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1.
Artigo em Inglês | MEDLINE | ID: mdl-32004065

RESUMO

Evidence suggests that mitochondrial network integrity is impaired in cardiomyocytes from failing hearts. While oxidative stress has been implicated in heart failure (HF)-associated mitochondrial remodeling, the effect of mitochondrial-targeted antioxidants, such as mitoquinone (MitoQ), on the mitochondrial network in a model of heart failure (HF) (e.g. pressure overload) has not been demonstrated. Furthermore, the mechanism of this regulation is not completely understood with an emerging role for post-transcriptional regulation via long non-coding RNAs (lncRNA). We hypothesize that MitoQ preserves mitochondrial fusion proteins (i.e. Mfn2) through redox-sensitive lncRNAs, leading to improved mitochondrial network integrity in HF. To test the hypothesis, 8-weeks old C57BL/6J mice were subjected to ascending aortic constriction (AAC), which caused substantial left ventricular (LV) chamber remodeling and contractile dysfunction in one week. Transmission electron microscopy and immunostaining revealed defective inter-mitochondrial and mitochondrial-sarcoplasmic reticulum (SR) ultrastructure in AAC mice compared to Sham-operated animals, which was accompanied by elevated oxidative stress and suppressed MFN2 expression. MitoQ (1.36 mg/day/mouse, 7 consecutive days) significantly ameliorated LV contractile dysfunction, attenuated Mfn2 protein downregulation, improved inter-organellar contact, and increased metabolism-related gene expression. Moreover, our data from both mice and isolated cardiomyocytes revealed that MitoQ alleviated the dysregulation of a Mfn2-associated lncRNA (i.e. Plscr4). In summary, the present study supports a unique mechanism by which MitoQ improves myocardial inter-organellar network in HF by maintaining Mfn2 expression via regulation by lncRNAs. These findings underscore the role of lncRNAs in the pathogenesis of HF, and the potential of targeting lncRNAs as novel therapeutic strategy for HF treatment.

2.
Clin Nucl Med ; 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32049729

RESUMO

A 54-year-old man presented with a history of upper lip pain for 4 weeks. Biopsy of the lip lesion revealed extranodal natural killer/T-cell lymphoma. F-FDG PET/CT scan showed the solely high uptake in the right upper lip without any other nodal or extranodal involvements.

3.
J Exp Bot ; 2020 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-32053723

RESUMO

The rhizosheath is known to be beneficial for drought resistance in many plants, but the regulation of rhizosheath formation in rice plants is unclear. Here, we investigate rhizosheath formation in different rice varieties and root hair mutants. Our results showed that moderate water stress in rice induced rhizosheath formation. The soil porosity and water content were higher in the rice rhizosheath than in the rice bulk soil under moderate water stress. Additionally, rhizosheath formation in short root hair mutants was lower than in wild-type rice under moderate water stress. Moreover, transcriptomic results indicated that abscisic acid (ABA) and auxin were involved in root and root hair responses in rhizosheath formation. Further, blocking ABA and auxin pathways in wild type and in rhl1-1, the shortest root hair mutant, rhizosheath formation and root hair length were significantly decreased under moderate water stress. However, wild type plants maintained a higher root ABA content, root basipetal auxin transport, root hair length, and amount of rhizosheath than did rhl1-1. Our results suggest that moderate water stress in rice induces rhizosheath formation by modulating the ABA and auxin responses to regulate root and root hair growth, which may be used to breed rice varieties resistant to drought.

