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1.
Article in English | MEDLINE | ID: mdl-38713616

ABSTRACT

Inflammatory bowel disease (IBD) encompasses a number of debilitating chronic gastrointestinal (GI) inflammatory disorders, including Crohn's disease and ulcerative colitis. In both conditions, mucosal inflammation is a key clinical presentation and is associated with altered serotonin (5-hydroxytryptamine; 5-HT) signaling. This altered 5-HT signaling is also found across various animal models of colitis. Of the 14 known receptor subtypes, 5-HT receptor type 7 (5-HT7) is one of the most recently discovered. We previously reported that blocking 5-HT signaling, with either a selective 5-HT7 receptor antagonist (SB-269970) or genetic ablation alleviated intestinal inflammation in murine experimental models of colitis. Here, we developed novel antagonists, namely MC-170073 and MC-230078, which target 5-HT7 receptors with high selectivity. We also investigated the in vivo efficacy of these antagonists in experimental colitis by utilizing dextran sulfate sodium (DSS) and the transfer of CD4+CD45RBhigh T cells to induce intestinal inflammation. Inhibition of 5-HT7 receptor signaling with the antagonists, MC-170073 and MC-230078, ameliorated intestinal inflammation in both acute and chronic colitis models, which was accompanied by lower histopathological damage and diminished levels of pro-inflammatory cytokines in comparison to vehicle-treated controls. Together, the data reveal that the pharmacological inhibition of 5-HT7 receptors by these selective antagonists ameliorates the severity of colitis across various experimental models and may, in the future, serve as a potential treatment option for patients with IBD. In addition, these findings support that 5-HT7 is a viable therapeutic target for IBD.

2.
J Pharm Biomed Anal ; 246: 116216, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38772204

ABSTRACT

The Qiye Shen'an tablet is formulated using total saponins extracted from Notoginseng stems and leaves. At present, the study on its chemical composition remains scarce and the quality control indicators are limited, which seriously hindering the effective quality control and clinical research. Hence, this study aims to comprehensively identify and characterize the Qiye Shen'an tablet while controlling its main component contents. To achieve a comprehensive understanding of this tablet, an ultra-high performance liquid coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) method was employed for its separation and characterization. Through the analysis of 99 batches of Qiye Shen'an tablet produced by 9 enterprises, the characteristic quantitative components were further obtained. A total of 113 compounds were characterized and identified, among which 17 representative compounds were selected, and the ultra-high performance liquid-triple quadrupole tandem mass spectrometry (UPLC-TQS-MS/MS) method was established for further quantitative determination. It has been successfully applied to the content determination of 99 batches of Qiye Shen'an tablet, and a new quality control method is being formed. This study provides a new method for chemical spectrum analysis and determination of labeled compounds of Qiye Shen'an tablet, and lays a solid foundation for further study of potential active ingredients and comprehensive quality evaluation.

3.
Materials (Basel) ; 17(10)2024 May 15.
Article in English | MEDLINE | ID: mdl-38793437

ABSTRACT

For a micro-indentation hardness test with non-destructivity, the Nix-Gao model is widely used to describe tested hardness or microhardness variation with an indentation depth induced by indentation size effect, in which tested hardness approaches the macrohardness when the indentation depth is large enough. Based on an analysis of hardness measurements on 10 body-centered cubic steels with diverse microstructure, this paper proposes an analytical relation between microhardness to macrohardness ratio and the indentation depth by explicitly linking characteristic indentation depth (a data-fitting parameter) to grain size and ferrite volume fraction using two different methods. In addition, the normal distribution theory is incorporated to consider the inevitable scatter of identical measurements resulting from material heterogeneity and machining/testing errors. Results show that the proposed model, with 96% reliability, can effectively predict microhardness variation with the indentation depth and its scatter.

