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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.
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Infecções Bacterianas , Nanopartículas , Humanos , Matriz Extracelular de Substâncias Poliméricas/metabolismo , Biofilmes , Sistemas de Liberação de Medicamentos , Infecções Bacterianas/metabolismo , NanotecnologiaRESUMO
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.
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Lagos , Metagenômica , Antibacterianos/análise , Antibacterianos/farmacologia , Bactérias/genética , China , Resistência Microbiana a Medicamentos/genética , Genes Bacterianos , Lagos/microbiologia , Metagenômica/métodos , Prevalência , ÁguaRESUMO
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.
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Monitoramento Ambiental , Hidrocarbonetos Clorados/análise , Resíduos de Praguicidas/análise , Praguicidas/análise , Poluentes Químicos da Água/análise , Organismos Aquáticos/efeitos dos fármacos , China , Água Subterrânea/análise , Hidrocarbonetos Clorados/efeitos adversos , Resíduos de Praguicidas/efeitos adversos , Praguicidas/efeitos adversos , Medição de Risco , Rios , Poluentes Químicos da Água/efeitos adversosRESUMO
The odour emission characteristics of 22 recreational rivers in Nanjing were investigated and analysed. Eight odorous compounds (ammonia (NH3), hydrogen sulphide (H2S), sulphur dioxide (SO2), carbon disulphide (CS2), nitrobenzene (C6H5NO2), aniline (C6H5NH2), dimethylamine (C2H7N), and formaldehyde (HCHO)) were measured in odour emission samples collected using a custom-made emission flux hood chamber. The results showed that all odorants were detected in all monitoring rivers. NH3 was the main odorant, with emission rates ranging from 4.86 to 15.13 µg/min m(2). The total odour emission rate of the Nan River, at 1 427.07 OU/s, was the highest of the all investigated rivers. H2S, NH3 and nitrobenzene were three key odour emission contributors according to their contributions to the total odour emission. A correlation analysis of the pollutants showed there was a significant positive correlation between the emission rate of NH3 and the concentration of ammonia nitrogen (NH4 (+)-N) and total nitrogen (TN). The H2S and SO2 emission rates had a significant positive correlation with sulphides (S(2-)) and available sulphur (AS) in the water and sediment. The content of TN, NH4(+)-N, S(2-) and AS in the water and sediment affected the concentration of H2S, SO2 and NH3 in the emission gases. NH4(+)-N, S(2-) and AS are suggested as the key odour control indexes for reducing odours emitted from these recreational rivers. The study provides useful information for effective pollution control, especially for odour emission control for the recreational rivers of the city. It also provides a demonstrate example to show how to monitor and assess a contaminated river when odour emission and its control need to be focused on.
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Poluentes Atmosféricos/análise , Monitoramento Ambiental , Odorantes/análise , Rios/química , Poluição do Ar/estatística & dados numéricos , Amônia/análise , Cidades , Sulfeto de Hidrogênio/análise , Nitrogênio/análise , Dióxido de Enxofre/análiseRESUMO
Usage of antibiotics in agriculture has increased dramatically recently, significantly raising the influx of antibiotic resistance genes (ARGs) into river systems through organic manure runoff, seriously threatening water security. However, the dynamics, transmission mechanisms, and potential water security risk of ARGs, as well as their response to land use spatial scale and seasonal variations in agricultural river systems remain unclear. To address these challenges, this work employed metagenomic technique to systematically evaluate the pollution and dissemination of ARGs in overlying water and sediment within a typical agricultural catchment in China. The results demonstrated significant differences between overlying water and sediment ARGs. Overlying water dominated by multidrug ARGs exhibited higher diversity, whereas sediment predominantly containing sulfonamide ARGs had higher abundance. The dynamics of ARGs in overlying water were more responsive to seasonal variations compared to sediment due to greater changes in hydrodynamics and nutrient conditions. The profiles of ARGs in overlying water were largely regulated by microbiota, whereas mobile genetic elements (MGEs) were the main forces driving the dissemination of ARGs in sediment. The variation in dissemination mechanisms led to different resistance risks, with sediment presenting a higher resistance risk than overlying water. Furthermore, Mantel test was applied to discover the impact of land use spatial scale and composition on the transmission of ARGs in river systems. The findings showed that cultivated land within 5â¯km of the riverbank was the key influencing factor. Cultivated land exacerbated ARGs spread by increasing MGEs abundance and nutrient concentrations, resulting in the abundance of ARGs in high-cultivated sites being twice that in low-cultivated sites, and raising the regional water security risk, with a more pronounced effect in sediment. These findings contribute to a better understanding of ARGs dissemination in agricultural watersheds, providing a basis for implementing effective resistance control measures and ensuring water security.
