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The intricate structure of lignin in straw makes it challenging to hydrolyze, making it a key focus of current research. However, there has been limited study on the effect of enzyme inducer (MnSO4) combined with functional microorganisms on lignin degradation during straw composting. Based on this, four composting treatment groups were set up in this study. Control (CK), functional microorganism addition treatment (F), Mn2+ enzyme inducer (Mn), and Mn2+ enzyme inducer coupled with functional microorganism addition treatment (FMn) were tested for composting. Manganese(II)-coupled microorganisms improved lignin degradation: FMn > Mn > F > CK. They increased the lignin loss rate from 25.54 % to 42.61 %. Laccase activity increased from 3.45 to 43.74 U/g and manganese peroxidase activity increased from 145.52 to 264.91 U/g. And gene abundance was increased. Microbial community structure and dominant genera changed. Structural equations support the idea that functional microorganisms coupled with manganese can modify physicochemical indices, thereby regulating gene expression and enhancing enzyme activity. Furthermore, the stimulation of fungal growth and increased extracellular laccase and manganese peroxidase activities can affect the degradation of lignin. This study provides new insights and theoretical support for efficient lignin degradation and efficient resource utilization of compost products.
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The Qinghai-Tibetan Plateau has a booming tourism industry and an increasingly sophisticated road system. There is a paucity of studies quantifying the contributions of anthropogenic and natural factors to microplastic pollution in remote plateau areas. In this study, water and sediment samples were collected from eight lake tourist attractions and four remote lakes in northern and southern regions of the Qinghai-Tibetan Plateau. Microplastics were detected in all samples, with a mean abundance of 0.78 items/L in water and 44.98 items/kg in sediment. The abundance of microplastics in the study area was lower than previously observed in more populated areas of China. Small-sized (<1 mm and 1-2 mm), fiber, and transparent microplastics were predominant, with polyethylene and polypropylene microplastics as the primary polymer types. The compositions of microplastic communities indicated that tourism and road networks were the major sources of microplastics in the lakes. Distance-decay models revealed greater influence of environmental distances on microplastic community similarity than geographic distance. Compared to climate factors, urban spatial impact intensity and traffic flow impact played a leading role in the structuring of microplastic communities in lake water and sediment. Our findings provide novel quantitative insights into the role of various factors in shaping the distribution patterns of microplastic communities in plateau lakes.
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BACKGROUND: The transcription factor GATA4 is pivotal in cancer development but is often silenced through mechanisms like DNA methylation and histone modifications. This silencing suppresses the transcriptional activity of GATA4, disrupting its normal functions and promoting cancer progression. However, the precise molecular mechanisms and implications of GATA4 silencing in tumorigenesis remain unclear. Here, we aim to elucidate the mechanisms underlying GATA4 silencing and explore its role in breast cancer progression and its potential as a therapeutic target. METHODS: The GATA4-breast cancer prognosis link was explored via bioinformatics analyses, with GATA4 expression measured in breast tissues. Functional gain/loss experiments were performed to gauge GATA4's impact on breast cancer cell malignancy. GATA4-PRC2 complex interaction was analyzed using silver staining and mass spectrometry. Chromatin immunoprecipitation, coupled with high-throughput sequencing, was used to identify GATA4-regulated downstream target genes. The in vitro findings were validated in an in situ breast cancer xenograft mouse model. RESULTS: GATA4 mutation and different breast cancer subtypes were correlated, suggesting its involvement in disease progression. GATA4 suppressed cell proliferation, invasion, and migration while inducing apoptosis and senescence in breast cancer cells. The GATA4-PRC2 complex interaction silenced GATA4 expression, which altered the regulation of FAS, a GATA4 downstream gene. In vivo experiments verified that GATA4 inhibits tumor growth, suggesting its regulatory function in tumorigenesis. CONCLUSIONS: This comprehensive study highlights the epigenetic regulation of GATA4 and its impact on breast cancer development, highlighting the PRC2-GATA4-FAS pathway as a potential target for therapeutic interventions in breast cancers.