4.
World Neurosurg ; 2024 May 22.
Article in English | MEDLINE | ID: mdl-38789030

ABSTRACT

The analysis aims to provide a comprehensive understanding of the current landscape of research on the Intestinal barrier damage after traumatic brain injury (TBI), elucidate specific mechanisms, and address knowledge gaps to help guide the development of targeted therapeutic interventions and improve outcomes for individuals with TBI.A total of 2,756 relevant publications by 13,778 authors affiliated within 3,198 institutions in 79 countries were retrieved from the Web of Science. These publications have been indexed by 1,139 journals and cited 158, 525 references. The most productive author in this field was Sikiric P, and the University of Pittsburgh was identified as the most influential institution. The United States was found to be the leading country in terms of article output and held a dominant position in this field. The International Journal of Molecular Sciences was identified as a major source of publications in this area. In terms of collaboration, the cooperation between the United States and China was found to be the most extensive among countries, institutions, and authors, indicating a high level of influence in this field. Keyword co-occurrence network analysis revealed several hotspots in this field, including the microbiome-gut-brain axis, endoplasmic reticulum stress, cellular autophagy, ischemia-reperfusion, tight junctions, and intestinal permeability. The analysis of keyword citation bursts suggested that ecological imbalance and gut microbiota may be the forefront of future research. The findings of this study can serve as a reference and guiding perspective for future research in this field.

5.
Environ Sci Technol ; 58(21): 9350-9360, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38743617

ABSTRACT

The practicality of intensifying organic matter capture for bioenergy recovery to achieve energy-neutral municipal wastewater treatment is hindered by the lack of sustainable methods. This study developed innovative processes integrating iron recycle-driven organic capture with a sidestream anaerobic membrane bioreactor (AnMBR). Iron-assisted chemically enhanced primary treatment achieved elemental redirection with 75.2% of chemical oxygen demand (COD), 20.2% of nitrogen, and 97.4% of phosphorus captured into the sidestream process as iron-enhanced primary sludge (Fe-PS). A stable and efficient biomethanation of Fe-PS was obtained in AnMBR with a high methane yield of 224 mL/g COD. Consequently, 64.1% of the COD in Fe-PS and 48.2% of the COD in municipal wastewater were converted into bioenergy. The acidification of anaerobically digested sludge at pH = 2 achieved a high iron release efficiency of 96.1% and a sludge reduction of 29.3% in total suspended solids. Ultimately, 87.4% of iron was recycled for coagulant reuse, resulting in a theoretical 70% reduction in chemical costs. The novel system evaluation exhibited a 75.2% improvement in bioenergy recovery and an 83.3% enhancement in net energy compared to the conventional system (primary sedimentation and anaerobic digestion). This self-reliant and novel process can be applied in municipal wastewater treatment to advance energy neutrality at a lower cost.


Subject(s)
Bioreactors , Iron , Wastewater , Wastewater/chemistry , Anaerobiosis , Waste Disposal, Fluid/methods , Sewage/chemistry , Biological Oxygen Demand Analysis , Methane , Biofuels , Phosphorus , Membranes, Artificial
6.
ACS Omega ; 9(19): 20906-20918, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38764650

ABSTRACT

The aim of the study was to investigate the exhaust gas emissions and fuel consumption of a common rail direct injection (CRDI) diesel engine using mixed diesel (B10) and biodiesel (B20-B100) fuels. The study's primary objective was to determine the effects of blended diesel-biodiesel fuel on CRDI emissions based on different exhaust gas recirculation (EGR) rates, including carbon monoxide (CO), carbon dioxide (CO2), oxygen (O2), nitrogen oxide (NOx), and hydrocarbon (HC) emissions, smoke opacity, exhaust gas temperature, and fuel consumption. The CRDI experiments involved adjusting the different engine speeds (1400-3000 rpm) and EGR rates (0 and 12.5%), which were analyzed to determine their impact on these parameters for both blended diesel and biodiesel fuels. The results showed that under the conditions of no EGR (0%), the CO and HC emissions and the smoke opacity were lower than those with a 12.5% EGR rate for all fuel types and all cases. With 12.5% EGR rate, the O2 emissions and the EGT of the CRDI diesel engine decreased, which resulted in significantly lower NOx emissions because of EGR into the combustion chamber. For the maximum engine speed of 3000 rpm and with no EGR, the CO and HC emissions and the smoke opacity were lower than those with a 12.5% EGR rate for all fuel types. With a 12.5% EGR rate at 3000 rpm, the O2 emissions and the exhaust gas temperature were reduced by 0.07% and 2.27%, respectively, and the NOx emissions were reduced by 2.54%. However, with EGR, the CO and HC emissions and the smoke opacity increased by 7.70%, 18.61%, and 0.4%, respectively. Furthermore, the fuel consumption of pure biodiesel (B100) at 3000 rpm with a 12.5% EGR rate was reduced by 2.81% compared to that with a 0% EGR rate. Because the temperature in the combustion chamber is high enough for the engine to run, the EGR reuses a portion of the exhaust gases and can help to minimize the quantity of fuel in the combustion chamber. As a suggestion based on these observations, biodiesel fuel should not exceed B80 because the viscosity and density of fuel that are too high may affect the fuel injection system, both the injectors, and the pressure pump, causing the injectors to be unable to work correctly. These findings can contribute to the development of strategies and technologies for reducing emissions and improving fuel efficiency in CRDI diesel engines.

