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Paralytic shellfish toxins (PST) in shellfish products have led to severe risks to human health. To monitor the risk, the Canadian Shellfish Sanitation Program has been collecting longitudinal PST measurements in blue mussel (Mytilus edulis) and soft-shell clam (Mya arenaria) samples in six coastal provinces of Canada. The spatial distributions of major temporal variation patterns were studied via Functional Principal Component Analysis. Seasonal increases in PST contamination were found to vary the most in terms of magnitude along the coastlines, which provides support for location-specific management of the time-sensitive PST contamination. In British Columbia, the first functional principal component (FPC1) indicated the variance among the magnitudes, while FPC2 indicated the seasonality of the PST levels. The temporal variations tended to be positively correlated with the abundance of dianoflagellates Alexandrium spp., and negatively with precipitation and inorganic nutrients. These findings indicate the underlying mechanism of PST variation in various geographical settings. In New Brunswick, Prince Edward, and Nova Scotia, the top FPCs indicated that the PST contamination differed mostly in the seasonal increase of the PST level during summer. • Multi-decade Paralytic Shellfish Toxins (PST) in Canada were analyzed. • Shellfish harvesting sites differed the most in seasonal elevation of PST levels. • The spring-to-autumn period of increased PST was found in BC, QC, NB, and NS. • Rainfall, Alexandrium spp., nitrate/nitrite, and phosphate correlated with PST. • Higher seasonal increases tended to occur at locations of strong water mixing. [ABSTRACT FROM AUTHOR]

In this experiment, three different producing methods, that is pre-fermentation, refrigeration (4 ℃, 24 h) and then re-fermentation (C1), refrigeration (4 ℃, 24 h) and then fermentation (C2), fermentation and then refrigeration (4 ℃, 24 h) (C3), were conducted to compare their effects on physicochemical and fermentation properties of refrigerated dough. The results showed that under refrigerated storage, the number of yeast cells decreased slightly, while yeast activity in C2 dough was higher than that in C1 and C3 dough. Dough refrigeration (4 ℃) led to a decrease in reducing sugar, ethanol, and glycerol content, an increase in the glutathione (GSH) content, and a decrease in amylase activity. In refrigerated dough, the α-helix became irregularly curled, the degree of water binding to other macromolecules weakened, and the proportion of free water increased. Compared to the control group, the content of total sulfhydryl group, disulfide bond, hydrogen bonds, and hydrophobic interactions increased in the refrigerated dough, the tensile force and displacement of C1 and C3 refrigerated dough were higher than C2 dough, G′ and G" in C1 dough were higher than that in C2 and C3 dough. Yeast with interrupted growth was more vulnerable to low-temperature stress, low temperature affected the quality of dough by affecting the activity of yeast, yeast metabolites, and the intermolecular force of dough. • Yeast with interrupted growth was more vulnerable to low temperature stress. • In refrigerated dough, binding degree of water with other macromolecules weakened. • Dough rheological property was affected by yeast activity and intermolecular force. [ABSTRACT FROM AUTHOR]

Background: Whole-genome gene expression analysis has been successfully utilized to diagnose, prognosticate, and identify potential therapeutic targets for high-risk cardiovascular diseases. However, the feasibility of this approach to identify outcome-related genes and dysregulated pathways following first-time myocardial infarction (AMI) remains unknown and may offer a novel strategy to detect affected expressome networks that predict long-term outcome. Methods and results: Whole-genome expression microarray on blood samples from normal cardiac function controls (n=21) and first-time AMI patients (n=31) within 48-hours post-MI revealed expected differential gene expression profiles enriched for inflammation and immune-response pathways. To determine molecular signatures at the time of AMI associated with long-term outcomes, transcriptional profiles from sub-groups of AMI patients with (n=5) or without (n=22) any recurrent events over an 18-month follow-up were compared. This analysis identified 559 differentially-expressed genes. Bioinformatic analysis of this differential gene-set for associated pathways revealed 1) increasing disease severity in AMI patients is associated with a decreased expression of genes involved in the developmental epithelial-to-mesenchymal transition pathway, and 2) modulation of cholesterol transport genes that include ABCA1, CETP, APOA1, and LDLR is associated with clinical outcome. Conclusion: Differentially regulated genes and modulated pathways were identified that were associated with recurrent cardiovascular outcomes in first-time AMI patients. This cell-based approach for risk stratification in AMI could represent a novel, non-invasive platform to anticipate modifiable pathways and therapeutic targets to optimize long-term outcome for AMI patients and warrants further study to determine the role of metabolic remodeling and regenerative processes required for optimal outcomes. [ABSTRACT FROM AUTHOR]

