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1.
J Enzyme Inhib Med Chem ; 37(1): 339-354, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34979843

RESUMO

α-Fluorinated chalcones were prepared and evaluated for their cell growth inhibitory properties against six human cancer cell lines. The most potent chalcone 4c demonstrated excellent selective toxicity against cancer cells versus normal human cells, with IC50 values at nanomolar concentration ranges against 5 cancer cell lines. A further study revealed that 4c could bind to the colchicine site of tubulin, disrupt the cell microtubule networks, and effectively inhibit tubulin polymerisation. Cellular-based mechanism studies elucidated that 4c arrested MGC-803 cell cycle at G2/M phase. In addition, 4c dose-dependently caused Caspase-induced apoptosis of MGC-803 cells through mitochondrial dysfunction. Notably, compound 4c was found to inhibit the HUVECs tube formation, migration, and invasion in vitro. Furthermore, our data suggested that treatment with 4c significantly reduced MGC-803 cells metastasis and proliferation in vitro. Overall, this work showed that chalcone hybrid 4c is a potent inhibitor of tubulin assembly with prominent anti-angiogenesis and anti-cancer properties.

2.
Drug Discov Ther ; 15(6): 289-299, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34980761

RESUMO

The outbreak and rapid spread of coronavirus disease 2019 (COVID-19) poses a huge threat to human health and social stability. Shufeng Jiedu capsule (SFJDC), a patented herbal drug composed of eight medicinal plants, is used to treat different viral respiratory tract infectious diseases. Based on its antiviral, anti-inflammatory, and immunoregulatory activities in acute lung injury, SFJDC can be effectively used as a treatment for COVID-19 patients according to the diagnosis and treatment plan issued in China and existing clinical data. SFJDC has been recommended in 15 therapeutic regimens for COVID-19 in China. This review summarizes current data on the ingredients, chemical composition, pharmacological properties, clinical efficacy, and potential therapeutic effect of SFJDC on COVID-19, to provide a theoretical basis for its anti-viral mechanism and the clinical treatment of COVID-19.


Assuntos
COVID-19 , Medicamentos de Ervas Chinesas , Anti-Inflamatórios , Antivirais/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , SARS-CoV-2
3.
J Cell Mol Med ; 2022 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-35001521

RESUMO

Acute myeloid leukaemia (AML) is a biologically heterogeneous disease with an overall poor prognosis; thus, novel therapeutic approaches are needed. Our previous studies showed that 4-amino-2-trifluoromethyl-phenyl retinate (ATPR), a new derivative of all-trans retinoic acid (ATRA), could induce AML cell differentiation and cycle arrest. The current study aimed to determine the potential pharmacological mechanisms of ATPR therapies against AML. Our findings showed that E2A was overexpressed in AML specimens and cell lines, and mediate AML development by inactivating the P53 pathway. The findings indicated that E2A expression and activity decreased with ATPR treatment. Furthermore, we determined that E2A inhibition could enhance the effect of ATPR-induced AML cell differentiation and cycle arrest, whereas E2A overexpression could reverse this effect, suggesting that the E2A gene plays a crucial role in AML. We identified P53 and c-Myc were downstream pathways and targets for silencing E2A cells using RNA sequencing, which are involved in the progression of AML. Taken together, these results confirmed that ATPR inhibited the expression of E2A/c-Myc, which led to the activation of the P53 pathway, and induced cell differentiation and cycle arrest in AML.

4.
J Environ Manage ; 305: 114380, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34995945

RESUMO

The co-occurrence networks and interactions of bacterial communities in sediments are highly variable with environmental factors, which are vital to the nutrient biogeochemical cycle, pollutants biodegradation, and microbial community stability in lake ecosystems. Although pollution gradients reflect environmental variation comprehensively, few studies have characterized the changes in co-occurrence networks and interactions of bacterial communities along sediment pollution gradients. In order to investigate the impact of pollution gradients on compositions, co-occurrence networks, and interactions of sedimentary microbial communities, we studied the bacterial communities in the sediments of a typical shallow eutrophic lake, Taihu Lake, along pollution gradients using 16S rRNA gene high-throughput sequencing technology. All the sediment sampling sites were classified into mild, moderate, and severe pollution groups according to the sediments' physicochemical properties. Our results showed that the taxon richness was lowest in the severe pollution group, and the diversity of species decreased with the level of pollution. The complexity of the co-occurrence network decreased as the level of pollution increased, and the severe pollution group was characterized by a small-world network. The relative abundance of Proteobacteria, Bacteroidetes, and Chlorobi increased significantly as the level of pollution increased (P < 0.05). Strong inter-phyla co-occurrence or co-exclusion patterns demonstrated that the strength of interactions was enhanced in the severe pollution group, indicating stronger cooperative or competitive relationships. Chloroflexales and Chlorobiales were unique keystone taxa in the severe pollution group. The results of this study indicate that severe pollution reduces microbial diversity and network complexity, which may lead to community instability. The competition for nutrients of some copiotrophic bacteria may be enhanced as the level of pollution increased. The unique keystone taxa may contribute to photosynthesis and pollutant degradation in the severe pollution group. These findings expand our understanding of variation in bacterial co-occurrence networks and interactions along sediment pollution gradients.