7.
Front Aging Neurosci ; 16: 1372605, 2024.
Article in English | MEDLINE | ID: mdl-38681667

ABSTRACT

Background: Studies have reported that metabolic disturbance exhibits in patients with Alzheimer's disease (AD). Still, the presence of definitive evidence concerning the genetic effect of metabolites on AD risk remains insufficient. A systematic exploration of the genetic association between blood metabolites and AD would contribute to the identification of new targets for AD screening and prevention. Methods: We conducted an exploratory two-sample Mendelian randomization (MR) study aiming to preliminarily identify the potential metabolites involved in AD development. A genome-wide association study (GWAS) involving 7,824 participants provided information on 486 human blood metabolites. Outcome information was obtained from a large-scale GWAS meta-analysis of AD, encompassing 21,982 cases and 41,944 controls of Europeans. The primary two-sample MR analysis utilized the inverse variance weighted (IVW) model while supplementary analyses used Weighted median (WM), MR Egger, Simple mode, and Weighted mode, followed by sensitivity analyses such as the heterogeneity test, horizontal pleiotropy test, and leave-one-out analysis. For the further identification of metabolites, replication and meta-analysis with FinnGen data, steiger test, linkage disequilibrium score regression, confounding analysis, and were conducted for further evaluation. Multivariable MR was performed to assess the direct effect of metabolites on AD. Besides, an extra replication analysis with EADB data was conducted for final evaluation of the most promising findings. Results: After rigorous genetic variant selection, IVW, complementary analysis, sensitivity analysis, replication and meta-analysis with the FinnGen data, five metabolites (epiandrosterone sulfate, X-12680, pyruvate, docosapentaenoate, and 1-stearoylglycerophosphocholine) were identified as being genetically associated with AD. MVMR analysis disclosed that genetically predicted these four known metabolites can directly influence AD independently of other metabolites. Only epiandrosterone sulfate and X-12680 remained suggestive significant associations with AD after replication analysis with the EADB data. Conclusion: By integrating genomics with metabonomics, this study furnishes evidence substantiating the genetic association of epiandrosterone sulfate and X-12680 with AD. These findings hold significance for the screening, prevention, and treatment strategies for AD.

8.
Microorganisms ; 12(4)2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38674786

ABSTRACT

The author retracts the article, 'Drug Resistance and Molecular Characteristics of Car-bapenem-Resistant OXA-48-Producing Klebsiella pneumoniae Strains in Hainan, China' [...].

