thin film was homogeneous with a main single face-centered cubic (FCC) structure. Furthermore, it was observed that the hardness and the yield strength of the high-entropy alloy thin film was about three times that of the bulk samples, and the plastic deformation was inhomogeneous. Our results could provide an in-depth understanding of the mechanics and deformation mechanism for future design of nanocrystalline HEATFs with desired properties. [ABSTRACT FROM AUTHOR]