Intestinal metabolite xylulose inhibits colorectal cancer by inducing apoptosis through the MAPK signalling pathway.

BACKGROUND: The intestinal metabolites are involved in the initiation, progression and metastasis of colorectal cancer (CRC). They are a potential source of agents for cancer therapy. Our previous study identified altered faecal metabolites between CRC patients and healthy volunteers. However, no specific metabolite was clearly illustrated for CRC therapy. RESULTS: We found that the level of xylulose was lower in the stools of CRC patients than in those of healthy volunteers. Xylulose inhibited cell growth without affecting the cell cycle by inducing apoptosis in CRC cells, which was evidenced by increased expression of the proapoptotic proteins C-PARP and C-Caspase3 and decreased expression of the antiapoptotic protein BCL-2 in CRC cells. Mechanistically, xylulose reduced the activity of the MAPK signalling pathway, represented by reduced phosphorylation of JNK, ERK, and P38. Furthermore, an ALI model was used to show the tumour killing ability of xylulose on human CRC spheres, as well as human colorectal adenoma (AD) spheres. CONCLUSION: Xylulose inhibits CRC growth by inducing apoptosis through attenuation of the MAPK signalling pathway. These results suggest that xylulose may serve as an effective agent for CRC therapy.

The Norepinephrine-QseC Axis Aggravates F. nucleatum-associated Colitis Through Interkingdom Signaling.

AIMS: Inflammatory bowel disease (IBD) is associated with F. nucleatum, and chronic stress can increase the risk of aggravation. However, whether norepinephrine (NE) can enhance the pathogenicity of F. nucleatum to aggravate dextran sulfate sodium salt (DSS)-induced colitis is unclear. METHODS: Transcriptome sequencing was used to identify differentially expressed genes in bacteria treated with NE. Affinity testing and molecular docking were applied to calculate and predict the binding of NE and Quorum sensing  regulators C (QseC). The pathogenicity of Fusobacterium nucleatum treated with NE and QseC inhibitors was examined in vitro and further verified using the IBD mouse model induced by DSS. RESULTS: Norepinephrine could bind to QseC directly to upregulate the quorum sensing pathway of F. nucleatum and enhance its virulence gene expression (FadA, FomA, Fap2) and invasiveness in vitro. Meanwhile, it promoted the invasion of F. nucleatum into the intestine and increased the expression of host inflammatory cytokines (IL-6, IL-1ß) to aggravate colonic inflammation in IBD mice. The QseC inhibitor LED209 inhibited the effect of NE on F. nucleatum and partially restored short-chain fatty acid (SCFA)-producing bacteria (Prevotellaceae, Lactobacillaceae) to attenuate colonic inflammation in IBD mice. CONCLUSIONS: Generally, the NE-QseC axis enhanced the pathogenicity of F. nucleatum through interkingdom signaling to aggravate colonic inflammation in IBD mice. We see that QseC may be a potential target for microbiota management of IBD under chronic pressure.

Norepinephrine could bind to QseC directly to enhance the pathogenicity of F. nucleatum to aggravate colonic inflammation. The QseC inhibitor inhibited the effect of NE on F. nucleatum and partially restored short-chain fatty acid­producing bacteria to attenuate colonic inflammation.

An ultrafast and self-powered MoSxSe2-x/Si photodetector with high light-trapping structures and a SiOx interface layer.

MoSxSe2-x nanofilms, as a typical metal dichalcogenide, have attracted great interest, due to their adjustable bandgap and distinctive electronic and optical properties. However, the inherent bandgap of MoSxSe2-x and the strong interface recombination impede the actualization of a high-sensitivity photodetector (PD). Few-layer MoSxSe2-x nanofilms were prepared with vertically orientation at 450 °C, which would be a less restrictive choice of substrates. Herein, a self-powered MoSxSe2-x/SiOx/Si photodetector was fabricated which exhibits unprecedented performance with excellent reproducibility and stability from 405 nm to 980 nm, a high responsivity (0.450 A W-1), normalized detectivity (4.968 × 1012 Jones) and ultrafast photoresponse (τr = 1.20 µs, τf = 4.92 µs) at zero bias under 980 nm incident laser illumination with a density of 200 µW cm-2. Significantly, the self-powered PD is capable of detecting ultraweak IR signals below 200 µW cm-2 with high on-off ratios. More importantly, an oxidized atomic layer is generated through the wet oxidation in the Piranha solution. The PD can work well at high frequencies even at 100 kHz, which shows its potential application in high-frequency photoelectric devices and health monitors. Summing up, this work not only suggests that an ultrathin SiOx interface layer can reduce carrier recombination via simple interface engineering, but also proposes a novel strategy for the preparation of high-performance and low-cost optoelectronic devices.