9.
Angew Chem Int Ed Engl ; : e202402546, 2024 Apr 14.
Article in English | MEDLINE | ID: mdl-38616162

ABSTRACT

Phenylethanoid glycosides (PhGs) exhibit a multitude of structural variations linked to diverse pharmacological activities. Assembling various PhGs via multienzyme cascades represents a concise strategy over traditional synthetic methods. However, the challenge lies in identifying a comprehensive set of catalytic enzymes. This study explores biosynthetic PhG reconstruction from natural precursors, aiming to replicate and amplify their structural diversity. We discovered 12 catalytic enzymes, including four novel 6'-OH glycosyltransferases and three new polyphenol oxidases, revealing the intricate network in PhG biosynthesis. Subsequently, the crystal structure of CmGT3 (2.62 Å) was obtained, guiding the identification of conserved residue 144# as a critical determinant for sugar donor specificity. Engineering this residue in PhG glycosyltransferases (FsGT61, CmGT3, and FsGT6) altered their sugar donor recognition. Finally, a one-pot multienzyme cascade was established, where the combined action of glycosyltransferases and acyltransferases boosted conversion rates by up to 12.6-fold. This cascade facilitated the reconstruction of 26 PhGs with conversion rates ranging from 5-100 %, and 20 additional PhGs detectable by mass spectrometry. PhGs with extra glycosyl and hydroxyl modules demonstrated notable liver cell protection. This work not only provides catalytic tools for PhG biosynthesis, but also serves as a proof-of-concept for cell-free enzymatic construction of diverse natural products.

10.
Nat Commun ; 15(1): 3382, 2024 Apr 20.
Article in English | MEDLINE | ID: mdl-38643164

ABSTRACT

Cancer models play critical roles in basic cancer research and precision medicine. However, current in vitro cancer models are limited by their inability to mimic the three-dimensional architecture and heterogeneous tumor microenvironments (TME) of in vivo tumors. Here, we develop an innovative patient-specific lung cancer assembloid (LCA) model by using droplet microfluidic technology based on a microinjection strategy. This method enables precise manipulation of clinical microsamples and rapid generation of LCAs with good intra-batch consistency in size and cell composition by evenly encapsulating patient tumor-derived TME cells and lung cancer organoids inside microgels. LCAs recapitulate the inter- and intratumoral heterogeneity, TME cellular diversity, and genomic and transcriptomic landscape of their parental tumors. LCA model could reconstruct the functional heterogeneity of cancer-associated fibroblasts and reflect the influence of TME on drug responses compared to cancer organoids. Notably, LCAs accurately replicate the clinical outcomes of patients, suggesting the potential of the LCA model to predict personalized treatments. Collectively, our studies provide a valuable method for precisely fabricating cancer assembloids and a promising LCA model for cancer research and personalized medicine.


Subject(s)
Lung Neoplasms , Humans , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Tumor Microenvironment , Organoids/pathology , Precision Medicine/methods
11.
Bioresour Technol ; 401: 130710, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38636880

ABSTRACT

The integration of high-rate activated sludge (HRAS), an effective carbon redirection technology, with partial nitritation/anammox (PN/A) is a novel AB treatment process for municipal wastewater. In this study, an airlift HRAS reactor was operated in the continuous inflow mode for 200 d at a wastewater treatment plant. The balance between potential PN/A system stability and peak HRAS performance under decreasing hydraulic retention time (HRT) was optimized. Energy consumption and recovery and CO2 emissions were calculated. The results showed that the optimal HRT suitable with the PN/A process was 3 h, achieving 2-3 g/L mixed liquor volatile suspended solid, 67.8 % chemical oxygen demand (COD) recovery, 81 % total COD removal efficiency, 2.27 ± 1.03 g COD/L/d organic loading rate, 62 % aeration reduction, and 0.24 kWh/m3 power recovery potential. Such findings hold practical value and contribute to the development of the optimal AB process capable of achieving energy autonomy and carbon neutrality.


