N-acetylcysteine, a small molecule scavenger of reactive oxygen species, alleviates cardiomyocyte damage by regulating OPA1-mediated mitochondrial quality control and apoptosis in response to oxidative stress.

Background: Oxidative stress-induced mitochondrial damage is the major cause of cardiomyocyte dysfunction. Therefore, the maintenance of mitochondrial function, which is regulated by mitochondrial quality control (MQC), is necessary for cardiomyocyte homeostasis. This study aimed to explore the underlying mechanisms of N-acetylcysteine (NAC) function and its relationship with MQC. Methods: A hydrogen peroxide-induced oxidative stress model was established using H9c2 cardiomyocytes treated with or without NAC prior to oxidative stress stimulation. Autophagy with light chain 3 (LC3)-green fluorescent protein (GFP) assay, reactive oxygen species (ROS) with the 2',7'-dichlorodi hydrofluorescein diacetate (DCFH-DA) fluorescent, lactate dehydrogenase (LDH) release assay, adenosine triphosphate (ATP) content assay, and a mitochondrial membrane potential detection were used to evaluate mitochondrial dynamics in H2O2-treated H9c2 cardiomyocytes, with a focus on the involvement of MQC regulated by NAC. Cell apoptosis was analyzed using caspase-3 activity assay and Annexin V-fluorescein isothiocyanate (V-FITC)/propidium iodide (PI) double staining. Results: We observed that NAC improved cell viability, reduced ROS levels, and partially restored optic atrophy 1 (OPA1) protein expression under oxidative stress. Following transfection with a specific OPA1-small interfering RNA, the mitophagy, mitochondrial dynamics, mitochondrial functions, and cardiomyocyte apoptosis were evaluated to further explore the mechanisms of NAC. Our results demonstrated that NAC attenuated cardiomyocyte apoptosis via the ROS/OPA1 axis and protected against oxidative stress-induced mitochondrial damage via the regulation of OPA1-mediated MQC. Conclusions: NAC ameliorated the injury to H9c2 cardiomyocytes caused by H2O2 by promoting the expression of OPA1, consequently improving mitochondrial function and decreasing apoptosis.

Intravoxel incoherent motion and enhanced T2*-weighted angiography for preoperative prediction of microvascular invasion in hepatocellular carcinoma.

Objective: To investigate the value of the combined application of intravoxel incoherent motion (IVIM) and enhanced T2*-weighted angiography (ESWAN) for preoperative prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC). Materials and methods: 76 patients with pathologically confirmed HCC were retrospectively enrolled and divided into the MVI-positive group (n=26) and MVI-negative group (n=50). Conventional MRI, IVIM, and ESWAN sequences were performed. Three region of interests (ROIs) were placed on the maximum axial slice of the lesion on D, D*, and f maps derived from IVIM sequence, and R2* map derived from ESWAN sequence, and intratumoral susceptibility signal (ITSS) from the phase map derived from ESWAN sequence was also automatically measured. Receiver operating characteristic (ROC) curves were drawn to evaluate the ability for predicting MVI. Univariate and multivariate logistic regression were used to screen independent risk predictors in clinical and imaging information. The Delong's test was used to compare the differences between the area under curves (AUCs). Results: The D and D* values of MVI-negative group were significantly higher than those of MVI-positive group (P=0.038, and P=0.023), which in MVI-negative group were 0.892×10-3 (0.760×10-3, 1.303×10-3) mm2/s and 0.055 (0.025, 0.100) mm2/s, and in MVI-positive group were 0.591×10-3 (0.372×10-3, 0.824×10-3) mm2/s and 0.028 (0.006, 0.050)mm2/s, respectively. The R2* and ITSS values of MVI-negative group were significantly lower than those of MVI-positive group (P=0.034, and P=0.005), which in MVI-negative group were 29.290 (23.117, 35.228) Hz and 0.146 (0.086, 0.236), and in MVI-positive group were 43.696 (34.914, 58.083) Hz and 0.199 (0.155, 0.245), respectively. After univariate and multivariate analyses, only AFP (odds ratio, 0.183; 95% CI, 0.041-0.823; P = 0.027) was the independent risk factor for predicting the status of MVI. The AUCs of AFP, D, D*, R2*, and ITSS for prediction of MVI were 0.652, 0.739, 0.707, 0.798, and 0.657, respectively. The AUCs of IVIM (D+D*), ESWAN (R2*+ITSS), and combination (D+D*+R2*+ITSS) for predicting MVI were 0.772, 0.800, and, 0.855, respectively. When IVIM combined with ESWAN, the performance was improved with a sensitivity of 73.1% and a specificity of 92.0% (cut-off value: 0.502) and the AUC was significantly higher than AFP (P=0.001), D (P=0.038), D* (P=0.023), R2* (P=0.034), and ITSS (P=0.005). Conclusion: The IVIM and ESWAN parameters showed good efficacy in prediction of MVI in patients with HCC. The combination of IVIM and ESWAN may be useful for noninvasive prediction of MVI before clinical operation.