[Display omitted] Chirality dynamic tuning plays fundamental roles in chemistry, material science and biological system. Herein, a pair of azobenzene-bridged bis-tryptophan enantiomers (Azo-di- d / l -Trp) were designed and synthesized via simple reactions. With the fuel of glucono-δ-lactone (GdL), releasing protons during its hydrolysis, the alkaline solution of Azo-di- d / l -Trp gradually self-assembled into contrast chiral helical structures and displayed magnitude and mirror image of circular dichroism (CD) signals. While the chiral helices converted to CD silent nanoparticles when the azobenzene moiety isomerized from trans - to cis -form under UV irradiation. More importantly, this chiroptical switch, displaying reversible interconversion between chiral amplification and silent, can be smartly controlled via photoirradiation at various wavelengths. [ABSTRACT FROM AUTHOR]

The Lovelock theory of gravity is a natural extension of the Einstein's theory of general relativity to higher dimensions, which presents the criteria of general covariance and is free of ghosts. In this work, we consider a model that static spherically-symmetric black hole is surrounded by the modified Chaplygin gas with equation of state p = A ρ − B / ρ α . We find that the energy density of the modified Chaplygin gas can be characterized by four parameters. The black hole thermodynamical quantities, consisting of gravitational mass, temperature, entropy and heat capacity, as functions of horizon radius, are calculated. Concerning the thermodynamical stability of the black holes, we consider the third-order Lovelock gravity as a specific case and show in figures the heat capacity versus the horizon radius, observing that there exist a phase of thermodynamically stable small black hole and a phase of thermodynamically unstable large black hole for D = 7 , while an additional intermediate local unstable phase as well as an intermediate local stable phase appear for D = 8 with configuring properly the model parameters. The effects of the modified Chaplygin gas and Lovelock gravity on thermodynamical stability of the black holes are discussed. • Lovelock black holes surrounded by modified Chaplygin gas are studied. • D = 7 3-order case, there are a phase of stable small and a phase of unstable large BH. • D = 8 3-order case, additional local unstable/stable phases could intermediately appear. [ABSTRACT FROM AUTHOR]

In order to fully understand the carbon emission from different fuels in rural villages of China, especially in the typical atmospheric pollution areas. The characteristics of carbonaceous aerosols and carbon dioxide (CO 2) with its stable carbon isotope (δ13C) were investigated in six households, which two households used coal, two households used wood as well as two households used biogas and liquefied petroleum gas (LPG), from two rural villages in Fenwei Plain from March to April 2021. It showed that the fine particulate matter (PM 2.5) emitted from biogas and LPG couldn't be as lower as expected in this area. However, the clean fuels could relatively reduce the emissions of organic carbon (OC) and element carbon (EC) in PM 2.5 compare to the solid fuels. The pyrolyzed carbon (OP) accounted more total carbon (TC) in coal than the other fuels use households, indicating that more water-soluble OC existed, and it still had the highest secondary organic carbon (SOC) than the other fuels. Meantime, the coal combustions in the two villages had the highest CO 2 concentration of 527.6 ppm and 1120.6 ppm, respectively, while the clean fuels could effectively reduce it. The average δ13C values (−26.9‰) was much lighter than almost all the outdoor monitoring and similar to the δ13C values for coal combustion and vehicle emission, showing that they might be the main contributors of the regional atmospheric aerosol in this area. During the sandstorm, the indoor PM 2.5 mass and CO 2 were increasing obviously. The indoor cancer risk of PAHs for adults and children were greater than 1 × 10−6, exert a potential carcinogenic risk to human of solid fuels combustion in rural northern China. It is important to continue concern the solid fuel combustion and its health impact in rural areas. [Display omitted] • Biogas and liquefied petroleum gas (LPG) emitted high PM 2.5 as unexpected. • Biogas and LPG emitted lower PM 2.5 bounded PAHs and CO 2. • The CO 2 produced by coal burning was greater than other fuels, with lighter δ13C. • Sandstorm could aggravate the accumulation of indoor atmospheric CO 2. • Solid fuel users might face more serious cancer risks than biogas and LPG. [ABSTRACT FROM AUTHOR]