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The biogeochemical cycling of phosphorus (P) in river-lake systems presents significant challenges in tracing P sources, highlighting the importance of effective traceability approaches for formulating targeted management measures to mitigate lake eutrophication. In this study, we used the oxygen isotope of phosphate (δ18Op) as a tracer in the river-lake systems, establishing a tracing pathway from potential end-members, through inflow rivers, and eventually to the lake. Taking Dianshan Lake and its main inflow rivers as the study area, we measured δ18Op values of potential end-members, including domestic sewage treatment plant effluents, industrial effluents from phosphorus-related enterprises (printing and dyeing, electroplating, plastics, etc.), and farmland soils. Notably, the industrial effluent signatures ranged from 13.1 to 21.0 with an average of 16.8 ± 3.2 , enriching the δ18Op threshold database. Using the MixSIAR model, it was found that phosphorus in the Jishuigang River primarily originated from agricultural non-point sources and domestic sewage in the dry season, while the Qiandengpu River, with a higher proportion of urban area, had a greater influence from domestic sewage and industrial effluents. Moreover, significant differences were observed between δ18Op values at the lake entrances of the inflow rivers (13.7 ± 1.0 ) and in acid-soluble phosphate of the lake sediments (9.9 ± 1.0 ). Isotopic tracing revealed that phosphorus in the lake originated from both external inputs (80.6 %) and internal release (19.4 %) in the dry season. Alongside pollutant flux calculations based on the hydrological conditions and water quality of the inflow rivers, our findings indicated that phosphorus in Dianshan Lake was mainly attributed to agricultural non-point sources, domestic sewage and sediment release in the dry season. This study provided novel insights into the identification of pollution sources in the river-lake systems, with broad implications for pollution control and environmental protection.
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BACKGROUND: The global burden and trends in gynecological cancer (GC) by menopausal status worldwide remain unclear. METHODS: Data on the number of incident cases and deaths, as well as age-standardized rates (ASR) and risk factors for GC in pre- and post-menopausal women were obtained from the Global Burden of Disease (GBD) Study 2019. The estimated annual percent change was calculated to quantify the temporal trend of GC burden by menopausal status between 1990 and 2019. The Bayesian age-period-cohort model was used to predict the trends in age-standardized incidence and mortality rates for pre- and post-menopausal GC during 2020-2040. RESULTS: In 2019, an estimated 400,146 premenopausal and 879,476 postmenopausal GC cases were newly diagnosed worldwide, with approximately 111,420 and 442,821 GC-related deaths occurring in each menopausal group, respectively. The majority of both pre- and post-menopausal GC cases in low- to middle-SDI regions was due to cervical cancer. In high- and high-middle-SDI regions, premenopausal GC was primarily attributed to cervical cancer, while postmenopausal GC was mainly attributed to uterine cancer. Additionally, the contribution of uterine cancer to GC was higher among postmenopausal women than premenopausal women, across all SDI levels and geographical regions. ASIRs either remained stable or increased from 1990 to 2019 worldwide for both pre- and post-menopausal GC (an average change of 0.03% [95% CI -0.02 to 0.08] and 0.09% [0.05 to 0.13] per year, respectively). However, the age-standardized mortality rates (ASMRs) declined by an annual average of 0.86% (95% CI -0.92 to -0.8) and 0.63% (95% CI -0.66 to -0.6) globally during the same period. The risk-attributable proportion of postmenopausal GC deaths was higher than that of premenopausal GC and increased with increasing SDI. The projections indicate an increasing trend in the burden of premenopausal GC from 2020 to 2040, while the burden of postmenopausal GC is expected to decline. CONCLUSIONS: GC continues to be a significant public health concern worldwide, with notable regional and demographic disparities in the burden based on menopausal status. Policymakers and health-care providers must be proactively aware of these evolving trends and tailor age-appropriate and region-specific screening strategies, as well as allocate resources accordingly.
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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.
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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.
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Poluição Difusa , Poluentes Químicos da Água , Poluição Difusa/análise , Poluentes Químicos da Água/análise , Rios , Monitoramento Ambiental , Solo , China , Fósforo/análise , Nitrogênio/análiseRESUMO
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.
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Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Fotoquimioterapia/métodos , Terapia Fototérmica , Fototerapia/métodos , Nanopartículas/química , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Linhagem Celular TumoralRESUMO
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.
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Anemia , Neoplasias do Endométrio , Leucopenia , Radioterapia de Intensidade Modulada , Trombocitopenia , Neoplasias do Colo do Útero , Feminino , Humanos , Anemia/complicações , Anemia/tratamento farmacológico , Medula Óssea , Quimiorradioterapia/efeitos adversos , Cisplatino/efeitos adversos , Leucopenia/etiologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/efeitos adversos , Estudos Prospectivos , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/efeitos adversos , Trombocitopenia/induzido quimicamente , Trombocitopenia/tratamento farmacológico , Neoplasias do Colo do Útero/radioterapiaRESUMO
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.