Effects of Steel Slag on the Hydration Process of Solid Waste-Based Cementitious Materials.

Aiming to enhance the comprehensive utilization of steel slag (SS), a solid waste-based binder consisting of SS, granulated blast furnace slag (BFS), and desulfurization gypsum (DG) was designed and prepared. This study investigated the reaction kinetics, phase assemblages, and microstructures of the prepared solid waste-based cementitious materials with various contents of SS through hydration heat, XRD, FT-IR, SEM, TG-DSC, and MIP methods. The synergistic reaction mechanism between SS and the other two wastes (BFS and DG) is revealed. The results show that increasing SS content in the solid waste-based binder raises the pH value of the freshly prepared pastes, advances the main hydration reaction, and shortens the setting time. With the optimal SS content of 20%, the best mechanical properties are achieved, with compressive strengths of 19.2 MPa at 3 d and 58.4 MPa at 28 d, respectively. However, as the SS content continues to increase beyond 20%, the hydration process of the prepared binder is delayed. The synergistic activation effects between SS and BFS with DG enable a large amount of ettringite (AFt) formation, guaranteeing early strength development. As the reaction progresses, more reaction products CSH and Aft are precipitated. They are interlacing and overlapping, jointly refining and densifying the material's microstructure and contributing to the long-term strength gain. This study provides a reference for designing and developing solid waste-based binders and deepens the insightful understanding of the hydration mechanism of the solid waste-based binder.

Reduction of greenhouse gas emissions from closed activated sludge- to aerobic granular sludge-based biosystems via gas circulation.

Greenhouse gas (GHG) emissions from biological treatment units are challenging wastewater treatment plants (WWTPs) due to their wide applications and global warming. This study aimed to reduce GHG emissions (especially N2O) using a gas circulation strategy in a closed sequencing-batch reactor when the biological unit varies from activated sludge (AS) to aerobic granular sludge (AGS). Results show that gas circulation lowers pH to 6.3 ± 0.2, facilitating regular granules but elevating total N2O production. From AS to AGS, N2O emission factor increased (0.07-0.86 %) due to decreasing ammonia-oxidizing rates while the emissions of CO2 (0.3 ± 0.1 kg-CO2/kg-chemical oxygen demand) and CH4 remained in the closed biosystem. The gas circulation decreased N2O emission factor by 63 ± 15 % after granulation higher than 44 ± 34 % before granulation, which is implemented by heterotrophic denitrification. This study provides a feasible strategy to enhance heterotrophic N2O elimination in the biological WWTPs.

Novel oxicam nonsteroidal compound XK01 attenuates inflammation by suppressing the NF-κB and MAPK pathway in RAW264.7 macrophages.