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The onerous health and economic burden associated with head and neck squamous cell carcinoma (HNSCC) is a global predicament. Despite the advent of novel surgical techniques and therapeutic protocols, there is an incessant need for efficacious diagnostic and therapeutic targets to monitor the invasion, metastasis and recurrence of HNSCC due to its substantial morbidity and mortality. The differential expression patterns of histone deacetylases (HDACs), a group of enzymes responsible for modifying histones and regulating gene expression, have been demonstrated in neoplastic tissues. However, there is limited knowledge regarding the role of HDACs in HNSCC. Consequently, this review aims to summarize the existing research findings and explore the potential association between HDACs and HNSCC, offering fresh perspectives on therapeutic approaches targeting HDACs that could potentially enhance the efficacy of HNSCC treatment. Additionally, the Cancer Genome Atlas (TCGA) dataset, CPTAC, HPA, OmicShare, GeneMANIA and STRING databases are utilized to provide supplementary evidence on the differential expression of HDACs, their prognostic significance and predicting functions in HNSCC patients.
Sujet(s)
Tumeurs de la tête et du cou , Inhibiteurs de désacétylase d'histone , Histone deacetylases , Carcinome épidermoïde de la tête et du cou , Humains , Histone deacetylases/métabolisme , Carcinome épidermoïde de la tête et du cou/traitement médicamenteux , Carcinome épidermoïde de la tête et du cou/génétique , Carcinome épidermoïde de la tête et du cou/enzymologie , Carcinome épidermoïde de la tête et du cou/anatomopathologie , Tumeurs de la tête et du cou/traitement médicamenteux , Tumeurs de la tête et du cou/génétique , Tumeurs de la tête et du cou/anatomopathologie , Tumeurs de la tête et du cou/enzymologie , Inhibiteurs de désacétylase d'histone/usage thérapeutique , Inhibiteurs de désacétylase d'histone/pharmacologie , Thérapie moléculaire ciblée , Régulation de l'expression des gènes tumorauxRÉSUMÉ
Yanhe River Basin is located in the hilly gully area of the Loess Plateau with serious soil erosion. Strong human activities in the middle and lower reaches lead to fragile ecological environment. Soil erosion status varies among different geomorphic units within the watershed (loess liang hilly and gully region, loess mao hilly and gully region, and broken platform region). In this study, we surveyed the benthic community from the Yanhe River Basin in April (spring) and October (autumn) of 2021. To evaluate the water ecological health status of the watershed and investigate the effects of different geomorphic units on the benthic integrity of the benthos, we constructed the benthic-index of biotical integrity (B-IBI) based on the biological data. We identified a total of 113 species of 73 genera in 4 phyla of benthic fauna, with aquatic insects as the dominant taxa in both seasons. Through screening 26 candidate indicators, we found that the spring B-IBI consisted of three indicators: relative abundance of individuals of dominant taxonomic units, family biotic index (FBI), and relative abundance of predator individuals, and that autumn B-IBI was composed of the number of taxonomic units of Ephemeroptera, FBI value, and the relative abundance of predator individuals. Results of the B-IBI evaluation showed that 83.3% of the sampling sites in the upper mainstem and tributaries were at a healthy condition, while only 28.6% sampling sites in the middle and lower mainstem and tributaries were at a healthy condition. In addition, the health status of the watershed was better in spring than in autumn. The Kruskal-Wallis nonparametric tests showed that benthic density, species number, and B-IBI percentile scores in the fragmented loess area were significantly higher in spring than in autumn, and significantly lower in autumn than in the loess liang hilly and gully region and loess mao hilly and gully region, being mainly caused by the increasing erosion due to the concentrated rainfall in wet season. Results of the redundancy analysis showed that key environmental factors affecting benthic community structure in spring were boulder substrate, chlorophyll-a, oxidation reduction potential, turbidity, conductivity, and dissolved oxygen, and were nitrate-nitrogen, oxidation reduction potential, and pH in autumn.