5.
Environ Res ; : 112778, 2022 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-35065067

RESUMO

Diverging area is widespread in river networks, and understanding its biogeochemical process characteristics is of great significance to river ecological restoration and environmental quality improvement. Microbial communities affected by hydrodynamics play an important role in biogeochemical processes, but their relationship in diverging area is little known. Here, the composition of microbial community and its feedback to hydrodynamics and nitrogen conversion in the diverging area of river networks were first studied by coupling ecological theory, biogeochemical theory, microbial DNA sequencing and mathematical model of water environment. The results showed that there were five hydrodynamic zones with significant velocity differences in the diverging area, namely low velocity zone, maximum velocity zone, stagnant zone, separation zone, and deflection zone. According to the flow velocity grouping, there were significant differences in the microbial diversity and abundance among low velocity group, maximum velocity group and stagnant group had significant differences (p < 0.05, stress = 0.1207). In the low velocity group, Firmicutes was the dominant phylum which had a highest abundance and may promot the conversion of organic nitrogen into ammonia nitrogen. In the maximum velocity group, Bdellovibrionota was the dominant phylum which had a highest abundance and may promot the conversion of nitrate and nitric oxide to nitrogen. In the stagnant zone, Methylomirabilota was the dominant phylum which had a highest abundance and may promot the conversion of nitrogen into nitrate and ammonium. In addition, dissolved oxygen was the most sensitive environmental factor for shaping microorganisms and nitrogen conversion in the diverging area of the river networks by canonical correlation analysis. The denitrifying bacteria Rhodocyclaceae, was shown to negatively correlated with the flow velocity. This research improves the scientific basis for the study of the ecosystem in river networks, which will guide the construction of river ecological projects.

6.
Environ Res ; 204(Pt D): 112371, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34774512

RESUMO

The importance of suspended particulate matter (SPM) in nitrogen removal from aquatic environments has been acknowledged in recent years by recognizing the role of attached microbes. However, the succession of attached microbes on suspended particles and their role in nitrogen removal under specific surface microenvironment are still unknown. In this study, the causation among characteristics of SPM, composition and diversity of particle-attached microbial communities, and abundances of nitrogen-related genes in urban rivers was firstly quantitatively established by combing spectroscopy, 16 S rRNA amplicon sequencing, absolute gene quantification and supervised integrated machine learning. SPM in urban rivers, coated with organic layers, was mainly composed of silt and clay (87.59-96.87%) with D50 (medium particle size) of 8.636-30.130 µm. In terms of material composition of SPM, primary mineral was quartz and the four most abundant elements were O, Si, C, Al. The principal functional groups on SPM were hydroxyl and amide. Furthermore, samples with low, medium and high levels of ammoxidation potential were classified into three groups, among which significant differences of microbial communities were found. Samples were also separated into three groups with low, medium and high levels of denitrification potential and significant differences occurred among groups. The particle size, content of functional groups and concentration of SPM were identified as the most significant factors related with microbial communities, playing an important role in succession of particle-attached microbes. In addition, the path model revealed the significantly positive effect of organic matter and particle size on the microbial communities and potential nitrogen removal. The content of hydroxyl and temperature were identified as the most effective predicting factors for ammoxidation potential and denitrification potential respectively by Random Forests Regression models, which had good predictive performances for potential of ammoxidation (R2 = 0.71) and denitrification (R2 = 0.61). These results provide a basis for quickly assessing the ability of nitrogen removal in urban rivers.