Subject(s)
Bioreactors , Sewage , Water Purification , Water Purification/methods , Wastewater/chemistry , Biological Oxygen Demand Analysis , Waste Disposal, Fluid/methods , Time Factors , Nitrogen , Carbon Dioxide , Oxidation-Reduction , Cities
12.
Cancer Imaging ; 24(1): 47, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38566150

ABSTRACT

PURPOSE: To investigate the computed tomography (CT) characteristics of air-containing space and its specific patterns in neoplastic and non-neoplastic ground glass nodules (GGNs) for clarifying their significance in differential diagnosis. MATERIALS AND METHODS: From January 2015 to October 2022, 1328 patients with 1,350 neoplastic GGNs and 462 patients with 465 non-neoplastic GGNs were retrospectively enrolled. Their clinical and CT data were analyzed and compared with emphasis on revealing the differences of air-containing space and its specific patterns (air bronchogram and bubble-like lucency [BLL]) between neoplastic and non-neoplastic GGNs and their significance in differentiating them. RESULTS: Compared with patients with non-neoplastic GGNs, female was more common (P < 0.001) and lesions were larger (P < 0.001) in those with neoplastic ones. Air bronchogram (30.1% vs. 17.2%), and BLL (13.0% vs. 2.6%) were all more frequent in neoplastic GGNs than in non-neoplastic ones (each P < 0.001), and the BLL had the highest specificity (93.6%) in differentiation. Among neoplastic GGNs, the BLL was more frequently detected in the larger (14.9 ± 6.0 mm vs. 11.4 ± 4.9 mm, P < 0.001) and part-solid (15.3% vs. 10.7%, P = 0.011) ones, and its incidence significantly increased along with the invasiveness (9.5-18.0%, P = 0.001), whereas no significant correlation was observed between the occurrence of BLL and lesion size, attenuation, or invasiveness. CONCLUSION: The air containing space and its specific patterns are of great value in differentiating GGNs, while BLL is a more specific and independent sign of neoplasms.


Subject(s)
Lung Neoplasms , Multiple Pulmonary Nodules , Humans , Female , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/pathology , Retrospective Studies , Multiple Pulmonary Nodules/diagnostic imaging , Multiple Pulmonary Nodules/pathology , Tomography, X-Ray Computed/methods , Diagnosis, Differential
13.
Front Neurol ; 15: 1373390, 2024.
Article in English | MEDLINE | ID: mdl-38585348

ABSTRACT

Objective: To explore the modulations of electroacupuncture in subjective tinnitus (ST) by comparing the difference of functional connectivity (FC) in ST patients and healthy volunteers between the insular (INS) and the whole brain region. Methods: A total of 34 ST patients were selected into electroacupuncture group (EG) and 34 age- and sex-matched normal subjects were recruited into control group (CG). The EG received acupuncture at SI19 (Tinggong), GB11 (Touqiaoyin), TE17 (Yifeng), GV20 (Baihui), GV15 (Yamen), GV14 (Dazhui), SJ13 (Zhongzhu), among which the points of SI19 and GB11 were connected to the electroacupuncture instrument with the density wave of 2/50 Hz, and 3 treatments per week for 10 sessions in total. The severity of tinnitus was evaluated by Tinnitus Handicap Inventory (THI), the hearing status was recorded using pure tone audiometry, and resting-state functional magnetic resonance imaging (rs-fMRI) was performed on the brain before and after treatment, the CG received no intervention yet only rs-fMRI data were collected. Results: With the electroacupuncture treatment, the total THI score, average air conduction threshold of patients of EG were significantly lower than before (p < 0.01), and the total effective rate was 88.24%. Compared with CG, FC of ST patients between INS and left superior temporal gyrus and right hippocampal significantly decreased before treatment, while FC of ST patients between INS and right superior frontal gyrus, left middle frontal gyrus and right anterior cuneus significantly decreased after treatment (voxel p < 0.001, cluster p < 0.05, corrected with GRF). FC of ST patients between the INS and right middle frontal gyrus, left superior frontal gyrus and right paracentral lobule showed a significant decrease after treatment (voxel p < 0.001, cluster p < 0.05, corrected with GRF). In addition, THI score in EG was negatively correlated with the reduction of FC value in INS-left superior frontal gyrus before treatment (r = -0.41, p = 0.017). Therefore, this study suggests that abnormal FC of INS may be one of the significant central mechanisms of ST patients and can be modulated by electroacupuncture. Discussion: Electroacupuncture treatment can effectively reduce or eliminate tinnitus symptoms in ST patients and improve the hearing by decreasing FC between the INS and the frontal and temporal brain regions.