4.
Plant Cell Environ ; 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32012309

RESUMO

Hydrogen sulfide (H2 S) is emerging as an important signaling molecule that regulates plant growth and abiotic stress responses. However, the roles of H2 S in symbiotic nitrogen (N) assimilation and remobilization have not been characterized. Therefore, we examined how H2 S influences the soybean (Glycine max)/rhizobia interaction in terms of symbiotic N fixation and mobilization during N-deficiency induced senescence. H2 S enhanced biomass accumulation and delayed leaf senescence through effects on nodule numbers, leaf chlorophyll contents, leaf N resorption efficiency (NRE), and the N contents in different tissues. Moreover, grain numbers and yield were regulated by H2 S and rhizobia, together with N accumulation in the organs, and N use efficiency (NUE). The synergistic effects of H2 S and rhizobia were also demonstrated by effects on the enzyme activities, protein abundances and gene expressions associated with N metabolism, and senescence-associated genes (SAGs) expression in soybeans grown under conditions of N deficiency. Taken together, these results show that H2 S and rhizobia accelerate N assimilation and remobilization by regulation of the expression of SAGs during N deficiency-induced senescence. Thus, H2 S enhances the vegetative and reproductive growth of soybean, presumably through interactions with rhizobia under conditions of N deficiency. This article is protected by copyright. All rights reserved.

5.
Cancer Discov ; 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32046984

RESUMO

A hallmark of pancreatic ductal adenocarcinoma (PDAC) is an exuberant stroma comprised of diverse cell types that enable or suppress tumor progression. Here, we explored the role of oncogenic Kras in pro-tumorigenic signaling interactions between cancer cells and host cells. We show that Kras* drives cell autonomous expression of type I cytokine receptor complexes (IL2ry-IL4ra and IL2ry-IL13ra1) in cancer cells that in turn are capable of receiving cytokine growth signals (IL4 or IL13) provided by invading TH2 cells in the microenvironment. Early neoplastic lesions show close proximity of Kras* cancer cells and TH2 cells producing IL4 and IL13. Activated IL2ry-IL4ra and IL2ry-IL13ra1 receptors signal primarily via Jak1-Stat6. Integrated transcriptomic, chromatin occupancy and metabolomic studies identified cMyc, as a direct target of activated Stat6, and that cMyc drives glycolysis. Thus paracrine signaling in the tumor microenvironment plays a key role in the Kras*-driven metabolic reprogramming of PDAC.

6.
Nat Commun ; 11(1): 603, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32001676

RESUMO

Immunotherapy targeting T cells is increasingly utilized to treat solid tumors including non-small cell lung cancer (NSCLC). This requires a better understanding of the T cells in the lungs of patients with NSCLC. Here, we report T cell repertoire analysis in a cohort of 236 early-stage NSCLC patients. T cell repertoire attributes are associated with clinicopathologic features, mutational and immune landscape. A considerable proportion of the most prevalent T cells in tumors are also prevalent in the uninvolved tumor-adjacent lungs and appear specific to shared background mutations or viral infections. Patients with higher T cell repertoire homology between the tumor and uninvolved tumor-adjacent lung, suggesting a less tumor-focused T cell response, exhibit inferior survival. These findings indicate that a concise understanding of antigens and T cells in NSCLC is needed to improve therapeutic efficacy and reduce toxicity with immunotherapy, particularly adoptive T cell therapy.

7.
Artigo em Inglês | MEDLINE | ID: mdl-32006333

RESUMO

Artemisinin sustained-release microspheres (ASMs) with long-term inhibition effects (> 40 days) on harmful freshwater bloom-forming cyanobacteria have been found in previous studies, but the inhibition mechanism is not completely clear. In the present study, we examined the growth effect of ASMs on Microcystis aeruginosa (M. aeruginosa) cells at different physiological stages. Growth experiments indicated that M. aeruginosa of different initial densities could be inhibited immediately and chlorophyll-a content both showed significant decreases following exposure of cyanobacteria to optimal dosage of ASMs for 20 days. The algicidal mechanism of ASMs was tested through a suite of physiological parameters (membrane permeability, antioxidant enzymes activity, and lipid peroxidation). The rise of cell membrane permeability indices (intracellular protein, nucleic acid contents, and conductivity) showed that the cellular membrane structure of M. aeruginosa was attacked by ASMs directly causing the leakage of cytoplasm. Antioxidant enzyme activity was a sensitive indicator of the impacts of ASMs which showed a significant downtrend after a few days. ASMs caused a great increase in •O2- and malondialdehyde (MDA) level of the algal cells which indicated the increase in lipid peroxidation of M. aeruginosa. Irreversible membrane damage induced by ASMs via the oxidation of ROS may be an important factor responsible for the algicidal mechanism of ASMs on M. aeruginosa cells. The application of ASMs might provide a new direction to control M. aeruginosa, especially before the exponential phase according to the optimal economy and inhibition effect. Graphical abstract.

