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1.
Front Med (Lausanne) ; 11: 1254467, 2024.
Article En | MEDLINE | ID: mdl-38695016

Background: Preeclampsia (PE) is a pregnancy complication defined by new onset hypertension and proteinuria or other maternal organ damage after 20 weeks of gestation. Although non-invasive prenatal testing (NIPT) has been widely used to detect fetal chromosomal abnormalities during pregnancy, its performance in combination with maternal risk factors to screen for PE has not been extensively validated. Our aim was to develop and validate classifiers that predict early- or late-onset PE using the maternal plasma cell-free DNA (cfDNA) profile and clinical risk factors. Methods: We retrospectively collected and analyzed NIPT data of 2,727 pregnant women aged 24-45 years from four hospitals in China, which had previously been used to screen for fetal aneuploidy at 12 + 0 ~ 22 + 6 weeks of gestation. According to the diagnostic criteria for PE and the time of diagnosis (34 weeks of gestation), a total of 143 early-, 580 late-onset PE samples and 2,004 healthy controls were included. The wilcoxon rank sum test was used to identify the cfDNA profile for PE prediction. The Fisher's exact test and Mann-Whitney U-test were used to compare categorical and continuous variables of clinical risk factors between PE samples and healthy controls, respectively. Machine learning methods were performed to develop and validate PE classifiers based on the cfDNA profile and clinical risk factors. Results: By using NIPT data to analyze cfDNA coverages in promoter regions, we found the cfDNA profile, which was differential cfDNA coverages in gene promoter regions between PE and healthy controls, could be used to predict early- and late-onset PE. Maternal age, body mass index, parity, past medical histories and method of conception were significantly differential between PE and healthy pregnant women. With a false positive rate of 10%, the classifiers based on the combination of the cfDNA profile and clinical risk factors predicted early- and late-onset PE in four datasets with an average accuracy of 89 and 80% and an average sensitivity of 63 and 48%, respectively. Conclusion: Incorporating cfDNA profiles in classifiers might reduce performance variations in PE models based only on clinical risk factors, potentially expanding the application of NIPT in PE screening in the future.

2.
Radiat Oncol ; 18(1): 193, 2023 Nov 27.
Article En | MEDLINE | ID: mdl-38012675

BACKGROUND: FLT-PET/CT can accurately identify and locate functional bone marrow (FBM) with hematopoietic capability, the FBM were divided into two levels as FBM1 (strongest hemopoietic ability region)and FBM2 (moderate hemopoietic ability region) via FLT-PET/CT. The purpose of this study was to explore the relationship between dose-volume parameters of pelvic FBM and hematologic toxicity (HT) during radiotherapy with or without concurrent chemotherapy for uterine cervical/endometrial cancer. METHODS: From December 2016 to September 2021, ninety-seven uterine cervical/endometrial cancer patients received intensity-modulated radiation therapy were prospectively recruited in this single-arm, prospective, phase II trial. Blood counts were reviewed weekly during radiotherapy. Single- and multifactor regression methods were used to analyze the relationships between dose-volume parameters of FBM1/2 and grade ≥ 2 HT. ROC curves were used to determine the cutoff values for the dose-volume parameters of FBM1/2. RESULTS: The incidence of grade ≥ 2 leukopenia, neutropenia, thrombocytopenia and anemia in patients during radiotherapy was 63.9%, 45.4%, 19.6% and 38.8% respectively, and the median occurrence time was the 29th, 42th, 35th and 31th day, respectively. Multivariate regression analysis showed that the Dmax of FBM1 was significantly related to grade ≥ 2 leukopenia (OR = 1.277 95% CI 1.067-1.528, P = 0.008), Dmean of FBM2 was significantly related to grade ≥ 2 thrombocytopenia (OR = 1.262 95% CI 1.066-1.494, P = 0.007), and V10 of FBM1 was significantly related to grade ≥ 2 anemia (OR = 1.198 95% CI 1.003-1.431, P = 0.046). The incidence of grade ≥ 2 leukopenia for patients with FBM1 Dmax < 53 Gy was lower than that for patients with FBM1 Dmax ≥ 53 Gy (53.4% vs. 95.8%, P < 0.001). The incidence of grade ≥ 2 thrombocytopenia in patients with FBM2 Dmean < 33 Gy was lower than that in patients with FBM2 Dmean ≥ 33 Gy (0 vs. 28.4%, P < 0.001). The incidence of grade ≥ 2 anemia for patients with FBM1 V10 < 95% was lower than that in patients with FBM1 V10 ≥ 95% (24.4% vs. 57.1%, P = 0.003). CONCLUSIONS: Grade ≥ 2 HT usually occurs in the 4th week of radiotherapy for patients with uterine cervical/endometrial cancer. The Dmax and V10 of FBM1 and the Dmean of FBM2 were significantly associated with the occurrence of grade ≥ 2 HT. The recommended optimal dose constraints were FBM1 Dmax < 53 Gy, V10 < 95%, and FBM2 Dmean <33 Gy.


