Efficient phosphate and hydrogen recovery from sludge fermentation liquid by sacrificial iron anode in electro-fermentation system.

Electro-fermentation (EF) has been extensively studied for recovering hydrogen and phosphorus from waste activated sludge (WAS), while was limited for the further application due to the low hydrogen yield and phosphorus recovery efficiency. This study proposed an efficient strategy for hydrogen and vivianite recovery from the simulated sludge fermentation liquid by sacrificial iron anode in EF. The optimum hydrogen productivity and the utilization efficiency of short chain fatty acids (SCFAs) reached 45.2 mmol/g COD and 77.6% at 5 d in pH 8. Phosphate removal efficiency achieved at 90.8% at 2 d and the high crystallinity and weight percentage of vivianite (84.8%) was obtained. The functional microbes, i.e., anaerobic fermentative bacteria, electrochemical active bacteria, homo-acetogens and iron-reducing bacteria were highly enriched and the inherent interaction between the microbial consortia and environmental variables was thoroughly explored. This work may provide a theoretical basis for energy/resource recovery from WAS in the further implementation.

Predictive Model of Restart-Up Pressure Drop after Shutdown for Heavy Oil-Water Ring Transportation Pipeline.

Aiming at the problem of restart-up for a heavy oil-water ring transportation pipeline due to instability and damage of the water ring, based on the self-developed design of a small indoor loop simulation experimental device and taking four kinds of ordinary heavy oil in the Lvda oilfield as the research object, the change trend of restart-up pressure drop with time is experimentally studied when the pipeline is restarted-up after shutdown at a constant water flow. On the basis of the regression analysis of the orthogonal restart-up experimental data of four factors (oil holdup, oil viscosity, standstill period, and water cleaning superficial velocity) and mixed levels by the statistical product and service solutions statistical analysis software, a multivariate nonlinear restart-up maximum pressure drop prediction model is established. Through analysis of the characteristics of each stage of the restart-up process, an exponential decay model of restart-up pressure drop with time is created. The research results show that the variations in restart-up pressure drop with time can be divided into two stages: the attenuation stage and the equilibrium stage. The predicted value of restart-up pressure drop with time is in good agreement with the measured one, and the goodness of fit is very close to 1. The maximum restart-up pressure drop rises along with the increase in oil holdup, oil viscosity, standstill period, and water cleaning superficial velocity. The restart-up time prolongs with the increase in oil holdup, oil viscosity, and standstill period but shortens with the increase in water cleaning superficial velocity.

Marein Ameliorates Myocardial Fibrosis by Inhibiting HIF-1α and TGF-ß1/Smad2/3 Signaling Pathway in Isoproterenol-stimulated Mice and TGF-ß1-stimulated Cardiac Fibroblasts.

BACKGROUND: Myocardial fibrosis significantly contributes to the pathogenesis and progression of heart failure. OBJECTIVE: We probe into the impact of marein, a key bioactive compound in functional food Coreopsis tinctoria, on isoproterenol-stimulated myocardial fibrotic mice and transforming growth factor ß1 (TGF-ß1)-stimulated cardiac fibroblasts (CFs). METHODS: Isoproterenol was administered to the experimental mice via subcutaneous injection, and simultaneous administration of marein (25-100 mg/kg) was performed via oral gavage. CFs were stimulated with TGF- ß1 to trigger differentiation and collagen synthesis, followed by treatment with marein at concentrations of 5-20 µM. RESULTS: Treatment with marein in mice and CFs resulted in a significant reduction in the protein expression levels of α-smooth muscle actin, collagen type I, and collagen type III. Additionally, marein treatment decreased the protein expression levels of TGF-ß1, hypoxia-inducible factor-1α (HIF-1α), p-Smad2/3, and Smad2/3. Notably, molecular docking analysis revealed that marein directly targets HIF-1α. CONCLUSION: Marein might exert a protective function in isoproterenol-stimulated myocardial fibrotic mice and TGF-ß1-stimulated CFs, which might result from the reduction of TGF-ß1 induced HIF-1α expression, then inhibiting p-Smad2/3 and Smad2/3 expressions.

Evaluation of metoprolol standard dosing pathway in Chinese patients with acute coronary syndrome: a prospective multicenter single-arm interventional study.