8.
Macromol Rapid Commun ; : e1900570, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31894599

RESUMO

Covalent organic frameworks (COFs) as drug delivery systems have shown great promise, but their pharmaceutical applications are often limited by complex building blocks, tedious preparations, irregular shape, and uncontrolled drug release within target cells. Herein, a facile strategy is developed to prepare PEGylated redox-responsive nanoscale COFs (denoted F68@SS-COFs) for efficiently loading and delivering doxorubicin (DOX) by use of FDA-approved Pluronic F68 and commercially available building blocks. The obtained F68@SS-COFs with controlled size, high stability, and good biocompatibility can not only achieve a very high DOX-loading content (about 21%) and very low premature leakage at physiological condition but can also rapidly respond to the tumor intracellular microenvironment and efficiently release DOX to kill tumor cells. Considering the readily available raw materials, simple preparation process, and desirable redox-responsiveness, the strategy provided here opens up a promising avenue to develop well-defined COFs-based nanomedicines for cancer therapy.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31987960

RESUMO

PURPOSE: Patients receiving pelvic radiation for cervical cancer experience high rates of acute gastrointestinal (GI) toxicity. The association of changes in the gut microbiome with bowel toxicity from radiation is not well characterized. METHODS AND MATERIALS: Thirty-five patients undergoing definitive chemoradiation therapy (CRT) underwent longitudinal sampling (baseline and weeks 1, 3, and 5) of the gut microbiome and prospective assessment of patient-reported GI toxicity. DNA was isolated from stool obtained at rectal examination and analyzed with 16S rRNA sequencing. GI toxicity was assessed with the Expanded Prostate Cancer Index Composite instrument to evaluate frequency, urgency, and discomfort associated with bowel function. Shannon diversity index was used to characterize alpha (within sample) diversity. Weighted UniFrac principle coordinates analysis was used to compare beta (between sample) diversity between samples using permutational multivariate analysis of variance. Linear discriminant analysis effect size highlighted microbial features that best distinguish categorized patient samples. RESULTS: Gut microbiome diversity continuously decreased over the course of CRT, with the largest decrease at week 5. Expanded Prostate Cancer Index Composite bowel function scores also declined over the course of treatment, reflecting increased symptom burden. At all individual time points, higher diversity of the gut microbiome was linearly correlated with better patient-reported GI function, but baseline diversity was not predictive of eventual outcome. Patients with high toxicity demonstrated different compositional changes during CRT in addition to compositional differences in Clostridia species. CONCLUSIONS: Over time, increased radiation toxicity is associated with decreased gut microbiome diversity. Baseline diversity is not predictive of end-of-treatment bowel toxicity, but composition may identify patients at risk for developing high toxicity.

10.
Biomater Sci ; 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31960834

RESUMO

An efficient theranostic nanoplatform responding to tumour microenvironments with characters of simple and flexible combinations owns great potential in cancer diagnosis and therapy. Herein, a series of triblock copolymers, mPEG-b-PDPA-b-P(nBMA-r-cystamine) (EPB), were synthesized and among them, the structure of EPB-3 was optimized for both fluorescence imaging-guided cancer diagnosis and multi-modal therapy with good biocompatibility. (1) The self-assembled nanoparticles of EPB-3-ICG1 obtained by conjugating one ICG on EPB-3 via S-S bonds effectively performed reduction-sensitive OFF/ON fluorescence signal transition, thus inducing tumour cell-specific amplified fluorescence imaging in vitro and in vivo. (2) By entrapping Au nanorods into the co-assembled NPs of EPB-3 and EPB-3-ICG1, EPB-3-ICG1@Au NPs could synchronously induce strong tumour fluorescence imaging and high local photothermal effect, indicating the potential of imagine-guided photothermal therapy. (3) EPB-3 NPs could efficiently co-load paclitaxel (PTX) and ICG to form stable EPB-3@PTX@ICG NPs, which provided long periods of intracellular pH-sensitive sustainable drug release and highly enhanced apoptosis of 4T1 cells in vitro by the chemo-photothermal effect. Excitingly, a single intravenous injection of EPB-3@PTX@ICG NPs followed by a one-time local near-infrared light (NIR, 808 nm) irradiation treatment for 10 min could lead to significant inhibition of tumour growth, avoiding tumor metastasis and extending the survival of mice. All the above-mentioned results suggest that EPB-3 provides a nanoplatform with the characters of simple structure, convenience of use and flexible combination, holding potential for multi-modal diagnosis and therapy.