Anemia , Endometrial Neoplasms , Leukopenia , Radiotherapy, Intensity-Modulated , Thrombocytopenia , Uterine Cervical Neoplasms , Female , Humans , Anemia/complications , Anemia/drug therapy , Bone Marrow , Chemoradiotherapy/adverse effects , Cisplatin/adverse effects , Leukopenia/etiology , Positron Emission Tomography Computed Tomography/adverse effects , Prospective Studies , Radiotherapy Dosage , Radiotherapy, Intensity-Modulated/adverse effects , Thrombocytopenia/chemically induced , Thrombocytopenia/drug therapy , Uterine Cervical Neoplasms/radiotherapy
3.
Environ Sci Pollut Res Int ; 30(54): 115950-115964, 2023 Nov.
Article En | MEDLINE | ID: mdl-37897581

Agricultural nonpoint source (NPS) pollution loss is closely related to hydrological processes. Understanding the differences in NPS pollution load loss under hydrological processes is useful for the management and prevention of NPS pollution. In this paper, hydrological and water quality data from 2016 to 2018 and monitoring data of physical and chemical indicators in 1347 field soil samples in the Shaying River Basin (SYRB) were used to analyze spatiotemporal variations in NPS pollution using the Soil and Water Assessment Tool and multifactor analysis of variance. The intensities and differences in NPS pollution losses for different soil types and land use patterns were evaluated under different hydrological zones. The annual rainfall in the SYRB decreased gradually from 1136.50 to 404.04 mm, showing a significant zoning. Areas with high loss intensities were mainly distributed in areas with steep slopes and in the 800-1000 mm rainfall zone. Cultivated land had the largest loss of NPS pollution, followed by forest land and rural residential land. Fluvo-aquic soil had the largest loss of NPS pollution, followed by cinnamon soil and lime concretion black soil. A nonlinear regression model was established for rainfall and the NPS pollution loss intensity and had a correlation coefficient of 0.60-0.99 at a 95% confidence level. Slope and rainfall were the main factors influencing the nitrogen and phosphorus losses. In the 800-1000 mm rainfall zone, the soil background nitrogen and phosphorus load was also a major factor influencing the nitrogen and phosphorus loss intensities.


Non-Point Source Pollution , Water Pollutants, Chemical , Non-Point Source Pollution/analysis , Water Pollutants, Chemical/analysis , Rivers , Environmental Monitoring , Soil , China , Phosphorus/analysis , Nitrogen/analysis
4.
Colloids Surf B Biointerfaces ; 231: 113547, 2023 Nov.
Article En | MEDLINE | ID: mdl-37729797

Cancer synergistic therapy usually shows improved therapeutic efficacy with low side effects. In this contribution, an aza-BODIPY-derived photosensitizer NBDP with asymmetric structure and the periphery phenyl ring modified with bromine atom was designed and synthesized for synergistic photothermal therapy (PTT) and photodynamic therapy (PDT). Photosensitizer NBDP exhibited good singlet oxygen (1O2) generation capacity (1.43 times higher than that of ICG), and NBDP NPs showed an outstanding photothermal conversion efficiency (η) of 46.0% under 660 nm photoirradiation. Guided by in vivo photoacoustic (PA) imaging, NBDP NPs were found to targetedly accumulate in the tumor tissues in 6 h. All results showed that the aza-BODIPY-derived photosensitizer NBDP had great potential for PA/photothermal imaging-guided synergistic PTT/PDT.


Nanoparticles , Neoplasms , Photochemotherapy , Humans , Photosensitizing Agents/pharmacology , Photosensitizing Agents/chemistry , Photochemotherapy/methods , Photothermal Therapy , Phototherapy/methods , Nanoparticles/chemistry , Neoplasms/therapy , Neoplasms/drug therapy , Cell Line, Tumor
5.
Cell Death Dis ; 14(8): 568, 2023 08 26.
Article En | MEDLINE | ID: mdl-37633920

Sustained activation of DNA damage response (DDR) signaling has been demonstrated to play vital role in chemotherapy failure in cancer. However, the mechanism underlying DDR sustaining in cancer cells remains unclear. In the current study, we found that the expression of the DDUP microprotein, encoded by the CTBP1-DT lncRNA, drastically increased in cisplatin-resistant ovarian cancer cells and was inversely correlated to cisplatin-based therapy response. Using a patient-derived human cancer cell model, we observed that DNA damage-induced DDUP foci sustained the RAD18/RAD51C and RAD18/PCNA complexes at the sites of DNA damage, consequently resulting in cisplatin resistance through dual RAD51C-mediated homologous recombination (HR) and proliferating cell nuclear antigen (PCNA)-mediated post-replication repair (PRR) mechanisms. Notably, treatment with an ATR inhibitor disrupted the DDUP/RAD18 interaction and abolished the effect of DDUP on prolonged DNA damage signaling, which resulted in the hypersensitivity of ovarian cancer cells to cisplatin-based therapy in vivo. Altogether, our study provides insights into DDUP-mediated aberrant DDR signaling in cisplatin resistance and describes a potential novel therapeutic approach for the management of platinum-resistant ovarian cancer.