Gut microbiota-derived autoinducer-2 regulates lung inflammation through the gut-lung axis.

OBJECTIVE: This study aimed to determine whether autoinducer-2 (AI-2), a crucial bacterial metabolite and quorum sensing molecule, is involved in lung immunity through the gut-lung axis. METHODS: The level of AI-2 and the gut microbiome composition were analysed in the stools from pneumonic patients and the mouse model of acute lung injury. The effect of AI-2 on lung inflammation was further investigated in the mouse model. RESULTS: The diversity of the faecal microbiota was reduced in pneumonic patients treated with antibiotics compared with healthy volunteers. The AI-2 level in the stool was positively correlated with inflammatory molecules in the serum of pneumonic patients. Intraperitoneal injection of AI-2 reinforced lung inflammation in the acute lung injury mouse model, characterized by increased secretion of inflammatory molecules, including IL-6, IL-1ß, C-C chemokines, and CXCL chemokines, which were alleviated by the AI-2 inhibitor D-ribose. CONCLUSIONS: Our results suggested that gut microbiota-derived AI-2 could modulate lung inflammation through the gut-lung axis.

Effects of polyvinylchloride microplastics on the toxicity of nanoparticles and antibiotics to aerobic granular sludge: Nitrogen removal, microbial community and resistance genes.

Copper oxide nanoparticles (CuO NPs) and ciprofloxacin (CIP) have ecological risk to humans and ecosystems. Polyvinylchloride microplastics (PVC MPs), as a representative of microplastics, may often coexist with CuO NPs and CIP in wastewater treatment systems due to their widespread application. However, the co-impact of PVC MPs in wastewater systems contained with CuO NPs and CIP on nitrogen removal and ecological risk is not clear. In this work, PVC MPs co-impacts on the toxicity of CuO NPs and CIP to aerobic granular sludge (AGS) systems and potential mechanisms were investigated. 10 mg/L PVC MPs co-addition did not significantly affect the nitrogen removal, but it definitely changed the microbial community structure and enhanced the propagation and horizontal transfer of antibiotics resistance genes (ARGs). 100 mg/L PVC MPs co-addition resulted in a raise of CuO NP toxicity to the AGS system, but reduced the co-toxicity of CuO NPs and CIP and ARGs expression. The co-impacts with different PVC MPs concentration influenced Cu2+ concentrations, cell membrane integrity, extracellular polymeric substances (EPS) contents and microbial communities in AGS systems, and lead to a change of nitrogen removal.

Rapid start-up of partial nitrification reactor by exogenous AHLs and Vanillin combined with intermittent aeration.

Quorum sensing (QS) and quorum quenching (QQ) are common phenomena in microbial systems and play an important role in the nitrification process. However, rapidly start up partial nitrification regulated by N-acyl-homoserine lactones (AHLs)-mediated QS or QQ has not been reported. Hence, we chose N-butyryl homoserine lactone (C4-HSL) and N-hexanoyl homoserine lactone (C6-HSL) as the representative AHLs, and Vanillin as the representative quorum sensing inhibitor (QSI) combined intermittent aeration to investigate their effects on the start-up process of partial nitrification. The start-up speed in the group with C4-HSL or C6-HSL addition was 1.42 or 1.26 times faster than that without addition, respectively. Meanwhile, the ammonium removal efficiency with C4-HSL or C6-HSL addition was increased by 13.87 % and 17.30 % than that of the control group, respectively. And, partial nitrification could maintain for a certain period without AHLs further addition. The increase of Nitrosomonas abundance and ammonia monooxygenase (AMO) activity, and the decrease of Nitrobacter abundance and nitrite oxidoreductase (NXR) activity were the reasons for the rapid start-up of partial nitrification in the AHLs groups. Vanillin addition reduced AMO and hydroxylamine oxidoreductase (HAO) activity, and increased Nitrobacter abundance and NXR activity, thus these were not conducive to achieving partial nitrification. Denitrifying bacteria (Hydrogenophaga, Thauera and Aquimonas) abundance increased in the Vanillin group. QS-related bacteria and gene abundance were elevated in the AHLs group, and reduced in the Vanillin group. Function prediction demonstrated that AHLs promoted the nitrogen cycle while Vanillin enhanced the carbon cycle. This exploration might provide a new technical insight into the rapid start-up of partial nitrification based on QS control.