OBJECTIVE: To evaluate the feasibility and tolerability of metoprolol standard dosing pathway (MSDP) in Chinese patients with acute coronary syndrome (ACS). METHODS: In this multicenter, prospective, open label, single-arm and interventional study that was conducted from February 2018 to April 2019 in fifteen Chinese hospitals. A total of 998 hospitalized patients aged ≥ 18 years and diagnosed with ACS were included. The MSDP was applied to all eligible ACS patients based on the standard treatment recommended by international guidelines. The primary endpoint was the percentage of patients achieving the target dose at discharge (V2). The secondary endpoints included the heart rate and blood pressure at V2 and four weeks after discharge (V4), and percentage of patients experiencing bradycardia (heart rate < 50 beats/min), hypotension (blood pressure < 90/60 mmHg) and transient cardiac dysfunction at V2 and V4. RESULTS: Of the 998 patients, 29.46% of patients achieved the target dose (≥ 95 mg/d) at V2. The total population was divided into two groups: target group (patients achieving the target dose at V2) and non-target group (patients not achieving the target dose at V2). There was significant difference in the reduction of heart rate from baseline to discharge in the two groups (-4.97 ± 11.90 beats/min vs. -2.70 ± 9.47 beats/min, P = 0.034). There was no significant difference in the proportion of bradycardia that occurred in the two groups at V2 (0 vs. 0, P = 1.000) and V4 (0.81% vs. 0.33%, P = 0.715). There was no significant difference in the proportion of hypotension between the two groups at V2 (0.004% vs. 0.004%, P = 1.000) and V4 (0 vs. 0.005%, P = 0.560). No transient cardiac dysfunction occurred in two groups during the study. A total of five adverse events (1.70%) and one serious adverse event (0.34%) were related to the pathway in target group. CONCLUSIONS: In Chinese ACS patients, the feasibility and tolerability of the MSDP have been proved to be acceptable.

Establishing Human Observer Criterion in Evaluating Artificial Social Intelligence Agents in a Search and Rescue Task.

Artificial social intelligence (ASI) agents have great potential to aid the success of individuals, human-human teams, and human-artificial intelligence teams. To develop helpful ASI agents, we created an urban search and rescue task environment in Minecraft to evaluate ASI agents' ability to infer participants' knowledge training conditions and predict participants' next victim type to be rescued. We evaluated ASI agents' capabilities in three ways: (a) comparison to ground truth-the actual knowledge training condition and participant actions; (b) comparison among different ASI agents; and (c) comparison to a human observer criterion, whose accuracy served as a reference point. The human observers and the ASI agents used video data and timestamped event messages from the testbed, respectively, to make inferences about the same participants and topic (knowledge training condition) and the same instances of participant actions (rescue of victims). Overall, ASI agents performed better than human observers in inferring knowledge training conditions and predicting actions. Refining the human criterion can guide the design and evaluation of ASI agents for complex task environments and team composition.

CRISPR/Cas9 in zebrafish: An attractive model for FBN1 genetic defects in humans.

BACKGROUND: Mutations in the fibrillin-1 gene (FBN1) are associated with various heritable connective tissue disorders (HCTD). The most studied HCTD is Marfan syndrome. Ninety percent of Marfan syndrome is caused by mutations in the FBN1 gene. The zebrafish share high genetic similarity to humans, representing an ideal model for genetic research of human diseases. This study aimed to generate and characterize fbn1+/- mutant zebrafish using the CRISPR/Cas9 gene-editing technology. METHODS: CRISPR/Cas9 was applied to generate an fbn1 frameshift mutation (fbn1+/- ) in zebrafish. F1 fbn1+/- heterozygotes were crossed with transgenic fluorescent zebrafish to obtain F2 fbn1+/- zebrafish. Morphological abnormalities were assessed in F2 fbn1+/- zebrafish by comparing with the Tuebingen (TU) wild-type controls at different development stages. RESULTS: We successfully generated a transgenic line of fbn1+/- zebrafish. Compared with TU wild-type zebrafish, F2 fbn1+/- zebrafish exhibited noticeably decreased pigmentation, increased lengths, slender body shape, and abnormal cardiac blood flow from atrium to ventricle. CONCLUSION: We generated the first fbn1+/- zebrafish model using CRISPR/Cas9 gene-editing approach to mimic FBN1 genetic defects in humans, providing an attractive model of Marfan syndrome and a method to determine the pathogenicity of gene mutation sites.