11.
J Cell Biochem ; 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31960992

RESUMO

Glioblastoma multiforme (GBM) is a highly malignant brain tumor. We explored the prognostic gene signature in 443 GBM samples by systematic bioinformatics analysis, using GSE16011 with microarray expression and corresponding clinical data from Gene Expression Omnibus as the training set. Meanwhile, patients from The Chinese Glioma Genome Atlas database (CGGA) were used as the test set and The Cancer Genome Atlas database (TCGA) as the validation set. Through Cox regression analysis, Kaplan-Meier analysis, t-distributed Stochastic Neighbor Embedding algorithm, clustering, and receiver operating characteristic analysis, a two-gene signature (GRIA2 and RYR3) associated with survival was selected in the GSE16011 dataset. The GRIA2-RYR3 signature divided patients into two risk groups with significantly different survival in the GSE16011 dataset (median: 0.72, 95% confidence interval [CI]: 0.64-0.98, vs median: 0.98, 95% CI: 0.65-1.61 years, logrank test P < .001), the CGGA dataset (median: 0.84, 95% CI: 0.70-1.18, vs median: 1.21, 95% CI: 0.95-2.94 years, logrank test P = .0017), and the TCGA dataset (median: 1.03, 95% CI: 0.86-1.24, vs median: 1.23, 95% CI: 1.04-1.85 years, logrank test P = .0064), validating the predictive value of the signature. And the survival predictive potency of the signature was independent from clinicopathological prognostic features in multivariable Cox analysis. We found that after transfection of U87 cells with small interfering RNA, GRIA2 and RYR3 influenced the biological behaviors of proliferation, migration, and invasion of glioblastoma cells. In conclusion, the two-gene signature was a robust prognostic model to predict GBM survival.

12.
Bioresour Technol ; 297: 122459, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31784252

RESUMO

Stable sewage nitrogen removal with nitrogen removal efficiency of 87.5 ± 2.2% was achieved in a partial nitrification-anammox (PNA) biofilm system at low temperatures (12.8-16.3 °C). High-throughput sequencing analysis indicated that the microbial community structure in the sequencing batch biofilm reactor (SBBR) remained reasonably stable. Candidatus Brocadia was the only detected anammox genus and remained stable at 0.3-0.5%. Some psychrotolerant microorganisms that could secrete cryoprotective extracellular polymeric substances (EPS), including Flavobacterium and Thermomonas, were enriched at low temperatures. This could be conducive to the stable operation of the PNA-SBBR. Moreover, according to the EPS composition and characteristics analysis, the secretion of tightly-bound EPS that bound to the cell surface containing plentiful protein was stimulated at low temperatures, further improving the system stability. Overall, the reasonably stable microbial community structure, enrichment of psychrotolerant microorganisms, and increased secretion of EPS could play important roles for stable sewage nitrogen removal at low temperatures.


Assuntos
Microbiota , Nitrificação , Biofilmes , Reatores Biológicos , Desnitrificação , Matriz Extracelular de Substâncias Poliméricas , Nitrogênio , Oxirredução , Esgotos , Temperatura Ambiente
13.
ACS Appl Mater Interfaces ; 12(1): 980-988, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31815416