7.
Chemosphere ; 287(Pt 2): 132196, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34517239

RESUMO

The intimate coupling of photocatalysis and biodegradation (ICPB) possesses an enhanced ability of recalcitrant contaminant removal and energy generation, owing to the compact communication between biotic components and photocatalysts during the system operation. The photocatalysts in the ICPB system could dispose of noxious contaminants to relieve the external pressure on microorganisms which could realize the mineralization of the photocatalytic degradation products. However, due to the complex components in the composite system, the mechanism of the ICPB system has not been completely understood. Moreover, the variable environmental conditions would play a significant role in the ICPB system performance. The further development of the ICPB scheme requires clarification on how to reach an accurate understanding of the system condition during the practical application. This review starts by offering detailed information on the system construction and recent progress in the system components' amelioration. We then describe the potential influences of relevant environmental factors on the system performance, and the analytical strategies applicable for comprehending the critical processes during the system operation are further summarized. Finally, we put forward the research gaps in the current system and envision the system's prospective application. This review provides a valuable reference for future researches that are devoted to assessing the environmental disturbance and exploring the reaction mechanisms during the practical application of the ICPB system.


Assuntos
Titânio , Biodegradação Ambiental
8.
Sci Total Environ ; 806(Pt 3): 151210, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34715211

RESUMO

Increasing attention has been focused on the diminishing health of coastal ecosystems. Understanding the effects of eutrophication on tidal flat ecosystems is beneficial for the restoration and management of coastal ecosystems. However, previous studies did not consider the effects of nitrogen on the structure and function of bacterial and archaeal communities in longitudinal and vertical profiles. Here, the diversity, composition, assembly mechanism, and potential metabolic function of the bacterial and archaeal communities were studied in two longitudinal tidal sections at different eutrophic levels. Nitrogen and salinity were the critical factors that influenced the bacterial and archaeal community composition using canonical correspondence and multivariate regression tree analyses. For the bacterial community, the higher nitrogen loading in tidal mudflats resulted in the convergence of diversity and structure in the longitudinal profile of bacteria, but divergence was detected in the vertical profile. For archaea, the diversity tended to be convergent in longitudinal and vertical profiles in the higher nitrogen area, but the change of structure was similar to that of bacteria. Besides the homogeneous processes influenced by salinity, the assembly process of the bacterial community was mainly influenced by heterogeneous selection (34.8%) and that of archaea by dispersal limitation (19.5%). However, the bacterial and archaeal communities in the higher nitrogen section presented more of an influence of heterogeneous selection (respectively, 39 and 5.6%) than that of the lower nitrogen section (respectively, 10 and 0.2%). Structural equation modeling indicated that nitrogen may have inhibited the effects of the bacterial community on nitrogen turnover in nitrogen-rich anoxic sediment environments, but may have strengthened the effect of the archaeal community on carbon metabolism compared to bacteria. This work deepens our understanding of the responses of bacterial and archaeal community structure and potential function to nitrogen pollution in tidal mudflats.


Assuntos
Archaea , Nitrogênio , Archaea/genética , Bactérias/genética , Ecossistema , Sedimentos Geológicos , Filogenia , RNA Ribossômico 16S
9.
J Environ Manage ; 304: 114267, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-34896801

RESUMO

Prioritizing the relationship between heterogeneity of sediment habitats and river bends is critical when planning and reconstructing urban rivers. However, the exact relationship between ecological heterogeneity and river bends remains ambiguous. Therefore, this research proposed a new approach to quantify and predict bend-induced ecological heterogeneity, incorporating the bacteria-based index of biotic integrity (Ba-IBI), path model, and random forest regression model. The developed Ba-IBI quantified heterogeneity in sediment microbial communities, ranging from low (1.40) to high (3.97). A path model was developed and validated in order to further investigate the relative contributions of environmental factors to the Ba-IBI. The established path model, which was considered acceptable with a CMIN/df = 1.949 < 4, suggested that primary environmental factors affecting the sediment bacterial communities were flow velocity and ammonium concentration in sediment. To further characterize the relationship between environmental factors and the Ba-IBI, a function was constructed using the random forest regression model that predicts the responses of sediment bacterial communities to environmental factors with R2 = 0.6126. The proposed approach and prediction tools will provide knowledge to improve natural channel design and post-project evaluations in river restoration projects.


