Hydrothermal carbonization (HTC) emerges as a promising technology to reduce the volume of activated sewage sludge (SS) and generate solid products as fuels. During HTC, extracellular polymeric ...substance and cell wall degrade to form low molecular compounds, which can further carry out hydrolysis, dehydration, polymerization, etc. The temperature has a notable impact on the HTC, which ultimately changes the composition of the aqueous phase. A large amount of the aqueous phase remains a by-product containing high amounts of organic and inorganic compounds. Herein, the HTC of SS process and aqueous phase treatment were discussed, especially in industrial applications within China. This review depicts the influence of aqueous phase properties on the hydrochar properties of SS, especially using the aqueous phase recirculation process. The mechanism during HTC of SS has been discussed, especially Maillard reaction, which would significantly influence the aqueous phase and hydrochar. The systematic information on the current research, new applications and new perspectives in this field to promote its further development were provided.
•Hydrothermal carbonization of sewage sludge receives great attention.•The main reactions involved in hydrochar formation are reviewed.•The aqueous phase treatment is summarized.•Hydrochar physicochemical characteristics from sewage sludge are summarized.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
d‐Glycero‐d‐manno‐heptose‐1β,7‐bisphosphate (HBP) and d‐glycero‐d‐manno‐heptose‐1β‐phosphate (H1P) are bacterial metabolites that were recently shown to stimulate inflammatory responses in host cells ...through the activation of the TIFA‐dependent NF‐κB pathway. To better understand structure‐based activity in relation to this process, a family of nonhydrolyzable phosphonate analogues of HBP and H1P was synthesized. The inflammation modulation by which these molecules induce the TIFA‐NF‐κB signal axis was evaluated in vivo at a low‐nanomolar concentration (6 nM) and compared to that of the natural metabolites. Our data showed that three phosphonate analogues had similar stimulatory activity to HBP, whereas two phosphonates antagonized HBP‐induced TIFA‐NF‐κB signaling. These results open new horizons for the design of pro‐inflammatory and innate immune modulators that could be used as vaccine adjuvant.
Small change, big difference: A series of nonhydrolyzable analogues of bacterial heptosides has been synthesized and assayed on whole cells. Interestingly, depending on the functional groups at the 7‐position of the heptose scaffold and in the vicinity of the anomeric position, some molecules could trigger an inflammatory response whereas others were antagonists of heptose‐1,7‐bisphosphate.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Effective screening and early detection are critical to improve the prognosis of gastric cancer (GC). Our study aims to explore noninvasive multianalytical biomarkers and construct integrative models ...for preliminary risk assessment and GC detection. Whole genomewide methylation marker discovery was conducted with CpG tandems target amplification (CTTA) in cfDNA from large asymptomatic screening participants in a high‐risk area of GC. The methylation and mutation candidates were validated simultaneously using one plasma from patients at various gastric lesion stages by multiplex profiling with Mutation Capsule Plus (MCP). Helicobacter pylori specific antibodies were detected with a recomLine assay. Integrated models were constructed and validated by the combination of multianalytical biomarkers. A total of 146 and 120 novel methylation markers were found in CpG islands and promoter regions across the genome with CTTA. The methylation markers together with the candidate mutations were validated with MCP and used to establish a 133‐methylation‐marker panel for risk assessment of suspicious precancerous lesions and GC cases and a 49‐methylation‐marker panel as well as a 144‐amplicon‐mutation panel for GC detection. An integrated model comprising both methylation and specific antibody panels performed better for risk assessment than a traditional model (AUC, 0.83 and 0.63, P < .001). A second model for GC detection integrating methylation and mutation panels also outperformed the traditional model (AUC, 0.82 and 0.68, P = .005). Our study established methylation, mutation and H. pylori‐specific antibody panels and constructed two integrated models for risk assessment and GC screening. Our findings provide new insights for a more precise GC screening strategy in the future.
What's new?
Genetic and epigenetic markers and environmental factors including Helicobacter pylori promote gastric cancer. Here, the authors established methylation, mutation and H. pylori‐specific antibody biomarker panels based on the analysis of precancerous lesions and gastric cancer cases to construct and validate two integrative models. The risk assessment model aimed to identify suspicious precancerous lesions and gastric cancer cases among asymptomatic screening participants and the detection model to further distinguish gastric cancer from suspected cases. The models showed better performance than a traditional model and high feasibility, paving the way for a noninvasive multianalytical approach for risk assessment and gastric cancer detection.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Based on our previous screening hit compound 1, a series of novel indole-pyrimidine hybrids possessing morpholine or thiomorpholine moiety were synthesized via an efficient one-pot multistep ...synthetic method. The antiproliferative activities of the synthesized compounds were evaluated in vitro against four cancer cell lines including HeLa, MDA-MB-231, MCF-7, and HCT116. The results revealed that most compounds possessed moderate to excellent potency. The IC50 values of the most promising compound 15 are 0.29, 4.04, and 9.48 μM against MCF-7, HeLa, and HCT116 cell lines, respectively, which are 48.0, 4.9, and 1.8 folds more active than the lead compound 1. Moreover, fluorescence-activated cell sorting analysis revealed that compound 14 showing the highest activity against HeLa (IC50 = 2.51 μM) displayed a significant effect on G2/M cell-cycle arrest in a concentration-dependent manner in HeLa cell line. In addition, representative nine active hybrids were evaluated for tubulin polymerization inhibitory activities, and compound 15 exhibited the most potent anti-tubulin activity showing 42% inhibition at 10 μM. These preliminary results encourage a further investigation on indole-pyrimidine hybrids for the development of potent anticancer agents that inhibit tubulin polymerization.