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Écosystème , Surveillance de l'environnement , Invertébrés , Rivières , Chine , Animaux , Surveillance de l'environnement/méthodes , Invertébrés/classification , Invertébrés/croissance et développement , Insectes , Biodiversité , SaisonsRÉSUMÉ
Flooding is an important process in natural fluvial floodplains. How the flood shapes aquatic community diversity in highland floodplains is still poorly understood. The aim of this study was to unravel the multi-faceted responses of benthic macroinvertebrate diversity to flooding and habitat environments in the Baihe River Basin from a taxonomic, phylogenetic, and functional perspective. We examined the alpha and beta diversity patterns of benthic macroinvertebrate communities in the mainstream, tributaries, and oxbow lakes during the normal water and flood periods. The results showed that the traditional alpha taxonomic diversity (TD) varied across habitats, despite minor changes after flood pulse. Alpha phylogenetic diversity (PD) decreased and alpha functional diversity (FD) markedly increased after flooding, with functional traits transiting toward risk avoidance. While all the three facets of beta diversity significantly responded to habitat differences, beta TD and PD shifted in response to flooding. Species turnover prominently increased in beta TD and PD after flood pulse, which contrasted with a weaker response of this process in FD. The explanatory power of significant environmental factors on both alpha and beta diversity was reduced by flooding. Compared with traditional TD, cooperating multi-faceted diversity could better depict the responses of benthic macroinvertebrate communities to flooding. The assessment and conservation of aquatic biodiversity in highland floodplains should take into account the three facets of alpha and beta diversity.
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Biodiversité , Inondations , Invertébrés , Animaux , Invertébrés/physiologie , Chine , Rivières , Phylogenèse , ÉcosystèmeRÉSUMÉ
In the context of the increasing global greenhouse effect, the Chinese government has proposed a "dual carbon" target. As a major carbon-emitting province in China, Shandong Province needs to improve its carbon productivity to coordinate carbon emission reductions and sustainable economic growth. This study analyzes the spatial and temporal evolution of carbon productivity at the county scale and the factors influencing it in Shandong Province from 2000 to 2017. The study uses the Dagum Gini coefficient, kernel density analysis, spatial autocorrelation model, and geographically and temporally weighted regression model. The results indicate that the carbon productivity in Shandong Province nearly doubled during the study period, revealing a spatial distribution characteristic of "high in the east and low in the west," together with a significant positive spatial autocorrelation. Intra-regional differences, the most important source of development differences among the three economic circles, rose to 32.11% during the study period, whereas inter-regional differences declined to 26.6%. Gross domestic product per capita and population density play a significant positive role in the development of carbon productivity. The balance of deposits in financial institutions at the end of the year has a weak positive effect, and the local average public finance expenditure and secondary industry structure on carbon productivity are negative in general. Shandong Province should identify specific regions with weak carbon productivity levels and understand the key factors to improve carbon productivity to promote the achievement of the "dual carbon" goal.
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Carbone , Développement économique , Carbone/analyse , Analyse spatiale , Chine/épidémiologie , Produit intérieur brutRÉSUMÉ
Rivers play a vital role in the maintenance of the biosphere and human society, since they participate in the global water cycle and provide varied habitats to support biodiversity. Microhabitat heterogeneity is regarded as a key factor driving biodiversity and it plays an active ecological role in different types of mountain rivers. Whether river microhabitat heterogeneity exhibits the same ecological patterns across hydrological periods remains unclear. Here, we analyzed the changes in macroinvertebrate community composition, functional traits, and multi-faceted α-diversity in five debris flow gullies in the Xiaojiang River Basin (southwestern China) between two different hydrological periods. We explored the responses of biodiversity to river microhabitat heterogeneity and its driving factors before and after hydrological disturbance. The results indicated that river microhabitat heterogeneity and three facets of macroinvertebrate α-diversity decreased after hydrological disturbance, with macroinvertebrate state traits becoming more unbalanced. Macroinvertebrate taxonomic diversity increased with increasing river microhabitat heterogeneity across hydrological periods, and this pattern was more prominent before hydrological disturbance. A high correlation emerged between macroinvertebrate phylogenetic diversity and river microhabitat heterogeneity only before hydrological disturbance. Hydrogeomorphic parameters prominently affected macroinvertebrate communities before hydrological disturbance. Water environmental parameters worked together with hydrogeomorphic parameters to shape macroinvertebrate communities in hydrologically disturbed debris flow gullies, indicating a reduced ecological role of river microhabitat heterogeneity. The ecological health of debris flow gullies can be improved by increasing vegetation coverage on river bank slopes to increase slope stability and mitigate hydrological disturbances, as well as placing large rocks into river channels to enhance riverbed stability and create habitats for more biological groups.