Traditional non-steroidal anti-inflammatory drugs (NSAIDs) show serious adverse effects during clinical use, which limits their usage. Oxicams (e.g., piroxicam, meloxicam) are widely used as NSAIDs. However, selectivity to cyclooxygenase (COX) 2 may cause cardiovascular problems considering the long-term use of the drugs. Therefore, it is important to develop new non-steroidal compounds as anti-inflammatory drugs. In the present study, we evaluated the anti-inflammatory activity of a newly developed nonsteroidal drug XK01. Our data showed that XK01 reduced the contents of nitric oxide (NO) and reactive oxygen species (ROS)and inhibited the transcription levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1ß in a dose-dependent manner in lipopolysaccharide (LPS)-stimulated mouse RAW264.7 macrophages. XK01 showed no significant inhibitory effect on COX-1, but inhibited the expression of COX-2. At molecular level, XK01 prevented the translocation of p65 protein from the cytoplasm to the nucleus and inhibited the phosphorylation of p65, IκB, and MAPKs proteins. And high concentration of XK01 also inhibited the phosphorylation of JNK, p38 and ERK, showing stronger effect than that of meloxicam. In addition, the anti-inflammatory activity of XK01 was further validated in Xylene-induced mouse ear swelling model. Thus, this study verified that XK01 inhibits the expression of inflammatory mediators and COX-2, and exhibits potential anti-inflammatory effects via suppressing the NF-κB and MAPK pathway.

Bibliometric analysis of biochar-based organic fertilizers in the past 15 years: Focus on ammonia volatilization and greenhouse gas emissions during composting.

Biochar-based organic fertilizer is a new type of ecological fertilizer formulated with organic fertilizers using biochar as the primary conditioning agent, which has received wide attention and application in recent years. This study conducted a comprehensive bibliometric analysis of the main hot spots and research trends in the field of biochar-based organic fertilizer research by collecting indicators (publication year, number, prominent authors, and research institutions) in the Web of Science database. The results showed that the research in biochar-based organic fertilizer has been in a rapid development stage since 2015, with exponential growth in publications number; the main institution with the highest publications number was Northwest Agriculture & Forestry University; the researchers with the highest number of publications was Mukesh Kumar Awasthi; the most publications country is China by Dec 30, 2022. The hot spots of biochar-based organic fertilizer research have been nitrogen utilization, greenhouse gas emission, composting product quality and soil fertility. Biochar reduces ammonia volatilization and greenhouse gas emissions from compost mainly through adsorption. The results showed that adding 10% biochar was an effective measure to achieve co-emission reduction of ammonia and greenhouse gases in composting process. In addition, biochar modification or combination with other additives should be the focus of future research to mitigate ammonia and greenhouse gas emissions from composting processes.

An odorant receptor tuned to an attractive plant volatile vanillin in Spodoptera litura.

The insect olfaction plays crucial roles in many important behaviors, in which ORs are key determinants for signal transduction and the olfactory specificity. Spodoptera litura is a typical polyphagous pest, possessing a large repertoire of ORs tuning to broad range of plant odorants. However, the specific functions of those ORs remain mostly unknown. In this study, we functionally characterized one S. litura OR (OR51) that was highly expressed in the adult antennae. First, by using Xenopus oocyte expression and two-electrode voltage clamp recording system (XOE-TEVC), OR51 was found to be strongly and specifically responsive to vanillin (a volatile of S. litura host plants) among 77 tested odorants. Second, electroantennogram (EAG) and Y-tube behavioral experiment showed that vanillin elicited significant EAG response and attraction behavior especially of female adults. This female attraction was further confirmed by the oviposition experiment, in which the soybean plants treated with vanillin were significantly preferred by females for egg-laying. Third, 3D structural modelling and molecular docking were conducted to explore the interaction between OR51 and vanillin, which showed a high affinity (-4.46 kcal/mol) and three residues (Gln163, Phe164 and Ala305) forming hydrogen bonds with vanillin, supporting the specific binding of OR51 to vanillin. In addition, OR51 and its homologs from other seven noctuid species shared high amino acid identities (78-97%) and the same three hydrogen bond forming residues, suggesting a conserved function of the OR in these insects. Taken together, our study provides some new insights into the olfactory mechanisms of host plant finding and suggests potential applications of vanillin in S. litura control.

