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This study assesses the effects of TLR4 gene modified BMSCs transplantation on the expression of bFGF and FSTL1 in myocardial ischemia-reperfusion rats. 30 male SD rats were assigned into control group (myocardial ischemia model), BMSCs group (model + BMSCs transplantation) and transfection group (model + TLR4 gene modified BMSCs transplantation) followed by analysis of TLR4 expression, EGFP, apoptosis and expression of bFGF and FSTL1. Compared with control group (TLR4 concentration 2.86 pg/5×105 cells/mL). The expression of TLR4 in BMSCs group (25.24 pg/5×105 cells/mL) and transfection group (31.55 pg/5×105 cells/mL) was significantly increased (P P P < 0.05). In conclusion, transplantation of BMSCs modified with TLR4 can increase bFGF and FSTL1 levels, reduce the rate of myocardial apoptosis and improve the myocardial pathological tissue, thus playing a therapeutic role.

SALL4 is one of the important members of SALL4 gene family and participates in embryo development, including organogenesis, maintenance and reconstruction of pluripotency, such as heart development and function. This study explores the effects of SALL4A-mediated DNA demethylation on heart development and function. The ventricular weight/body weight, ventricular diameter, septal thickness, LVEF% and LVFS% of the SALL4A gene knockout and normal SD mice were compared. ChIP/DIP-Seq and RNA-Seq technology were used to assess the mechanism by how SALL4Adependent DNA demethylation affects heart development and function. We found that compared with control group of SD mice, the ventricular weight/body weight of SD mice in SALL4A knockout group was significantly lower. In addition, SALL4A knockout group showed significantly lower interval thickness, LVEF%, LVFS% and other indicators related to heart development than normal SD mice. In addition, SALL4A-mediated DNA demethylation was closely related to TET. Both TET1 and TET2 were enriched in the SALL4A binding site. SALL4A targeted 5hmC gene in vitro and occupied the enhancer in mouse embryonic stem cells (ESCs) to promote 5hmC oxidation depending on TET enzyme. Therefore, SALL4A promoted oxidation of 5hmC and caused DNA demethylation which finally affected heart development and function. In conclusion, SALL4A, as a gene that can target and bind 5hmC, promotes the oxidation of 5hmC by stabilizing TET enzyme binding, thereby regulating the DNA demethylation process in ESCs to further regulate heart development and function.

Anammox granule sludge (AnGS) has great potential in the field of wastewater nitrogen removal, but its development and promotion have been limited by the slow granulation speed and fragile operating stability. Based on the reviews about the AnGS formation mechanism in this paper, "micro-nuclei" was found to play an important role in the granulation of AnGS, and adding "micro-nuclei" directly into the reactor may be an efficient way to accelerate the formation of AnGS. Then, accelerating AnGS granulation with inert particles, multivalent positive ions, and broken granule sludge as "micro-nuclei" was summarized and discussed. Among inert particles, iron-based particles may be a more advantageous candidate for "micro-nuclei" due to their ability to provide attachment sites and release ferric/ferrous ions. The precipitations of multivalent positive ions are also a potential option for "micro-nuclei" that can be generated in-situ, but a suitable dosing strategy is necessary. About broken granular sludge, the broken active AnGS may have advantages in terms of anaerobic ammonium oxidation bacteria-affinity and granulation speed, while using inactive granular sludge as "micro-nuclei" can avoid interfering bacterial invasion and has a higher cost performance than broken active AnGS. In addition, possible research directions for accelerating the formation of AnGS by dosing "micro-nuclei" were highlighted. This paper is intended to provide a possible pathway for the rapid start-up of AnGS systems, and references for the optimization and promotion of the AnGS process.

Denitrification is the key driving force of nitrogen cycle in surface water and plays an important role in eutrophication water remediation. Compared with some other common carbon sources, such as glucose and sodium acetate, polyhydroxyalkanoates (PHAs) were found to have the distinguished advantages in screening specific denitrifying bacteria of natural surface water bodies. In this study, the large ensembles of taxa were obtained from surface water samples and then sub-cultured with PHA or glucose as the sole carbon source. The microbial community that could be screened by PHA was identified, and the environmental functions of these bacteria were analyzed. At the genus level, the main communities regulated by PHA included Pseudomonas (56.30 %), Acinetobacter (27.75 %), Flavobacterium (10.19 %) and Comamonas (3.14 %), which all had good denitrification ability. The changes in carbon source, nitrogen source and biomass (expressed by DNA) were simultaneously monitored when culturing the model strain (P. stuzeri) with PHA or glucose. Compared with the glucose group, less PHA was consumed to remove the same amount of nitrate within a shorter incubation time, and there was no significant difference in bacterial growth with PHA or glucose as the carbon source (glucose:ΔN:ΔC:ΔDNA = 1:18:0.072; PHA:ΔN:ΔC:ΔDNA = 1:11:0.063). PHA improved the denitrification efficiency by increasing the expression of NarGHI, NirB, NirK and NorB, i.e., the key enzymes in the denitrification process. In addition, PHA accelerated the assimilating rate of extracellular nitrate by bacteria through increasing the expression of NarK. Finally, PHA-regulated electron transfer during denitrification was studied by observing the changes in NADH and NAD