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•22 novel indole-pyrimidine hybrids were designed and synthesized.•Antiproliferative activities of these compounds were evaluated.•Compound 14 arrested HeLa cells in G2/M phase of cell cycle.•Hybrid 15 exhibited powerful tubulin inhibitory activity.•Molecular modeling suggested that 15 binds well in the colchicine binding site of α,β-tubulin.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
A novel series of 5‐substituted/unsubstituted 1,2,4triazolo3,4‐b1,3,4 thiadiazine compounds has been achieved successfully through chemoselective reduction of the C = N bond, based on our prior work. ...Initial biological evaluation illustrated that the most active derivative 7j exhibited significant cell growth inhibitory activity toward MCF‐7, A549, HCT116, and A2780 with the IC50 values of 0.75, 0.94, 2.90, and 4.15 μM, respectively. Most importantly, all the representative analogs did not demonstrate obvious cytotoxic activity against the non‐tumoural cell line HEK‐293 (IC50 > 100 μM). The mechanism study revealed that 7j caused the G2/M phase arrest, induced cell apoptosis in HeLa cells in a concentration‐dependent manner, and also showed potent tubulin polymerization inhibitory effect. Meanwhile, 7j exerted significant antivascular activity in the wound‐healing and tube formation assays. These observations indicate that 5‐unsubstituted 6,7‐dihydro‐5H‐1,2,4triazolo3,4‐b1,3,4thiadiazine scaffold might be considered as a potential lead for antitubulin inhibitors to develop highly efficient anticancer agents with potent selectivity over normal human cells.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Thirty-six novel indole-based 1,2,4-triazole derivatives were designed and synthesized through the molecular hybrid strategy. The bioassay results revealed that
9p
displayed excellent ...antiproliferative efficacies in the nanomolar range against HeLa cells. Importantly, the compound exhibited no obvious cytotoxic activity (IC
50
> 100 μM) toward HEK-293, a normal human embryonic kidney cell line. Mechanism analysis indicated that
9p
significantly arrested the cell cycle at the G2/M phase and induced apoptosis in HeLa cells in a dose-dependent manner. Further evidence demonstrated that the promising compound effectively inhibited tubulin polymerization with an IC
50
value of 8.3 μM, and molecular docking studies revealed that
9p
well occupied the colchicine-site in tubulin. The present study highlights that indole-triazole hybrids might be used as a promising scaffold to develop novel tubulin polymerization inhibitors for cancer treatment.
Thirty-six novel indole-based 1,2,4-triazole derivatives were designed and synthesized through the molecular hybrid strategy.
ABSTRACT
Cluster of differentiation (CD) 69 is a leukocyte activation receptor involved in the maintenance of immune homeostasis and is positively selected in activated regulatory T (Treg) cells, ...implicating its role during Treg‐cell differentiation. By RNA interference, we show that CD69 is not sufficient to support the conversion of CD4+ naive T cells into Treg cells, whereas it does that of human peripheral blood mononuclear cells (hPBMCs) (P < 0.01), suggesting that a ligand‐receptor interaction is required for CD69 function. Using immunoprecipitation and mass spectrometry, we identified the S100A8/S100A9 complex as the natural ligand of CD69 in hPBMCs. CD69 specifically associates with S100A8/S100A9 complex as confirmed by in vitro binding and competition assay, and the treatment of CD69 with peptide‐N‐glycosidase significantly abolishes such association. In agreement, the glycomics analysis determines the glycosylation site and the N‐glycan composition of CD69, and terminal removal of sialic acid from that N‐linked glycans reverses the generation of forkhead box P3‐positive Treg cells (23.21%; P < 0.05). More specifically, we showed that CD69‐S100A8/S100A9 association is required for the up‐regulation of suppressor of cytokine signaling 3 resulting in inhibited signaling of signal transducer and activator of transcription 3 (36.54% increase upon CD69 silencing; P< 0.01). This might in turn support the secretion of key regulator TGF‐β (∼3.28‐fold decrease upon CD69 silencing; P < 0.05), leading to reduced production of IL‐4 in hPBMCs. Our results demonstrate the functional and mechanistic interplays between CD69 and S100A8/S100A9 in supporting Treg‐cell differentiation.—Lin, C.‐R., Wei, T.‐Y. W., Tsai, H.‐Y., Wu, Y.‐T., Wu, P.‐Y., Chen, S.‐T. Glycosylation‐dependent interaction between CD69 and S100A8/S100A9 complex is required for regulatory T‐cell differentiation. FASEB J. 29, 5006–5017 (2015). www.fasebj.org
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract
