Many dyes and pigments are used in textile and printing industries, and their wastewater has been classed as a top source of pollution. Biodegradation of dyes by fungal laccase has great potential. ...In this work, the influence of reaction time, pH, temperature, dye concentration, metal ions, and mediators on laccase-catalyzed Remazol Brilliant Blue R dye (RBBR) decolorization were investigated in vitro using crude laccase from the white-rot fungus
. The optimal decolorization percentage (50.3%) was achieved at 35 °C, pH 4.0, and 200 ppm RBBR in 30 min. The mediator effects from syringaldehyde, 1-hydroxybenzotriazole, and vanillin were compared, and 0.1 mM vanillin was found to obviously increase the decolorization percentage of RBBR to 98.7%. Laccase-mediated decolorization percentages significantly increased in the presence of 5 mM Na
and Cu
, and decolorization percentages reached 62.4% and 62.2%, respectively. Real-time fluorescence-quantitative PCR (RT-PCR) and protein mass spectrometry results showed that among the 15 laccase isoenzyme genes,
was the main laccase-contributing gene, contributing the most to the laccase enzyme activity and decolorization process. These results also indicate that under optimal conditions,
laccases, especially Glac1, have a strong potential to remove RBBR from reactive dye effluent.
Ecological ditches (eco-ditches) are being recognized as a green method for treating wastewater from domestic sewage sources. However, the relationship between the efficiency of nutrient removal from ...wastewater and N
2
O emissions is unclear given that a higher nutrient removal efficiency might result in more N
2
O emissions. Therefore, we constructed an eco-ditch system with three combinations of different plants (local wetland species) to treat rural sewage in the mountainous regions of China and monitored water quality and N
2
O emissions. Eco-ditches are important sources of atmospheric N
2
O, with nutrient removal efficiencies of 22–84% and 23–87% for total nitrogen (TN) and total phosphorus (TP), respectively, and emissions of N
2
O ranging from 16 to 243 µg m
−2
h
−1
. The seasonal variations in pollutant removal efficiency and N
2
O emissions followed similar patterns—both were considerably greater in summer than in the other seasons, with the lowest values observed in winter. Among the three plant configurations tested, ditch sections containing
Acorus calamus
L. and
Phyllostachys heteroclada
Oliv. had the highest nutrient removal efficiency and the lowest N
2
O emissions, with removal efficiencies of 24% and 32%, respectively, for TN and TP, and a 16% average reduction in N
2
O emissions, which was positively associated with NO
3
–N. This study highlights the importance of selecting appropriate combination of plant species for eco-ditches to efficiently remove nutrients from rural domestic sewage and reduce N
2
O emissions.
Fecal diversion after bowel resection is a safe and effective procedure in high-risk patients with Crohn's disease, but the better approach between primary anastomosis with protective stoma and split ...stoma with delayed anastomosis has not yet been investigated. This study aimed to compare the outcomes of these approaches in high-risk patients with Crohn's disease.
A retrospective investigation on consecutive high-risk patients with Crohn's disease was conducted at a tertiary referral hospital from August 2009 to March 2019. The primary outcomes were the overall early postoperative complications and overall anastomosis-related adverse events in an intention-to-treat approach.
A total of 118 consecutive patients who underwent 121 surgeries (35 procedures with a protective stoma and 86 procedures with a split stoma) were enrolled. After a median follow-up period of 659 days and 728 days, respectively, 25 patients underwent a stoma-reversal procedure in the protective-stoma group, and 54 patients underwent delayed anastomosis in the split stoma group. Overall, early 30-day surgical morbidity and anastomosis-related adverse events were observed in more patients in the protective-stoma group than in the split-stoma group (51.4% 18/35 vs 30.2% 26/86; P = .028 and 37.1% 13/35 vs 2.3% 2/86; P < .001, respectively; intention-to-treat analysis). Similar results were found in the per-protocol analysis (44.0% 11/25 vs 20.4% 11/54; P = .029 and 36.0% 12/25 vs 3.7% 2/54; P < .001, respectively.)