Emerging evidence has linked autophagy to skin wound healing; however, the underlying cellular and molecular mechanisms remain poorly understood. The present study was designed to determine the role of autophagy in endothelial cell (EC)-mediated skin wound healing in mice. Autophagy-related gene (Atg7) in mouse ECs was inactivated by the Cre-loxP system under the control of an EC-specific VE-Cadherin (Cdh5) promoter (Atg7EC−/− mice). Full-thickness skin wounds were created on the dorsum of wild-type (WT), Cdh5-Cre+, floxed Atg7 (Atg7F/F), and Atg7EC−/− mice. Autophagic activity was determined by autophagic flux assay in the primary culture of ECs isolated from these mice. The wound re-epithelialization and angiogenesis was examined by histological analyses. The angiogenic activity of ECs was evaluated by tube formation assay in vitro. EC proliferation was examined by a cell count CCK-8 kit. EC-originated intercellular communication with dermal fibroblasts and keratinocytes was assessed by measuring the effect of EC conditional medium on the growth of keratinocytes and fibroblasts. The levels of VEGF, EGF, bFGF in EC conditional medium were measured by ELISA. Autophagy deficiency in ECs markedly enhanced the re-epithelialization and the wound closure during skin wound healing. However, it has minimal impact on angiogenesis in the wounded skin. Notably, autophagy deficiency in ECs did not affect their proliferation and migration or angiogenic activity per se but enhanced the EC conditional medium-induced proliferation and migration of keratinocytes and fibroblasts. These results demonstrate for the first time an inhibitory role of autophagy in the EC-originated paracrine regulation of skin wound healing. [ABSTRACT FROM AUTHOR]

Studies have proved the role of GAS5 in the development of different cancers. This study was undertaken to investigate the role and explore therapeutic implications of GAS5 in human cervical cancer. The results showed that GAS5 was significantly (p < 0.05) downregulated in human cervical cancer tissues. The results also showed that cervical cancer progresses with the suppression of GAS5 expression levels. Additionally, the expression of GAS5 was also significantly (p < 0.05) downregulated in human cervical cancer cell lines. Nonetheless, overexpression of GAS5 caused a remarkable decrease in the proliferation of C33A and HeLa cervical cancer cells. The decrease in the proliferation rate was attributed to the induction of apoptosis of C33A and HeLa cells which was accompanied with upregulation of Bax and suppression of Bcl-2. Additionally, GAS5 overexpression also promoted the arrest of C33A and HeLa cells at the G2/M check point of cell cycle via suppression of cyclin B1 and CDK1 expression. The transwell assays showed that GAS5 overexpression significantly (p < 0.05) inhibited the migration and invasion of the C33A and HeLa cervical cancer cells. The bioinformatics analysis as well as the dual luciferase assay showed GAS5 acts as a target of miR-135a. Interestingly, the expression of miR-135a was upregulated in the human cervical cancer cells and its suppression exerted growth inhibitory effects on the C33A and HeLa cells. However, silencing of GAS5 could nullify the effects of miR-135a suppression on the proliferation of C33A and HeLa cells. Taken together, the results of this study point towards the therapeutic implications of GAS5 in the treatment of cervical cancer. [ABSTRACT FROM AUTHOR]