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Surveillance de l'environnement , Invertébrés , Animaux , Humains , Invertébrés/physiologie , Phylogenèse , Biodiversité , Écosystème , RivièresRÉSUMÉ
Oral squamous cell carcinoma (OSCC) is the most prevalent cancer of the mouth, characterised by rapid progression and poor prognosis. Hence, an urgent need exists for the development of predictive targets for early diagnosis, prognosis determination, and clinical therapy. Dysregulation of lymphoid enhancer-binding factor 1 (LEF1), an important transcription factor involved in the Wnt-ß-catenin pathway, contributes to the poor prognosis of OSCC. Herein, we aimed to explore the correlation between LEF1 and histone lysine demethylase 4 A (KDM4A). Results show that the KDM4A complex is recruited by LEF1 and specifically binds the LATS2 promoter region, thereby inhibiting its expression, and consequently promoting cell proliferation and impeding apoptosis in OSCC. We also established NOD/SCID mouse xenograft models using CAL-27 cells to conduct an in vivo analysis of the roles of LEF1 and KDM4A in tumour growth, and our findings show that cells stably suppressing LEF1 or KDM4A have markedly decreased tumour-initiating capacity. Overall, the results of this study demonstrate that LEF1 plays a pivotal role in OSCC development and has potential to serve as a target for early diagnosis and treatment of OSCC.
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Tumeurs de la bouche , Carcinome épidermoïde de la tête et du cou , Animaux , Humains , Souris , bêta-Caténine/génétique , bêta-Caténine/métabolisme , Carcinogenèse/génétique , Lignée cellulaire tumorale , Prolifération cellulaire/génétique , Facteur de transcription LEF-1/génétique , Facteur de transcription LEF-1/métabolisme , Souris de lignée NOD , Souris SCID , Tumeurs de la bouche/génétique , Tumeurs de la bouche/anatomopathologie , Protein-Serine-Threonine Kinases/métabolisme , Carcinome épidermoïde de la tête et du cou/génétique , Carcinome épidermoïde de la tête et du cou/anatomopathologie , Protéines suppresseurs de tumeurs/métabolisme , Voie de signalisation Wnt/génétiqueRÉSUMÉ
Uncovering the mechanisms underlying phytoplankton community assembly remains a major challenge in freshwater ecology. The roles of environmental filtering and spatial processes in shaping phytoplankton metacommunity in Tibetan floodplain ecosystems under various hydrological conditions are still unclear. Here, multivariate statistics and a null model approach were used to compare the spatiotemporal patterns and assembly processes of phytoplankton communities in the river-oxbow lake system of Tibetan Plateau floodplain between non-flood and flood periods. The results showed that phytoplankton communities had significant seasonal and habitat variations, with the seasonal variations being more remarkable. Phytoplankton density, biomass, and alpha diversity were distinctly lower in the flood than non-flood period. The habitat differences (rivers vs. oxbow lakes) in phytoplankton community were less pronounced during the flood than non-flood period, most likely due to the increased hydrological connectivity. There was a significant distance-decay relationship only in lotic phytoplankton communities, and such relationship was stronger in the non-flood than flood period. Variation partitioning and PER-SIMPER analysis showed that the relative role of environmental filtering and spatial processes affecting phytoplankton assemblages varied across hydrological periods, with environmental filtering dominating in the non-flood period and spatial processes in the flood period. These results suggest that the flow regime plays a key role in balancing environmental and spatial factors in shaping phytoplankton communities. This study contributes to a deeper understanding of ecological phenomena in highland floodplains and provides a theoretical basis for floodplain ecosystem maintenance and ecological health management.
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Herein, we report a synthesis of cyclohexanones bearing multi-continuous stereocenters by combining copper-catalyzed asymmetric conjugate addition of dialkylzinc reagents to cyclic enones with iridium-catalyzed asymmetric allylic substitution reaction. Good to excellent yields, diastereoselectivity and enantioselectivity can be obtained. Unlike the stereodivergent construction of adjacent stereocenters (1,2-position) reported in the literature, the current reaction can achieve the stereodivergent construction of nonadjacent stereocenters (1,3-position) by a proper combination of two chiral catalysts with different enantiomers.