Assuntos
Monitoramento Ambiental , Microbiota , Algoritmos , Bactérias , Ecossistema , Rios , Aprendizado de Máquina Supervisionado
10.
Front Immunol ; 12: 780897, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34887868

RESUMO

Mesenchymal stem cells (MSCs)-derived exosomes were considered a novel therapeutic approach in many aging-related diseases. This study aimed to clarify the protective effects of human placenta MSCs-derived exosomes (hPMSC-Exo) in aging-related CD4+ T cell senescence and identified the underlying mechanisms using a D-gal induced mouse aging model. Senescent T cells were detected SA-ß-gal stain. The degree of DNA damage was evaluated by detecting the level of 8-OH-dG. The superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) activities were measured. The expression of aging-related proteins and senescence-associated secretory phenotype (SASP) were detected by Western blot and RT-PCR. We found that hPMSC-Exo treatment markedly decreased oxidative stress damage (ROS and 8-OH-dG), SA-ß-gal positive cell number, aging-related protein expression (p53 and γ-H2AX), and SASP expression (IL-6 and OPN) in senescent CD4+ T cells. Additionally, hPMSC-Exo containing miR-21 effectively downregulated the expression of PTEN, increased p-PI3K and p-AKT expression, and Nrf2 nuclear translocation and the expression of downstream target genes (NQO1 and HO-1) in senescent CD4+ T cells. Furthermore, in vitro studies uncovered that hPMSC-Exo attenuated CD4+ T cell senescence by improving the PTEN/PI3K-Nrf2 axis by using the PTEN inhibitor bpV (HOpic). We also validated that PTEN was a target of miR-21 by using a luciferase reporter assay. Collectively, the obtained results suggested that hPMSC-Exo attenuates CD4+ T cells senescence via carrying miRNA-21 and activating PTEN/PI3K-Nrf2 axis mediated exogenous antioxidant defenses.

11.
Heart Rhythm ; 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34843967

RESUMO

BACKGROUND: Mutations in cardiac sodium channel Nav1.5 cause Brugada syndrome (BrS). MOG1 is a chaperon that binds to Nav1.5, facilitates Nav1.5 trafficking to cell surface, and enhances amplitude of sodium current INa. OBJECTIVE: To identify structural elements involved in MOG1-Nav1.5 interaction and their relevance to the pathogenesis of BrS. METHODS: Systematic analyses of large deletions, microdeletions and point mutations. Glutathione S-transferases pull-down, co-immunoprecipitation, cell surface protein quantification and patch-clamping of INa. RESULTS: Large deletion analysis defined the MOG1-Nav1.5 interaction domain to amino acids S476-H585 of Nav1.5 Loop I connecting transmembrane domains I and II. Microdeletion and point mutation analyses further defined the domain to F530T531F532R533R534R535. Mutations F530A, F532A, R533A and R534A, but not T531A and R535A, significantly reduced MOG1-Nav1.5 interaction, and eliminated MOG1-enhanced INa. Mutagenesis analysis identified D24, E36, D44, E53, and E101A of MOG1 as critical residues for interaction with Nav1.5 Loop I. We then characterized three mutations at the MOG1-Nav1.5 interaction domain, p.F530V, p.F532C and p.R535Q reported from patients with LQTS and BrS. We found that p.F532C reduced MOG1-Nav1.5 interaction, and eliminated MOG1 function on INa; p.R535Q is also a loss-of-function mutation that reduces INa amplitude in a MOG1-independent manner, whereas p.F530V is benign as it does not have apparent effect on MOG1 and INa. CONCLUSIONS: Our findings define the MOG1-Nav1.5 interaction domain to a 5-amino-acid motif of F530T531F532R533R534 in Loop I. Mutation p.F532C associated with BrS abolishes Nav1.5 interaction with MOG1 and reduces MOG1-enhanced INa density, thereby uncovering a novel molecular mechanism for the pathogenesis of BrS.