CH4 emissions from landfills present temporal and spatial variation due to the changing meteorological conditions. The combined effect of meteorological parameter on CH4 transport, oxidation and emission are not fully understood. In this study a water-heat-gas transfer model embedding a meteorological module and CH4 oxidation was built to elucidate the CH4 transport, oxidation and emissions in landfill cover soils. A series of parametric studies are carried out to investigate the influence of barometric pressure, air temperature and rainfall on CH4 transport, oxidation and emissions in landfill cover soil. Finally, a real-time climatic condition was conducted to predict the daily CH4 oxidation and emissions from different climatic zones. The simulated results indicated that a low atmospheric pressure would convert the dominant gas transport mechanism from diffusion to advection and therefore result in a lower CH4 oxidation efficiency. In a landfill, the cover soil would also have a higher CH4 oxidation capacity because of the heat conduction from the waste layer under cold conditions. A significant decrease of CH4 emission flux was observed during the rainfall. After rainfall event, the CH4 emission flux was significantly positively correlated with rain intensity. This study proved that building a real-time landfill CH4 emission model considering varying climatic conditions is necessary to improve the accuracy of model predicting.

Denitrification, a typical biological process mediated by complex environmental factors, i.e., carbon sources and dissolved oxygen (DO), has attracted great attention due to its contribution to the control of eutrophication and the biochemical cycling of nitrogen. However, the effects of carbon source on electron distribution and enzyme expression for enhanced denitrification under competition of electron acceptors (DO and nitrate) remain unclear. Here, we profile the carbon metabolic pathway of polyhydroxybutyrate (PHB) and glucose (Glu) at high and low DO levels (50% and 10% saturated DO, respectively). It was found that PHB enhanced the growth of Pseudomonas stutzeri (model denitrifying bacterium) and improved the specific nitrogen removal rate (SNRR) at all DO levels. The functional proteins had a better affinity for the cofactor nicotinamide-adenine dinucleotide (NADH) than for nicotinamide adenine dinucleotide phosphate (NADPH); thus, more electrons were involved in nitrogen reduction and intracellular PHB production in the PHB groups than in the Glu groups. Furthermore, the expression difference of enzymes in glucose and PHB metabolism was demonstrated by metaproteomic and target protein analysis, implying that PHB-driven intracellular carbon accumulation could optimize the intracellular electron allocation and correspondingly promote nitrogen metabolism. Our work integrated the mechanisms of intracellular carbon metabolism with preferences for electron transfer pathways in denitrification, providing a new perspective on how the selective parameters regulated microbial functions involved in denitrification.

Radial oxygen loss (ROL) by the spreading root systems of vegetation can improve soil aeration for subsequent oxidation of methane (CH4) by microbes in landfill cover soils. This study proposes a theoretical model that elucidated the effects of ROL on microbial oxidation of CH4 to understand landfill gas transportation and oxidation in landfill cover soils. Parametric analyses were conducted to investigate the effects of root depth, root architecture, and ROL rate on the CH4 oxidation efficiency of landfill cover soils. The simulation results suggested that disregarding O2 emissions by plants root systems could underestimate the CH4 oxidation efficiency, especially when the water content ranged from 20% to 35%. Additionally, plants with a parabolic root architecture indicated 7–13% higher CH4 oxidation efficiency than other root architectures, i.e., uniform, triangular, and exponential. The CH4 oxidation efficiency increased rapidly at root depths less than 0.25 m. Therefore, plants characterized by a parabolic root architecture, longer root length, and higher ROL capacity should be selected as the preferred species for mitigating CH4 emissions from landfills in humid areas.