Effects of Treadmill Exercise on Liver Apoptosis in Fluoride-Exposed Mice.

Hepatotoxicity induced by excessive fluoride (F) exposure has been extensively studied in both humans and animals. Chronic fluorosis can result in liver apoptosis. Meanwhile, moderate exercise alleviates apoptosis caused by pathological factors. However, the effect of moderate exercise on F-induced liver apoptosis remains unclear. In this research, sixty-four three-week-old Institute of Cancer Research (ICR) mice, half male and half female, were randomly divided into four groups: control group (distilled water); exercise group (distilled water and treadmill exercise); F group [100 mg/L sodium fluoride (NaF)]; and exercise plus F group (100 mg/L NaF and treadmill exercise). The liver tissues of mice were taken at 3 months and 6 months, respectively. Hematoxylin-eosin (HE) staining and situ terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) results showed that nuclear condensation and apoptotic hepatocytes occurred in the F group. However, this phenomenon could be reversed with the intervention of treadmill exercise. The results of QRT-PCR and western blot displayed NaF- induced apoptosis via tumor necrosis factor recpter 1 (TNFR1) signaling pathway, while treadmill exercise could restore the molecular changes caused by excessive NaF exposure.

Revealing calcium ion behavior during anaerobic phosphorus release process in aerobic granular sludge system.

Calcium ions (Ca2+) are important for biological phosphorus (P) removal from wastewater, but its behavior has not been well documented during the anaerobic P release process. This study is aimed to explore the mechanisms of Ca2+ release in bacterial aerobic granular sludge (AGS) system. During the non-aeration (anaerobic) phase, nearly 40 % increase in Ca2+ concentration was detected at the bottom of AGS reactor where decrease in pH and increase in Mg2+ concentration occurred. The pH decrease due to anaerobic P release caused CaCO3 dissolution inside the granules, leading to Ca2+ release. In addition, the increased Mg2+ ions from hydrolysis of polyphosphates were detected to reversibly exchange with Ca2+ in granules at a molar ΔCa/ΔMg ratio of 0.51-0.65. Results from this work revealed that dissolution of CaCO3 and ions exchange between Ca2+ and Mg2+ were the two major contributors to Ca2+ release during anaerobic P release process.

Neuroprotective Effects of the Psychoactive Compound Biatractylolide (BD) in Alzheimer's Disease.

Mitochondria play a central role in the survival or death of neuronal cells, and they are regulators of energy metabolism and cell death pathways. Many studies support the role of mitochondrial dysfunction and oxidative damage in the pathogenesis of Alzheimer's disease. Biatractylolide (BD) is a kind of internal symmetry double sesquiterpene novel ester compound isolated from the Chinese medicinal plant Baizhu, has neuroprotective effects in Alzheimer's disease. We developed a systematic pharmacological model based on chemical pharmacokinetic and pharmacological data to identify potential compounds and targets of Baizhu. The neuroprotective effects of BD in PC12 (rat adrenal pheochromocytoma cells) and SH-SY5Y (human bone marrow neuroblastoma cells) were evaluated by in vitro experiments. Based on the predicted results, we selected 18 active compounds, which were associated with 20 potential targets and 22 signaling pathways. Compound-target, target-disease and target-pathway networks were constructed using Cytoscape 3.2.1. And verified by in vitro experiments that BD could inhibit Aß by reducing oxidative stress and decreasing CytC release induced mPTP opening. This study provides a theoretical basis for the development of BD as an anti-Alzheimer's disease drug.

Moderate exercise relieves fluoride-induced liver and kidney inflammatory responses through the IKKß/NFκB pathway.