14.
Molecules ; 29(5)2024 Feb 21.
Article in English | MEDLINE | ID: mdl-38474444

ABSTRACT

Non-viral vectors have been developing in gene delivery due to their safety and low immunogenicity. But their transfection effect is usually very low, thus limiting the application. Hence, we designed eight peptides (compounds 1-8). We compared their performances; compound 8 had the best transfection efficacy and biocompatibility. The transfection effect was similar with that of PEI, a most-widely-employed commercial transfection reagent. Atomic force microscope (AFM) images showed that the compound could self-assemble and the self-assembled peptide might encapsulate DNA. Based on these results, we further analyzed the inhibitory result in cancer cells and found that compound 8 could partially fight against Hela cells. Therefore, the compound is promising to pave the way for the development of more effective and less toxic transfection vectors.


Subject(s)
Neoplasms , Peptides , Humans , HeLa Cells , Transfection , Peptides/chemistry , Genetic Vectors , DNA/chemistry , Polyethyleneimine/chemistry
15.
Discov Oncol ; 15(1): 67, 2024 Mar 06.
Article in English | MEDLINE | ID: mdl-38446389

ABSTRACT

Next generation sequencing (NGS) is typically used to reveal tumor gene variation feature for targeted therapy of various types of human cancers, including non-small cell lung cancer (NSCLC). Here, we report the role and potential applicable value of combining DNA and RNA sequencing in gene variation detection in NSCLC. 386 NSCLC patients with stage II-IV were enrolled and detected using NGS sequencing of DNA and RNA panels that covered all well-documented target driver genes from the Chinese Society of Clinical Oncology (CSCO). The rate of epidermal growth factor receptor (EGFR) single nucleotide variation (SNV)/indel, mesenchymal-epithelial transition factor (MET) copy number variation (CNV) and anaplastic lymphoma kinase (ALK) fusion were 52.1%, 4.1% and 6.0% in the NSCLC cohort. The landscapes of SNV/indel, CNV and gene fusion in the cohort were depicted as well. Meanwhile, we assessed detection efficacy of DNA and RNA sequencing in gene fusion. Detected number and types of gene fusion using the RNA sequencing were better than those using the DNA sequencing. Gene fusion with intergenic region was only detected by DNA sequencing and MET exon 14 skipping (METΔex14) was more easily identified by RNA sequencing. Finally, we investigated clinical correlations of SNV/indel/CNV/fusion with clinicopathologic features in the NSCLC cohort. Taken together, RNA sequencing significantly complements deficiency of DNA sequencing for gene fusion, which cooperatively presents comprehensive and reliable gene variation features and facilitate the identification of potential drug targets for NSCLC patients.

16.
Front Biosci (Landmark Ed) ; 29(3): 120, 2024 Mar 21.
Article in English | MEDLINE | ID: mdl-38538251

ABSTRACT

BACKGROUND: Osteosarcoma cells are prone to metastasis, and the mechanism of N6-methyladenosine (m6A) methylation modification in this process is still unclear. Methylation modification of m6A plays an important role in the development of osteosarcoma, which is mainly due to abnormal expression of enzymes related to methylation modification of m6A, which in turn leads to changes in the methylation level of downstream target genes messenger RNA (mRNA) leading to tumor development. METHODS: We analyzed the expression levels of m6A methylation modification-related enzyme genes in GSE12865 whole-genome sequencing data. And we used shRNA (short hairpin RNA) lentiviral interference to interfere with METTL3 (Methyltransferase 3) expression in osteosarcoma cells. We studied the cytological function of METTL3 by Cell Counting Kit-8 (CCK8), flow cytometry, migration and other experiments, and the molecular mechanism of METTL3 by RIP (RNA binding protein immunoprecipitation), Western blot and other experiments. RESULTS: We found that METTL3 is abnormally highly expressed in osteosarcoma and interferes with METTL3 expression in osteosarcoma cells to inhibit metastasis, proliferation, and apoptosis of osteosarcoma cells. We subsequently found that METTL3 binds to the mRNA of CBX4 (chromobox homolog 4), a very important regulatory protein in osteosarcoma metastasis, and METTL3 regulates the mRNA and protein expression of CBX4. Further studies revealed that METTL3 inhibited metastasis of osteosarcoma cells by regulating CBX4. METTL3 has been found to be involved in osteosarcoma cells metastasis by CBX4 affecting the protein expression of matrix metalloproteinase 2 (MMP2), MMP9, E-Cadherin and N-Cadherin associated with osteosarcoma cells metastasis. CONCLUSIONS: These results suggest that the combined action of METTL3 and CBX4 plays an important role in the regulation of metastasis of osteosarcoma, and therefore, the METTL3-CBX4 axis pathway may be a new potential therapeutic target for osteosarcoma.