Mercury (Hg) release and migration from municipal solid waste landfills has been an important issue to nearby ecosystems and human health. To completely understand the Hg biogeochemical cycle in landfills, this review presents the Hg emission processes via different pathways, related controlling mechanisms, and critical Hg transport and transformation processes involving the diffusion and advection of Hg, Hg volatilization, Hg adsorption and desorption, Hg redox reactions, and Hg methylation and demethylation. These critical physical, chemical, and biological processes result in the phase transfer of Hg and the distribution of different Hg species in landfill gas (LFG), leachates, and cover soils. In addition, key factors (e.g., LFG, meteorological conditions, cover soils, and vegetation) affecting Hg emission processes and their impacts are discussed here. This work provides a comprehensive picture of Hg behavior in landfills, and has positive implications for the development of a process-based model and the control of Hg emissions from landfills.

Sediment is an important part of the aquatic ecosystem, which involves material storage and energy exchange. However, heavy metal pollution in sediment is on the increase, becoming an important concern for the world. In this paper, the state-of-art in situ remediation technology for contaminated sediment was elaborated, including water diversion, capping, electrokinetic remediation, chemical amendments, bioremediation and combined remediation. The mechanisms for these techniques to reduce/immobilize heavy metals include physical, electrical, chemical and biological processes. Furthermore, application principle, efficiency and scope, advantages and disadvantages, as well as the latest research progress for each restoration technology, are systematically reviewed. This information will benefit in selecting appropriate and effective remediation techniques for heavy metal-contaminated sediment in specific scenarios.

Anaerobic digestion is known for its effectiveness and environmental friendliness in treating food waste. However, it produces anaerobically digested liquor (ADL). ADL usually has a high solid content and high concentrations of nitrogen (N), phosphorus (P), and chemical oxygen demand (COD) carried by suspended solids (SS). Thus, when ADL with amounts of SS reaches the subsequent biochemical treatment units, they negatively impact the microbial stability of corresponding processes, causing unstable effluent qualities. For this reason, the solid-liquid separation of ADL acts as a crucial step for the wide application of anaerobic digestion. In this work, the typical sludge conditioning approaches, including flocculation/coagulation, coagulation, oxidation and advanced oxidation processes (AOPs), were systematically screened for their feasibility in enhancing the solid-liquid separation of ADL. The modified Fenton treatment combined with centrifugation was found to be the most effective approach, which realized the removal of 91.36% SS with FeSO

The water occurrence states in waste-activated sludge (WAS) are crucial to its dewaterability and significantly influenced by the water-retaining capacity of extracellular polymeric substances (EPS) matrix. Accordingly, the non-selective •OH-oxidation processes were widely reported for the sludge dewaterability improvement, just because it can non-selectively destruct complex structure units of EPS, no matter these structure units are crucial to EPS water-holding capacity or not. But these non-selective processes may also require the large consumption of oxidant chemicals, which limits their wide application. This study specifically focused on the •OH-induced variation in molecular compositions of EPS and the corresponding effects on water occurrence states of WAS, which is expected to lay a foundation for optimizing the efficiency of oxidation-based sludge conditioning. Especially, through a novel method based on the equilibrium dialysis with alkaline titration, the typical hydrophilic functional groups of EPS were quantitatively analyzed. The results indicated that the free amino group (-NH

High-efficiency desulfurization is key to the recovery and use of landfill gases. In this study, a nano‑iron oxide desulfurization agent modified from iron pentacarbonyl was prepared in n-decane (DE) and hexadecane (HE) by ultrasonic disruption without any supporting materials and its hydrogen sulfide removal ability and desulfurization mechanism were studied. The yield of the desulfurization agent was higher when HE was used as the solvent; however, the products generated by both solvents had the same crystal type and similar properties. The efficiency of the desulfurization agent was significantly improved at 150-200 °C, exceeding 90% at 150 °C with single sulfur production. The maximum sulfur adsorption capacity of the desulfurization agent produced after 3 h of DE ultrasonic treatment at 200 °C (DE3) was 492 mg/g (desulfurization efficiency = 97.33%), while that of the agent produced after 3 h of HE ultrasonic treatment at 250 °C (HE3) was 522 mg/g (desulfurization efficiency = 99.30%). The desulfurization reaction involved both chemical adsorption and catalytic decomposition and the catalytic decomposition reaction rate was lower than that of chemical adsorption. Therefore, the more Fe