RESUMO

Brain-like neuromorphic computing system provides an alternative approach for the future computer for its characteristics of high-efficiency, power-efficient, self-learning, and parallel computing. Therefore, the imitation of synapse behavior based on microelectronics is particularly important. Recently, the synaptic transistors have received widespread attention. Among them, solid oxide-based synaptic transistors are more compatible with the large-scale fabrication than the liquid and organic-based transistors. So the development of oxide synaptic transistor is required. Here, a novel aqueous solution-processed Gd2O3 is suggested to be the solid electrolyte for synaptic transistors. The microstructure and the dielectric properties of Gd2O3 film are investigated, which show the potential for the simulation of synaptic transmission. Then, the fully aqueous solution-processed In2O3/Gd2O3 thin-film transistor (TFT) is fabricated. The device exhibits an acceptable electrical performance with a small threshold voltage of 1.24 V, and a small subthreshold swing of 0.12 V/decade. The artificial synapse behavior is stimulated and the short-term plasticity of In2O3/Gd2O3 TFT is studied. The dependence of its excitatory postsynaptic current on presynaptic pulse magnitude, width, and frequency is verified. Besides, the synapse behavior of devices under continuous illumination stresses is investigated. The lights with different photon energy have different effects on the synaptic transmission, which is related to the ionization of oxygen vacancies. Our results demonstrate that fully aqueous solution-processed In2O3 TFT with Gd2O3 solid electrolyte is a candidate for the synaptic transistor.

14.
Vaccine ; 38(3): 549-561, 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31740094

RESUMO

Mycoplasma bovis is an important pathogenic bacterium affecting cows and cattle. Clinically, an inactivated vaccine of M. bovis is mainly used to prevent infection by this bacterium. The changes that occur in the antigen when M. bovis is continuously passaged in vitro remain unknown. Therefore, we performed an in vitro serial passage of the M. bovis NM-28 strain, which was isolated and identified in our laboratory. An isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomics method was used to analyse the differences between generations 3 and 60. Many major membrane proteins or protective antigens reported in the literature did not exhibit changes between these generations. We found an imbalance between growth rate and nutrition in the 60th generation. The proteomics results were verified by western blotting and real-time PCR. Growth curves were also prepared based on colony-forming units (CFUs) between the 3rd and 60th generations. The number of colonies in the 60th generation in the stationary phase was 5 × 109 CFU mL-1, which was 10-fold higher than that in the 3rd generation. The 60th generation of the NM-28 strain can be used as an inactivated vaccine strain of M. bovis to lower production costs compared to use of the 3rd generation.

15.
Plant J ; 101(3): 604-618, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31621135

RESUMO

Carbon reserves in rice straw before flowering contribute greatly to grain filling. Moderate soil drying imposed at the post-anthesis stage significantly promotes carbon reserve remobilization in straws of rice, but the regulation of this process at the proteomic and transcriptomic level remains poorly understood. In this study, we applied moderate soil drying (MD) to rice at the post-anthesis stage, which was followed by dynamic proteomic and transcriptomic studies using SWATH-MS and RNA-seq analysis. MD treatment upregulated the proteins alpha-glucosidase, beta-glucosidase and starch phosphorylase, which are responsible for starch degradation. Furthermore, MD treatment enhanced the expression of proteins involved in the sucrose synthesis pathway, including SPS8 and SPP1. In addition, various monosaccharide transporters (MSTs) and sucrose transporter 2 (SUT2), which are pivotal in carbon reserve remobilization, were also upregulated in straw by MD treatment. Differentially expressed transcription factors, including GRAS, TCP, trihelix, TALE, C3H, and NF-YC, were predicted to interact with other proteins to mediate carbon reserve remobilization in response to MD treatment. Further correlation analysis revealed that the abundances of most of the differentially expressed proteins were not correlated with the corresponding transcript levels, indicating that the carbon reserve remobilization process was probably regulated by posttranscriptional modification. Our results provide insights into the molecular mechanisms underlying the regulation of carbon reserve remobilization from straw to grain in rice under MD conditions.