12.
Environ Res ; : 112166, 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34619129

RESUMO

The ecological heterogeneity created by river bends benefits the diversity of microorganisms, which is vital for the pollutant degradation and overall river health. However, quantitative tools capable of determining the interactions among different trophic levels and species are lacking, and research regarding ecological heterogeneity has been limited to a few species. By integrating the multi-species-based index of biotic integrity (Mt-IBI) and the structure equation model (SEM), an interactions-based prediction modeling framework was established. Based on DNA metabarcoding, a multi-species (i.e., bacteria, protozoans, and metazoans) based index of biotic integrity including 309 candidate metrics was developed. After a three-step screening process, eight core metrics were obtained to assess the ecological heterogeneity, quantitatively. The Mt-IBI value, which ranged from 2.08 to 7.17, was calculated as the sum of each single core metric value. The Mt-IBI revealed that the ecological heterogeneity of concave banks was higher than other sites. According to the result of the SEM, D90 was the controlling factor (r = -0.779) of the ecological heterogeneity under the influence of the river bends. The bend-induced redistribution of sediment particle further influenced the concentrations of carbon, nitrogen, and sulphur. The nitrogen group (r = 0.668) also played an essential role in determining the ecological heterogeneity, follow by carbon group (r = 0.455). Furthermore, the alteration of niches would make a difference on the ecological heterogeneity. This multi-species interactions-based prediction modeling framework proposed a novel method to quantify ecological heterogeneity and provided insight into the enhancement of ecological heterogeneity in river bends.

13.
Water Res ; 206: 117730, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34619413

RESUMO

The nitrogen (N) cycle is one of the most important nutrient cycles in river systems, and it plays an important role in maintaining biogeochemical balance and global climate stability. One of the main ways that humans have altered riverine ecosystems is through the construction of hydropower dams, which have major effects on biogeochemical cycles. Most previous studies examining the effects of damming on N cycling have focused on the whole budget or flux along rivers, and the role of river as N sources or sinks at the global or catchment scale. However, so far there is still lack of comprehensive and systematic summarize on N cycling and the controlling mechanisms in reservoirs affected by dam impoundment. In this review, we firstly summarize N cycling processes along the longitudinal riverine-transition-lacustrine gradient and the vertically stratified epilimnion-thermocline-hypolimnion gradient. Specifically, we highlight the direct and indirect roles of multi-trophic microbiota and their interactions in N cycling and discuss the main factors controlling these biotic processes. In addition, future research directions and challenges in incorporating multi-trophic levels in bioassessment, environmental flow design, as well as reservoir regulation and restoration are summarized. This review will aid future studies of N fluxes along dammed rivers and provide an essential reference for reservoir management to meet ecological needs.


Assuntos
Microbiota , Rios , China , Ecossistema , Monitoramento Ambiental , Humanos , Nitrogênio , Ciclo do Nitrogênio
14.
Environ Res ; : 112182, 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34648762

RESUMO

Microplastics are frequently detected in natural aquatic systems proximate to populated areas, such as urban rivers and lakes, and can be rapidly colonized by microbial communities. Microplastics and silver nanoparticles (AgNPs) share similar pathways into natural waters and tend to form heteroaggregations. However, very little is known about the long-term impacts on the structure and function of microplastic biofilms when chronically exposed to silver nanoparticles. Thus, the present study assessed the accumulation property of AgNPs on polymethyl methacrylate (PMMA) microplastics via adsorption tests and studied the chronic effects of AgNPs on the structure and function of microplastic biofilms via 30-day microcosmic experiments in eutrophic water. The adsorption tests showed that the biofilms-colonized PMMA microplastics presented the highest adsorption of 0.98 mg/g in the 1 mg/L AgNPs microcosms. After the 30-day exposure, lactic dehydrogenase release and reactive oxygen species generation of PMMA biofilms increased by 33.23% and 23.98% compared to the MPs-control group with no-AgNPs, indicating that the number of dead cells colonizing microplastics significantly increased. Network analysis suggested that the stabilization of the bacterial community declined with the long-term exposure to AgNPs through the reduction of the modularity and average path length of the network. Compared to the MPs-control group, long-term exposure to AgNPs caused cumulatively inhibitory effects on the nitrogen removal and the N2O emissions in eutrophic water. The isotopomer analysis revealed that the contribution rate of NO2- reduction to N2O emissions was gradually increasing with the AgNPs exposure. Real-time PCR analysis showed that denitrification genes were less sensitive to AgNPs than the nitrification genes, with gene nosZ performed the most negligible response. Overall, our results revealed that long-term exposure to AgNPs could alter biogeochemical cycling involved by microplastic biofilms and cumulatively reduce the self-recovery of the eutrophic ecosystem.