• C. perfringens triggers classical phagocyte ETs formation. • Bacteria induce ETs release via ERK1/2-, P38 MAPK- and SOCE-dependent mechanisms. • A beneficial role of phagocyte ETs on pathogen control in vitro and in vivo. Clostridium perfringens (C. perfringens) is an important Gram-positive anaerobic spore-forming pathogen that provokes life-threatening gas gangrene and acute enterotoxaemia, although it colonizes as a component of the symbiotic bacteria in humans and animals. However, the mechanisms by which C. perfringens is cleared from the host remains poorly understood, thereby impeding the development of novel strategies for control this infection. Here, we uncover a beneficial effect of extracellular traps (ETs) formation on bacterial killing and clearance by phagocytes. C. perfringens strain ATCC13124, and wild-type isolates CP1 and CP3 markedly trigger ETs formation in macrophages and neutrophils. As expected, visualization of DNA decorated with histone, myeloperoxidase (MPO) and neutrophils elastase (NE) in C. perfringens -triggered classical ETs structures. Notably, the bacteria-induced ETs formation is an ERK1/2-, P38 MAPK-, store-operated calcium entry (SOCE)-, NADPH oxidase-, histone-, NE-, and MPO-dependent process, and is independent of LDH activity. Meanwhile, the defect of bactericidal activity is mediated by impairing ETs formation in phagocytes. Moreover, In vivo studies indicated that degradation of ETs by DNase I administration leads to a defect in the protection against experimental gas gangrene, with higher mortality rates, exacerbated tissue damage, and more bacterial colonization. Together, these results suggest that phagocyte ETs formation is essential for the host defense against C. perfringens infection. [ABSTRACT FROM AUTHOR]

Although exposure to ambient air pollution has been associated with mental disorder, little is known about its potential effects on children and adolescents, especially in Chinese population. We aimed to reveal the relationship of air pollutants with hospital outpatient visits for child and adolescence psychiatry (HOVCAP) in Shenzhen. A case-crossover study based on time-series data was applied, and a distributed lag non-linear model (DLNM) was used to evaluate the non-linear and delayed effects of 4 major air pollutants (NO 2 , PM 2.5 , SO 2 and O 3) on HOVCAP. Least absolute shrinkage and selection operator (LASSO) regression was used to control the multicollinearity between covariates and to filter variables. A total of 94,660 cases aged 3–18 were collected from 2014 to 2019 in the Mental Health Center of Shenzhen. Results of pollutants at mode value (M 0) showed that in the single lag effect result, when the average daily concentration of NO 2 at 24 μg/m3, there was a significant effect on HOVCAP over lag 1, lag 4 and lag 5, respectively. The cumulative RR of NO 2 M 0 value to the outpatient visits were 1.438 (1.137–1.818) over lag 0–2, 1.454 (1.120–1.887) over lag 0–3, 1.466 (1.084–1.982) over lag 0–4, 1.680 (1.199–2.354) over lag 0–5, 1.993 (1.369–2.903) over lag 0–6, and 2.069 (1.372–3.119) over lag 0–7. However, PM 2.5 , SO 2 , O 3 were not associated with HOVCAP over neither single lag effects nor cumulative effects. The RR values both shown an increase either when NO 2 increases by 10 units or when the maximum concentration of NO 2 is reached. Our study suggests that exposure to the normal air quality of NO2 in Shenzhen may associated with the risk of HOVCAP. However, PM2.5, SO2, O3 were not associated with HOVCAP. • A distributed lag non-linear model (DLNM) was used to evaluate the non-linear and delayed effects of pollutants on HOVCAP (hospital outpatient visits for child and adolescence psychiatry). • Exposure to the normal air quality of NO2 in Shenzhen may associated with the risk of HOVCAP. • The overall effect curve of NO2 on HOVCAP demonstrated an inverted U shape. [ABSTRACT FROM AUTHOR]