16.
J Cell Physiol ; 235(4): 3569-3578, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31556110

RESUMO

Studies have shown that microRNAs (miRNAs) play a vital role in tumor progression and patients' prognosis. Therefore, we aimed to construct a miRNA model for forecasting the survival of hepatocellular carcinoma (HCC) patients. The gene expression data of 433 patients with HCC from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus public databases were remined by survival analysis and receptor manipulation characteristic curve (ROC). A prognostic model including six miRNAs (hsa-mir-26a-1-3p, hsa-mir-188-5p, hsa-mir-212-5p, hsa-mir-149-5p, hsa-mir-105-5p, and hsa-mir-132-5p) were constructed in the training dataset (TCGA, n = 333). HCC patients were stratified into a high-risk group and a low-risk group with significantly different survival (median: 2.75 vs. 8.93 years, log-rank test p < .001). Then we proved its performance of stratification in another independent dataset (GSE116182, median: 2.55 vs 6.96 years, log-rank test p = .008). Cox regression analysis showed that the prognostic model was an independent prognostic indicator for HCC patients. Then time-dependent ROC analyses were performed to test the prognostic ability of the model with that of TNM staging, we found the model had a better performance, especially at 5 years (AUC = 0.76). Functional prediction showed that the genes targeted by the six prognostic miRNAs in the prognostic model were highly expressed in the P53-related pathway. In conclusion, we constructed a prognostic miRNA model that could indicate the survival of HCC patients.

17.
Ann Thorac Surg ; 109(2): 358-366, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31550464

RESUMO

BACKGROUND: High tumor mutational burden (TMB) and programmed death ligand 1 (PD-L1) expression are leading biomarkers in metastatic non-small cell lung cancer (NSCLC) and predict favorable response to checkpoint inhibitors. We sought to identify clinicopathologic characteristics associated with elevated TMB and PD-L1 expression among patients who underwent resection for NSCLC. METHODS: NSCLC patients undergoing primary resection (2016-2018) were prospectively enrolled in an immunogenomic profiling project. Multiplex immunofluorescence quantified densities (cells/mm2) of CD3+, CD3+CD8+, CD3+CD8+PD-1+, malignant cells (MCs), MCsPD-L1+, CD68+, CD68+PD-L1+, and CD20+ cells. Whole-exome sequencing quantified TMB (mutations/megabase). TMB and MCsPD-L1+ were dichotomized according to the median of each. RESULTS: A total of 55 patients completed multiplex immunofluorescence and whole-exome sequencing profiling. In this sample, 41.8% (23 of 55) had pathologic stage I disease. Median TMB and MCsPD-L1+ were 3.91 and 0.62 cells/mm2, respectively. TMB was higher among smokers (P = .001) and tumors with lymphovascular invasion (LVI) (P = .051). TMB was positively correlated with densities of MCsPD-L1+ (r = 0.293, P = .030), CD68+PD-L1+ (r = 0.289, P = .033), and CD20+ (r = 0.310, P = .043) cells. The density of MCsPD-L1+ was associated with increased CD3+CD8+ (r = 0.319, P = .018) and CD68+PD-L1+ (r = 0.371, P = .005) cells. Patients with PD-L1HighTMBHigh tumors (30.9%, 17 of 55) had higher intratumoral densities of CD3+, CD3+CD8+, CD68+, CD68+PD-L1+, and CD20+ cells. On multivariable analysis LVI was associated with synchronous elevated TMB and PD-L1 expression (odds ratio 3.53, P = .039). CONCLUSIONS: NSCLC tumors with elevated TMB and PD-L1 expression are associated with LVI and increased intratumoral immune cell infiltration. These findings may potentially improve patient selection for checkpoint inhibitor therapy trials in the adjuvant setting.

18.
J Hazard Mater ; 384: 121325, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31586910

RESUMO

The difficulties in enriching anammox bacteria and maintaining stable partial nitrification during start-up phase limit the application of mainstream anammox process. In this study, the feasibility of starting up simultaneous partial nitrification, anammox and denitrification (SNAD) reactor treating municipal wastewater by inoculating ordinary nitrification sludge (96.2%) and a small amount of anammox sludge (3.8%) was investigated. A sequencing batch reactor with intermittent aeration was used for the SNAD process. The SNAD reactor was started up in 75 days with a nitrogen removal efficiency of 85.4% at ambient temperature. The nitrogen removal performance maintained stable despite the fluctuating inflow. Anammox bacterial activity exponentially increased although nitrite oxidizing bacteria (NOB) activity in seeding sludge was high. The enhanced ammonium oxidizing bacterial activity and partial denitrification provided sufficient nitrite for anammox bacteria. Moreover, NOB was inhibited by intermittent aeration, anammox bacteria had competitive advantage on nitrite. The improved particle size and settleability of activated sludge also favored the anammox bacterial enrichment. This study provided an improved and easily-implemented start-up strategy for mainstream anammox. The seeding sludge was easily obtained and the operation strategy was simple. These findings were meaningful to the engineering application of mainstream anammox.