15.
ACS Appl Mater Interfaces ; 13(39): 46840-46847, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34546028

RESUMO

Fiber-based nanogenerators have great potential applications in wearable electronics such as portable nanodevices, e-skin, and artificial intelligence system. Here, we report a kind of fiber-based electret nanogenerator (FENG) with a semisupported core-shell structure. Owing to its unique structure, the open-circuit voltage and short-circuit current of the FENG reach 40 V and 0.6 µA, respectively, under a short working distance (∼25 µm). No obvious degradation of the output performance under a long-time continuous work (>16 h) and different humidity environments (20-95%) is observed, which demonstrates the FENG's good reliability and stability. Many universal materials, such as cotton rope, conductive sewing thread, and polyvinyl chloride tube, have been successfully used to fabricate FENG. Meanwhile, the FENG-based wearable fabric has been successfully developed to effectively harvest mechanical energy of human motion. The FENG is highly effective, reliable, and stable, promoting the development of fiber-based nanogenerators and their applications in self-powered wearable electronics.

16.
Proc Natl Acad Sci U S A ; 118(36)2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34470821

RESUMO

Mechanical forces generated by cells and the tension of the extracellular matrix (ECM) play a decisive role in establishment, homeostasis maintenance, and repair of tissue morphology. However, the dynamic change of cell-derived force during large-scale remodeling of soft tissue is still unknown, mainly because the current techniques of force detection usually produce a nonnegligible and interfering feedback force on the cells during measurement. Here, we developed a method to fabricate highly stretchable polymer-based microstrings on which a microtissue of fibroblasts in collagen was cultured and allowed to contract to mimic the densification of soft tissue. Taking advantage of the low-spring constant and large deflection range of the microstrings, we detected a strain-induced contraction force as low as 5.2 µN without disturbing the irreversible densification. Meanwhile, the microtissues displayed extreme sensitivity to the mechanical boundary within a narrow range of tensile stress. More importantly, results indicated that the cell-derived force did not solely increase with increased ECM stiffness as previous studies suggested. Indeed, the cell-derived force and collagen tension exchanged dramatically in dominating the microtissue strain during the densification, and the proportion of cell-derived force decreased linearly as the microtissue densified, with stiffness increasing to ∼500 Pa. Thus, this study provides insights into the biomechanical cross-talk between the cells and ECM of extremely soft tissue during large-extent densification, which may be important to guide the construction of life-like tissue by applying appropriate mechanical boundary conditions.

17.
J Environ Manage ; 299: 113585, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34438311

RESUMO

Cascade dams have exerted significant effects on river ecosystems. To quantitatively assess dam-induced effects on river ecological status, a novel multi-species interaction-based index of biotic integrity (Mt-IBI) was developed. Benthic microbiota was selected as a bio-indicator for its sensitivity to the environmental disturbance. An environmental DNA metabarcoding tool was used to identify microbiota (bacteria, protozoan, and metazoan). The Mt-IBI was applied to assess the ecological status of the Hanjiang River, a representative dam-affected river in China. Fifteen sampling sites along the Hanjiang River were sampled in June 2018. Seven core metrics were screened from a total of 364 candidate metrics to calculate the value of the Mt-IBI. The Mt-IBI of the Hanjiang River ranged from 1.90 to 6.39, with a mean value of 4.02. The mean values of Mt-IBI at the reservoir and riverine side of dams were 2.11 and 3.81, respectively. The downstream reach without dam constructions had the highest mean Mt-IBI (5.79). Thus, the continuity of the river was strongly related to the Mt-IBI. Structural equation models (SEMs) were further established to identify the dominant environmental variables in the dam-affected river. The SEMs indicated that flow velocity (coefficient 0.749) was the most important determinant of ecological status in the Hanjiang River. Water organic matter also played a vital role in determining the ecological status of the Hanjiang River, and exerted the strongest direct effect (P < 0.001, r = 0.712). The reliability of SEMs was verified by building a support vector regression model (R2 = 0.8141). This study can provide new tools for ecological assessment and diagnosis, and provide a new perspective for the management of cascade dams.