Ovarian Neoplasms , RNA, Long Noncoding , Female , Humans , Cisplatin/therapeutic use , DNA-Binding Proteins/genetics , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/genetics , Proliferating Cell Nuclear Antigen , RNA, Long Noncoding/genetics , Ubiquitin-Protein Ligases , Micropeptides
6.
Small ; 19(6): e2206220, 2023 02.
Article En | MEDLINE | ID: mdl-36470671

Bacterial biofilm-related infectious diseases severely influence human health. Under typical situations, pathogens can colonize inert or biological surfaces and form biofilms. Biofilms are functional aggregates that coat bacteria with extracellular polymeric substances (EPS). The main reason for the failure of biofilm infection treatment is the low permeability and enrichment of therapeutic agents within the biofilm, which results from the particular features of biofilm matrix barriers such as negatively charged biofilm components and highly viscous compact EPS structures. Hence, developing novel therapeutic strategies with enhanced biofilm penetrability is crucial. Herein, the current progress of nanotechnology methods to improve therapeutic agents' penetrability against biofilm matrix, such as regulating material morphology and surface properties, utilizing the physical penetration of nano/micromotors or microneedle patches, and equipping nanoparticles with EPS degradation enzymes or signal molecules, is first summarized. Finally, the challenges, perspectives, and future implementations of engineered delivery systems to manage biofilm infections are presented in detail.


Bacterial Infections , Nanoparticles , Humans , Extracellular Polymeric Substance Matrix/metabolism , Biofilms , Drug Delivery Systems , Bacterial Infections/metabolism , Nanotechnology
7.
Acta Biomater ; 146: 107-118, 2022 07 01.
Article En | MEDLINE | ID: mdl-35545186

The development of degradable hydrogel fillers with high antibacterial activity and wound-healing property is urgently needed for the treatment of infected wounds. Herein, an injectable, degradable, photoactivated antibacterial hydrogel (MPDA-BNN6@Gel) was developed by incorporating BNN6-loaded mesoporous polydopamine nanoparticles (MPDA-BNN6 NPs) into a fibrin-based hydrogel. After administration, MPDA-BNN6@Gel created local hyperthermia and released large quantities of NO gas to treat methicillin-resistant Staphylococcus aureus infection under the stimulation of an 808 nm laser. Experiments confirmed that the bacteria were eradicated through irreversible damage to the cell membrane, genetic metabolism, and material energy. Furthermore, in the absence of laser irradition, the fibrin and small amount of NO that originated from MPDA-BNN6@Gel promoted wound healing in vivo. This work indicates that MPDA-BNN6@Gel is a promising alternative for the treatment of infected wounds and provides a facile tactic to design a photoregulated bactericidal hydrogel for accelerating infected wound healing. STATEMENT OF SIGNIFICANCE: The development of a degradable hydrogel with high antibacterial activity and wound-healing property is an urgent need for the treatment of infected wounds. Herein, an injectable, degradable, and photo-activated antibacterial hydrogel (MPDA-BNN6@Gel) has been developed by incorporating BNN6-loaded mesoporous polydopamine nanoparticles (MPDA-BNN6 NPs) into a fibrin-based hydrogel. After administration of MPDA-BNN6@Gel, the MPDA-BNN6@Gel could generate local hyperthermia and release large quantities of NO gas to treat the methicillin-resistant Staphylococcus aureus infection under the irradiation of 808 nm laser. Furthermore, in the absence of a laser, the fibrin and a small amount of NO originating from MPDA-BNN6@Gel could promote wound healing in vivo.


Anti-Bacterial Agents , Hydrogels , Methicillin-Resistant Staphylococcus aureus , Nanoparticles , Nitric Oxide , Wound Infection , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/chemistry , Fibrin/administration & dosage , Fibrin/chemistry , Hydrogels/administration & dosage , Hydrogels/chemistry , Methicillin-Resistant Staphylococcus aureus/drug effects , Nanoparticles/administration & dosage , Nanoparticles/chemistry , Nitric Oxide/administration & dosage , Nitric Oxide/chemistry , Phenylenediamines/administration & dosage , Phenylenediamines/chemistry , Staphylococcal Infections/drug therapy , Staphylococcal Infections/microbiology , Wound Healing/drug effects , Wound Infection/drug therapy , Wound Infection/microbiology
8.
Environ Sci Pollut Res Int ; 29(29): 44490-44503, 2022 Jun.
Article En | MEDLINE | ID: mdl-35133589