With the intensification of environmental pollution, the content of fluoride is increasing in human and animal living environments. Long-term fluoride exposure can cause damage to the liver and kidney, which are the main sites for fluoride metabolism, storage and removal. Moreover, exercise often accompanies the entire process of fluoride exposure in humans and animals. However, the mechanism of exercise on fluoride-induced liver and kidney injury remains unclear. Hence, we established a fluoride exposure and/or exercise mouse model to explore the influence of exercise on fluoride-induced liver and kidney inflammation and the potential mechanism. The results showed that fluoride caused obvious structural and functional damage and the notable recruitment of immunocytes in the liver and kidney. In addition, fluoride increased the levels of IL-1ß, IL-2, IL-4, IL-6, IL-10, IL-12, IL-13, IL-21, TNF-α, and TGF-ß but decreased the ratio of IFN-γ/IL-4 and IL-2/IL-10, which indicated that fluoride disturbed the inflammatory balance and caused hepatonephritis. In addition, the expression levels of IKKß and NFκB were increased, and the expression of IκBα was decreased after fluoride exposure, indicating that fluoride activated the IKKß/NFκB pathway. In summary, long-term moderate treadmill exercise relieved fluoride-induced liver and kidney inflammatory responses through the IKKß/NFκB pathway, and exercise can be used to prevent fluoride-induced liver and kidney damage.

Insight into aerobic phosphorus removal from wastewater in algal-bacterial aerobic granular sludge system.

This study aimed to figure out the main contributors to aerobic phosphorus (P) removal in the algal-bacterial aerobic granular sludge (AGS)-based wastewater treatment system. Kinetics study showed that aerobic P removal was controlled by macropore (contributing to 64-75% P removal) and micropore diffusion, and the different light intensity (0, 4.0, 12.3, and 24.4 klux) didn't exert significant (p > 0.05) influence on P removal. On the other hand, the increasing light intensity did promote microalgae metabolism, leading to the elevated wastewater pH (8.0-9.8). The resultant pH increase had a strongly negative relationship (R2 = 0.9723) with P uptake by polyphosphate-accumulating organisms, while promoted chemical Ca-P precipitation at a molar Ca/P ratio of 1.05. Results from this work could provide an in-depth understanding of microalgae-bacteria symbiotic interaction, which is helpful to better design and operate the algal-bacterial AGS systems.

Exercise Ameliorates Fluoride-induced Anxiety- and Depression-like Behavior in Mice: Role of GABA.

Fluoride exposure caused anxiety- and depression-like behavior in mice. Meanwhile, exercise contributes to relieve anxiety and depression. However, the effects of exercise on anxiety- and depression-like behavior in fluorosis mice remain unclear. In the current study, thirty-six Institute of Cancer Research (ICR) female mice were randomly assigned to four groups: control group (C, gavage with distilled water); exercise group (E, gavage with distilled water and treadmill exercise (speed, 10 m/min; time, 30 min/day)); fluoride group (F, gavage with 24 mg/kg sodium fluoride (NaF)); and exercise plus fluoride group (EF, gavage with 24 mg/kg NaF and treadmill exercise). All treatments lasted for 8 weeks. A number of entries into and time spent in the open zone in the elevated zero maze (EZM), resting time in the tail suspension test (TST) and levels of serotonin (5-HT) and gamma-aminobutyric acid (GABA), were significantly altered in F when compared to C. Meanwhile, the anxiety-like behavior in the EZM and the depression-like behavior in the TST were significantly improved in EF when compared to group F. Exercise significantly enhanced fluoride-induced low GABA level, with less effect on the concentration of 5-HT. Moreover, the mRNA and protein expressions of GABA synthesis and transport-related proteins of glutamic acid decarboxylase (GAD) 65 and GAD67 and vesicular GABA transporter (VGAT) were all strikingly decreased in F, while those in EF were increased. In conclusion, exercise ameliorates anxiety- and depression-like behavior in fluorosis mice through increasing the expressions of GABA synthesis and transport-related proteins, rather than 5-HT system.