Split stoma with delayed anastomosis is associated with a reduction in anastomotic adverse events and overall early surgical complications and thus may be a better surgical option for high-risk patients with Crohn's disease.
The safety and effectiveness of prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) in pathological T3-4 locally advanced (pT3N + M0 and pT4NxM0) colon cancer (CC) patients with radical ...resection need further study.
Clinical and pathological information of pT3-4 locally advanced CC patients who received radical surgery in our hospital from January 2018 to December 2020 were analyzed. The prognosis of patients was estimated using Cox proportional hazards regression analysis and Kaplan–Meier method.
Among 927 patients, 10.4% (96/927) received prophylactic HIPEC based on 5-FU, 4.6% (43/927) received prophylactic HIPEC based on lobaplatin, 85.0% (788/927) received conventional therapy. The incidence of metachronous peritoneal carcinomatosis (mPC) was 9.4%. Complications occurred in 32 patients (4.1%) in the conventional therapy group, 6 patients (6.3%) in the prophylactic HIPEC group based on 5-FU and 3 patients (7.0%) in the prophylactic HIPEC group based on lobaplatin within 30 days after surgery (5-FU vs. conventional therapy group, p = 0.464; Lobaplatin vs. conventional therapy group, p = 0.591). Multivariate Cox regression analysis revealed that prophylactic HIPEC based on either 5-FU or lobaplatin regimen could not effectively improve mPC-free survival (5-FU: p = 0.020, HR = 1.927, 95% CI, 1.111–3.343; Lobaplatin: p = 0.167, HR = 0.247, 95% CI, 0.034–1.796), overall survival (5-FU: p = 0.361, HR = 1.360, 95% CI, 0.703–2.634; Lobaplatin: p = 0.780, HR = 0.816, 95% CI, 0.195–3.416) and disease-free survival (5-FU: p = 0.525, HR = 1.149, 95% CI, 0.749–1.760; Lobaplatin: p = 0.117, HR = 0.488, 95% CI, 0.199–1.198).
Early prophylactic HIPEC based on 5-FU or lobaplatin subsequent to radical resection for patients with pT3-4 locally advanced CC is safe, but not effective in reducing the risk for mPC.
Abstract Background and Aim: Ferroptosis is an iron-dependent form of programmed cell death characterized by lipid peroxidation, with the potential as a novel cancer therapy. The application of ...ferroptosis-inducers has been limited to preclinical studies due to toxic side effects and drug-resistance. Our study aims to explore the metabolic mechanism in regulating ferroptosis-resistance, thereby identifying combinational therapeutic target for ferroptosis-inducers. Methods: The ferroptosis-resistant CRC cell lines were induced by chronic exposure to ferroptosis inducer Erastin and verified by cell viability assay. Metabolomics and transcriptomics were performed to identify the metabolic characteristics in ferroptosis-resistant CRC cells. Quantitative RT-PCR and western blot was applied to confirm the differentially expressed serine-glycine-one-carbon metabolism (SGOC) enzymes. The MTT cell viability assay, colony formation assay, 3D spheroid formation assay and cell derived xenograft (CDX) model were carried out to investigate the therapeutic effect of targeting SGOC key enzyme-phosphoglycerate dehydrogenase (PHGDH) in combination of ferroptosis inducers. Gene set enrichment analysis (GSEA) was performed to identify molecular mechanism for the upregulation of SGOC enzymes based on RNA-seq data from TCGA-COAD cohort. Results: Metabolomic and transcriptomic data revealed that SGOC metabolism was significantly increased in ferroptosis-resistant CRC cells. Moreover, the mRNA and protein level of SGOC key enzyme-PHGDH were remarkably upregulated in ferroptosis-resistant CRC cells. PHGDH inhibitor NCT-503 or knockdown of PHGDH exhibited a great synergistic effect with ferroptosis inducers for CRC cells in vitro or in vivo. Additionally, targeting PHGDH could dramatically restore the sensitivity of ferroptosis-inducers in ferroptosis-resistant cells. The RNA methyltransferase-like 3 (METTL3) was identified as the upstream regulator responsible for the upregulation of PHGDH in an m6A-dependent manner. The ferroptosis stress induced deacetylation of METTL3, thereby promoting its nuclear translocation and enzyme activity. Conclusions: In summary, we have uncovered that CRC cells resisted ferroptosis inducers via METTL3-PHGDH axis. Targeting PHGDH combined with ferroptosis inducers exhibited with synergistic effect for CRC in vitro and in vivo. Our findings identified the metabolic vulnerability in ferroptosis-resistant CRC cells, which could serve as a novel therapeutic target. Citation Format: Guanzhan Liang, Jing Chen, Xiaofeng Wen, Zongjin Zhang, Zexian Chen, Yongle Chen, Zhenyu Xian, Xiaowen He, Xianrui Wu, Ping Lan, Tuo Hu. PHGDH-mediated serine-glycine-one-carbon metabolism drives ferroptosis- and chemotherapy-resistance in colorectal cancer abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3275.