Temporal and spatial variations in river water quality and the factors influencing such variations are important basis and prerequisites for identifying pollution sources and improving river water environment. Monthly data for 22 indicators at 485 surface water quality (SWQ) monitoring sites (46,560 groups) in the Huaihe River Basin (HRB) from 2011 to 2018 were analyzed. This paper assessed temporal and spatial changes in SWQ in the HRB and identified the main factors influencing the changes and each factor's contribution to the changes. The five-day biological oxygen demand, permanganate index, fluoride, ammonium nitrogen, and total phosphorus were the main pollutants. Spatial cluster analysis indicated that the HRB could be divided by SWQ into areas I-IV from light to heavy pollution. Areas I and IV were nitrogen and phosphorus nutrients pollution, and areas II and III were heavy metals and organic pollution. Area IV (poor SWQ) locates mainly north of the Huaihe mainstream with annual average rainfall ≤ 640 mm. SWQ in the HRB has been improving for two decades, with an inflection point in 2015 between 2011 and 2018, and rainfall change is an important factor for the inflection point. The urbanization rate, industrial water consumption, and rainfall were the key factors influencing SWQ changes in the watershed with significant hydrological zonation, with urbanization rate and rainfall increased, industrial water consumption decreased, the SWQ was gradually improved. The key factors contributing to SWQ changes in the future will be the sewage treatment rate and rainfall changes caused by natural variations.


Rivers , Water Pollutants, Chemical , China , Environmental Monitoring , Nitrogen/analysis , Phosphorus/analysis , Water Pollutants, Chemical/analysis , Water Quality
9.
Environ Geochem Health ; 44(8): 2531-2543, 2022 Aug.
Article En | MEDLINE | ID: mdl-34292452

In recent decades, antibiotics and antibiotic resistance genes (ARGs) have been regarded as emerging pollutants. In Taihu Lake, as a typical representative of freshwater system in China, the ARGs occurrence and abundance was of great importance for ecological risk control and public health protection. In this research, high-throughput sequencing and metagenomics technique were used to investigate the seasonal ARGs profile in overlying water and sediment at typical area of Taihu Lake. Besides, taxonomy pattern of ARGs host bacteria and potential pathogens were identified. The results showed that 33 ARG subtypes and 11 ARG types were detected in research area, among which bacitracin, multidrug and sulfonamides resistance gene were with the highest abundance. The relative abundance of ARGs in overlying water and sediment ranged from 1.68 to 661.05 ppm and from 1.93 to 49.47 ppm, respectively. ARG host (18 bacteria genus) were identified and annotated, among which Clostridium botulinum, Pseudomonas aeruginosa and Klebsiella pneumonia were pathogenic bacteria. The pathogens were mostly detected at Xukou Bay in spring and fall, which might be caused by the inlet water from aquaculture area of Yangcheng Lake. Pseudomonas was the most abundant ARGs host (ant2ib, baca, bl2d_oxa2,mexb, mexf, mexw and oprn), which may facilitate the propagation of ARGs in freshwater system.


Lakes , Metagenomics , Anti-Bacterial Agents/analysis , Anti-Bacterial Agents/pharmacology , Bacteria/genetics , China , Drug Resistance, Microbial/genetics , Genes, Bacterial , Lakes/microbiology , Metagenomics/methods , Prevalence , Water
10.
Nan Fang Yi Ke Da Xue Xue Bao ; 40(1): 20-26, 2020 Jan 30.
Article Zh | MEDLINE | ID: mdl-32376564

OBJECTIVE: To investigate the effect of overexpression of leukemia inhibitory factor (LIF) on cisplatin and paclitaxel resistance of endometrial cancer cells in vitro. METHODS: Endometrial cancer cell lines HEC-1B and RL95-2 were infected with a recombinant lentivirus to overexpress LIF, and the changes in LIF expression was verified using RT-qPCR and ELISA. The viability of the LIF-overexpressing cells was assessed using CCK-8 assay, and the cell apoptosis and changes in mitochondrial membrane potential in response to cisplatin or paclitaxel treatment were analyzed with annexin V-FITC/PI staining and JC-1 assay, respectively. The effect of LIF overexpression on the expressions of Bcl-2 family proteins and STAT3 pathway was evaluated using Western blotting; dual-luciferase reporter gene assay was employed to detect the transcriptional activity of STAT3. The effect of STAT3 silencing on apoptosis of the LIF-overexpressing cells induced by cisplatin or paclitaxel was investigated. RESULTS: The cell lines infected with the recombinant lentivirus showed significantly increased mRNA and protein levels of LIF (P < 0.05) without obvious changes in the cell viability (P>0.05). LIF overexpression significantly attenuated cisplatin-or paclitaxel-induced apoptosis of the endometrial cancer cells (P < 0.05) and markedly increased mitochondrial membrane potential of the cells (P < 0.05). The expressions of Bcl-2, Bcl-xL and p-STAT3 proteins increased obviously while the expressions of Bax, Bad and STAT3 either decreased or showed no obvious changes in the LIF-overexpressing cells. Overexpressing LIF significantly enhanced the transcriptional activity of STAT3 (P < 0.05), and silencing STAT3 obviously enhanced apoptosis of the endometrial cancer cells overexpressing LIF (P < 0.05). CONCLUSIONS: s Overexpression of LIF can enhance cisplatin and paclitaxel resistance to endometrial cancer cells in vitro.