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Exploring the spatial correlation characteristics and influencing factors of industrial agglomeration and pollution discharge, which is of great significance to reduce industrial pollution discharge and promote China's construction of an ecological civilization. Taking 284 prefecture-level cities in China in 2017 as the research object, this study used spatial autocorrelation analysis method to explore the spatial agglomeration characteristics and spatial correlation of industrial agglomeration and industrial pollution discharge, and spatial econometric analysis method was used to explore the main factors affecting industrial pollution discharge. The research results showed that the level of industrial agglomeration in China exhibited a spatial distribution characteristic of "high in the east and low in the west". The total discharge and discharge intensity of industrial pollutants showed a spatial pattern of "high in the north and low in the south" in general, and industrial agglomeration, total discharge, and discharge intensity of industrial pollution showed significant spatial autocorrelation. Moreover, industrial agglomeration had a strong local spatial correlation with the total and intensity of industrial wastewater, industrial SO2, and industrial smoke and dust, and the main agglomeration types were high agglomeration-low pollution, low agglomeration-high pollution, and low agglomeration-low pollution. In addition, industrial agglomeration had a positive impact on the total industrial wastewater discharge, and had a negative impact on the total industrial smoke and dust discharge, industrial wastewater discharge intensity, industrial SO2 discharge intensity, and industrial smoke and dust discharge intensity.
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Poussière , Eaux usées , Villes , Chine , Fumée , Développement économiqueRÉSUMÉ
In the context of an overall improvement in the national economy, residents' demand for nutrition and health has been increasing. An industry that provides healthy eating plays an increasingly important role in urban development. Few studies, however, have focused on the relationship between the urban road network structure and the vitality of the healthy catering industry (VHCI). Based on social media data and urban traffic network data, in this study, we explored the impact mechanism of street centrality on the VHCI through a case study of Jinan, China, using geographic detectors and multiscale geographically weighted regression (MGWR) methods. The results show the following: First, the vitality of the catering industry in the main urban area of Jinan has multicore spatial distribution characteristics, and the high-value areas of the vitality of the catering industry are highly matched with the main business districts in the city in space. Second, we found clear spatial differences in street centrality between the walking and driving modes. With an increase in the search radius, the trend of high-value areas closely gathering in the urban center became clearer. The distribution of betweenness was observed from sheet to grid, and the multicenter structure of straightness was more prominent. Third, differences in the residents' perception of the road network structure caused by different travel modes affected their choice of dining places. In the driving mode, betweenness and straightness had a greater impact on the vitality of the catering industry, and the effect of closeness in the walking mode was more obvious. Fourth, the influence of street centrality on the vitality of the healthy catering industry had obvious spatial heterogeneity. In the walking mode, the spatial heterogeneity of straightness was the strongest, followed by betweenness, and closeness was the weakest; in the driving mode, the spatial heterogeneity of closeness was the strongest, followed by straightness, and betweenness was the weakest. From the perspective of residents' travel, the results of this study revealed the influence mechanism of urban road network characteristics on the VHCI. This information can aid planning for urban space optimization and improve residential living quality.
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État de santé , Industrie , Humains , Chine , Commerce , VoyageRÉSUMÉ
BACKGROUND: To conduct a systematic review of the efficacy of Chinese herbal bath therapy on children with Atopic dermatitis. METHODS: We searched Chinese databases (CNKI, VIP, and Wanfang) and English databases (PubMed, Embase, Web of science, Cochrane library) for studies from the establishment of the database to September 2022. The included literature was randomized control studies investigating the treatment of Atopic dermatitis in children by Chinese herbal bath therapy. The outcomes included the cure rate, scoring atopic dermatitis (SCORAD) index, adverse reactions and recurrence rate. RevMan 5.4 was used to analyze the extracted data. RESULTS: A total of 8 related studies were included containing 854 cases. The meta-analysis showed that Chinese herbal bath therapy group was superior to control group in terms of cure rate, SCORAD index, adverse reactions and recurrence rate in children with Atopic dermatitis [RRâ =â 1.11, 95%(1.02, 1.21), Pâ =â .01; SMDâ =â -0.77, 95%(-0.99, -0.55), Pâ <â .00001; RRâ =â 0.44, 95%CI(0.28,0.67), Pâ =â .0002; RRâ =â 0.25, 95%CI(0.10, 0.59), Pâ =â .0002]. CONCLUSION: The present study shows that Chinese herbal bath therapy is an effective treatment for children with Atopic dermatitis in China.