Peritumoral Microgel Reservoir for Long-Term Light-Controlled Triple-Synergistic Treatment of Osteosarcoma with Single Ultra-Low Dose.

Local minimally invasive injection of anticancer therapies is a compelling approach to maximize the utilization of drugs and reduce the systemic adverse drug effects. However, the clinical translation is still hampered by many challenges such as short residence time of therapeutic agents and the difficulty in achieving multi-modulation combination therapy. Herein, mesoporous silica-coated gold nanorods (AuNR@SiO2 ) core-shell nanoparticles are fabricated to facilitate drug loading while rendering them photothermally responsive. Subsequently, AuNR@SiO2 is anchored into a monodisperse photocrosslinkable gelatin (GelMA) microgel through one-step microfluidic technology. Chemotherapeutic drug doxorubicin (DOX) is loaded into AuNR@SiO2 and 5,6-dimethylxanthenone-4-acetic acid (DMXAA) is loaded in the microgel layer. The osteosarcoma targeting ligand alendronate is conjugated to AuNR@SiO2 to improve the tumor targeting. The microgel greatly improves the injectability since they can be dispersed in buffer and the injectability and degradability are adjustable by microfluidics during the fabrication. The drug release can, in turn, be modulated by multi-round light-trigger. Importantly, a single super low drug dose (1 mg kg-1 DOX with 5 mg kg-1 DMXAA) with peritumoral injection generates long-term therapeutic effect and significantly inhibited tumor growth in osteosarcoma bearing mice. Therefore, this nanocomposite@microgel system can act as a peritumoral reservoir for long-term effective osteosarcoma treatment.

Ionic response of algal-bacterial granular sludge system during biological phosphorus removal from wastewater.

Biological phosphorus removal (BPR) from wastewater can be generally realized through alternative non-aeration and aeration operation to create anaerobic and aerobic conditions respectively for P release and uptake/accumulation by polyphosphate accumulating organisms (PAOs), with P removal finally achieved by controlled discharge of P-rich sludge. In this study, the response of algal-bacterial aerobic granular sludge (AB-AGS) during BPR to main ions including Ac- (acetate), Cl-, SO42-, NH4+, K+, Mg2+, Ca2+ and Na+ in wastewater was investigated with conventional bacterial AGS (B-AGS) as control and acetate as the sole carbon source. Results show that BPR process mainly involved the changes of Ac-, K+, Mg2+, and Ca2+ rather than Cl-, SO42-, NH4+ and Na+. The mole ratio of ΔP/ΔAc kept almost unchanged during the non-aeration (P release) phase in both B-AGS and AB-AGS systems (ΔPB-AGS/ΔAcB-AGS > ΔPAB-AGS/ΔAcAB-AGS), and it was negatively influenced by the light in AB-AGS systems, in which 62% of acetate was not utilized for P release at the high illuminance of 81 k lux. During the entire non-aeration/aeration period, both ΔK/ΔP and ΔMg/ΔP remained constant, while ΔKAB-AGS/ΔPAB-AGS > ΔKB-AGS/ΔPB-AGS and ΔMgAB-AGS/ΔPAB-AGS ≈ ΔMgB-AGS/ΔPB-AGS. The presence of algae seemed not beneficial for PAOs to remove P, while more K+ and P uptake by algae in AB-AGS suggest its great potential for manufacturing biofertilizer.

Effect of exercise on microglial activation and transcriptome of hippocampus in fluorosis mice.