Cisplatin/pharmacology , Drug Resistance, Neoplasm , Endometrial Neoplasms/genetics , Leukemia Inhibitory Factor/genetics , Paclitaxel/pharmacology , Signal Transduction , Antineoplastic Agents/pharmacology , Apoptosis , Cell Line, Tumor , Female , Humans , Proto-Oncogene Proteins c-bcl-2/metabolism , STAT3 Transcription Factor/metabolism , bcl-X Protein/metabolism
11.
Photochem Photobiol ; 96(5): 1154-1160, 2020 09.
Article En | MEDLINE | ID: mdl-32242937

A simple and effective ratiometric fluorescence sensor of CdTe QDs/GCNNs for on-site and rapid analysis of Cu2+ has been established by mixing physically CdTe QDs and graphite carbon nitride (GCNNs). Two emissions peaks of CdTe QDs at 572 nm and GCNNs at 436 nm are both excitated at 340 nm. Under a UV lamp, fluorescent of traffic yellow CdTe QDs is linearly quenched by Cu2+ (as the detection signal), while blue GCNNs remains unchanged (as the reference), resulting in a distinguishable color change gradually from pink yellow to blue. The limit of detection (LOD) of this new sensor for Cu2+ is as low as 0.47 ng mL-1 with 1.4 % RSD. The established method has been successfully applied to detection of Cu2+ in various drinks with satisfactory results. Moreover, a paper-based sensor, which has been prepared by soaking cellulose acetate membrane in CdTe QDs/GCNNs sensor solution, has a wide semiquantitative detection range for Cu2+ (0.01 ~ 5.0 µg mL-1 ). It has realized successfully on-site and rapid determination of Cu2+ in red wine without any pretreatment procedure and is of great promotion and application value in determination of Cu2+ in liquid samples.


Beverages/analysis , Cadmium Compounds/chemistry , Copper/analysis , Graphite/chemistry , Nitrogen Compounds/chemistry , Paper , Quantum Dots , Tellurium/chemistry , Fluorescence , Fluorescent Dyes/chemistry , Spectrometry, Fluorescence/methods
12.
Article En | MEDLINE | ID: mdl-31261730

Identifying nitrogen-transforming genes and the microbial community in the lacustrine sedimentary environment is critical for revealing nitrogen cycle processes in eutrophic lakes. In this study, we examined the diversity and abundance of ammonia-oxidizing bacteria (AOB), ammonia-oxidizing archaea (AOA), denitrifying bacteria (DNB), and anammox bacteria (AAOB) in different trophic status regions of Lake Taihu using the amoA, Arch-amoA, nirS, and hzo genes as functional markers. Quantitative Polymerase Chain Reaction (qPCR) results indicated that the abundance of the nirS gene was the highest, while the amoA gene had the lowest abundance in all regions. Except for the primary inflow area of Lake Taihu, Arch-amoA gene abundance was higher than the hzo gene in three lake bays, and the abundance of the nirS gene increased with decreasing trophic status. The opposite pattern was observed for the amoA, Arch-amoA, and hzo genes. Phylogenetic analyses showed that the predominant AOB and AOA were Nitrosomonas and Nitrosopumilus maritimus, respectively, and the proportion of Nitrosomonas in the eutrophic region (87.9%) was higher than that in the mesotrophic region (71.1%). Brocadia and Anammoxoglobus were the two predominant AAOB in Lake Taihu. Five novel unknown phylotypes of AAOB were observed, and Cluster AAOB-B was only observed in the inflow area with a proportion of 32%. In the DNB community, Flavobacterium occurred at a higher proportion (22.6-38.2%) in all regions, the proportion of Arthrobacter in the mesotrophic region (3.6%) was significantly lower than that in the eutrophic region (15.6%), and the proportions of Cluster DNB-E in the inflow area (24.5%) was significantly higher than that in the lake bay (7.3%). The canonical correspondence analysis demonstrated that the substrate concentration in sedimentary environments, such as NOx--N in the sediment, NH4+-N in the pore water, and the total organic matter, were the key factors that determined the nitrogen-transforming microbial community. However, the temperature was also a predominant factor affecting the AOA and AAOB communities.