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Eczéma atopique , Enfant , Humains , Eczéma atopique/traitement médicamenteux , PubMed , Asiatiques , Chine , Groupes témoinsRÉSUMÉ
In the existing literature on the correlation between street centrality and land use intensity (LUI), only a few studies have explored the disparity of this correlation for different types of LUI and the differences across various locations. In response to the above shortcomings, in this study, the main urban area of Jinan, China, was taken as an example, and the disparity and spatial heterogeneity of the correlation between street centrality and LUI were explored for different categories of land use. The multiple centrality assessment (MCA) model was used to calculate the closeness centrality, betweenness centrality, and straightness centrality of the traffic network. Based on the floor area ratio (FAR) of each parcel, the utilization intensities of the residential, industrial, commercial, and public service land uses were measured. Employing the kernel density estimation (KDE) method, the street centrality of the traffic network vis-à-vis the urban LUI was rasterized into the same spatial analysis framework. The Pearson correlation coefficient and geographically weighted regression (GWR) were used to measure the correlation between the two variables and the spatial heterogeneity of the correlation, respectively. The results showed that traffic network street centrality strongly correlated with the LUI of the residential, commercial, and public service land use types, but it had a very weak association with the LUI of industrial land use. The GWR results also confirmed the spatial heterogeneity of the correlation. The results of this research highlighted the important role of traffic network street centrality in understanding the urban spatial structure. The study also helped to explain the dynamic mechanism of the road network form and the topological structure of urban spatial evolution.
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Industrie , Régression spatiale , Analyse spatiale , ChineRÉSUMÉ
A resource-based city is a type of city characterized by the exploitation and processing of natural resources as the leading industry in the region. Such cities provide essential resources for China's economic development and support long-term rapid economic growth. However, resource-based cities (RBCs) face challenges, including resource depletion, economic recession, environmental pollution, and ecological damage, to which not enough attention has been paid. In the context of China's increased focus on environmental protection and the economy, improving industrial ecological efficiency of RBCs has become ever more important. In the present study, the Super-SBM model was used to measure the industrial ecological efficiency of 114 RBCs in China from 2003 to 2016. The results show that during the study period, the industrial ecological efficiency of RBCs in China improved significantly, particularly in the central and western regions. The results from a Tobit model show that appropriate environmental regulation and financial pressure have a positive impact on the industrial ecological efficiency of RBCs. However, when faced with the dual pressures of environmental regulation and financial difficulty, improvement in industrial ecological efficiency was inhibited. The impact of environmental regulation and financial pressure on industrial ecological efficiency of cities in different regions and development stages and with different resource types shows heterogeneity. In accordance with the study findings, differentiated measures and suggestions are proposed to improve the industrial ecological efficiency of RBCs.
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Développement économique , Stress financier , Chine , Villes , Rendement , IndustrieRÉSUMÉ
Dispersal is an essential natural process that influences community assembly, yet directional dispersal through wind and water may have distinctive effects. Environmental and spatial factors jointly influence community structure, but their relative importance is anticipated to vary with spatial distance, dispersal mode, and season. Accordingly, a systemic survey was conducted in subtropical Chinese mountain lotic systems to distinguish the relative contributions of environmental control and spatial structuring upon communities of macroinvertebrates with different dispersal ability. Macroinvertebrate samples were collected from the upper reaches and five tributaries of the Hanjiang River in October 2017 (autumn) and April 2018 (spring). These macroinvertebrates were identified and classified into three dispersal groups: aquatic passive (AqPa), terrestrial passive (TePa), and terrestrial active (TeAc). Variation partitioning analyses were performed on environmental factors and different sets of spatial factors (overland dispersal: Overland, directional downwind dispersal: AEM_Wind, along watercourse dispersal: Watercourse, and directional downstream dispersal: AEM_Water). Findings showed that both environmental filtering and spatial structuring influenced the structure of macroinvertebrate metacommunities. For AqPa and TePa groups, pure environmental effects were stronger than pure spatial effects based on most distance matrices; however, in AEM_Water, the effects of spatial processes surpassed those of environmental filtering. For TeAc group, the role of environmental control and spatial structuring varied depending on different spatial models. The results also highlighted seasonal shifts in metacommunity structuring processes. Spatial structures featuring direction, especially AEM_Water, were predominant in explaining the construction of macroinvertebrate communities. This work suggests that directional dispersal should be explicitly considered when examining the structure of ecological communities.