Fluorosis is a widespread endemic disease. Reports have shown that high fluoride causes the dysfunction of central nervous system (CNS) in animals. The neurotoxicity of fluoride may be related to the activation of microglia. Moreover, numerous studies have found that exercise facilitates the plasticity of structure and function in CNS, partly owing to the regulation of microglia activation. The present study was conducted to explore the effect of exercise on the microglial activation of hippocampus in fluorosis mice. One hundred adult female Institute of Cancer Research (ICR) mice were randomly divided into 4 groups: control group (group C, distilled water by gavage); exercise group (group E, distilled water by gavage and treadmill exercise); fluoride group [group F, 24 mg/kg sodium fluoride (NaF) by gavage]; fluoride plus exercise group (group F + E, 24 mg/kg NaF by gavage and treadmill exercise). After 8 weeks, hippocampal morphological structure, microglial activation and RNA transcriptome of mice in each group were evaluated by hematoxylin and eosin (HE) staining, Nissl staining, immunohistochemistry (IHC), quantitative real time PCR (QRT-PCR) and transcriptome sequencing. We discovered that the number of M1-type microglia in fluorosis-mice hippocampus was significantly increased when compared to group C; group F + E showed a decrease in the number of M1-type microglia with the comparison to group F. In addition, the hippocampal transcriptome analysis showed that 576 differential expression genes (DEG) were confirmed in group F, compared to group C, and 670 DEG were differently expressed in group F + E when compared to group F. Gene Ontology (GO) analysis showed that changed genes were implicated in regulation of transcription, DNA-templated, integral component of membrane and adenosine triphosphate (ATP) binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of 670 DEG was helpful to find neuroactive ligand-receptor interaction pathway. In conclusion, these results indicate that treadmill running inhibits the excessive activation of microglia in hippocampus of the fluoride-toxic mice, accompanied with the alteration of neuroactive ligand-receptor interaction pathway.

lncRNA KCNQ1OT1 promotes the proliferation, migration and invasion of retinoblastoma cells by upregulating HIF-1α via sponging miR-153-3p.

It is reported that lncRNA KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) is oncogenic in many cancers. This work aimed at probing into its expression and biological functions in retinoblastoma (RB) as well as its regulatory effects on miR-153-3p and hypoxia-inducible factor-1α (HIF-1α). In our study, RB samples in pair were collected, and quantitative real-time PCR (qRT-PCR) was employed for examining the expression levels of KCNQ1OT1, miR-153-3p and HIF-1α. KCNQ1OT1 short hairpin RNAs were transfected into SO-Rb50 and HXO-RB44 cell to inhibit the expression of KCNQ1OT1. The proliferative activity, colony formation ability and apoptosis were examined through cell counting kit-8 assay, colony formation assays, Transwell assay and flow cytometry, respectively. qRT-PCR and western blot analysis were used for analyzing the changes of miR-153-3p and HIF-1α induced by KCNQ1OT1. The regulatory relationships between miR-153-3p and KCNQ1OT1, miR-153-3p and HIF-1α were examined by dual luciferase reporter gene assay and RNA-binding protein immunoprecipitation assay. The results of our study showed that KCNQ1OT1 expression was markedly enhanced in RB tissue samples, and KCNQ1OT1 knockdown had an inhibitory effect on the proliferation, migration, invasion and viability of RB cells. There were two validated binding sties between KCNQ1OT1 and miR-153-3p, and KCNQ1OT1 negatively regulated the expression of miR-153-3p in RB cells. HIF-1α was a target gene of miR-153-3p, and could be positively regulated by KCNQ1OT1. In conclusion, our study indicates that KCNQ1OT1 can increase the malignancy of RB cells via regulating miR-153-3p/HIF-1α axis.

Fast cultivation and harvesting of oil-producing microalgae Ankistrodesmus falcatus var. acicularis fed with anaerobic digestion liquor via biogranulation in addition to nutrients removal.