Lakes/microbiology , Microbiota , Nitrogen/metabolism , Seasons , Ammonia/analysis , Geologic Sediments/chemistry , Nitrogen Cycle , Oxidation-Reduction , Phylogeny
13.
Mol Ther Oncolytics ; 14: 94-106, 2019 Sep 27.
Article En | MEDLINE | ID: mdl-31193124

Leucine-rich-repeat-containing G protein-coupled receptors (LGRs) have been widely found to be implicated with development and progression in multiple cancer types. However, the clinical significance and biological functions of LGR6 in ovarian cancer remains unclear. In this study, LGR6 expression was mainly examined by immunohistochemistry. Functional assays in vitro and animal experiments in vivo were carried out to explore the effect of LGR6 on cancer stem cell (CSC) characteristics and chemotherapeutic responses in ovarian cancer cells. Luciferase assays and GSEA were used to discern the underlying mechanisms contributing to the roles of LGR6 in ovarian cancer. Here, we reported that LGR6 was upregulated in ovarian cancer, which positively correlated with poor chemotherapeutic response and progression survival in ovarian cancer patients. Loss-of-function assays showed that downregulating LGR6 abrogated the CSC-like phenotype and chemoresistance in vitro. More importantly, silencing LGR6 improved the chemoresistance of ovarian cancer cells to cisplatin in vivo. Mechanistic investigation further revealed that silencing LGR6 inhibited stemness and chemoresistance by repressing Wnt/ß-catenin signaling. Collectively, our results uncover a novel mechanism contributing to LGR6-induced chemotherapeutic resistance in ovarian cancer, providing the evidence for LGR6 as a potential therapeutic target in ovarian cancer.

14.
Chemosphere ; 234: 89-97, 2019 Nov.
Article En | MEDLINE | ID: mdl-31203045

Renewable additional carbon sources for groundwater denitrification, such as sustainable-releasing compound carbon source materials (SCCMs), are required. This work reports long-term groundwater denitrification with permeable reactive barriers filled with SCCMs; the coupling of biological denitrification and chemical reduction avoided the need for a continuous carbon source supply. Four 370-day lab-scale permeable reactive barrier experiments with four SCCMs showed that NO3- removal efficiency in zero-valent iron (ZVI) SCCMs was higher than in ZVI-free SCCMs. In the ZVI SCCMs, the NO3- removal reaction began quickly in the early stage, owing to ZVI chemical reduction, whereas biological denitrification was lower and incomplete with a NO2- concentration of 0.8 mg L-1 in the ZVI SCCM system. As the chemical reduction efficiency decreased, the biological denitrification efficiency increased, and the highest NO3- removal efficiency was 98.8%. Decreasing the Fe2+concentration decreased ZVI chemical reduction. High-throughput sequencing indicated that the proportion of denitrifying bacteria attached to the SCCMs was up to 34.4% at the family level, leading to the denitrification gene being predominant. Quantitative PCR indicated increased microbial metabolic activity, richer bacterial community diversity, and more bacteria. Long-term monitoring data for SCCMs will help realize the use of biological denitrification coupled with chemical reduction for groundwater NO3- remediation.


Bacteria/metabolism , Carbon/chemistry , Denitrification , Environmental Restoration and Remediation/methods , Groundwater/chemistry , Nitrates/chemistry , Water Pollutants, Chemical/chemistry , Iron/chemistry , Nitrates/analysis , Water Purification/methods
15.
Environ Pollut ; 248: 438-447, 2019 May.
Article En | MEDLINE | ID: mdl-30826606

The contamination with antibiotic resistance genes (ARGs) in raw drinking water source may pose a direct threat to human health. In this study, metagenomics sequencing and analysis were applied to investigate the ARG pattern in 12 drinking water sources in upper and middle reach of Huaihe River Basin, China. Based on the redundant analysis and multi-linear regression model, location, specific microbial taxa, number of livestock and health facilities significantly influenced the ARG profile in drinking water sources. Besides the cluster effect of ARG in samples from plain and bedrock mountain areas, the samples from fracture aquifer areas also showed a distinctive biogeographic pattern with that from porous aquifer areas. Putative ARGs host Opitutus and Flavobacterium were the enriched biomarkers in plain and fracture aquifer area respectively, which mainly carried bacitracin, multidrug, beta-lactam and tetracycline ARGs. This result illuminated that both natural background and anthropogenic activities in the watershed influenced the ARG profile in natural freshwater system significantly. The low MGEs abundance and absence of pathogen revealed a low ARG dissemination risk in sampled drinking water sources, while Polynucleobacter was an abundant ARGs host and was significantly related to the ARG profile, which indicated that specific bacteria was responsible for ARGs propagation and accumulation in surface freshwater system. Further researches are needed to assess human exposure to raw drinking water source and the potential risk, as well as the species interaction in microbial community and its impact on ARG propagation under oligotrophic condition.