Chronic activation of the myocardial renin angiotensin system (RAS) elevates the local level of angiotensin II (Ang II) thereby inducing pathological cardiac hypertrophy, which contributes to heart failure. However, the precise underlying mechanisms have not been fully delineated. Herein we report a novel paracrine mechanism between cardiac fibroblasts (CF)s and cardiomyocytes whereby Ang II induces pathological cardiac hypertrophy. In cultured CFs, Ang II treatment enhanced exosome release via the activation of Ang II receptor types 1 (AT 1 R) and 2 (AT 2 R), whereas lipopolysaccharide, insulin, endothelin (ET)-1, transforming growth factor beta (TGFβ)1 or hydrogen peroxide did not. The CF-derived exosomes upregulated the expression of renin, angiotensinogen, AT 1 R, and AT 2 R, downregulated angiotensin-converting enzyme 2, and enhanced Ang II production in cultured cardiomyocytes. In addition, the CF exosome-induced cardiomyocyte hypertrophy was blocked by both AT 1 R and AT 2 R antagonists. Exosome inhibitors, GW4869 and dimethyl amiloride (DMA), inhibited CF-induced cardiomyocyte hypertrophy with little effect on Ang II-induced cardiomyocyte hypertrophy. Mechanistically, CF exosomes upregulated RAS in cardiomyocytes via the activation of mitogen-activated protein kinases (MAPKs) and Akt. Finally, Ang II-induced exosome release from cardiac fibroblasts and pathological cardiac hypertrophy were dramatically inhibited by GW4869 and DMA in mice. These findings demonstrate that Ang II stimulates CFs to release exosomes, which in turn increase Ang II production and its receptor expression in cardiomyocytes, thereby intensifying Ang II-induced pathological cardiac hypertrophy. Accordingly, specific targeting of Ang II-induced exosome release from CFs may serve as a novel therapeutic approach to treat cardiac pathological hypertrophy and heart failure. [ABSTRACT FROM AUTHOR]

Interendothelial junctions play an important role in the maintenance of endothelial integrity and the regulation of vascular functions. We report here that cationic amino acid transporter-1 (CAT-1) is a novel interendothelial cell adhesion molecule (CAM). We identified that CAT-1 protein localized at cell–cell adhesive junctions, similar to the classic CAM of VE-cadherin, and knockdown of CAT-1 with siRNA led to an increase in endothelial permeability. In addition, CAT-1 formed a cis -homo-dimer and showed Ca 2 + -dependent trans -homo-interaction to cause homophilic cell–cell adhesion. Co-immunoprecipitation assays showed that CAT-1 can associate with β-catenin. Furthermore, we found that the sub-cellular localization and function of CAT-1 are associated with cell confluency, in sub-confluent ECs CAT-1 proteins distribute on the entire surface and function as l -Arg transporters, but most of the CAT-1 in the confluent ECs are localized at interendothelial junctions and serve as CAMs. Further functional characterization has disclosed that extracellular l- Arg exposure stabilizes endothelial integrity via abating the cell junction disassembly of CAT-1 and blocking the cellular membrane CAT-1 internalization, which provides the new mechanisms for l- Arg paradox and trans -stimulation of cationic amino acid transport system (CAAT). These results suggest that CAT-1 is a novel CAM that directly regulates endothelial integrity and mediates the protective actions of l- Arg to endothelium via a NO-independent mechanism. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRs) dysregulation is a general feature of colorectal cancer (CRC) and other solid tumors, and is associated cancer progression. In the current study, we demonstrate that microRNA-101 (miR-101) inhibits CRC cells probably through down-regulating sphingosine kinase 1 (SphK1). Our results showed that exogenously expressing miR-101 inhibited CRC cell (HT-29 and HCT-116 lines) growth in vitro . At the molecular level, miR-101 dramatically down-regulated SphK1 mRNA and protein expression, causing pro-apoptotic ceramide production in above CRC cells. On the other hand, inhibition of miR-101 through expressing antagomiR-101 increased SphK1 expression to down-regulate ceramide level in HT-29 cells. miR-101 expression increased the in vitro anti-CRC activity of conventional chemo-agents: paclitaxel and doxorubicin. CRC cells with SphK1-shRNA knockdown showed similar phenotypes as the miR-101-expressed CRC cells, presenting with elevated level of ceramide and high sensitivity to paclitaxel or doxorubicin. In vivo, HCT-116 xenograft growth in severe combined immuno-deficient (SCID) mice was dramatically inhibited by over-expressing miR-101. Further, miR-101 enhanced paclitaxel-induced anti-HCT-116 activity in vivo . Together, these results indicate that miR-101 exerts its anti-CRC activities probably through down-regulating SphK1. [ABSTRACT FROM AUTHOR]