This study examined the feasibility of cultivation and harvesting of oil-producing microalgae (i.e. Ankistrodesmus falcatus var. acicularis) via biogranulation in two identical sequencing batch reactors (SBRs) fed with synthetic anaerobic digestion liquor. Easily settled algae granules with compact structure appeared around day 90 and mature granules were obtained after 150 days' operation. The microalgae settleability was remarkably improved, signaling by the substantial decrease of sludge volume index (SVI30) from initially >3000 to 53.44 ± 3.31 mL/g, with settling velocity correspondingly increased from nearly 0 to 18.47 ± 0.23 m/h. Although the percentage of the target microalgae (Ankistrodesmus falcatus var. acicularis) decreased along with the granulation process, the biomass concentration (2-4 g/L) and biomass productivity (130-270 mg/L/d) using biogranulation were 10-20 times and 16-34 times that by the traditional suspension method. Compared to the seed microalgae cells, more extracellular polymeric substances (EPS) (162.54 ± 3.60 mg/g-mixed liquor volatile suspended solids (MLVSS)) with a higher proteins/polysaccharides ratio (7.62) were excreted from the mature algae granules. Moreover, the mature microalgae granules showed comparable nutrients removal, averagely 96% and 86% of dissolved organic carbon (DOC) and NH4+-N from the digestion liquor, respectively, reflecting its great potential for simultaneous microalgae cultivation, harvesting and wastewater treatment.

Molecularly Imprinted Synthetic Antibodies: From Chemical Design to Biomedical Applications.

Billions of dollars are invested into the monoclonal antibody market every year to meet the increasing demand in clinical diagnosis and therapy. However, natural antibodies still suffer from poor stability and high cost, as well as ethical issues in animal experiments. Thus, developing antibody substitutes or mimics is a long-term goal for scientists. The molecular imprinting technique presents one of the most promising strategies for antibody mimicking. The molecularly imprinted polymers (MIPs) are also called "molecularly imprinted synthetic antibodies" (MISAs). The breakthroughs of key technologies and innovations in chemistry and material science in the last decades have led to the rapid development of MISAs, and their molecular affinity has become comparable to that of natural antibodies. Currently, MISAs are undergoing a revolutionary transformation of their applications, from initial adsorption and separation to the rising fields of biomedicine. Herein, the fundamental chemical design of MISAs is examined, and then current progress in biomedical applications is the focus. Meanwhile, the potential of MISAs as qualified substitutes or even to transcend the performance of natural antibodies is discussed from the perspective of frontier needs in biomedicines, to facilitate the rapid development of synthetic artificial antibodies.

Prediction of Major Adverse Cardiovascular Events and Slow/No-Reflow by Virtual Histology Imaging After Percutaneous Interventions on Saphenous Vein Grafts.

Saphenous vein grafts disease (SVGD) is a common complication after coronary artery bypass graft (CABG) and usually treated by percutaneous coronary intervention (PCI). In this prospective cohort study, we performed virtual histology-intravascular ultrasound to investigate whether plaque composition and morphological characteristics were associated with post-PCI major adverse cardiac events (MACEs) and slow/no-reflow in patients with SVGD. Patients (n = 90) were studied (76.7% men, mean age 64.9 ± 8.2 years and mean duration of SVG 8.0 ± 3.6 years). There were 77.8% lesions with a plaque burden of at least 70%; 18 MACE incidences accumulated in 14 patients over 12 months post-PCI and slow/no-reflow was observed in 12 patients. On adjusted multivariate analysis, lesion length (hazard ratio [HR] = 1.05; 95% confidence interval [CI]: 1.01-1.08]); age of CABG (HR = 1.51 [95% CI: 1.11-2.05], and absolute necrotic core (NC) area (HR = 8.04 [95% CI: 1.86-34.73]) were independently associated with MACEs. Factors independently associated with slow/no-reflow post-PCI were preprocedure systolic blood pressure (odds ratio [OR] = 0.98; 95% CI: 0.96-0.99) and absolute NC area (OR = 2.47 (95% CI: 1.14-5.36). A cutoff value of absolute NC area at ≥1.1 mm2 may serve as a significant risk predictor for no-reflow after SVG-PCI. Factors associated with MACEs and the slow/no-reflow phenomenon following PCI of the SVG can be used in risk assessment of SVG.