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Écosystème , Rivières , Biote , 1,1',1''-Phosphoryltriaziridine , EauRÉSUMÉ
A delicate balance of BMP activity is critical for tissue formation and organogenesis. However, the mechanical molecular details in ensuring the proper duration and intensity of BMP signaling have yet to be fully elucidated. Here, we identified a zebrafish mutant with a disrupted gene encoding for the BTB/POZ and zinc finger protein myoneurin (Mynn). mynn -/- mutants exhibited severe loss of pharyngeal cartilage elements, owing to poor proliferation, blocked differentiation, and low viability of cranial neural crest cells. Depletion of mynn in both zebrafish embryos and mammalian cells led to a reduction of the BMP signal activity. Mechanistically, Mynn interacts with Smad proteins in the nucleus, thereby disrupting the association between Smad protein and the phosphatase Ppm1a. Ultimately, this interaction prevents Smad dephosphorylation. More broadly, our findings may provide a new strategy to balance BMP signal activity via competitive binding of Mynn and Ppm1a to Smad proteins during pharyngeal cartilage formation.
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Hypomyelinating leukodystrophies (HLDs) are a rare group of heterogeneously genetic disorders characterized by persistent deficit of myelin observed on magnetic resonance imaging (MRI). To identify a new disease-associated gene of HLD, trio-based whole exome sequencing was performed for unexplained patients with HLD. Functional studies were performed to confirm the phenotypic effect of candidate protein variants. Two de novo heterozygous variants, c.227T>G p.(L76R) or c.227T>C p.(L76P) in TMEM163 were identified in two unrelated HLD patients. TMEM163 protein is a zinc efflux transporter localized within the plasma membrane, lysosomes, early endosomes, and other vesicular compartments. It has not been associated with hypomyelination. Functional zinc flux assays in HeLa cells stably-expressing TMEM163 protein variants, L76R and L76P, revealed distinct attenuation or enhancement of zinc efflux, respectively. Experiments using a zebrafish model with knockdown of tmem163a and tmem163b (morphants) showed that loss of tmem163 causes dysplasia of the larvae, locomotor disability and myelin deficit. Expression of human wild type TMEM163 mRNAs in morphants rescues the phenotype, while the TMEM163 L76P and L76R mutants aggravated the condition. Moreover, poor proliferation, elevated apoptosis of oligodendrocytes, and reduced oligodendrocytes and neurons were also observed in zebrafish morphants. Our findings suggest an unappreciated role for TMEM163 protein in myelin development and add TMEM163 to a growing list of genes associated with hypomyelination leukodystrophy.
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Maladies démyélinisantes , Maladies lysosomiales , Protéines membranaires , Maladies neurodégénératives , Animaux , Maladies démyélinisantes/métabolisme , Cellules HeLa , Humains , Maladies lysosomiales/métabolisme , Protéines membranaires/génétique , Protéines membranaires/métabolisme , Gaine de myéline/génétique , Gaine de myéline/métabolisme , Maladies neurodégénératives/métabolisme , Danio zébré/génétique , Danio zébré/métabolisme , Zinc/métabolismeRÉSUMÉ
The first example of the Pd(II)-catalyzed enantioselective amination of aryl C-H bonds is reported. The key to the successful realization of this asymmetric catalytic transformation was the identification of mono-N-protected α-amino-O-methylhydroxamic acid (MPAHA) ligands, which promote reactivity under mild conditions and control enantioselectivity. The counteranions in the solvent medium, hexafluoroacetylacetate and acetate, were also found to play key roles in stereocontrol and reactivity enhancement.