Tumor necrosis factor receptor-associated factor-interacting protein with a forkhead-associated domain (TIFA), a key regulator of inflammation, may be involved in the pathogenesis of ...pulmonary arterial hypertension (PAH). A total of 48 PAH patients (age 50.1 ± 13.1 years, 22.9% men), 25 hypertensive subjects, and 26 healthy controls were enrolled. TIFA protein expression in peripheral blood mononuclear cells (PBMCs) and plasma interleukin (IL)-1β and tumor necrosis factor (TNF)-α were measured. Pulmonary arterial hemodynamics were derived from right heart catheterization. PAH patients had the highest expression of TIFA, TNF-α, and IL-1β. TIFA protein expression was significantly associated with IL-1β (r = 0.94;
P
< 0.001), TNF-α (r = 0.93;
P
< 0.001), mean pulmonary artery pressure (r = 0.41;
P
= 0.006), and pulmonary vascular resistance (r = 0.41;
P
= 0.007). TIFA protein expression could independently predict the presence of PAH (odds ratio 95% confidence interval per-0.1 standard deviation: 1.72 1.37–2.16;
P
< 0.001) and outperformed echocardiographic estimation. Ex vivo silencing of TIFA protein expression in PBMCs led to the suppression of the cellular expression of IL-1β and TNF-α. IL-1β and TNF-α mediated 80.4% and 56.6% of the causal relationship between TIFA and PAH, respectively, supporting the idea that TIFA protein is involved in the pathogenesis of PAH.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The natural outcome of coronary plaque in acute coronary syndrome (ACS) patients with chronic kidney disease (CKD) is unique, which can be analyzed quantitatively by optical flow ratio (OFR) ...software.
A total of 184 ACS patients with at least one nonculprit subclinical atherosclerosis (NSA) detected by optical coherence tomography (OCT) at baseline and 1-year follow-up were divided into non-CKD group (n = 106, estimated glomerular filtration rate (eGFR)> 90 mL/(min×1.73 m2)) and mild CKD group (n = 78, 60≤eGFR<90 mL/(min×1.73 m2)). Changes of normalized total atheroma volume (TAVn) of NSA was the primary endpoint at the 1-year follow-up.
Patients with mild CKD showed more TAVn progression of NSA than non-CKD (p = 0.019) from baseline to the 1-year follow-up, which was mainly due to an increase in calcium TAVn (p<0.001). The morphological change in the maximal calcification thickness (p = 0.026) was higher and the change in the distance from the calcified surface to the contralateral coronary media membrane (ΔC-to-M) at the maximal cross-sectional calcium area was lower (p<0.001) in mild CKD group than in non-CKD group. Mild CKD had more NSA related MACEs at the 5-year follow-up than non-CKD (30.8% vs. 5.8%, p = 0.045).
Mild CKD patients had more plaque progression of NSA which showed the increase of calcium component with more protrusion into the lumen morphologically at the 1-year follow-up and a higher corresponding incidence of NSA-related MACEs at the 5-year follow-up.
Clinical Trial registration ClinicalTrials.gov. NCT02140801. https://classic.clinicaltrials.gov/ct2/show/NCT02140801.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
There are many commercially available glycogen particles in the market due to their bioactive functions as food additive, drug carrier and natural moisturizer, etc. It would be beneficial to rapidly ...determine the origins of commercially-available glycogen particles, which could facilitate the establishment of quality control methodology for glycogen-containing products. With its non-destructive, label-free and low-cost features, surface enhanced Raman spectroscopy (SERS) is an attractive technique with high potential to discriminate chemical compounds in a rapid mode. In this study, we applied the combination of SERS technique and machine leaning algorithms on glycogen analysis, which successfully predicted the origins of glycogen particles from a variety of organisms with convolutional neural network (CNN) algorithm plus attention mechanism having the best computational performance (5-fold cross validation accuracy = 96.97 %). In sum, this is the first study focusing on the discrimination of commercial glycogen particles originated from different organisms, which holds the application potential in quality control of glycogen-containing products.
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•AgNPs substrate greatly enhances the Raman intensity and information richness for glycogen particles.•PCA and t-SNE are able to cluster SERS spectra of different glycogen samples into different groups.•Supervised machine learning algorithms predict the organismal origins of glycogen with high accuracy and robustness.•Computational analyses consistently achieved better results via SERS spectra than RS spectra.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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