Subject(s)
Adenine , Bone Neoplasms , Matrix Metalloproteinase 2 , Osteosarcoma , Humans , Adenine/analogs & derivatives , Epigenesis, Genetic , Ligases/genetics , Matrix Metalloproteinase 2/metabolism , Methyltransferases/genetics , Methyltransferases/metabolism , Osteosarcoma/genetics , Osteosarcoma/secondary , Polycomb-Group Proteins/genetics , RNA, Messenger/genetics , RNA, Small Interfering , Bone Neoplasms/pathology
17.
Sci Total Environ ; 926: 171900, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38527552

ABSTRACT

The long-stabilized mainstream partial nitritation/Anammox (PN/A) process continues to encounter significant challenges from nitrite-oxidizing bacteria (NOB). Therefore, this study aimed to determine an efficient, rapid, and easily implementable strategy for inhibiting NOB. A laboratory-scale reactor was operated continuously for 325 days, experiencing NOB outbreak in mainstream and recovery with simulated sidestream support. The results show that direct inhibitory strategies including intermittent aeration and approximately 35 mg/L free ammonia had unusual weak inhibitory effects on NOB activity. Subsequently, the exogenous Anammox from sidestream employed as a competitive bio-augmentation approach rapidly inhibited NOB dynamics. Evidence suggests that the damaged hydroxyapatite granules under low pH conditions might have contributed to NOB dominance by diminishing Anammox bacteria activity, thereby creating a substrate-rich environment favoring NOB survival. In contrast, the introduction of exogenous Candidatus Kuenenia facilitated the nitrogen removal efficiency from 32.5 % to over 80 %. This coincided with a decrease in the relative abundance of Nitrospira from 16.5 % to 2.7 % and NOB activity from 0.34 to 0.07 g N/(g mixed liquor volatile suspended solid)/d. Metagenomic analysis reveals a decrease in the functional potential of most nitrite transport proteins, coupled with a significant increase in eukaryotic-like serine/threonine-protein kinase involved in cellular regulation, during the Anammox activity recovery. This study's findings reveal the feasibility of the bio-augmentation based on substrate competition, wherein sidestream processes support the mainstream PN/A integration, offering significant potential for practical applications.


Subject(s)
Ammonium Compounds , Nitrites , Nitrites/metabolism , Oxidation-Reduction , Bioreactors/microbiology , Bacteria/metabolism , Nitrogen/metabolism , Sewage/microbiology , Ammonium Compounds/metabolism
18.
Chemosphere ; 353: 141551, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38430935

ABSTRACT

Groundwater pollution caused by the leakage of petroleum and various fuel oils is becoming a serious environmental problem. In this study, carbon-based materials including biochar and hydrochar were applied to investigate the effects of additives on the toluene removal in the extracted groundwater under microaerobic condition with the addition of nitrate. Biochar and hydrochar could adsorb toluene, and thus enhance the toluene removal in the system. The toluene removal efficiency was 8.2-8.9 mg/(g·h) at the beginning, and then decreased with time in the control and the hydrochar treatment, while it remained the stable values in the biochar treatment, owing to the fact that biochar could reduce the NO3--N loss by partial denitrification. Moreover, biochar could prompt the growth of toluene-degrading bacteria including Thauera, Rhodococcus, Ideonella and Denitratisoma, which had the capability of denitrification. However, hydrochar could stimulated the growth of denitrifiers without toluene-degrading capacity including Candidatus Competibacter and Ferrovibrio, which might play a key role in the partial denitrification of the system. The findings are helpful for developing remediation techniques of contaminated groundwater.