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Neoplasias Ovarianas , RNA Longo não Codificante , Feminino , Humanos , Cisplatino/uso terapêutico , Proteínas de Ligação a DNA/genética , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Antígeno Nuclear de Célula em Proliferação , RNA Longo não Codificante/genética , Ubiquitina-Proteína Ligases , MicropeptídeosRESUMO
The contents of 16 priority water-borne polycyclic aromatic hydrocarbons (PAHs) in water, potential external pollution sources and sediment from the famous landscape of the Qinghuai River were measured by gas chromatography-mass spectrometry (GC-MS). The distribution, composition, source and ecological risk of PAHs were analyzed. The following results were obtained: (1) Benzo[a]pyrene and benzo[ghi] perylene were not detected in all samples. The total contents of 16 priority PAHs (PAH16) varied from 52.5 to 745.3 ng l(-1) with the average of 174.0 ng l(-1) in water, from 96.0 to 1,064.6 ng l(-1) with the average of 329.2 ng l(-1) in potential sources, from 931.7 to 15,295.5 ng g(-1) with the average of 7,133.6 ng g(-1) in sediments. (2) The concentration of PAH16 in water is lower than in sediment and higher rings are more easily detected in sediment. The percentage of higher ring (four- to six-rings) PAHs accounted for more than 55.6% of PAHs in sediment. (3) The value of FLA/(FLA+Pyr) was higher than 0.5 at most sampling points which illustrated the source was related with petrogenic such as liquid fossil fuel combustion. (4) The potential ecosystem risk of low ring PAH for upstream conflux of external Qinhuai River was less than 10%, while it was 10-50% for other sampling points; The four rings PAH shows lower potential ecosystem risk than other ring PAH in this study area; Dibenzo [ah] anthracene (DahA) shows high potential ecosystem risk at all sampling points.
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Ecossistema , Hidrocarbonetos Policíclicos Aromáticos/química , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Rios , Poluentes Químicos da Água/química , Poluentes Químicos da Água/toxicidade , China , Cidades , Monitoramento Ambiental/métodosRESUMO
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.
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Rios , Poluentes Químicos da Água , China , Monitoramento Ambiental , Nitrogênio/análise , Fósforo/análise , Poluentes Químicos da Água/análise , Qualidade da ÁguaRESUMO
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.
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Antibacterianos , Hidrogéis , Staphylococcus aureus Resistente à Meticilina , Nanopartículas , Óxido Nítrico , Infecção dos Ferimentos , Antibacterianos/administração & dosagem , Antibacterianos/química , Fibrina/administração & dosagem , Fibrina/química , Hidrogéis/administração & dosagem , Hidrogéis/química , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Nanopartículas/administração & dosagem , Nanopartículas/química , Óxido Nítrico/administração & dosagem , Óxido Nítrico/química , Fenilenodiaminas/administração & dosagem , Fenilenodiaminas/química , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Cicatrização/efeitos dos fármacos , Infecção dos Ferimentos/tratamento farmacológico , Infecção dos Ferimentos/microbiologiaRESUMO
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.
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Bebidas/análise , Compostos de Cádmio/química , Cobre/análise , Grafite/química , Compostos de Nitrogênio/química , Papel , Pontos Quânticos , Telúrio/química , Fluorescência , Corantes Fluorescentes/química , Espectrometria de Fluorescência/métodosRESUMO
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.
Assuntos
Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos , Neoplasias do Endométrio/genética , Fator Inibidor de Leucemia/genética , Paclitaxel/farmacologia , Transdução de Sinais , Antineoplásicos/farmacologia , Apoptose , Linhagem Celular Tumoral , Feminino , Humanos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Fator de Transcrição STAT3/metabolismo , Proteína bcl-X/metabolismoRESUMO
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.
Assuntos
Burkholderiaceae/genética , Água Potável/microbiologia , Resistência Microbiana a Medicamentos/genética , Flavobacterium/genética , Rios/microbiologia , Verrucomicrobia/genética , Antibacterianos/farmacologia , Bacitracina/farmacologia , Burkholderiaceae/efeitos dos fármacos , China , Flavobacterium/efeitos dos fármacos , Genes Bacterianos/genética , Humanos , Metagenômica , Microbiota/efeitos dos fármacos , Tetraciclinas/farmacologia , Verrucomicrobia/efeitos dos fármacos , beta-Lactamas/farmacologiaRESUMO
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 0.8â¯mgâ¯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.
Assuntos
Bactérias/metabolismo , Carbono/química , Desnitrificação , Recuperação e Remediação Ambiental/métodos , Água Subterrânea/química , Nitratos/química , Poluentes Químicos da Água/química , Ferro/química , Nitratos/análise , Purificação da Água/métodosRESUMO
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.