19.
J Environ Sci (China) ; 88: 273-282, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31862068

RESUMO

The effects of disinfection efficiency on microbial communities and the corrosion of cast iron pipes in drinking water distribution systems (DWDSs) were studied. Two annular reactors (ARs) that simulated actual running conditions with UV/Cl2 disinfection and chlorination alone were used. High chlorine consumption and corrosion rate were found in the AR with UV/Cl2. According to functional genes and pyrosequencing tests, a high percentage of iron recycling bacteria was detected within the biofilm of the AR with Cl2 at early running stage, whereas siderophore-producing bacteria were dominant in the biofilm of the AR with UV/Cl2. At the early running stage, the sequential use of UV light and an initial high chlorine dosage suppressed the biomass and iron-recycling bacteria in both bulk water and biofilms, thereby forming less protective scales against further corrosion, which enhanced chlorine consumption. Non-metric multidimensional scaling analysis showed that the bacterial communities in the ARs shaped from within rather than being imported by influents. These results indicate that the initial high disinfection efficiency within the distribution system had not contributed to the accumulation of iron-recycling bacteria at the early running stages. This study offer certain implications for controlling corrosion and water quality in DWDSs.

20.
Gut ; 69(1): 18-31, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31171626

RESUMO

OBJECTIVE: Peritoneal carcinomatosis (PC) occurs frequently in patients with gastric adenocarcinoma (GAC) and confers a poor prognosis. Multiplex profiling of primary GACs has been insightful but the underpinnings of PC's development/progression remain largely unknown. We characterised exome/transcriptome/immune landscapes of PC cells from patients with GAC aiming to identify novel therapeutic targets. DESIGN: We performed whole-exome sequencing (WES) and whole transcriptome sequencing (RNA-seq) on 44 PC specimens (43 patients with PC) including an integrative analysis of WES, RNA-seq, immune profile, clinical and pathological phenotypes to dissect the molecular pathogenesis, identifying actionable targets and/or biomarkers and comparison with TCGA primary GACs. RESULTS: We identified distinct alterations in PC versus primary GACs, such as more frequent CDH1 and TAF1 mutations, 6q loss and chr19 gain. Alterations associated with aggressive PC phenotypes emerged with increased mutations in TP53, CDH1, TAF1 and KMT2C, higher level of 'clock-like' mutational signature, increase in whole-genome doublings, chromosomal instability (particularly, copy number losses), reprogrammed microenvironment, enriched cell cycle pathways, MYC activation and impaired immune response. Integrated analysis identified two main molecular subtypes: 'mesenchymal-like' and 'epithelial-like' with discriminating response to chemotherapy (31% vs 71%). Patients with the less responsive 'mesenchymal-like' subtype had high expression of immune checkpoint T-Cell Immunoglobulin And Mucin Domain-Containing Protein 3 (TIM-3), its ligand galectin-9, V-domain Ig suppressor of T cell activation (VISTA) and transforming growth factor-ß as potential therapeutic immune targets. CONCLUSIONS: We have uncovered the unique mutational landscape, copy number alteration and gene expression profile of PC cells and defined PC molecular subtypes, which correlated with PC therapy resistance/response. Novel targets and immune checkpoint proteins have been identified with a potential to be translated into clinics.


Assuntos
Adenocarcinoma/secundário , Neoplasias Peritoneais/secundário , Neoplasias Gástricas/genética , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Instabilidade Cromossômica , Variações do Número de Cópias de DNA/genética , DNA de Neoplasias/genética , Feminino , Perfilação da Expressão Gênica/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular/métodos , Mutação , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/genética , Neoplasias Peritoneais/imunologia , Ploidias , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/imunologia , Sequenciamento Completo do Exoma/métodos
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