Introduction: In a multicenter, open-label, parallel-group, randomized, phase 2 study for pretreated advanced hepatocellular carcinoma (HCC), camrelizumab showed potent antitumor activity and acceptable safety profile. The aim of this report was to provide long-term data and evaluate potential benefit of treatment with camrelizumab beyond progression. Methods: From November 15, 2016, to November 16, 2017, 217 patients received camrelizumab 3 mg/kg intravenously every 2 or 3 weeks. Treatment beyond first Response Evaluation Criteria in Solid Tumors (RECIST)-defined progression (TBP) with camrelizumab was allowed. Results: At data cutoff of December 16, 2019 (>2 years after the last patient enrollment; median duration of follow-up, 13.2 months [IQR 5.7–25.8]), 14 (43.8%) of the 32 responses per blinded independent central review were ongoing. The median duration of response was not reached (range 2.5–30.5 + months). The ongoing response rates at 12, 18, and 24 months were 68.3% (95% confidence interval [CI] 47.7–82.2), 59.8% (95% CI 38.8–75.6), and 53.1% (95% CI 31.0–71.0), respectively. The median overall survival (OS) was 14.2 months (95% CI 11.5–16.3). The 18- and 24-month OS rates were 41.3% (95% CI 34.6–47.9) and 33.7% (95% CI 27.3–40.2), respectively. Of the 172 patients who experienced RECIST-defined progression per investigator, 102 received TBP, while 70 did not (non-TBP). The median OS was 16.9 months (95% CI 13.3–22.6) in the TBP group versus 9.4 months (95% CI 5.8–14.8) in the non-TBP group, and the 18- and 24-month OS rates were 47.5% (95% CI 37.3–56.9) versus 33.1% (95% CI 22.3–44.3) and 38.8% (95% CI 29.2–48.4) versus 23.2% (95% CI 13.8–34.1), respectively. No new safety signals of camrelizumab were observed. Conclusions: With prolonged follow-up, camrelizumab continues to demonstrate the durable response and long survival in pretreated advanced HCC patients with manageable toxicities, especially in those who continued the treatment beyond first RECIST-defined progression.

In this study, a poly(3-hydroxybutyrate-co-3-hydroxyvalerate)/poly(lactic acid) (PHBV/PLA)-supported denitrification system was built to remove nitrogen from municipal wastewater treatment plant secondary effluent, and the influence of operating temperature on nitrogen removal was further investigated. Results indicated that a PHBV/PLA-supported denitrification system could effectively fulfill the tertiary nitrogen removal. The nitrogen removal efficiency gradually declined with the operating temperature decreasing, and the denitrification rate at 30 °C was 5 times higher than that at 10 °C. Meanwhile, it was found that a slight TOC accumulation only occurred at 30 °C (with an average of 2.03 mg/L) and was avoided at 10~20 °C. The reason for effluent TOC variation was further explained through the consumption and generation pathways of TOC in this system. Furthermore, the temperature coefficient was about 0.02919, indicating that the PHBV/PLA-supported denitrification system was a little sensitive to temperature. A better knowledge of the effect of operating temperature will be significant for the practical application of the solid-phase denitrification system.

In this study, a poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) supported denitrification system was developed for nitrate removal. Results showed that nitrate removal efficiency exceeded 95% and the maximal volumetric denitrification rate reached 0.77 kg m−3 day-1 with a hydraulic retention time (HRT) of 0.5 h. The effluent total organic carbon (TOC) decreased while the effluent pH increased with a shortage of HRT. Meanwhile, the weight-averaged molecular weight distribution analysis indicated that PHBV polymer’s intermediate degradation products was divided into three ranges, and the low-molecular-weight substances were mainly identified as acetate by a gas chromatography. The fourier transformation infrared spectra (FTIR) analysis indicated that these degradation products contained lots of C O and O H. Moreover, the microbial community structure of the PHBV biofilm was different with that of the inoculation sludge, and the abundant denitrifying bacteria mainly included Dechloromonas, Flavobacteriumand Stenotrophomonas. Functional protein, biological process and KEGG pathways were explored by Meta-proteomic approach, which further revealed the degradation and utilization mechanism of PHBV polymer.

The physical states of water are crucial for the dewatering efficiency of waste-activated sludge (WAS). However, to date, there is still lack of promising methods for the distinct differentiation of water states in colloidal microbial aggregates. This study proposed that the transverse spin-spin relaxation time (T2) distribution of low-field nuclear magnetic resonance (NMR) could be a useful tool to unravel the occurrence state of water in WAS. Due to the different interaction strengths of protons with the surrounding environment, the three water states with different T2 ranges were identified. The water strongly trapped on the surface of solid phase through hydrogen bound could be classified as vicinal water; interstitial water refers to the water physically trapped in bio-floc by steric hindrance or adsorption; and the water that is least affected by solid compositions is categorized as moderately mobile water. The potential ways of typical conditioning approaches for shifting water states were also investigated. The removal of hydrophilic compounds in extracellular polymeric substances (EPS) and surface charge neutralization were both found to be possible ways to influence the percentage of vicinal water (Pearson correlation coefficient Rp > 0.950, p-value ≤ 0.05). The disintegration or compaction of colloidal microbial aggregates could induce the transformation of interstitial water into moderately mobile water. All the above results are believed to deepen the mechanism insights into the differentiation and interactive transformation of water states in bio-floc of WAS.