Assuntos
Ecossistema , Microbiota , Animais , Bactérias , Código de Barras de DNA Taxonômico , Monitoramento Ambiental , Reprodutibilidade dos Testes , Rios
18.
Water Res ; 203: 117538, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34416651

RESUMO

Catastrophic shifts in river ecosystems can abruptly degrade their structures and functions, often reducing the efficacy of traditional remediation targeting physicochemical properties. Alternative stable states theory can not only explain this phenomenon but also provide a new insight into river restoration; however, little is known about the existence and implications of alternative stable states in a river. Considering the important role of benthic microbiota in sustaining river ecosystem structures and functions, ecological theory and high-throughput sequencing were combined to firstly investigate multi-stability in microbial communities and its relationship with environmental factors in river sediments. The Nanjing reach of the Yangtze River was selected as the study area because of its huge spatial heterogeneity and varying degrees of pollution. Bimodal distributions combined with temporal variations of microbiota status provided direct evidence of bistability by showing the instability at the intermediate. In addition, environmental stress, particularly concentrations of NH4+-N and NO3--N, was identified as an important driver of alternative microbiota states from the perspectives of the behavior of bistable ecosystems. Comparison of α-diversity indices and network properties between two alternative microbiota states revealed that the diversity and co-occurrence pattern of microbial communities will be high if they are settled in favorable environments (i.e., comprehensive sediment quality identification index > 3.7). Key taxa, including Clostridiales, Nitrospirales and Myxococcales, were discerned by combining LEfSe and network analysis, and their strong interspecies interactions were believed to be an important factor in triggering alternative microbiota states. This study suggests alternative stable states theory should be considered in river remediation to better understand the response of river ecosystems to environmental stress and the effect of hysteresis, benefiting the implementation of effective monitoring and restoration strategies in a river of urban area.


Assuntos
Microbiota , Rios , Bactérias , China , Ecossistema , Monitoramento Ambiental , Sedimentos Geológicos
19.
Protein Cell ; 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34331666

RESUMO

LIN28 is an RNA binding protein with important roles in early embryo development, stem cell differentiation/reprogramming, tumorigenesis and metabolism. Previous studies have focused mainly on its role in the cytosol where it interacts with Let-7 microRNA precursors or mRNAs, and few have addressed LIN28's role within the nucleus. Here, we show that LIN28 displays dynamic temporal and spatial expression during murine embryo development. Maternal LIN28 expression drops upon exit from the 2-cell stage, and zygotic LIN28 protein is induced at the forming nucleolus during 4-cell to blastocyst stage development, to become dominantly expressed in the cytosol after implantation. In cultured pluripotent stem cells (PSCs), loss of LIN28 led to nucleolar stress and activation of a 2-cell/4-cell-like transcriptional program characterized by the expression of endogenous retrovirus genes. Mechanistically, LIN28 binds to small nucleolar RNAs and rRNA to maintain nucleolar integrity, and its loss leads to nucleolar phase separation defects, ribosomal stress and activation of P53 which in turn binds to and activates 2C transcription factor Dux. LIN28 also resides in a complex containing the nucleolar factor Nucleolin (NCL) and the transcriptional repressor TRIM28, and LIN28 loss leads to reduced occupancy of the NCL/TRIM28 complex on the Dux and rDNA loci, and thus de-repressed Dux and reduced rRNA expression. Lin28 knockout cells with nucleolar stress are more likely to assume a slowly cycling, translationally inert and anabolically inactive state, which is a part of previously unappreciated 2C-like transcriptional program. These findings elucidate novel roles for nucleolar LIN28 in PSCs, and a new mechanism linking 2C program and nucleolar functions in PSCs and early embryo development.

20.
Biochem Biophys Res Commun ; 569: 79-85, 2021 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-34237431

RESUMO

Ferroptosis is a newly identified type of regulated cell death that is affected by lipid peroxidation and reactive oxygen species (ROS). In the current study, we showed that cisplatin and PRLX93936, an analog of erastin that has been tested in clinical trials, demonstrated synergistic effects against non-small cell lung cancer (NSCLC) cells. Cotreatment with cisplatin and PRLX93936 induced ferroptosis, as evidenced by the upregulation of ROS, lipid peroxidation and Fe2+. Further investigation revealed that cotreatment with cisplatin and PRLX93936 inhibited GPX4 and that overexpression of GPX4 prevented cell death. Moreover, the Nrf2/Keap1 pathway also regulated the sensitivity to cisplatin and PRLX93936 in NSCLC cells. Nrf2 silencing increased this sensitivity while inhibition of Keap1 attenuated it. Overall, our data reveal a new effective treatment for NSCLC by synergizing cisplatin and PRLX93936 to induce ferroptosis.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Cisplatino/farmacologia , Ferroptose/efeitos dos fármacos , Neoplasias Pulmonares/metabolismo , Bibliotecas de Moléculas Pequenas/farmacologia , Células A549 , Antineoplásicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sinergismo Farmacológico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/genética , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética
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