Subject(s)
Charcoal , Groundwater , Water Pollutants, Chemical , Nitrates/analysis , Denitrification , Water Pollutants, Chemical/analysis , Biodegradation, Environmental
19.
Synth Syst Biotechnol ; 9(2): 234-241, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38385152

ABSTRACT

Precisely controlling gene expression is beneficial for optimizing biosynthetic pathways for improving the production. However, promoters in nonconventional yeasts such as Ogataea polymorpha are always limited, which results in incompatible gene modulation. Here, we expanded the promoter library in O. polymorpha based on transcriptional data, among which 13 constitutive promoters had the strengths ranging from 0-55% of PGAP, the commonly used strong constitutive promoter, and 2 were growth phase-dependent promoters. Subsequently, 2 hybrid growth phase-dependent promoters were constructed and characterized, which had 2-fold higher activities. Finally, promoter engineering was applied to precisely regulate cellular metabolism for efficient production of ß-elemene. The glyceraldehyde-3-phosphate dehydrogenase gene GAP was downregulated to drive more flux into pentose phosphate pathway (PPP) and then to enhance the supply of acetyl-CoA by using phosphoketolase-phosphotransacetylase (PK-PTA) pathway. Coupled with the phase-dependent expression of synthase module (ERG20∼LsLTC2 fusion), the highest titer of 5.24 g/L with a yield of 0.037 g/(g glucose) was achieved in strain YY150U under fed-batch fermentation in shake flasks. This work characterized and engineered a series of promoters, that can be used to fine-tune genes for constructing efficient yeast cell factories.

20.
Mol Biol Rep ; 51(1): 255, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38302782

ABSTRACT

BACKGROUND: Mounting evidence suggests that lung adenocarcinoma (LAC) and lung squamous cell carcinoma (LSC) have different biological behaviors and therapeutic regimens in clinical practice. However, limited improvements in molecular differential diagnosis of the two entities have been achieved in recent decades. We aimed to find novel markers that could define non-small cell lung cancer (NSCLC) subtypes. METHODS: We first explored publically available databases to search for DNA methylation signatures that enable a precise discrimination of LAC and LSC. Next-generation sequencing (NGS) was then used to analyze the methylation status and sites of candidate genes in LAC/LSC tissue samples, and a quantitative methylation-sensitive PCR (qMS-PCR) assay was conducted to test the performance of the selected maker in tissue samples and bronchoalveolar lavage fluid (BALF) specimens. RESULTS: We screened 19 top-ranked methylation loci that are differentially methylated between LAC and LSC. Among these hits, 6 methylation sites are enriched within the PREX1 gene promoter, thus becoming our focus. NGS analysis confirmed markedly higher PREX1 methylation levels in LAC than in LSC and revealed the right sites for detection of PREX1 methylation. Furthermore, PREX1 methylation analysis in lung cancer tissue samples defined 9 of 11 pathologically proven LACs, as well as 12 of 14 LSCs. In addition, ~ 80% LAC BALF samples showed methylated PREX1 compared to substantially lower test positivity (0-9%) of it in LSC and other lung conditions (P < 0.01). CONCLUSION: Our pilot study identified a unique epigenetic signature that could effectively distinguish LAC from LSC in various lung samples. It may enhance our in-depth understanding of the biology of lung cancer and pave the way for better accurate diagnosis and treatment stratification in the future.


Subject(s)
Adenocarcinoma of Lung , Adenocarcinoma , Carcinoma, Non-Small-Cell Lung , Carcinoma, Squamous Cell , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/genetics , Lung Neoplasms/pathology , Pilot Projects , Adenocarcinoma/pathology , DNA Methylation/genetics , Adenocarcinoma of Lung/genetics , Carcinoma, Squamous Cell/genetics , Epigenesis, Genetic/genetics , Biomarkers, Tumor/genetics
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