Burkholderiaceae/genetics , Drinking Water/microbiology , Drug Resistance, Microbial/genetics , Flavobacterium/genetics , Rivers/microbiology , Verrucomicrobia/genetics , Anti-Bacterial Agents/pharmacology , Bacitracin/pharmacology , Burkholderiaceae/drug effects , China , Flavobacterium/drug effects , Genes, Bacterial/genetics , Humans , Metagenomics , Microbiota/drug effects , Tetracyclines/pharmacology , Verrucomicrobia/drug effects , beta-Lactams/pharmacology
16.
Chemosphere ; 220: 668-677, 2019 Apr.
Article En | MEDLINE | ID: mdl-30605809

Riverbank filtration (RBF) as a barrier of pathogenic microorganisms and organic micropollutants recently has been proven capable of removing sulfonamides. However, the study about the effect of redox conditions on biodegradation of common and persistent sulfonamides in RBF is limited and the response of microbial communities to sulfonamides stress during RBF is unknown. In this study, two column set-ups (with residence time 5 days and 11 days respectively), simulating different redox conditions of riverbank filtration systems, were operated for seven months to investigate 1) the long-term effect of redox conditions on ng∙L-1 level sulfonamides (sulfapyridine, sulfadiazine, sulfamethoxazole, sulfamethazine, sulfaquinoxaline) removal, and 2) the microbial community evolution represented by the phylogenetic and metabolic function shift under non-lethal selective pressures of sulfonamides. The results showed that sulfonamides were more degradable under anoxic conditions than oxic and suboxic conditions. In the sulfonamides stressed community, the phylogenetic diversity increased slightly. Relative abundance of an intrinsic sulfonamides resistant bacteria Bacillus spp. increased, suggesting that sulfonamide resistance developed in specific bacteria under sulfonamides contamination pressure in RBF systems. At the same time, an activated transport function in the stressed microbial community was noticed. The predicted relative abundance of gene folP, which encodes dihydropteroate synthase, also increased significantly, indicating a detoxification mechanism and sulfonamides resistance potential under non-lethal selective pressures of sulfonamides in RBF systems.


Microbiota/drug effects , Sulfonamides/isolation & purification , Biodegradation, Environmental , Filtration , Microbiota/physiology , Oxidation-Reduction , Phylogeny , Rivers , Sulfonamides/pharmacology
17.
Chemosphere ; 205: 635-642, 2018 Aug.
Article En | MEDLINE | ID: mdl-29729621

Recently, reductant and carbon source were frequently used in groundwater nitrate remediation worldwide. Agricultural waste as a promising organic carbon source, has been paid much attention but the problem of sustainability, bioavailability and secondary pollution remained unsolved. This study was conducted to depict the characteristic and performance of developed sustainable-releasing compound carbon source material (SCCM) applied on the in-situ remediation of nitrate in shallow groundwater. Results showed the SCCM based on agricultural waste and zero valent-iron (ZVI) has a stable carbon releasing rate, which is suitable for stimulating the low microbial active environment in groundwater continuously, and capable of avoiding rapid TOC releasing in the early stage. The released carbon sources in SCCM leachate were mainly small molecular alcohols and acids with high microbial availability. As in-situ permeable reactive barrier (PRB) filling material, SCCM can form an optimal carbon source radiation range of 20 cm, with a maximum efficient carbon source radius of 1 m, which can reach an extended active zone. A positive correlation between the ZVI content and nitrate removal rate was found. The chemical and microbiological evidence both indicated that the expected chemical reduction and biological denitrification was gradually established. Additionally, the absorption of ammonia and chroma by attapulgite effectively avoided the secondary pollution. In conclusion, the application of SCCM in groundwater nitrate in-situ remediation optimized the nitrate removal efficiency and provided theoretical basis for engineer carbon sources development from straw-type agricultural waste.


Carbon/chemistry , Denitrification/physiology , Environmental Restoration and Remediation/methods , Groundwater/chemistry , Nitrates/chemistry , Water Pollutants, Chemical/chemistry , Water Purification/methods , Water Pollutants, Chemical/analysis
18.
Environ Geochem Health ; 40(6): 2525-2538, 2018 Dec.
Article En | MEDLINE | ID: mdl-29748733