Quorum sensing shaped microbial consortia and enhanced hydrogen recovery from waste activated sludge electro-fermentation on basis of free nitrous acid treatment.

In this study, the feasibility of free nitrous acid (FNA) pretreatment coupled with quorum sensing (QS) was investigated to enhance hydrogen recovery from waste activated sludge (WAS) via electro-fermentation (EF). 3-oxo-hexanoyl-homoserine lactone (3OC6-HSL), as the signal molecule, was only added in the first three cycles of sludge inoculation at the phase of microbial electrolysis cells (MECs) startup. Results showed that QS combined FNA (AHL-FMEC) enabled highest hydrogen yield and current (4.3 mg/g VSS and 4.5 mA), while that generated from sole FNA/QS treated WAS (FMEC/AHL-RMEC) were only 3.5/3.0 mg/g VSS and 1.5/1.5 mA, respectively. Fourier transform infrared (FT-IR) spectra illustrated the effective conversion of organics in AHL-FMEC, the utilization efficiencies of proteins and carbohydrates achieved to 75.0% and 79.7%, respectively. Besides, the internal resistance decreased from 34.5 Ω (FMEC) to 22.9 Ω (AHL-RMEC), further to 18.0 Ω, indicating the promoted bioelectrochemical activity of electroactive bacteria (EAB) in AHL-FMEC. Correspondingly, both EAB (21.7%), e.g., Geobacter (9.3%) and Pseudomonas (3.2%) and anaerobic fermentation bacteria (AFB, 28.6%), e.g., Proteiniclasticum (14.2%) and Petrimonas (3.6%) enriched to peaks in AHL-FMEC. Moreover, molecular ecological network (MEN) analysis revealed the underling relationships among AFB, EAB and homo-acetogen in EF system, suggesting the possible cooperative QS has been constructed. The results obtained in this study may provide a new insight for efficient hydrogen recovery from electro-fermentation of WAS.

Alteration of the IL-33-sST2 pathway in hypertensive patients and a mouse model.

Inflammatory cells play an important role in the occurrence of hypertension. Recent studies have demonstrated that interleukin-33/suppression of tumorigenicity 2 (IL-33/ST2) signaling plays a critical role in the pathogenesis of several cardiovascular diseases. We aimed to evaluate the association of IL-33 and its receptor levels with the occurrence of hypertension in angiotensin II (Ang II)-infused mice using microarray analysis and validated our results in human specimens. Male wild-type mice were infused with Ang II (1500 ng/kg/min) for 1, 3 and 7 days. Patients with essential hypertension (EH) (n = 166) and healthy control subjects (n = 306) were enrolled. Levels of IL-33 and ST2 mRNAs in serum and peripheral blood mononuclear cells (PBMCs) were analyzed by Luminex assay or ELISA and qPCR analysis. We found that IL-33 expression was significantly increased in the aortas of mice receiving Ang II infusion compared with that of control mice. In contrast, the levels of IL-33 in serum and PBMCs were not significantly different between hypertensive patients and normal controls. However, the levels of soluble ST2 (sST2) in serum and PBMCs were markedly higher in hypertensive patients than in controls (P < 0.001 and P = 0.014, respectively). In addition, the ST2L level in PBMCs was also significantly decreased in hypertensive patients (P = 0.028). Further, logistic analysis showed that the odds ratios of having hypertension based on sST2 levels in serum and PBMCs were 9.714 and 2.244 (P = 0.013 and P = 0.024, respectively) compared with the control group. Above all, sST2 acted as a risk factor for the occurrence of hypertension and may be a promising novel predictive marker for EH.

The potential phototoxicity of nano-scale ZnO induced by visible light on freshwater ecosystems.

With the development of nanotechnology, nanomaterials have been widely applied in anti-bacterial coating, electronic device, and personal care products. NanoZnO is one of the most used materials and its ecotoxicity has been extensively studied. To explore the potential phototoxicity of nanoZnO induced by visible light, we conducted a long-term experiment on litter decomposition of Typha angustifolia leaves with assessment of fungal multifaceted natures. After 158 d exposure, the decomposition rate of leaf litter was decreased by nanoZnO but no additional effect by visible light. However, visible light enhanced the inhibitory effect of nanoZnO on fungal sporulation rate due to light-induced dissolution of nanoZnO. On the contrary, enzymes such as ß-glucosidase, cellobiohydrolase, and leucine-aminopeptidase were significantly increased by the interaction of nanoZnO and visible light, which led to high efficiency of leaf carbon decomposition. Furthermore, different treatments and exposure time separated fungal community associated with litter decomposition. Therefore, the study provided the evidence of the contribution of visible light to nanoparticle phototoxicity at the ecosystem level.