Ubiquitin proteasome system (UPS) consists of ubiquitin, ubiquitin-activating enzymes (E1s), ubiquitin-conjugating enzymes (E2s), ubiquitin ligases (E3s), proteasomes, and deubiquitinating enzymes (DUBs). Ubiquitin, E1s, several E2s, E3s, and proteasomes play an important role in the regulation of cardiac homeostasis and dysfunction; however, less is known about the role of DUBs in the heart. Here, we uncovered a crucial role of cyclindromatosis (CYLD), a DUB, in mediating cardiac maladaptive remodeling and dysfunction. CYLD expression was dramatically upregulated in the cardiomyocytes of hypertrophic and failing human and murine hearts. Knockout of CYLD improved survival rate and alleviated cardiac hypertrophy, fibrosis, apoptosis, oxidative stress, and dysfunction in mice that were subjected to sustained pressure overload induced by transverse aortic constriction. Deep sequencing and gene array analyses revealed that the most dramatically changed genes are those involving in the free radical scavenging pathway and cardiovascular disease, including fos, jun, myc, and nuclear factor erythroid-2 related factor 2 (Nrf2) in the heart. Moreover, knockdown of CYLD enhanced mitogen-activated protein kinase (MAPK) ERK- and p38-mediated expression of c-jun, c-fos, and c-myc, which govern Nrf2 expression in cardiomyocytes. The CYLD deficiency-induced suppression of reactive oxygen species (ROS) formation, death and hypertrophy in cardiomyocytes was blocked by additional knockdown of Nrf2. Taken together, our findings demonstrate for the first time that CYLD mediates cardiac maladaptive remodeling and dysfunction, most likely via enhancing myocardial oxidative stress in response to pressure overload. At the molecular level, CYLD interrupts the ERK- and p38-/AP-1 and c-Myc pathways to suppress Nrf2-operated antioxidative capacity, thereby enhancing oxidative stress in the heart. [ABSTRACT FROM AUTHOR]

Recently GLP-1 was found to have cardioprotective effects independent of those attributable to tight glycemic control. Methods and results We employed ultrasound targeted microbubble destruction (UTMD) to deliver piggybac transposon plasmids encoding the GLP-1 gene with a nuclear localizing signal to rat hearts with adriamycin cardiomyopathy. After a single UTMD treatment, overexpression of transgenic GLP-1 was found in nuclei of rat heart cells with evidence that transfected cardiac cells had undergone proliferation. UTMD-GLP-1 gene therapy restored LV mass, fractional shortening index, and LV posterior wall diameter to nearly normal. Nuclear overexpression of GLP-1 by inducing phosphorylation of FoxO1-S256 and translocation of FoxO1 from the nucleus to the cytoplasm significantly inactivated FoxO1 and activated the expression of cyclin D1 in nuclei of cardiac muscle cells. Reversal of adriamycin cardiomyopathy appeared to be mediated by dedifferentiation and proliferation of nuclear FoxO1-positive cardiac muscle cells with evidence of embryonic stem cell markers (OCT4, Nanog, SOX2 and c-kit), cardiac early differentiation markers (NKX2.5 and ISL-1) and cellular proliferation markers (BrdU and PHH3) after UTMD with GLP-1 gene therapy. Conclusions Intranuclear myocardial delivery of the GLP-1gene can reverse established adriamycin cardiomyopathy by stimulating myocardial regeneration. [ABSTRACT FROM AUTHOR]