Organochlorine pesticides (OCPs) are pesticides with global scale ubiquity, persistence and bioaccumulation, which leave long-term residuals in the water body. OCPs' high toxicity poses significant threats to human health and aquatic biodiversity, making assessment of OCPs' impact on aquatic ecology and human health urgently necessary. In this research, the presence of 16 OCPs in surface water and groundwater along Shaying River, China, as well as OCPs concentration correlations, was investigated at 24 selected sampling sites. At the same time, the ecological risk and human carcinogenic risk were also analyzed by risk quotient method and USEPA's Risk Assessment Guidance, respectively. Results showed that the total concentration of OCPs ranged from 21.0 to 61.4 ng L-1 in groundwater, and 12.3-77.5 ng L-1 in surface water. Hexachlorocyclohexane (HCHs) and heptachlor were the prominent contaminants in groundwater, which indicated their use in the recent past and confirmed their persistence. The α-HCH/γ-HCH ratios in groundwater confirmed that γ-HCH (lindane) was used as main substitute of technical HCH in the study area. The correlation analysis illustrated that δ-HCH and γ-HCH played a dominant role in HCHs residue. Heptachlor and α-HCH, as well as endosulfan and heptachlor epoxide, had a strongly significant positive correlation, suggesting an associated usage of the two pair OCPs. An extremely high ecological risk for aquatic organism was observed for γ-HCH, heptachlor and dieldrin, while the carcinogenic risks posed by the selected OCPs in surface water and groundwater were all acceptable.


Environmental Monitoring , Hydrocarbons, Chlorinated/analysis , Pesticide Residues/analysis , Pesticides/analysis , Water Pollutants, Chemical/analysis , Aquatic Organisms/drug effects , China , Groundwater/analysis , Hydrocarbons, Chlorinated/adverse effects , Pesticide Residues/adverse effects , Pesticides/adverse effects , Risk Assessment , Rivers , Water Pollutants, Chemical/adverse effects
19.
Sci Total Environ ; 592: 78-85, 2017 Aug 15.
Article En | MEDLINE | ID: mdl-28314133

Straw return is becoming a routine practice in disposing of crop residues worldwide. However, the potential effect of such operation on the chemistry of local groundwater is not well documented. Here, shallow groundwater in an area where wheat-maize straw return is practiced was analyzed, and the seasonal changes in the nitrate concentration and the isotope compositions of NO3- and H2O were determined along two flow paths. Measured δD and δ18O in waters indicated that the groundwater was mainly recharged by atmospheric precipitation, while measured δ15N and δ18O in nitrate suggested that the sources for groundwater NO3- included urea fertilizer, soil nitrogen, and sewage/manure. Reduced NO3- concentrations coincided with an enrichment of organic matter in the groundwater of the straw return area, revealing an environmental condition that facilitates nitrate reduction, whereas increased δ15N-NO3- and δ18O-NO3- along the flow path suggested the occurrence of denitrification. Further analyses showed that, compared to the cases in the absence of straw return, as much as 80% and 90% of groundwater nitrate was removed in low and high water seasons in the straw return area, pointing to a potential positive effect of straw return to groundwater quality.


Environmental Monitoring , Groundwater/chemistry , Nitrates/analysis , Triticum , Water Pollutants, Chemical/analysis , Zea mays , Agriculture/methods , China , Nitrogen Isotopes/analysis , Oxygen Isotopes/analysis , Plant Stems , Rivers , Water Quality
20.
Microbiologyopen ; 6(4)2017 08.
Article En | MEDLINE | ID: mdl-28173613

Sediment bacterial community is the main driving force for nutrient cycling and energy transfer in aquatic ecosystem. A thorough understanding of the community's spatiotemporal variation is critical for us to understand the mechanisms of cycling and transfer. Here, we investigated the sediment bacterial community structures and their relations with environmental factors, using Lake Taihu as a model system to explore the dependence of biodiversity upon trophic level and seasonality. To combat the limitations of conventional techniques, we employed Illumina MiSeq Sequencing and LeFSe cladogram to obtain a more comprehensive view of the bacterial taxonomy and their variations of spatiotemporal distribution. The results uncovered a 1,000-fold increase in the total amount of sequences harvested and a reverse relationship between trophic level and the bacterial diversity in most seasons of a year. A total of 65 phyla, 221 classes, 436 orders, 624 families, and 864 genera were identified in the study area. Delta-proteobacteria and gamma-proteobacteria prevailed in spring/summer and winter, respectively, regardless trophic conditions; meanwhile, the two classes dominated in the eutrophication and mesotrophication lake regions, respectively, but exclusively in the Fall. For LEfSe analysis, bacterial taxon that showed the strongest seasonal or spatial variation, majority had the highest abundance in spring/summer or medium eutrophication region, respectively. Pearson's correlation analysis indicated that 5 major phyla and 18 sub-phylogenetic groups showed significant correlation with trophic status. Canonical correspondence analysis further revealed that porewater NH4+ -N as well as sediment TOM and NOx -N are likely the dominant environmental factors affecting bacterial community compositions.


Bacteria/classification , Bacteria/isolation & purification , Biota , Fresh Water/microbiology , Geologic Sediments/microbiology , Lakes/microbiology , Phylogeny , Cluster Analysis , DNA, Bacterial/chemistry , DNA, Bacterial/genetics , DNA, Ribosomal/chemistry , DNA, Ribosomal/genetics , High-Throughput Nucleotide Sequencing , RNA, Ribosomal, 16S/genetics , Seasons , Sequence Analysis, DNA , Spatio-Temporal Analysis
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