As the most abundant memory T cells and major source of tumor necrosis factor α in the intestinal mucosa of Crohn’s disease (CD) patients, CD4+ tissue-resident memory T (TRM) cells play a critical ...role in CD pathogenesis. We investigated the role of metabolic reprogramming in the regulation of proinflammatory and apoptosis-resistant phenotype for CD4+ TRM cells.
CD4+ TRM cells were collected from intestinal resection tissues from control and CD patients. Transcriptomic and metabolomic analysis were performed to identify metabolic characteristics of CD4+ TRM cells. Enzyme-linked immunosorbent assay and quantitative polymerase chain reaction experiments were used to assess cytokines level in CD4+ TRM cells; activation-induced cell apoptosis rate was evaluated by flow cytometry. Transwell assay and wound healing assay were performed to detect the effect of CD4+ TRM cells on the migration of normal intestinal epithelial cells.
Transcriptomic data combined with unbiased metabolomic analysis revealed an increased fatty acid oxidation (FAO) phenotype existed in CD4+ TRM cells from CD patients. The lipidomic data and stable isotope tracer experiments demonstrated that CD4+ TRM cells up-regulated their lipid lipolysis and fatty acid uptake to fuel FAO in CD patients. Mechanistically, the activated nuclear factor kappa B signaling increased transcription of genes involved in lipid lipolysis, fatty acid uptake, and oxidation in CD4+ TRM cells from CD patients. Targeting FAO of CD4+ TRM cells reversed their apoptosis-resistant and proinflammatory phenotype in CD patients.
CD4+ TRM cells process an accelerated FAO mediated by activated nuclear factor kappa B signaling in CD patients; targeting FAO could reverse their apoptosis-resistant and proinflammatory phenotype. These findings shed a new light on the pathogenic mechanism investigation and novel therapy development in CD patients.
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It is important to implement a preventive strategy for early detection and endoscopic removal of metachronous adenoma in patients with colorectal cancer (CRC). Here, we retrospectively explored the ...associated factors of metachronous adenoma in these patients.
This study recruited 551 patients with stage I and II CRC who underwent radical surgery between January 1, 2012 and July 1, 2017 with postoperative colonoscopic surveillance. Data on clinicopathological characteristics and surveillance colonoscopies were obtained from medical records. Univariate analysis by Kaplan-Meier method and multivariate analysis by Cox proportional hazards model were used to identify the factors associated with metachronous adenoma.
Metachronous adenoma was detected in 110 (20.0%) patients. In these patients, 94.5% (104/110) had metachronous adenoma within 3 years postoperatively. Age, synchronous adenoma, hypertension, tumor stage, and surgical resection were correlated with metachronous adenoma in patients with stage I-II CRC after radical resection (log rank test, P<0.05). Multivariate analyses showed that synchronous adenoma (HR =2.515, 95% CI: 1.691-3.742, P<0.01); stage II (HR =2.066, 95% CI: 1.329-3.210, P<0.01); and left-side colorectal resection (HR =2.207, 95% CI: 1.292-3.772, P<0.01) were independent risk factors.