Abstract: Nuclear factor erythroid-2 related factor 2 (Nrf2) is a master transcription factor that controls the basal and inducible expression of a battery of antioxidant genes and other cytoprotective phase II detoxifying enzymes. While knockout of Nrf2 exaggerates cardiac pathological remodeling and dysfunction in diverse pathological settings, pharmacological activation of Nrf2 protects against cardiomyocyte injury and cardiac dysfunction. In contrast, there is also a concern that the chronic activation of Nrf2 secondary to oxidative stress is a contributing mechanism for the reductive stress-mediated heart failure. However, a direct link between cardiac specific activation of Nrf2 and cardiac protection or dysfunction in vivo remains to be established. Therefore, we investigated the effect of cardiomyocyte-specific transgenic activation of Nrf2 (Nrf2ctg) on cardiac pathological remodeling and dysfunction. We found that the cardiomyocyte-specific activation of Nrf2 suppressed myocardial oxidative stress as well as cardiac apoptosis, fibrosis, hypertrophy, and dysfunction in a setting of sustained pressure overload induced by transverse aortic arch constriction (TAC) in mice. Notably, the constitutive activation of Nrf2 increased the steady level of autophagosomes while decreasing the ubiquitinated protein aggregates in the heart after TAC. Nrf2 gene gain- and loss-of-function approaches revealed that Nrf2 enhances autophagosome formation and autophagic flux in cardiomyocytes. Unexpectedly, while Nrf2 minimally regulated apoptosis, it suppressed significantly the proteotoxic necrosis in cardiomyocytes. In addition, Nrf2 attenuated the proteocytotoxicity presumably via enhancing autophagy-mediated clearance of ubiquitinated protein aggregates in cardiomyocytes. Taken together, we demonstrated for the first time that cardiac specific activation of Nrf2 suppresses cardiac maladaptive remodeling and dysfunction most likely by enhancing autophagic clearance of toxic protein aggregates in the heart. [Copyright &y& Elsevier]

With rapid improvements in industrialization and urbanization, antibiotics are now extensively used to prevent and treat human and animal diseases and husbandry and aquaculture. Some research has been conducted to assess the environmental distribution and risk level of antibiotics, but their distribution remains largely uncharacterized. Thus, this study investigated the distribution and abundance of 39 antibiotics belonging to five groups, and their associated risks in surface water around Luoma Lake in the north of Jiangsu province, China. Nineteen antibiotics were detected, at a detection frequency (DF) ranging from 2.27% to 100%. The total antibiotics (ΣABs) concentrations ranged from 34.91 to 825.93 ng/L, with a median concentration of 195.45 ng/L. Among these antibiotics, chlortetracycline (DF: 100%; median: 172.02 ng/L) was the dominant antibiotic, accounting for a median percentage of 91.0% of ΣABs concentrations. Spearman rank correlation method found a significant correlation between clindamycin (DF: 72.7%; median: 2.01 ng/L) and lincomycin (DF: 79.5%; median: 4.58 ng/L). The ecological risk quotient (RQ) values for two out of 44 sampling sites were higher than 1, indicating a high risk; 11.4% of the RQ values fell between 0.1 and 1, indicating a medium risk. Moreover, roxithromycin was found to be the dominant contributor to the ecological risk, accounting for a median of 79.7% of ΣABs. However, the total non-carcinogenic (<6.54 × 10−4) and carcinogenic risks (<1.64 × 10−7) of ΣABs were negligible at the detected concentrations. Image 1 • Concentrations and distributions of 39 antibiotics around Luoma Lake were revealed. • Chlortetracyclin was found to be the dominant antibiotic, with a median of 172.02 ng/L. • Ecological risks of antibiotics were at medium level (11.4%) or slightly high level (4.6%). • Non-carcinogenic and carcinogenic risks of antibiotics were low at the detected concentrations. [ABSTRACT FROM AUTHOR]

Service composition is a research hotspot with practical value. With the development of Web service, many Web services with the same functional attributes emerge. However, service composition optimization is still a big challenge since the complex and unstable composition environment. To solve this problem, we propose an adaptive service composition based on deep reinforcement learning, where recurrent neural network (RNN) is utilized for predicting the objective function, improving its expression and generalization ability, and effectively solving the shortcomings of traditional reinforcement learning in the face of large-scale or continuous state space problems. We leverage heuristic behavior selection strategy to divide the state set into hidden state and fully visible state. Effective simulation of hidden state space and fully visible state of the evaluation function can further improve the accuracy and efficiency of the combined results. We conduct comprehensive experiment and experimental results have shown the effectiveness of our method. [ABSTRACT FROM AUTHOR]