Co-existence effect of copper oxide nanoparticles and ciprofloxacin on simultaneous nitrification, endogenous denitrification, and phosphorus removal by aerobic granular sludge.

Nanoparticles and antibiotics are toxic to humans and ecosystems, and they inevitably coexist in the wastewater treatment plants. Hence, the co-existence effects and stress mechanism of copper (II) oxide nanoparticles (CuO NPs) and ciprofloxacin (CIP) on simultaneous nitrification, endogenous denitrification and phosphorus removal (SNEDPR) by aerobic granular sludge (AGS) were investigated here. The co-existence stress of 5 mg/L CuO NPs and 5 mg/L CIP resulted in the synergistic inhibitory effect on nutrient removal. Transformation inhibition mechanisms of carbon (C), nitrogen (N) and phosphorus (P) with CuO NPs and CIP addition were time-dependent. Furthermore, the long-term stress mainly inhibited PO43--P removal by inhibiting phosphorus release process, while short-term stress mainly inhibited phosphorus uptake process. The synergistic inhibitory effect of CuO NPs and CIP may be due to the changes of physicochemical characteristics under the co-existence of CuO NPs and CIP. This further altered the sludge characteristics, microbial community structure and functional metabolic pathways under the long-term stress. Resistance genes analysis exhibited that the co-existence stress of CuO NPs and CIP induced the amplification of qnrA (2.38 folds), qnrB (4.70 folds) and intI1 (3.41 folds) compared with the control group.

Short-term responses of the anammox process to Ni(II): nitrogen removal, mechanisms and inhibition recovery.

Anaerobic ammonia oxidizing (anammox) has already been recognized as an innovative and economical nitrogen removal technology. However, the effect of heavy metals on anammox bacteria in aquatic ecosystem remains largely unknown. Ni(II) is a common kind of heavy metals detected in industrial wastewater and municipal sewage treatment plants. Hence, the responses of the anammox process to Ni(II) were studied here. The results showed that anammox was the dominant reaction with Ni(II) concentrations no more than 25 mg/L. 1 mg/L of Ni(II) addition promoted nitrogen removal by anammox. The higher the Ni(II) concentrations and longer exposure time, the more inhibition for anammox bacteria was gotten. The IC50 of Ni(II) to anammox was determined as 83.86 mg/L by an exponential regression equation. The inhibition of Ni(II) on anammox activity was mainly attributed to intracellular accumulation Ni(II) inhibition to HDH activity. Two times increase of IC50 after 4 times circles of domestication suggests multiple intermittent domestication can increase the tolerance of anammox bacteria to Ni(II). EDTA washing can eliminate the inhibition of anammox activity by Ni(II) with Ni(II) addition no more than 25 mg/L.

OTNet: A CNN Method Based on Hierarchical Attention Maps for Grading Arteriosclerosis of Fundus Images with Small Samples.

The severity of fundus arteriosclerosis can be determined and divided into four grades according to fundus images. Automatically grading of the fundus arteriosclerosis is helpful in clinical practices, so this paper proposes a convolutional neural network (CNN) method based on hierarchical attention maps to solve the automatic grading problem. First, we use the retinal vessel segmentation model to separate the important vascular region and the non-vascular background region from the fundus image and obtain two attention maps. The two maps are regarded as inputs to construct a two-stream CNN (TSNet), to focus on feature information through mutual reference between the two regions. In addition, we use convex hull attention maps in the one-stream CNN (OSNet) to learn valuable areas where the retinal vessels are concentrated. Then, we design an integrated OTNet model which is composed of TSNet that learns image feature information and OSNet that learns discriminative areas. After obtaining the representation learning parts of the two networks, we can train the classification layer to achieve better results. Our proposed TSNet reaches the AUC value of 0.796 and the ACC value of 0.592 on the testing set, and the integrated model OTNet reaches the AUC value of 0.806 and the ACC value of 0.606, which are better than the results of other comparable models. As far as we know, this is the first attempt to use deep learning to classify the severity of atherosclerosis in fundus images. The prediction results of our proposed method can be accepted by doctors, which shows that our method has a certain application value.