Genetic and Functional Sequence Variants of the SIRT3 Gene Promoter in Myocardial Infarction.

Coronary artery disease (CAD), including myocardial infarction (MI), is a common complex disease that is caused by atherosclerosis. Although a large number of genetic variants have been associated with CAD, only 10% of CAD cases could be explained. It has been proposed that low frequent and rare genetic variants may be main causes for CAD. SIRT3, a mitochondrial deacetylase, plays important roles in mitochondrial function and metabolism. Lack of SIRT3 in experimental animal leads to several age-related diseases, including cardiovascular diseases. Therefore, SIRT3 gene variants may contribute to the MI development. In this study, SIRT3 gene promoter was genetically and functionally analyzed in large cohorts of MI patients (n = 319) and ethnic-matched controls (n = 322). Total twenty-three DNA sequence variants (DSVs) were identified, including 10 single-nucleotide polymorphisms (SNPs). Six novel heterozygous DSVs, g.237307A>G, g.237270G>A, g.237023_25del, g.236653C>A, g.236628G>C, g.236557T>C, and two SNPs g.237030C>T (rs12293349) and g.237022C>G (rs369344513), were identified in nine MI patients, but in none of controls. Three SNPs, g.236473C>T (rs11246029), g.236380_81ins (rs71019893) and g.236370C>G (rs185277566), were more significantly frequent in MI patients than controls (P<0.05). These DSVs and SNPs, except g.236557T>C, significantly decreased the transcriptional activity of the SIRT3 gene promoter in cultured HEK-293 cells and H9c2 cells. Therefore, these DSVs identified in MI patients may change SIRT3 level by affecting the transcriptional activity of SIRT3 gene promoter, contributing to the MI development as a risk factor.

Keratin 18 attenuates estrogen receptor alpha-mediated signaling by sequestering LRP16 in cytoplasm.

BACKGROUND: Oncogenesis in breast cancer is often associated with excess estrogen receptor alpha(ERalpha) activation and overexpression of its coactivators. LRP16 is both an ERalpha target gene and an ERalpha coactivator, and plays a crucial role in ERalpha activation and proliferation of MCF-7 breast cancer cells. However, the regulation of the functional availability of this coactivator protein is not yet clear. RESULTS: Yeast two-hybrid screening, GST pulldown and coimmunoprecipitation (CoIP) identified the cytoplasmic intermediate filament protein keratin 18 (K18) as a novel LRP16-interacting protein. Fluorescence analysis revealed that GFP-tagged LRP16 was primarily localized in the nuclei of mock-transfected MCF-7 cells but was predominantly present in the cytoplasm of K18-transfected cells. Immunoblotting analysis demonstrated that the amount of cytoplasmic LRP16 was markedly increased in cells overexpressing K18 whereas nuclear levels were depressed. Conversely, knockdown of endogenous K18 expression in MCF-7 cells significantly decreased the cytoplasmic levels of LRP16 and increased levels in the nucleus. CoIP failed to detect any interaction between K18 and ERalpha, but ectopic expression of K18 in MCF-7 cells significantly blunted the association of LRP16 with ERalpha, attenuated ERalpha-activated reporter gene activity, and decreased estrogen-stimulated target gene expression by inhibiting ERalpha recruitment to DNA. Furthermore, BrdU incorporation assays revealed that K18 overexpression blunted the estrogen-stimulated increase of S-phase entry of MCF-7 cells. By contrast, knockdown of K18 in MCF-7 cells significantly increased ERalpha-mediated signaling and promoted cell cycle progression. CONCLUSIONS: K18 can effectively associate with and sequester LRP16 in the cytoplasm, thus attenuating the final output of ERalpha-mediated signaling and estrogen-stimulated cell cycle progression of MCF-7 breast cancer cells. Loss of K18 increases the functional availability of LRP16 to ERalpha and promotes the proliferation of ERalpha-positive breast tumor cells. K18 plays an important functional role in regulating the ERalpha signaling pathway.