Irrigation of stabilized landfill leachate to landfill cover soil is a cost-effective operation for leachate treatment. The contribution of ammonia-oxidizing bacteria (AOB) in the cover soil to CH4 oxidation, however, is unclear, because AOB and methane-oxidizing bacteria (MOB) can co-oxidize CH4 and NH4+-N. Thus, the contribution of AOB and the inhibitory effect of NH4+-N to CH4 oxidation were determined by using an acetylene pretreatment discrimination method. The results showed that the contributions of AOB to CH4 oxidation varied with the soil type and the concentration of NH4+-N addition. The relative contribution of AOB to CH4 oxidation for compost without NH4+-N addition was the highest (65.0%), and was 2.5 and 3.4 times higher than the corresponding values for aged refuse and landfill cover soil, respectively. The inhibitory effect of NH4+-N was enhanced by increasing the concentration of NH4+-N addition for all the soil samples. At equal NH4+-N addition concentrations, the inhibitory effect was always the lowest for the compost sample. The abundances of particulate methane monooxygenase (pmoA) and ammonia monooxygenase (amoA) genes were key factors influencing the CH4 oxidation rate and contribution of AOB to CH4 oxidation. The higher abundance of pmoA and lower abundance of amoA in landfill cover soil could explain the higher CH4 oxidation rate and lower contribution of AOB to CH4 oxidation in this soil type. Meanwhile, the higher contribution of AOB to CH4 oxidation for compost could be attributed to the higher abundance of the amoA gene and lower abundance of pmoA.

The rigid cell membrane structure is widely thought to retain the intracellular water and positively contributes to the presence of bound water in waste-activated sludge (WAS), which is the main obstacle of its highly-efficient dewatering. However, few studies realized the quantification of intracellular water fraction in the total bound water. Thus, there still may be some debates on whether and what extent of cell lysis is optimal for the dewaterability improvement. This study specifically focused on the effect of microbial cell lysis on the water occurrence states of WAS. The sonication, cyclic freezing-thawing and dimethyl sulfoxide (DMSO) amendment were used as the non-chemical means for cell lysis without altering the chemical compositions of WAS. The extent of cell lysis was quantified by the aqueous lactate dehydrogenase (LDH) released from intracellular cytoplasm and the water occurrence states of WAS were characterized by the transverse relaxation time (T

The highly hydrated colloidal structure of waste-activated sludge (WAS) is the main obstacle of enhanced dewatering for sludge volume minimization. Extracellular polymeric substances (EPS) maintain the colloidal stability of bio-flocs in a three-dimensional matrix due to bindings with bivalent cations (i.e., Ca2+ and Mg2+) and hydrophobic interactions. However, few studies specifically focused on the quantitative relationships among spatial distribution of EPS, microstructure of bio-flocs and fractions of bound water (e.g. vicinal water and interstitial water). Thus, there may be still some debates on whether and what extent of the lysis or flocculation of sludge flocs is optimal for the dewaterability improvement. This study applied the gradient addition of cation exchange resin (CER) to remove EPS-complexed cations and loosen the spatial distribution of EPS. Consequently, how the spatial extension of EPS layers with relief of complex cations influenced the particle size distribution, fractal dimension, interfacial free energy and water occurrence states of WAS was systematically investigated. The quartz crystal microbalance with dissipation (QCM-D) was also applied to analyze the water-EPS interactions with and without the presence of Ca2+ and Mg2+. All the results confirmed that the dispersed EPS adhering layers led to the higher fractal dimension (Df) but the lower space filling degree of bio-flocs. Also, the 4-fold reduction in the polar/acid-based interfacial free energy could be induced by the removal of cations from EPS matrix, which indicated the significant increase in hydrophobicity. Predictably, the fractions of vicinal water and interstitial water were dominated by the polar/acid-based interfacial free energy and pore structure of microbial aggregates, respectively, which were confirmed by the strong Pearson correlation (Rp>0.80, p-value