Automatic arteriosclerotic retinopathy grading using four-channel with image merging.

BACKGROUND AND OBJECTIVE: Arteriosclerosis can reflect the severity of hypertension, which is one of the main diseases threatening human life safety. But Arteriosclerosis retinopathy detection involves costly and time-consuming manual assessment. To meet the urgent needs of automation, this paper developed a novel arteriosclerosis retinopathy grading method based on convolutional neural network. METHODS: Firstly, we propose a good scheme for extracting features facing the fundus blood vessel background using image merging for contour enhancement. In this step, the original image is dealt with adaptive threshold processing to generate the new contour channel, which merge with the original three-channel image. Then, we employ the pre-trained convolutional neural network with transfer learning to speed up training and contour image channel parameter with Kaiming initialization. Moreover, ArcLoss is applied to increase inter-class differences and intra-class similarity aiming to the high similarity of images of different classes in the dataset. RESULTS: The accuracy of arteriosclerosis retinopathy grading achieved by the proposed method is up to 65.354%, which is nearly 4% higher than those of the exiting methods. The Kappa of our method is 0.508 in arteriosclerosis retinopathy grading. CONCLUSIONS: An experimental study on multiple metrics demonstrates the superiority of our method, which will be a useful to the toolbox for arteriosclerosis retinopathy grading.

[Effect of Ni(â ¡) on Anaerobic Ammonium Oxidation and Changes in Kinetics].

Anaerobic ammonium oxidation (ANAMMOX) is widely used for treatment of ammonium-rich wastewater because of its economic and environmental benefits. However, ANAMMOX bacteria are sensitive to environmental conditions, especially to heavy metals. The short-term and long-term effects of Ni(Ⅱ) on ANAMMOX were studied by batch and continuous flow experiments, respectively. Results showed that low concentrations of Ni(Ⅱ) had promoted nitrogen removal by ANAMMOX and high concentrations inhibited ANAMMOX performance during a short-term period. Compared with the specific anaerobic ammonium oxidation activity (SAA) without Ni(Ⅱ) addition, SAA with 1 mg·L-1 Ni(Ⅱ) addition increased by 11.14% and the SAA with 100 mg·L-1 Ni(Ⅱ) addition reduced by 49.55%. The IC50 of Ni(Ⅱ) for ANAMMOX was determined to be 83.86 mg·L-1. In contrast, long-term Ni(Ⅱ) addition significantly suppressed nitrogen removal of ANAMMOX, and the suppression threshold of Ni(Ⅱ) on ANAMMOX was 15 mg·L-1. The Monod model was applied to simulate the kinetics of ANAMMOX without Ni(Ⅱ) addition. The qmax0(TN/VSS) and KS0 values were 12.25 mg·(g·h)-1 and 405.36 mg·L-1, respectively. The modified Haldane model was suitable to describe the kinetics of ANAMMOX with 50 mg·L-1 Ni(Ⅱ) addition. The qmax(TN/VSS), KS, and Ki values were 6.78 mg·(g·h)-1, 313.2 mg·L-1, and 1.32, respectively. The inhibition of ANAMMOX by Ni(Ⅱ) is anticompetitive inhibition. In addition, the inhibition of Ni(Ⅱ) on ANAMMOX was mainly related to the content of intracellular Ni(Ⅱ). The IC50intracellular Ni(Ⅱ)(VSS) of intracellular Ni(Ⅱ) was 0.072 mg·g-1.

17 beta-estradiol biodegradation by anaerobic granular sludge: Effect of iron sources.