Synchronous adenoma, left-side colorectal resection, and stage II cancer are independent risk factors of metachronous adenoma in patients with previous stage I and II CRC. In patients with risk factors, an enhanced colonoscopic strategy might be needed for early detection and timely endoscopic removal of metachronous adenoma.
Background & Aims: As the most abundant memory T cells and major source of tumor necrosis factor α in the intestinal mucosa of Crohn’s disease (CD) patients, CD4+ tissue-resident memory T (TRM) cells ...play a critical role in CD pathogenesis. We investigated the role of metabolic reprogramming in the regulation of proinflammatory and apoptosis-resistant phenotype for CD4+ TRM cells. Methods: CD4+ TRM cells were collected from intestinal resection tissues from control and CD patients. Transcriptomic and metabolomic analysis were performed to identify metabolic characteristics of CD4+ TRM cells. Enzyme-linked immunosorbent assay and quantitative polymerase chain reaction experiments were used to assess cytokines level in CD4+ TRM cells; activation-induced cell apoptosis rate was evaluated by flow cytometry. Transwell assay and wound healing assay were performed to detect the effect of CD4+ TRM cells on the migration of normal intestinal epithelial cells. Results: Transcriptomic data combined with unbiased metabolomic analysis revealed an increased fatty acid oxidation (FAO) phenotype existed in CD4+ TRM cells from CD patients. The lipidomic data and stable isotope tracer experiments demonstrated that CD4+ TRM cells up-regulated their lipid lipolysis and fatty acid uptake to fuel FAO in CD patients. Mechanistically, the activated nuclear factor kappa B signaling increased transcription of genes involved in lipid lipolysis, fatty acid uptake, and oxidation in CD4+ TRM cells from CD patients. Targeting FAO of CD4+ TRM cells reversed their apoptosis-resistant and proinflammatory phenotype in CD patients. Conclusions: CD4+ TRM cells process an accelerated FAO mediated by activated nuclear factor kappa B signaling in CD patients; targeting FAO could reverse their apoptosis-resistant and proinflammatory phenotype. These findings shed a new light on the pathogenic mechanism investigation and novel therapy development in CD patients.
This papers aims to explore the response of ammonia oxidizing bacteria（AOB） and ammonia oxidizing archaea（AOA） communities to elevation changes in the dry-hot valleys of Panzhihua City, China, and ...further reveal the nitrogen biogeochemical cycling of this area. Soil samples were collected from the tobacco cultivation field of different altitudes（e.g. 1600 m, 1800 m, and 2000 m） in the dry-hot valleys of Miyi county, Panzhihua City, China. Chemical analysis and terminal restriction fragment length polymorphism（T-RFLP） were used to analyze the soil physicochemical properties and community structures and diversity of AOB and AOA, respectively. The variation of AOA and AOB communities and the driving factors in farmland soils at different altitudes were also investigated. The results showed that the pH value of soils from the three different elevations were below seven which suggests that the soils being studied were acidic soils. The contents of soil organic carbon（SOC）, total nitrogen（TN）, available potassium（AK） and ammonium nitrogen（NH+4-N） decreased along the increase of elevation. The contents of alkali-hydrolyzable nitrogen（AN）, available phosphorus（AP）, and nitrate nitrogen（NO-3-N） first increased and then decreased along the increase of elevation. The highest contents of the AN, AP, and NO-3-N were detected in the 1800 m elevation while the lowest were detected in the 2000 m. The diversity index of AOA community increased along the increase of altitude while the diversity index of AOB peaked in 1800 m, and both the lowest diversity index of AOA and AOB were detected in 1600 m elevation. Nitrososphaera and Nitrosospira were the dominant species of AOA and AOB in the dry-hot valleys of Panzhihua City. Redundancy analysis（RDA） showed that the SOC, AK, and NO-3-N were key factors in shaping the AOA and AOB communities. In total, both of the composition and diversity of soil AOA and AOB community varied significantly along the increase of altitude in the dry-hot valleys in Panzhihua City, and closely related with SOC, AK, and NO-3-N. The results provide a theoretical basis for revealing the altitude distribution pattern of nitrogen cycling related microorganisms in red soil in dry-hot valley.
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