Steroid estrogens, as typical endocrine disrupting chemicals (EDCs), have raised an increasing concern due to their endocrine disrupting effects on aquatic animals and potential hazards on human health. Batch experiments were conducted to study 17 beta-estradiol (E2) removal and Estradiol Equivalent Quantity (EEQ) elimination by anaerobic granular sludge (AnGS) combined with different valence iron sources. Results showed that E2 was effectively biodegraded and transformed into E1 by AnGS. The addition of different valence iron sources all promoted E2 degradation, reduced E2 Equivalent Quotient (EEQ) concentration, and increased methane production in the batch experiments. The enhancement effect of zero-valent iron (ZVI) on E2 removal and EEQ elimination was stronger than that of Fe2+ and Fe3+ in our experiments. The enhancement effect proportion of ZVI corrosion, Fe2+, and Fe3+ in the process of E2 degradation by AnGS combined with ZVI were 42.26%, 40.21% and 17.53%, respectively.

Fabrication of a highly dispersed/active Pd nanoparticle supported catalyst: a cation-assisted reduction method in ethylene glycol-water solution at mild temperature.

Development of sustainable routes to synthesize precious metal supported catalysts is of great importance because of their wide applications in the catalysis field. This paper reported a controllable and recyclable cation-assisted reduction route to fabricate a palladium nanoparticle supported catalyst. At 323 K, highly dispersed Pd/Al2O3-CARM was prepared through introducing M2+ (M = Mn, Zn or Cu) ions to promote the reduction of H2PdCl4 in ethylene glycol-water solution, and the residual filtrate after preparation could be recycled to prepare Pd/Al2O3 catalysts. A turnover frequency of 300 × 102 h-1 was obtained for Pd/Al2O3-CARMn in solvent-free aerobic oxidation of benzyl alcohol to benzaldehyde.

Phytosphinganine Affects Plasmodesmata Permeability via Facilitating PDLP5-Stimulated Callose Accumulation in Arabidopsis.

Plant plasmodesmata (PDs) are specialized channels that enable communication between neighboring cells. The intercellular permeability of PDs, which affects plant development, defense, and responses to stimuli, must be tightly regulated. However, the lipid compositions of PD membrane and their impact on PD permeability remain elusive. Here, we report that the Arabidopsis sld1 sld2 double mutant, lacking sphingolipid long-chain base 8 desaturases 1 and 2, displayed decreased PD permeability due to a significant increase in callose accumulation. PD-located protein 5 (PDLP5) was significantly enriched in the leaf epidermal cells of sld1 sld2 and showed specific binding affinity to phytosphinganine (t18:0), suggesting that the enrichment of t18:0-based sphingolipids in sld1 sld2 PDs might facilitate the recruitment of PDLP5 proteins to PDs. The sld1 sld2 double mutant seedlings showed enhanced resistance to the fungal-wilt pathogen Verticillium dahlia and the bacterium Pseudomonas syringae pv. tomato DC3000, which could be fully rescued in sld1 sld2 pdlp5 triple mutant. Taken together, these results indicate that phytosphinganine might regulate PD functions and cell-to-cell communication by modifying the level of PDLP5 in PD membranes.

Long-term effects of N-acyl-homoserine lactone-based quorum sensing on the characteristics of ANAMMOX granules in high-loaded reactors.

Laboratory experiments were carried out to determine the long-term effects of N-acyl-homoserine lactone (AHL)-based quorum sensing on the characteristics of ANAMMOX granules in high-loaded reactors. Results clearly showed that adding 30 mg L-1 N-octanoyl-DL-homoserinelactone (C8-HSL) at the initial stage (1-40 d) of the experiment had long-term positive effects on the settleability of granules and controlled the sludge floatation effectively. C8-HSL decreased the content of bound extracellular polymeric substances (B-EPS) and the ratio of protein to carbohydrate (PN/PS) by 17% and 48%, respectively and increased the relative hydrophobicity (RH) of the granules by 28%. The results of batch tests indicated that C8-HSL significantly reduced the content of loosely-bound EPS (LB-EPS) in the B-EPS, which was responsible for variations in granule settleability and stability. Thus, the settleability of the granules was improved significantly due to addition of C8-HSL, contributing to operational stability and the high TN removal efficiency of the reactor. On day 150, when the nitrogen loading rates of all reactors were 13.4 kg TN m-3 d-1, the nitrogen removal rate and nitrogen removal efficiency of the reactor with C8-HSL (R3) were up to 11.2 kg TN m-3 d-1 and 88%, respectively. N-hexanoyl-DL-homoserine lactone (C6-HSL) improved activity of the granules, while N-dodecanoyl-DL-homoserine lactone (C12-HSL) had no effect on the characteristics of the granules. The long-term effects of C8-HSL on the settleability of granules may be attributed to sustainable release of endogenous signals induced by exogenous signal.

Microbial Internal Storage Alters the Carbon Transformation in Dynamic Anaerobic Fermentation.

Microbial internal storage processes have been demonstrated to occur and play an important role in activated sludge systems under both aerobic and anoxic conditions when operating under dynamic conditions. High-rate anaerobic reactors are often operated at a high volumetric organic loading and a relatively dynamic profile, with large amounts of fermentable substrates. These dynamic operating conditions and high catabolic energy availability might also facilitate the formation of internal storage polymers by anaerobic microorganisms. However, so far information about storage under anaerobic conditions (e.g., anaerobic fermentation) as well as its consideration in anaerobic process modeling (e.g., IWA Anaerobic Digestion Model No. 1, ADM1) is still sparse. In this work, the accumulation of storage polymers during anaerobic fermentation was evaluated by batch experiments using anaerobic methanogenic sludge and based on mass balance analysis of carbon transformation. A new mathematical model was developed to describe microbial storage in anaerobic systems. The model was calibrated and validated by using independent data sets from two different anaerobic systems, with significant storage observed, and effectively simulated in both systems. The inclusion of the new anaerobic storage processes in the developed model allows for more successful simulation of transients due to lower accumulation of volatile fatty acids (correction for the overestimation of volatile fatty acids), which mitigates pH fluctuations. Current models such as the ADM1 cannot effectively simulate these dynamics due to a lack of anaerobic storage mechanisms.

[Characteristic research of shortcut denitrification in synthetic ammonia industrial wastewater treatment process].

Active sludge was from a pilot-scale synthetic ammonia industrial wastewater treatment plant with a strengthen anoxic-oxic (A/O) technology. The zero order kinetic model was suit for describing shortcut and complete denitrification process. Experimental results showed that shortcut denitrification could reduce 14.1% carbon source consumption and 55.7% denitrification time, respectively, comparing with complete denitrification. The maximum specific denitrification rate was 0.509 g x (g x d)(-1) with an initial NO2(-) -N concentration of 36.82 mg x L(-1) and pH 7.5. In the industrial practice, it must be avoided pH higher than 9.0 in anoxic zone for industrial treatment. Replication-selective denitrifying bacteria showed a strong adaptability to methanol and ethanol, but showed maladaptation to other small molecular and easily biodegradable organics, such as glucose and acetic acid.

Modeling anaerobic digestion of aquatic plants by rumen cultures: cattail as an example.

Despite of the significance of the anaerobic digestion of lignocellulosic materials, only a limited number of studies have been carried out to evaluate the lignocellulosic digestion kinetics, and information about the modeling of this process is limited. In this work, a mathematical model, based on the Anaerobic Digestion Model No.1 (ADM1), was developed to describe the anaerobic conversion of lignocellulose-rich aquatic plants, with cattail as an example, by rumen microbes. Cattail was fractionated into slowly hydrolysable fraction (SHF), readily hydrolysable fraction (RHF) and inert fraction in the model. The SHF was hydrolyzed by rumen microbes and resulted in the production of RHF. The SHF and RHF had different hydrolysis rates but both with surface-limiting kinetics. The rumen microbial population diversity, including the cattail-, butyrate-, acetate- and H(2)-degraders, was all incorporated in the model structure. Experiments were carried out to identify the parameters and to calibrate and validate this model. The simulation results match the experimental data, implying that the fractionation of cattail into two biodegradation parts, i.e., SHF and RHF, and modeling their hydrolysis rate with a surface-limiting kinetics were appropriate. The model was capable of simulating the anaerobic biodegradation of cattail by the rumen cultures.